Effect of irradiation upon the bacterial flora in patients with head and neck cancer

International Nuclear Information System (INIS)

Rice, D.H.; Gill, G.

1979-01-01

Twenty-two consecutive patients with cancer of the head and neck, who were to receive a full tumoricidal dose of irradiation to a field that included the oral cavity and pharynx, were studied to determine the effect of the irradiation on their local bacterial flora. Aerobic cultures were taken prior to, at the completion of, and one month after the completion of their irradiation. The percentage of patients with potentially pathogenic organisms increased dramatically as the effect of the irradiation increased. This change in the local flora has obvious implications concerning the increased incidence of postoperative wound infections in patients who have received prior irradiation

15 CFR 971.602 - Significant adverse environmental effects.

Science.gov (United States)

2010-01-01

... Environmental Effects § 971.602 Significant adverse environmental effects. (a) Determination of significant adverse environmental effects. The Administrator will determine the potential for or the occurrence of any significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106...

Macrophage-induced cytostasis: kinetic analysis of bromodeoxyuridine-pulsed cells

International Nuclear Information System (INIS)

Stevenson, A.P.; Crissman, H.A.; Stewart, C.C.

1985-01-01

The effect of tumoricidal macrophages on the cell cycle progression of six different cell lines was studied using an anti-bromodeoxyuridine (BrdUrd) monoclonal antibody to follow the traverse of BrdUrd-labeled cells. Exponentially growing cultured mammalian cells, from six different cell lines, were prepulsed with BrdUrd before exposure to tumoricidal macrophages. The cultured cells were then analyzed as a function of time for DNA content (by propidium iodide staining) and for BrdUrd incorporation (using a fluoresceini-sothiocyanate [FITC]-conjugated anti-BrdUrd monoclonal antibody). The position of the cells in cycle and the progression of the BrdUrd-labeled cohort was followed using flow cytometry. The cell lines examined were: Colon 26; BALB/c-3T3, ST3T3 (a spontaneously transformed, tumorigenic clone of 3T3), WCHE5 (a clone of whole Chinese hamster embryo cells), RIF (a radiation-induced fibrosarcoma), and A101D (a human melanoma). The bivariate distributions showed that for all six cell lines the BrdUrd-labeled cohort in the control cultures progressed around the cell cycle during the first 12 h of culture, as the cells exponentially increased. In contrast, when each cell line was incubated with tumoricidal macrophages, the BrdUrd-labeled cohort did not progress through cell cycle but remained in S phase throughout the 12-h culture period. There was also no evidence for progression of cells out of G 1 . The data show that cells were arrested in every phase of cell cycle. This study suggests that cytostasis, as manifested by the termination of progression in all phases of the cell cycle, is a universal phenomenon induced by tumoricidal macrophages. 20 references, 4 figures

The usefulness of metal markers for CTV-based dose prescription in high-dose-rate interstitial brachytherapy

International Nuclear Information System (INIS)

Yoshida, Ken; Mitomo, Masanori; Nose, Takayuki; Koizumi, Masahiko; Nishiyama, Kinji; Yoshida, Mineo

2002-01-01

than the maximum normal tissue doses. The doses of 2 markers for (1 patient) for OAR (the urethra) were higher than the maximum normal tissue dose. Seven markers OAR (the mandible) were not visualized because of metal crowns. If the Paris system (reference dose is prescribed to an isodose surface of 85% of the basal dose) had been used, 16 patients had been ''underdosed'' and 4 patients (the rectum+the urethra: 2; the urethra: 1; the large vessel: 1) ''overdosed''. Dose non-uniformity ratio (DNR) and maximum diameter of hyperdose sleeve were 0.31±0.08 and 4-49 mm (median: 7 mm) in CTV-based dose prescription. A statistically significant difference was seen between CTV-based dose prescription and Paris system {0.28±0.08 and 3-99 mm (median: 6 mm)} (p<0.002, 0.0002). Two of 42 patients treated with higher than the tumoricidal dose had local recurrence, while 4 of 7 underdosed patients had local recurrence. A significant difference was found between them (p<0.0001). Metal markers were useful to prescribe the tumoricidal dose to CTV and to regulated the doses for OAR. Local control rate of the patients treated with higher than the tumoricidal dose was significantly better. Miss-implantation of metal markers was a problem that should be resolved. (author)

A hypoxia- and {alpha}-fetoprotein-dependent oncolytic adenovirus exhibits specific killing of hepatocellular carcinomas.

Science.gov (United States)

Kwon, Oh-Joon; Kim, Pyung-Hwan; Huyn, Steven; Wu, Lily; Kim, Minjung; Yun, Chae-Ok

2010-12-15

Oncolytic adenoviruses (Ad) constitute a new promising modality of cancer gene therapy that displays improved efficacy over nonreplicating Ads. We have previously shown that an E1B 19-kDa-deleted oncolytic Ad exhibits a strong cell-killing effect but lacks tumor selectivity. To achieve hepatoma-restricted cytotoxicity and enhance replication of Ad within the context of tumor microenvironment, we used a modified human α-fetoprotein (hAFP) promoter to control the replication of Ad with a hypoxia response element (HRE). We constructed Ad-HRE(6)/hAFPΔ19 and Ad-HRE(12)/hAFPΔ19 that incorporated either 6 or 12 copies of HRE upstream of promoter. The promoter activity and specificity to hepatoma were examined by luciferase assay and fluorescence-activated cell sorting analysis. In addition, the AFP expression- and hypoxia-dependent in vitro cytotoxicity of Ad-HRE(6)/hAFPΔ19 and Ad-HRE(12)/hAFPΔ19 was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cytopathic effect assay. In vivo tumoricidal activity on subcutaneous and liver orthotopic model was monitored by noninvasive molecular imaging. Ad-HRE(12)/hAFPΔ19 exhibited enhanced tumor selectivity and cell-killing activity when compared with Ad-hAFPΔ19. The tumoricidal activity of Ad-HRE(12)/hAFPΔ19 resulted in significant inhibition of tumor growth in both subcutaneous and orthotopic models. Histologic examination of the primary tumor after treatment confirmed accumulation of viral particles near hypoxic areas. Furthermore, Ad-HRE(12)/hAFPΔ19 did not cause severe inflammatory immune response and toxicity after systemic injection. The results presented here show the advantages of incorporating HREs into a hAFP promoter-driven oncolytic virus. This system is unique in that it acts in both a tissue-specific and tumor environment-selective manner. The greatly enhanced selectivity and tumoricidal activity of Ad-HRE(12)/hAFPΔ19 make it a promising therapeutic agent in the treatment

Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy.

Science.gov (United States)

Di Caro, Giuseppe; Cortese, Nina; Castino, Giovanni Francesco; Grizzi, Fabio; Gavazzi, Francesca; Ridolfi, Cristina; Capretti, Giovanni; Mineri, Rossana; Todoric, Jelena; Zerbi, Alessandro; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

2016-10-01

Tumour-associated macrophages (TAMs) play key roles in tumour progression. Recent evidence suggests that TAMs critically modulate the efficacy of anticancer therapies, raising the prospect of their targeting in human cancer. In a large retrospective cohort study involving 110 patients with pancreatic ductal adenocarcinoma (PDAC), we assessed the density of CD68-TAM immune reactive area (%IRA) at the tumour-stroma interface and addressed their prognostic relevance in relation to postsurgical adjuvant chemotherapy (CTX). In vitro, we dissected the synergism of CTX and TAMs. In human PDAC, TAMs predominantly exhibited an immunoregulatory profile, characterised by expression of scavenger receptors (CD206, CD163) and production of interleukin 10 (IL-10). Surprisingly, while the density of TAMs associated to worse prognosis and distant metastasis, CTX restrained their protumour prognostic significance. High density of TAMs at the tumour-stroma interface positively dictated prognostic responsiveness to CTX independently of T-cell density. Accordingly, in vitro, gemcitabine-treated macrophages became tumoricidal, activating a cytotoxic gene expression programme, inhibiting their protumoural effect and switching to an antitumour phenotype. In patients with human PDAC, neoadjuvant CTX was associated to a decreased density of CD206(+) and IL-10(+) TAMs at the tumour-stroma interface. Overall, our data highlight TAMs as critical determinants of prognostic responsiveness to CTX and provide clinical and in vitro evidence that CTX overall directly re-educates TAMs to restrain tumour progression. These results suggest that the quantification of TAMs could be exploited to select patients more likely to respond to CTX and provide the basis for novel strategies aimed at re-educating macrophages in the context of CTX. 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/

Anticancer effects of deproteinized asparagus polysaccharide on hepatocellular carcinoma in vitro and in vivo.

Science.gov (United States)

Xiang, Jianfeng; Xiang, Yanjie; Lin, Shengming; Xin, Dongwei; Liu, Xiaoyu; Weng, Lingling; Chen, Tao; Zhang, Minguang

2014-04-01

Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the world whose chemoprevention became increasingly important in HCC treatment. Although the anticancer effects of asparagus constituents have been investigated in several cancers, its effects on hepatocellular carcinoma have not been fully studied. In this study, we investigated the anticancer effects of the deproteinized asparagus polysaccharide on the hepatocellular carcinoma cells using the in vitro and in vivo experimental model. Our data showed that deproteinized asparagus polysaccharide might act as an effective inhibitor on cell growth in vitro and in vivo and exert potent selective cytotoxicity against human hepatocellular carcinoma Hep3B and HepG2 cells. Further study showed that it could potently induce cell apoptosis and G2/M cell cycle arrest in the more sensitive Hep3B and HepG2 cell lines. Moreover, deproteinized asparagus polysaccharide potentiated the effects of mitomycin both in vitro and in vivo. Mechanistic studies revealed that deproteinized asparagus polysaccharide might exert its activity through an apoptosis-associated pathway by modulating the expression of Bax, Bcl-2, and caspase-3. In conclusion, deproteinized asparagus polysaccharide exhibited significant anticancer activity against hepatocellular carcinoma cells and could sensitize the tumoricidal effects of mitomycin, indicating that it is a potential therapeutic agent (or chemosensitizer) for liver cancer therapy.

tabAnti-HER2 (erbB-2) oncogene effects of phenolic compounds directly isolated from commercial Extra-Virgin Olive Oil (EVOO)

International Nuclear Information System (INIS)

Menendez, Javier A; Vazquez-Martin, Alejandro; Garcia-Villalba, Rocio; Carrasco-Pancorbo, Alegria; Oliveras-Ferraros, Cristina; Fernandez-Gutierrez, Alberto; Segura-Carretero, Antonio

2008-01-01

The effects of the olive oil-rich Mediterranean diet on breast cancer risk might be underestimated when HER2 (ERBB2) oncogene-positive and HER2-negative breast carcinomas are considered together. We here investigated the anti-HER2 effects of phenolic fractions directly extracted from Extra Virgin Olive Oil (EVOO) in cultured human breast cancer cell lines. Solid phase extraction followed by semi-preparative high-performance liquid chromatography (HPLC) was used to isolate phenolic fractions from commercial EVOO. Analytical capillary electrophoresis coupled to mass spectrometry was performed to check for the composition and to confirm the identity of the isolated fractions. EVOO polyphenolic fractions were tested on their tumoricidal ability against HER2-negative and HER2-positive breast cancer in vitro models using MTT, crystal violet staining, and Cell Death ELISA assays. The effects of EVOO polyphenolic fractions on the expression and activation status of HER2 oncoprotein were evaluated using HER2-specific ELISAs and immunoblotting procedures, respectively. Among the fractions mainly containing the single phenols hydroxytyrosol and tyrosol, the polyphenol acid elenolic acid, the lignans (+)-pinoresinol and 1-(+)-acetoxypinoresinol, and the secoiridoids deacetoxy oleuropein aglycone, ligstroside aglycone, and oleuropein aglycone, all the major EVOO polyphenols (i.e. secoiridoids and lignans) were found to induce strong tumoricidal effects within a micromolar range by selectively triggering high levels of apoptotic cell death in HER2-overexpressors. Small interfering RNA-induced depletion of HER2 protein and lapatinib-induced blockade of HER2 tyrosine kinase activity both significantly prevented EVOO polyphenols-induced cytotoxicity. EVOO polyphenols drastically depleted HER2 protein and reduced HER2 tyrosine autophosphorylation in a dose- and time-dependent manner. EVOO polyphenols-induced HER2 downregulation occurred regardless the molecular mechanism

tabAnti-HER2 (erbB-2 oncogene effects of phenolic compounds directly isolated from commercial Extra-Virgin Olive Oil (EVOO

Directory of Open Access Journals (Sweden)

Carrasco-Pancorbo Alegria

2008-12-01

Full Text Available Abstract Background The effects of the olive oil-rich Mediterranean diet on breast cancer risk might be underestimated when HER2 (ERBB2 oncogene-positive and HER2-negative breast carcinomas are considered together. We here investigated the anti-HER2 effects of phenolic fractions directly extracted from Extra Virgin Olive Oil (EVOO in cultured human breast cancer cell lines. Methods Solid phase extraction followed by semi-preparative high-performance liquid chromatography (HPLC was used to isolate phenolic fractions from commercial EVOO. Analytical capillary electrophoresis coupled to mass spectrometry was performed to check for the composition and to confirm the identity of the isolated fractions. EVOO polyphenolic fractions were tested on their tumoricidal ability against HER2-negative and HER2-positive breast cancer in vitro models using MTT, crystal violet staining, and Cell Death ELISA assays. The effects of EVOO polyphenolic fractions on the expression and activation status of HER2 oncoprotein were evaluated using HER2-specific ELISAs and immunoblotting procedures, respectively. Results Among the fractions mainly containing the single phenols hydroxytyrosol and tyrosol, the polyphenol acid elenolic acid, the lignans (+-pinoresinol and 1-(+-acetoxypinoresinol, and the secoiridoids deacetoxy oleuropein aglycone, ligstroside aglycone, and oleuropein aglycone, all the major EVOO polyphenols (i.e. secoiridoids and lignans were found to induce strong tumoricidal effects within a micromolar range by selectively triggering high levels of apoptotic cell death in HER2-overexpressors. Small interfering RNA-induced depletion of HER2 protein and lapatinib-induced blockade of HER2 tyrosine kinase activity both significantly prevented EVOO polyphenols-induced cytotoxicity. EVOO polyphenols drastically depleted HER2 protein and reduced HER2 tyrosine autophosphorylation in a dose- and time-dependent manner. EVOO polyphenols-induced HER2 downregulation

Mechanisms of reduction of antitumor drug toxicity by liposome encapsulation

Energy Technology Data Exchange (ETDEWEB)

Rahman, Y. E.; Hanson, W. R.; Bharucha, J.; Ainsworth, E. J.; Jaroslow, B.

1977-01-01

The antitumor drug Actinomycin D is effective against the growth of some human solid tumors but its use is limited by its extreme toxicity. The development of a method of administering Act. D to reduce its systemic toxicity by incorporating the drug within liposomes reduced its toxicity but its tumoricidal activity was retained.

Evaluating significance in linear mixed-effects models in R.

Science.gov (United States)

Luke, Steven G

2017-08-01

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

Strontium-89 for prostate cancer with bone metastases. The potential of cancer control and improvement of overall survival

International Nuclear Information System (INIS)

Kuroda, Isao

2014-01-01

Strontium-89 (Sr-89) has been considered to have a tumoricidal effect with minimal adverse events. However, few reports have investigated these effects in detail. In this study, we examined the tumoricidal and pain-relief effects of Sr-89 on prostate cancer with bone metastasis as well as survival. A retrospective study was performed involving 31 prostate cancer patients with bone metastasis treated with Sr-89. Using prostate specific antigen (PSA) as an evaluation criterion of cancer control, patients were divided into PSA responder and non-responder groups, and the survival rates of these groups were compared. In addition, using the total amount of painkillers administered as an evaluation criterion of pain relief, patients were divided into pain responder and non-responder groups, and the survival rates of these groups were also compared. As secondary investigation items, age, PSA (ng/ml), pain site, extent of the disease, the presence or absence of castration-resistant prostatic cancer (CRPC), the presence or absence of a past medical history of treatment with docetaxel in CRPC cases, Gleason Score, hemoglobin (g/dl), platelet (Plt) (/μl), serum carboxyterminal telopeptide of type I collagen (ng/ml), and bone-alkaline phosphatase (BAP) (U/l) were investigated. Longer survival was expected for the PSA responder group than for the PSA non-responder group, and whether the spine was the pain site and the presence or absence of CRPC were useful as predictors of this. Plt was suggested to be a useful indicator. Furthermore, the survival time was significantly longer in the pain responder group than in the pain non-responder group, and whether the pain site was present in the spine was considered to be a predictor; however, no significant difference was noted in any of the items assumed to be biomarkers. Sr-89 has the potential to control PSA and prolong survival. A large-scale prospective study of the therapeutic effect of Sr-89 is expected. (author)

Significance assessment of the external control effects of lecturers

Directory of Open Access Journals (Sweden)

Kurbatova Margarita, V.

2015-06-01

Full Text Available The state policy regarding higher education has changed in the last decade. These changes were part of the efficiency programs of the public sector. Governments of different countries ruined previously existing system of higher education state regulation and attempted to build the quasi-market structure in the higher education industry. Such transformations served as timely and progressive reforms in the recent studies of the economics of education. Substitution of bureaucratic management mechanisms and modern competition managerial tools are articulated. Economic and institutional and sociological studies on the effects of the introduction of quasi-markets and managerial tools in higher education governance oppose to orthodox market approach. They drew attention to the fact that evaluation methods and improve the effectiveness of organizations and employees that are typical of the private sector often produce results that differ from those in the public sector. To assess the consequences of the introduction of managerial tools of external control activities of university lecturers used a methodology based on the allocation of the individual structural components (effects and building on their basis of a multi-level hierarchical model in the research. Each component of the model (single effect is characterized by a degree of significance (importance and the degree of severity. The results of the systematization and assessment of the significance of the effects of external control activity of lecturers of Russian universities implemented in conditions of quasi-market mechanisms of the higher education system are highlighted in the paper.

Thalidomide has a significant effect in patients with thalassemia intermedia.

Science.gov (United States)

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

2018-01-01

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

Potent antitumor activity of a urokinase-activated engineered anthrax toxin

Science.gov (United States)

Liu, Shihui; Aaronson, Hannah; Mitola, David J.; Leppla, Stephen H.; Bugge, Thomas H.

2003-01-01

The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy. We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and displays limited toxicity to normal tissue but broad and potent tumoricidal activity. Native anthrax toxin protective antigen, when administered with a chimeric anthrax toxin lethal factor, Pseudomonas exotoxin fusion protein, was extremely toxic to mice, causing rapid and fatal organ damage. Replacing the furin activation sequence in anthrax toxin protective antigen with an artificial peptide sequence efficiently activated by urokinase greatly attenuated toxicity to mice. In addition, the mutation conferred cell-surface urokinase-dependent toxin activation in vivo, as determined by using a panel of plasminogen, plasminogen activator, plasminogen activator receptor, and plasminogen activator inhibitor-deficient mice. Surprisingly, toxin activation critically depended on both urokinase plasminogen activator receptor and plasminogen in vivo, showing that both proteins are essential cofactors for the generation of cell-surface urokinase. The engineered toxin displayed potent tumor cell cytotoxicity to a spectrum of transplanted tumors of diverse origin and could eradicate established solid tumors. This tumoricidal activity depended strictly on tumor cell-surface plasminogen activation. The data show that a simple change of protease activation specificity converts anthrax toxin from a highly lethal to a potent tumoricidal agent.

Reporting effect sizes as a supplement to statistical significance ...

African Journals Online (AJOL)

The purpose of the article is to review the statistical significance reporting practices in reading instruction studies and to provide guidelines for when to calculate and report effect sizes in educational research. A review of six readily accessible (online) and accredited journals publishing research on reading instruction ...

Effect of 14-kDa and 47-kDa protein molecules of age garlic extract on peritoneal macrophages.

Science.gov (United States)

Daneshmandi, Saeed; Hajimoradi, Monire; Ahmadabad, Hasan Namdar; Hassan, Zuhair Mohammad; Roudbary, Maryam; Ghazanfari, Tooba

2011-03-01

Garlic (Allium sativum), traditionally being used as a spice worldwide, has different applications and is claimed to possess beneficial effects in several health ailments such as tumor and atherosclerosis. Garlic is also an immunomodulator and its different components are responsible for different properties. The present work aimed to assess the effect of protein fractions of garlic on peritoneal macrophages. 14-kDa and 47-kDa protein fractions of garlic were purified. Mice peritoneal macrophages were lavaged and cultured in a microtiter plate and exposed to different concentrations of garlic proteins. MTT assay was performed to evaluate the viability of macrophage. The amount of nitric oxide (NO) was detected in culture supernatants of macrophages by Griess reagent and furthermore, the cytotoxicity study of culture supernatants was carried out on WEHI-164 fibrosarcoma cell line as tumor necrosis factor-α bioassay. MTT assay results for both 14-kDa and 47-kDa protein fractions of stimulated macrophages were not significant (P > 0.05). Both 14-kDa and 47-kDa fractions significantly suppressed production of NO from macrophages (P = 0.007 and P = 0.003, respectively). Cytotoxicity of macrophages' supernatant on WEHI-164 fibrosarcoma cells was not affected by garlic protein fractions (P = 0.066 for 14-kDa and P = 0.085 for 47-kDa fractions). according to our finding, 14-kDa and 47-kDa fractions of aged garlic extract are able to suppress NO production from macrophages, which can be used as a biological advantage. These molecules had no cytotoxic effect on macrophages and do not increase tumoricidal property of macrophages.

Photodynamic Therapy Oxidative Stress as a Molecular Switch Controlling Therapeutic Gene Expression for the Treatment of Locally Recurrent Breast Carcinoma

National Research Council Canada - National Science Library

Gomer, Charles

2002-01-01

... a procedure offering local tumoricidal activity. We have demonstrated that PDT-mediated oxidative stress is a strong transcriptional inducer of stress proteins belonging to the heat shock protein (hsp...

Significance of autobiographical episodes and spacing effects in incidental memory.

Science.gov (United States)

Toyota, Hiroshi

2013-10-01

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

Reprogrammed chondrocytes engineered to produce IL-12 provide novel ex vivo immune-gene therapy for cancer.

Science.gov (United States)

Tada, Hiroyuki; Kishida, Tsunao; Fujiwara, Hitoshi; Kosuga, Toshiyuki; Konishi, Hirotaka; Komatsu, Shuhei; Shiozaki, Atsushi; Ichikawa, Daisuke; Okamoto, Kazuma; Otsuji, Eigo; Mazda, Osam

2017-03-01

The somatic cell reprogramming technology was applied to a novel and promising ex vivo immune-gene therapy strategy for cancer. To establish a novel ex vivo cytokine gene therapy of cancer using the somatic cell reprogramming procedures. Mouse fibroblasts were converted into chondrocytes and subsequently transduced with IL-12 gene. The resultant IL-12 induced chondrogenic cells were irradiated with x-ray and inoculated into mice bearing CT26 colon cancer. The irradiation at 20 Gy or higher totally eliminated the proliferative potential of the cells, while less significantly influencing the IL-12 production from the cells. An inoculation of the irradiated IL-12 induced chondrogenic cells significantly suppressed tumor by inducing tumor-specific cytotoxic T lymphocytes, enhancing natural killer tumoricidal activity and inhibiting tumor neoangiogenesis in the mice. The somatic cell reprogramming procedures may provide a novel and effective means to treat malignancies.

Late effects of normal tissues (lent) scoring system: the soma scale

International Nuclear Information System (INIS)

Mornex, F.; Pavy, J.J.; Denekamp, J.

1997-01-01

Radiation tolerance of normal tissues remains the limiting factor for delivering tumoricidal dose. The late toxicity of normal tissues is the most critical element of an irradiation: somatic, functional and structural alterations occur during the actual treatment itself, but late effects manifest months to years after acute effects heal, and may progress with time. The optimal therapeutic ratio ultimately requires not only complete tumor clearance, but also minimal residual injury to surrounding vital normal tissues. The disparity between the intensity of acute and late effects and the inability to predict the eventual manifestation of late normal tissue injury has made radiation oncologists recognize the importance of careful patient follow-up. There is so far no uniform toxicity scoring system to compare several clinical studies in the absence of a 'common toxicity language'. This justifies the need to establish a precise evaluation system for the analysis of late effects of radiation on normal tissues. The SOMA/LENT scoring system results from an international collaboration. European Organization Treatment of Cancer (EORTC) and Radiation Therapy Oncology Group (RTOG) have created subcommittees with the aim of addressing the question of standardized toxic effects criteria. This effort appeared as a necessity to standardize and improve the data recording, to then describe and evaluate uniform toxicity at regular time intervals. The current proposed scale is not yet validated, and should be used cautiously. (authors)

Single high dose intraoperative electrons for advanced stage pancreatic cancer: Phase I pilot study

International Nuclear Information System (INIS)

Goldson, A.L.; Ashaveri, E.; Espinoza, M.C.

1981-01-01

Phase I toxicity studies with intraoperative radiotherapy proved to be a feasible adjunct to surgery for unresectable malignancies of the pancreas at Howard University Hospital. There have been minimal side effects or complications related to the combination of limited surgical decompression and intraoperative radiotherapy alone. The toxic effects of intraoperative radiotherapy on normal tissues is being assessed on a dose volume basis. Doses of 2000 to 2500 rad in a single exposure to include the pancreas, regional nodes and duodenum are acceptable if the total treatment volume is less than or equal to 100 cm. The tumoricidal effects on the cancer are demonstratable when one reviews the pathological specimens that illustrate massive tumor necrosis and fibros replacement, but in all cases reviewed, viable cancer was noted. Intraoperative radiotherapy, therefore, represents a significant boost dose for resectable, partially resectable or non-resectable tumors when added to conventional external beam irradiation and/or chemotherapy. Preliminary clinical data and minimal toxicity justifies further investigation

Continuous lenalidomide treatment for newly diagnosed multiple myeloma

DEFF Research Database (Denmark)

Palumbo, Antonio; Hajek, Roman; Delforge, Michel

2012-01-01

Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma. This double-blind, multicenter, randomized study compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednis...

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

Science.gov (United States)

Fan, Xitao

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

Should we expect financial globalization to have significant effects on business cycles?

OpenAIRE

Iversen, Jens

2009-01-01

Empirical research suggests that financial globalization has insignificant effects on business cycles. Based on standard theoretical models it might be conjectured that the effects should be significant. I show that this conjecture is wrong. Theoretical effects of financial globalization can be determined to any level of precision by expanding the underlying artificial samples. In contrast, in the data the effects are imprecisely estimated because of short samples. I show that if the conclusi...

Significantly enhanced memory effect in metallic glass by multistep training

Science.gov (United States)

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

2017-11-01

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

Augmented macrophage differentiation and polarization of tumor-associated macrophages towards M1 subtype in listeria-administered tumor-bearing host.

Science.gov (United States)

Rai, Rakesh K; Vishvakarma, Naveen K; Mohapatra, Tribhuban M; Singh, Sukh Mahendra

2012-09-01

This study investigates the effect of Listeria administration on differentiation of macrophages from precursor bone marrow cells and functional status of tumor-associated macrophages (TAM). Listeria administration not only resulted in an augmented infiltration of tumor by F4/80 macrophages but also repolarized the functional status of TAM displaying features of some M1 macrophage subtype with upregulated phagocytosis and tumoricidal activity accompanied by altered expression of monocarboxylate transporter-1, toll-like receptor-2, surface markers: CD11c, interleukin-2 receptor, CD62L, and secreted molecules: nitric oxide, interleukin (IL)-1, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor. Declined tumor cell survival and modulated repertoire of cytokines: interferon-γ, IL-6, IL-10, and transforming growth factor-β in tumor microenvironment indicated their role in polarization of TAM towards proinflammatory state. Bone marrow cell of Listeria-administered tumor-bearing mice showed augmented survival, declined expression of p53 upregulated modulator of apoptosis with an upregulated differentiation into activation responsive bone marrow-derived macrophages along with altered expression of macrophage-colony stimulating factor, macrophage-colony stimulating factor receptor, and granulocyte macrophage-colony stimulating factor receptor. These findings indicate that Listeria infection is associated with an augmented differentiation of macrophages accompanied by tumoricidal activation of TAM.

Moderating Effects of Trust on Environmentally Significant Behavior in Korea

Directory of Open Access Journals (Sweden)

Seong-Gin Moon

2017-03-01

Full Text Available To treat environmental problems and to seek sustainable development, voluntary and cooperative efforts, which is really against the traditional mentality with the emphasis on the individual competitive optimization, became the key to maintain the sustainability of complex social and ecological systems. To understand the cooperative and voluntary individual’s environmentally significant behavior (ESB, this paper focuses on the role of trust, and assesses the effect of trust on the relationship between existing factors and ESB. A structural equation model (SEM is constructed to estimate the moderating effects of trust on ESB in Korea. We found that people with a negative view on strict environmental regulations do not exhibit ESB and thus nudge policies could be much more effective than the forceful measure. It is noteworthy that public private partnership, as a kind of optimal trust, should be more promoted in the environmental protection policies.

Vascular and metabolic response to bevacizumab-containing regimens in two patients with colorectal liver metastases measured by dynamic contrast-enhanced MRI and dynamic 18F-FDG-PET

NARCIS (Netherlands)

Vriens, Dennis; de Geus-Oei, Lioe-Fee; Heerschap, Arend; van Laarhoven, Hanneke W. M.; Oyen, Wim J. G.

2011-01-01

Early monitoring of response to treatment is one of the cornerstones of personalized treatment. As new and often expensive targeted therapies, which are tumoristatic rather than tumoricidal, become available, new demands are posed on response assessment. Bevacizumab, an antiangiogenic agent causing

Immunological Effects of Probiotics and their Significance to Human Health

Science.gov (United States)

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

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

Acridine Orange/exosomes increase the delivery and the effectiveness of Acridine Orange in human melanoma cells: A new prototype for theranostics of tumors.

Science.gov (United States)

Iessi, Elisabetta; Logozzi, Mariantonia; Lugini, Luana; Azzarito, Tommaso; Federici, Cristina; Spugnini, Enrico Pierluigi; Mizzoni, Davide; Di Raimo, Rossella; Angelini, Daniela F; Battistini, Luca; Cecchetti, Serena; Fais, Stefano

2017-12-01

Specifically targeted drug delivery systems with low immunogenicity and toxicity are deemed to increase efficacy of cancer chemotherapy. Acridine Orange (AO) is an acidophilic dye with a strong tumoricidal action following excitation with a light source at 466 nm. However, to date the clinical use of AO is limited by the potential side effects elicited by systemic administration. The endogenous nanocarrier exosomes have been recently introduced as a natural delivery system for therapeutic molecules. In this article, we show the outcome of the administration to human melanoma cells of AO charged Exosomes (Exo-AO), in both monolayer and spheroid models. The results showed an extended drug delivery time of Exo-AO to melanoma cells as compared to the free AO, improving the cytotoxicity of AO. This study shows that Exo-AO have a great potential for a real exploitation as a new theranostic approach against tumors based on AO delivered through the exosomes.

Cytotoxic effect of essential oil of thyme (Thymus broussonettii on the IGR-OV1 tumor cells resistant to chemotherapy

Directory of Open Access Journals (Sweden)

L. Ait M'Barek

2007-11-01

Full Text Available The anti-tumor effect of the Moroccan endemic thyme (Thymus broussonettii essential oil (EOT was investigated in vitro using the human ovarian adenocarcinoma IGR-OV1 parental cell line OV1/P and its chemoresistant counterparts OV1/adriamycin (OV1/ADR, OV1/vincristine (OV1/VCR, and OV1/cisplatin (OV1/CDDP. All of these cell lines elicited various degrees of sensitivity to the cytotoxic effect of EOT. The IC50 values (mean ± SEM, v/v were 0.40 ± 0.02, 0.39 ± 0.02, 0.94 ± 0.05, and 0.65 ± 0.03% for OV1/P, OV1/ADR, OV1/VCR, and OV1/CDDP, respectively. Using the DBA-2/P815 (H2d mouse model, tumors were developed by subcutaneous grafting of tumor fragments of similar size obtained from P815 (murin mastocytoma cell line injected in donor mouse. Interestingly, intra-tumoral injection of EOT significantly reduced solid tumor development. Indeed, by the 30th day of repeated EOT treatment, the tumor volumes of the animals were 2.00 ± 0.27, 1.35 ± 0.20, and 0.85 ± 0.18 cm³ after injection with 10, 30, or 50 µL per 72 h (six times, respectively, as opposed to 3.88 ± 0.50 cm³ for the control animals. This tumoricidal effect was associated with a marked decrease of mouse mortality. In fact, in these groups of mice, the recorded mortality by the 30th day of treatment was 30 ± 4, 18 ± 4, and 8 ± 3%, respectively, while the control animals showed 75 ± 10% of mortality. These data indicate that the EOT which contains carvacrol as the major component has an important in vitro cytotoxic activity against tumor cells resistant to chemotherapy as well as a significant antitumor effect in mice. However, our data do not distinguish between carvacrol and the other components of EOT as the active factor.

Detecting Novelty and Significance

Science.gov (United States)

Ferrari, Vera; Bradley, Margaret M.; Codispoti, Maurizio; Lang, Peter J.

2013-01-01

Studies of cognition often use an “oddball” paradigm to study effects of stimulus novelty and significance on information processing. However, an oddball tends to be perceptually more novel than the standard, repeated stimulus as well as more relevant to the ongoing task, making it difficult to disentangle effects due to perceptual novelty and stimulus significance. In the current study, effects of perceptual novelty and significance on ERPs were assessed in a passive viewing context by presenting repeated and novel pictures (natural scenes) that either signaled significant information regarding the current context or not. A fronto-central N2 component was primarily affected by perceptual novelty, whereas a centro-parietal P3 component was modulated by both stimulus significance and novelty. The data support an interpretation that the N2 reflects perceptual fluency and is attenuated when a current stimulus matches an active memory representation and that the amplitude of the P3 reflects stimulus meaning and significance. PMID:19400680

HAMLET: functional properties and therapeutic potential.

Science.gov (United States)

Ho C S, James; Rydström, Anna; Trulsson, Maria; Bålfors, Johannes; Storm, Petter; Puthia, Manoj; Nadeem, Aftab; Svanborg, Catharina

2012-10-01

Human α-lactalbumin made lethal to tumor cells (HAMLET) is the first member in a new family of protein-lipid complexes that kills tumor cells with high selectivity. The protein component of HAMLET is α-lactalbumin, which in its native state acts as a substrate specifier in the lactose synthase complex, thereby defining a function essential for the survival of lactating mammals. In addition, α-lactalbumin acquires tumoricidal activity after partial unfolding and binding to oleic acid. The lipid cofactor serves the dual role as a stabilizer of the altered fold of the protein and a coactivator of specific steps in tumor cell death. HAMLET is broadly tumoricidal, suggesting that the complex identifies conserved death pathways suitable for targeting by novel therapies. Sensitivity to HAMLET is defined by oncogene expression including Ras and c-Myc and by glycolytic enzymes. Cellular targets are located in the cytoplasmic membrane, cytoskeleton, mitochondria, proteasomes, lysosomes and nuclei, and specific signaling pathways are rapidly activated, first by interactions of HAMLET with the cell membrane and subsequently after HAMLET internalization. Therapeutic effects of HAMLET have been demonstrated in human skin papillomas and bladder cancers, and HAMLET limits the progression of human glioblastomas, with no evidence of toxicity for normal brain or bladder tissue. These findings open up new avenues for cancer therapy and the understanding of conserved death responses in tumor cells.

p-Curve and Effect Size: Correcting for Publication Bias Using Only Significant Results.

Science.gov (United States)

Simonsohn, Uri; Nelson, Leif D; Simmons, Joseph P

2014-11-01

Journals tend to publish only statistically significant evidence, creating a scientific record that markedly overstates the size of effects. We provide a new tool that corrects for this bias without requiring access to nonsignificant results. It capitalizes on the fact that the distribution of significant p values, p-curve, is a function of the true underlying effect. Researchers armed only with sample sizes and test results of the published findings can correct for publication bias. We validate the technique with simulations and by reanalyzing data from the Many-Labs Replication project. We demonstrate that p-curve can arrive at conclusions opposite that of existing tools by reanalyzing the meta-analysis of the "choice overload" literature. © The Author(s) 2014.

The potentiation of radiation effects on the Meth-a and RIF tumors and hela s-3 cells by the glycolytic inhibitor, Lonidamine

International Nuclear Information System (INIS)

Kim, J.H.; Alfieri, A.A.; Kim, S.H.; He, S.Q.; Young, C.W.

1984-01-01

The indazole carboxylic acid Lonidamine (L) a glycolytic inhibitor and antispermatogenic agent previously found to have hyperthermia sensitization properties was evaluated as a radiopotentiating agent in vitro and in vivo. Tumoricidal effects of (L) i.p. and single dose x-irradiation (3.0 or 3.2 Gy) was evaluated on 300-1000 mm/sup 3/ i.m. Meth-A in BALB/c and the RIF fibrosarcoma in C/sub 3/H/He mice L preceded or proceeded the radiation event to 1 hr intervals with maximum separation between treatments of 4 hrs. L conc in sera was biphasic (t1/2 -- 1 hr.). Optimal treatment efficacy was found at minimal time intervals between L and radiation interaction. TCD /sub 50/ for RIF and Meth-A resulted in DMF's of 1.15 - 1.35 (L dose dependent). Chronic L (50mg/kg/dy x 30) + fractionated radiation was found to be well tolerated as concomitant L potentiated combination therapy. Cell culture studies on monolayer and spheroids demonstrate L as an effective inhibitor of potential lethal radiation damage with L potential to be dependent upon both dose/fraction, number of fractions and total radiation dose accumulated

Electrostatic interactions play an essential role in the binding of oleic acid with α-lactalbumin in the HAMLET-like complex: a study using charge-specific chemical modifications.

Science.gov (United States)

Xie, Yongjing; Min, Soyoung; Harte, Níal P; Kirk, Hannah; O'Brien, John E; Voorheis, H Paul; Svanborg, Catharina; Hun Mok, K

2013-01-01

Human α-lactalbumin made lethal to tumor cells (HAMLET) and its analogs are partially unfolded protein-oleic acid (OA) complexes that exhibit selective tumoricidal activity normally absent in the native protein itself. To understand the nature of the interaction between protein and OA moieties, charge-specific chemical modifications of lysine side chains involving citraconylation, acetylation, and guanidination were employed and the biophysical and biological properties were probed. Upon converting the original positively-charged lysine residues to negatively-charged citraconyl or neutral acetyl groups, the binding of OA to protein was eliminated, as were any cytotoxic activities towards osteosarcoma cells. Retention of the positive charges by converting lysine residues to homoarginine groups (guanidination); however, yielded unchanged binding of OA to protein and identical tumoricidal activity to that displayed by the wild-type α-lactalbumin-oleic acid complex. With the addition of OA, the wild-type and guanidinated α-lactalbumin proteins underwent substantial conformational changes, such as partial unfolding, loss of tertiary structure, but retention of secondary structure. In contrast, no significant conformational changes were observed in the citraconylated and acetylated α-lactalbumins, most likely because of the absence of OA binding. These results suggest that electrostatic interactions between the positively-charged basic groups on α-lactalbumin and the negatively-charged carboxylate groups on OA molecules play an essential role in the binding of OA to α-lactalbumin and that these interactions appear to be as important as hydrophobic interactions. Copyright © 2012 Wiley Periodicals, Inc.

HAMLET interacts with lipid membranes and perturbs their structure and integrity.

Science.gov (United States)

Mossberg, Ann-Kristin; Puchades, Maja; Halskau, Øyvind; Baumann, Anne; Lanekoff, Ingela; Chao, Yinxia; Martinez, Aurora; Svanborg, Catharina; Karlsson, Roger

2010-02-23

Cell membrane interactions rely on lipid bilayer constituents and molecules inserted within the membrane, including specific receptors. HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a tumoricidal complex of partially unfolded alpha-lactalbumin (HLA) and oleic acid that is internalized by tumor cells, suggesting that interactions with the phospholipid bilayer and/or specific receptors may be essential for the tumoricidal effect. This study examined whether HAMLET interacts with artificial membranes and alters membrane structure. We show by surface plasmon resonance that HAMLET binds with high affinity to surface adherent, unilamellar vesicles of lipids with varying acyl chain composition and net charge. Fluorescence imaging revealed that HAMLET accumulates in membranes of vesicles and perturbs their structure, resulting in increased membrane fluidity. Furthermore, HAMLET disrupted membrane integrity at neutral pH and physiological conditions, as shown by fluorophore leakage experiments. These effects did not occur with either native HLA or a constitutively unfolded Cys-Ala HLA mutant (rHLA(all-Ala)). HAMLET also bound to plasma membrane vesicles formed from intact tumor cells, with accumulation in certain membrane areas, but the complex was not internalized by these vesicles or by the synthetic membrane vesicles. The results illustrate the difference in membrane affinity between the fatty acid bound and fatty acid free forms of partially unfolded HLA and suggest that HAMLET engages membranes by a mechanism requiring both the protein and the fatty acid. Furthermore, HAMLET binding alters the morphology of the membrane and compromises its integrity, suggesting that membrane perturbation could be an initial step in inducing cell death.

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

Science.gov (United States)

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

2016-05-01

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

Clinically significant bleeding in incurable cancer patients: effectiveness of hemostatic radiotherapy

International Nuclear Information System (INIS)

Cihoric, Nikola; Crowe, Susanne; Eychmüller, Steffen; Aebersold, Daniel M; Ghadjar, Pirus

2012-01-01

This study was performed to evaluate the outcome after hemostatic radiotherapy (RT) of significant bleeding in incurable cancer patients. Patients treated by hemostatic RT between November 2006 and February 2010 were retrospectively analyzed. Bleeding was assessed according to the World Health Organization (WHO) scale (grade 0 = no bleeding, 1 = petechial bleeding, 2 = clinically significant bleeding, 3 = bleeding requiring transfusion, 4 = bleeding associated with fatality). The primary endpoint was bleeding at the end of RT. Key secondary endpoints included overall survival (OS) and acute toxicity. The bleeding score before and after RT were compared using the Wilcoxon signed rank test. Time to event endpoints were estimated using the Kaplan Meier method. Overall 62 patients were analyzed including 1 patient whose benign cause of bleeding was pseudomyxoma peritonei. Median age was 66 (range, 37–93) years. Before RT, bleeding was graded as 2 and 3 in 24 (39%) and 38 (61%) patients, respectively. A median dose of 20 (range, 5–45) Gy of hemostatic RT was applied to the bleeding site. At the end of RT, there was a statistically significant difference in bleeding (p < 0.001); it was graded as 0 (n = 39), 1 (n = 12), 2 (n = 6), 3 (n = 4) and 4 (n = 1). With a median follow-up of 19.3 (range, 0.3-19.3) months, the 6-month OS rate was 43%. Forty patients died (65%); 5 due to bleeding. No grade 3 or above acute toxicity was observed. Hemostatic RT seems to be a safe and effective treatment for clinically and statistically significantly reducing bleeding in incurable cancer patients

Enhanced efficacy of radiation-induced gene therapy in mice bearing lung adenocarcinoma xenografts using hypoxia responsive elements

International Nuclear Information System (INIS)

Wang Wei-dong; Chen Zheng-tang; Li De-zhi; Duan Yu-zhong; Cao Zheng-huai; Li Rong

2005-01-01

The aim of the present study was to investigate whether the hypoxia responsive element (HRE) could be used to enhance suicide gene (HSV-tk) expression and tumoricidal activity in radiation-controlled gene therapy of human lung adenocarcinoma xenografts. A chimeric promoter, HRE-Egr, was generated by directly linking a 0.3-kb fragment of HRE to a 0.6-kb human Egr-1 promoter. Retroviral vectors containing luciferase or the HSV-tk gene driven by Egr-1 or HRE-Egr were constructed. A human adenocarcinoma cell line (A549) was stably transfected with the above vectors using the lipofectamine method. The sensitivity of transfected cells to prodrug ganciclovir (GCV) and cell survival rates were analyzed after exposure to a dose of 2 Gy radiation and hypoxia (1%). In vivo, tumor xenografts in BALB/c mice were transfected with the constructed retroviruses and irradiated to a total dose of 6 Gy, followed by GCV treatment (20 mg/kg for 14 days). When the HSV-tk gene controlled by the HRE-Egr promoter was introduced into A549 cells by a retroviral vector, the exposure to 1% O 2 and 2 Gy radiation induced significant enhancement of GCV cytotoxicity to the cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors infected with the hybrid promoter-containing virus gradually disappeared after GCV administration and radiation. These results indicate that HRE can enhance transgene expression and tumoricidal activity in HSV-tk gene therapy controlled by ionizing radiation in hypoxic human lung adenocarcinoma. (author)

IgG4 subclass antibodies impair antitumor immunity in melanoma

Science.gov (United States)

Karagiannis, Panagiotis; Gilbert, Amy E.; Josephs, Debra H.; Ali, Niwa; Dodev, Tihomir; Saul, Louise; Correa, Isabel; Roberts, Luke; Beddowes, Emma; Koers, Alexander; Hobbs, Carl; Ferreira, Silvia; Geh, Jenny L.C.; Healy, Ciaran; Harries, Mark; Acland, Katharine M.; Blower, Philip J.; Mitchell, Tracey; Fear, David J.; Spicer, James F.; Lacy, Katie E.; Nestle, Frank O.; Karagiannis, Sophia N.

2013-01-01

Host-induced antibodies and their contributions to cancer inflammation are largely unexplored. IgG4 subclass antibodies are present in IL-10–driven Th2 immune responses in some inflammatory conditions. Since Th2-biased inflammation is a hallmark of tumor microenvironments, we investigated the presence and functional implications of IgG4 in malignant melanoma. Consistent with Th2 inflammation, CD22+ B cells and IgG4+-infiltrating cells accumulated in tumors, and IL-10, IL-4, and tumor-reactive IgG4 were expressed in situ. When compared with B cells from patient lymph nodes and blood, tumor-associated B cells were polarized to produce IgG4. Secreted B cells increased VEGF and IgG4, and tumor cells enhanced IL-10 secretion in cocultures. Unlike IgG1, an engineered tumor antigen-specific IgG4 was ineffective in triggering effector cell–mediated tumor killing in vitro. Antigen-specific and nonspecific IgG4 inhibited IgG1-mediated tumoricidal functions. IgG4 blockade was mediated through reduction of FcγRI activation. Additionally, IgG4 significantly impaired the potency of tumoricidal IgG1 in a human melanoma xenograft mouse model. Furthermore, serum IgG4 was inversely correlated with patient survival. These findings suggest that IgG4 promoted by tumor-induced Th2-biased inflammation may restrict effector cell functions against tumors, providing a previously unexplored aspect of tumor-induced immune escape and a basis for biomarker development and patient-specific therapeutic approaches. PMID:23454746

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

Science.gov (United States)

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

2015-08-01

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

Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4

Directory of Open Access Journals (Sweden)

Bo Yoon Chang

2015-10-01

Full Text Available Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of immune stimulation and improved chemotherapeutic effect of M. alba L. fruit extract (MFE. MFE stimulated the production of cytokines, nitric oxide (NO and tumor necrosis factor-α (TNF-α and tumoricidal properties of macrophages. MFE activated macrophages through the mitogen-activated protein kinase (MAPKinase and nuclear factor-κB (NF-κB signaling pathways downstream from toll-like receptor (TLR 4. MFE was shown to exhibit cytotoxicity of CT26 cells via the activated macrophages, even though MFE did not directly affect CT26 cells. In a xenograft mouse model, MFE significantly enhanced anti-cancer activity combined with 5-fluorouracil and markedly promoted splenocyte proliferation, natural killer (NK cell activity, cytotoxic T lymphocyte (CTL activity and IFN-γ production. Immunoglobulin G (IgG antibody levels were significantly increased. These results indicate the indirect anti-cancer activity of MFE through improved immune response mediated by TLR4 signaling. M. alba L. fruit extract might be a potential anti-tumor immunomodulatory candidate chemotherapy agent.

Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4.

Science.gov (United States)

Chang, Bo Yoon; Kim, Seon Beom; Lee, Mi Kyeong; Park, Hyun; Kim, Sung Yeon

2015-10-13

Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of immune stimulation and improved chemotherapeutic effect of M. alba L. fruit extract (MFE). MFE stimulated the production of cytokines, nitric oxide (NO) and tumor necrosis factor-α (TNF-α) and tumoricidal properties of macrophages. MFE activated macrophages through the mitogen-activated protein kinase (MAPKinase) and nuclear factor-κB (NF-κB) signaling pathways downstream from toll-like receptor (TLR) 4. MFE was shown to exhibit cytotoxicity of CT26 cells via the activated macrophages, even though MFE did not directly affect CT26 cells. In a xenograft mouse model, MFE significantly enhanced anti-cancer activity combined with 5-fluorouracil and markedly promoted splenocyte proliferation, natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity and IFN-γ production. Immunoglobulin G (IgG) antibody levels were significantly increased. These results indicate the indirect anti-cancer activity of MFE through improved immune response mediated by TLR4 signaling. M. alba L. fruit extract might be a potential anti-tumor immunomodulatory candidate chemotherapy agent.

No significant effect of angiotensin II receptor blockade on intermediate cardiovascular end points in hemodialysis patients

DEFF Research Database (Denmark)

Peters, Christian Daugaard; Kjaergaard, Krista D; Jensen, Jens D

2014-01-01

Agents blocking the renin-angiotensin-aldosterone system are frequently used in patients with end-stage renal disease, but whether they exert beneficial cardiovascular effects is unclear. Here the long-term effects of the angiotensin II receptor blocker, irbesartan, were studied in hemodialysis......, and residual renal function. Brachial blood pressure decreased significantly in both groups, but there was no significant difference between placebo and irbesartan. Use of additional antihypertensive medication, ultrafiltration volume, and dialysis dosage were not different. Intermediate cardiovascular end...... points such as central aortic blood pressure, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal brain natriuretic prohormone, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic blood pressure during...

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

Science.gov (United States)

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

2015-01-01

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

Study of toxicity of Samarium-153-EDTMP in the treatment of painful skeletal metastasis. Final report for the period 15 December 1996 - 14 December 1997

International Nuclear Information System (INIS)

Zhu Shoupeng

1998-02-01

Favourable characteristics of Sm-153 EDTMP make it an effective agent for use in the palliative treatment of metastatic bone pain. It has also been postulated that Sm-153 might have some tumoricidal effect. But until today its mechanism of action in the treatment of skeletal metastasis is not known. This experimental study has been designed to study the cellular and molecular changes occurring in the bone tumour cells (osteosarcoma of femur of wister rats) following irradiation with different doses of Sm-153 EDTMP. Experimental osteosarcorna tumour cells were harvested and treated with Sm-153 EDTMP over different periods of time ranging from 1-24 hours. Electron microscope, fluorescence microscope, MTI assay and 3 HTdR release assay studies were conducted to observe for effects of radiation. Sm-153 EDTMP irradiation of bone tumour cells resulted in significant nuclear fragmentation, margination of condensed chromatin, marked pyknosis and increased formation of membrane bounded apoptotic bodies formation. The quantification analysis of fragmented DNA for bone tumour cells induced by Sm-153 EDTMP showed that the DNA fragmentation was enhanced with prolongation of irradiation time. The inhibition rate of proliferation of bone tumour cells as well as DNA fragmentation in bone tumour cells after irradiation with Sm-153 EDTMP increased significantly and progressively with prolongation of irradiation time, reaching levels of 63% and 78% respectively by 24 hours. (author)

The Significance of Effective Leadership in Organisations

Institute of Scientific and Technical Information of China (English)

王丽闻

2017-01-01

This essay will study leadership by critically analysing several key theories; it will begin with the concept of leadership to facility an understanding of the subject. Initially, the description of leadership in organisations will be explored to present the development of leadership, and simultaneously identify the purpose of effective leadership. Subse-quently, the demand for good leaders in current business environment will be discussed in order to identify the importance of effective lead-ership. Finally, an empirical case will be discussed to reveal how well the key theories help leaders to address various issues in organisations.

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

Science.gov (United States)

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

2017-08-01

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

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

Science.gov (United States)

Gaskin, Cadeyrn J; Happell, Brenda

2014-05-01

improvement. Most importantly, researchers should abandon the misleading practice of interpreting the results from inferential tests based solely on whether they are statistically significant (or not) and, instead, focus on reporting and interpreting effect sizes, confidence intervals, and significance levels. Nursing researchers also need to conduct and report a priori power analyses, and to address the issue of Type I experiment-wise error inflation in their studies. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Magnetic nanoparticles for targeted therapeutic gene delivery and magnetic-inducing heating on hepatoma

International Nuclear Information System (INIS)

Yuan, Chenyan; Zhang, Jia; Li, Hongbo; Zhang, Hao; Wang, Ling; Zhang, Dongsheng; An, Yanli

2014-01-01

Gene therapy holds great promise for treating cancers, but their clinical applications are being hampered due to uncontrolled gene delivery and expression. To develop a targeted, safe and efficient tumor therapy system, we constructed a tissue-specific suicide gene delivery system by using magnetic nanoparticles (MNPs) as carriers for the combination of gene therapy and hyperthermia on hepatoma. The suicide gene was hepatoma-targeted and hypoxia-enhanced, and the MNPs possessed the ability to elevate temperature to the effective range for tumor hyperthermia as imposed on an alternating magnetic field (AMF). The tumoricidal effects of targeted gene therapy associated with hyperthermia were evaluated in vitro and in vivo. The experiment demonstrated that hyperthermia combined with a targeted gene therapy system proffer an effective tool for tumor therapy with high selectivity and the synergistic effect of hepatoma suppression. (paper)

Inhibitory effects of 131I labeled 17-allylamino-17-demethoxygeldanamycin on breast cancer cell line

International Nuclear Information System (INIS)

Chen Daozhen; Liu Lu; Jiang Xinyu; Huang Ying; Yang Min; Yu Huixin; Luo Shineng; Lin Xiufeng

2007-01-01

Objective: 17-allylamino-17-demethoxygeldanamycin(17-AAG) is a less toxic analogue of geldanamycin (GA) that retains the tumoricidal features of GA. Same as its parent compound, 17-AAG inhibits several signaling pathways through binding to heat shock protein (HSP) 90, which results in destabilization of signaling complexes and degradation of client proteins in a variety of tumor cell growth. Treatment with 17-AAG was effective to inhibit tumor growth and induce apoptosis in colon cancer, glioblastoma, and breast cancer cell lines. This study aimed at exploring the anti-proliferation effects and mechanism of 131 I labeled 17-AAG on human breast cancer cell line MCF-7. Methods: 131 I-17-AAG was prepared by the reaction of 17-AAG with Na 131 I in the presence of hydrogen peroxide. The MCF-7 cells were divided into 5 groups with different additional drugs: group A, dimethyl sulfoxide (DMSO); group B, 370 kBq Na 131 I; group C, 2.5 mg/L 17-AAG; group D, 370 kBq 131 I-17-AAG; group E, 370 kBq 131 I-17-AAG + 2.5 mg/L 17-AAG. 3- (4,5-dimethylthiazol-2-yl)-2,5, diphenylte-trazolium bromide (MTT) assay was used to evaluate the effect of growth inhibition of MCF-7 cells. Cell cycle and apoptosis were analyzed by flow cytometry. The change of the expression of Akt2 mRNA in MCF-7 cells was examined by RT-PCR. Results: The labeling yield of 131 I-17-AAG was 83%. The radiochemical purity of 131 I-17-AAG after purification was 96.6%. The specific activity was 1.48 x 10 5 MBq/μmol. All drugs could significantly inhibit the growth of MCF-7 cells in vitro as the duration lasts longer, especially for group E. After 48 h, sub-G1 peaks detected by flow cytometry were(1.54±0.13)%, (5.72±1.05)%, (12.97±1.44)%, (20.65±1.36)%, (35.39±4.15)% for group A, B, C, D and E, respectively. The experimental groups (B-E) were all significantly higher than the control group (A, all P 131 I-17-AAG could suppress the growth of human breast cancer cell line MCF-7 and hasten the apoptosis. It could

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

Science.gov (United States)

2012-04-25

...] Draft Guidance for Industry: Assessing the Effects of Significant Manufacturing Process Changes... Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food... determining whether changes in manufacturing process, including the intentional reduction in particle size to...

C-reactive protein interaction with macrophages: in vitro induction of tumor cytotoxicity, and characterization of C-reactive protein binding to macrophages

International Nuclear Information System (INIS)

Zahedi, K.A.

1987-01-01

The ability of C-reactive protein (CRP) to activate macrophages to tumoricidal state was examined. CRP was able to activate macrophages to kill tumor cells. The activation was shown to be due to CRP and not to low levels of other activators present in the CRP preparations, since specific removal of CRP led to abrogation of the CRP mediated activation of macrophages. The role of lipopolysaccharide (LPS) as a contaminating activator was eliminated by showing the ability of CRP preparations to activate macrophages from LPS non-responsive strains of mice, and to activate macrophages under conditions which specifically inactivated or removed the contaminating LPS. In order to exclude the possibility of indirect activation of macrophages by other cells present in the peritoneal exudate cell population, effect of CRP on pure macrophages was examined. Bone marrow derived macrophages as well as well as macrophage cell lines exhibited a significant increase in their capacity to kill tumor cells after treatment with CRP. The nature of CRP and macrophage interaction was examined using radioiodinated CRP. Labelled CRP bound specifically to macrophages and macrophage cell lines

Suppression of developmental anomalies by maternal macrophages in mice

International Nuclear Information System (INIS)

Nomura, T.; Hata, S.; Kusafuka, T.

1990-01-01

We tested whether nonspecific tumoricidal immune cells can suppress congenital malformations by killing precursor cells destined to cause such defects. Pretreatment of pregnant ICR mice with synthetic (Pyran copolymer) and biological (Bacillus Calmette-Guerin) agents significantly suppressed radiation- and chemical-induced congenital malformations (cleft palate, digit anomalies, tail anomalies, etc.). Such suppressive effects were associated with the activation of maternal macrophages by these agents, but were lost either after the disruption of activated macrophages by supersonic waves or by inhibition of their lysosomal enzyme activity with trypan blue. These results indicate that a live activated macrophage with active lysosomal enzymes can be an effector cell to suppress maldevelopment. A similar reduction by activated macrophages was observed in strain CL/Fr, which has a high spontaneous frequency of cleft lips and palates. Furthermore, Pyran-activated maternal macrophages could pass through the placenta, and enhanced urethane-induced cell killing (but not somatic mutation) in the embryo. It is likely that a maternal immunosurveillance system eliminating preteratogenic cells allows for the replacement with normal totipotent blast cells during the pregnancy to protect abnormal development

Titanium implants in irradiated dog mandibles

International Nuclear Information System (INIS)

Schweiger, J.W.

1989-01-01

The use of osseointegrated titanium implants has been a great benefit to selected cancer patients who otherwise would not be able to wear conventional and/or maxillofacial prostheses. Cognizant of the risk of osteoradionecrosis, we used an animal model to seek experimental evidence for successful osseointegration in bone irradiated to tumoricidal levels. Five healthy male beagle dogs received 60 gray to a previously edentulated and healed area of the right hemimandible. The left hemimandible was kept as a nonirradiated control. After 9 months, titanium implants were placed and allowed an additional 5 1/2 months to osseointegrate. At that time, block specimens were obtained, radiographed, photographed, and analyzed histologically. Although statistical significance cannot be attached to the results, osseointegration was achieved in half of the irradiated specimens

Significant Tsunami Events

Science.gov (United States)

Dunbar, P. K.; Furtney, M.; McLean, S. J.; Sweeney, A. D.

2014-12-01

Tsunamis have inflicted death and destruction on the coastlines of the world throughout history. The occurrence of tsunamis and the resulting effects have been collected and studied as far back as the second millennium B.C. The knowledge gained from cataloging and examining these events has led to significant changes in our understanding of tsunamis, tsunami sources, and methods to mitigate the effects of tsunamis. The most significant, not surprisingly, are often the most devastating, such as the 2011 Tohoku, Japan earthquake and tsunami. The goal of this poster is to give a brief overview of the occurrence of tsunamis and then focus specifically on several significant tsunamis. There are various criteria to determine the most significant tsunamis: the number of deaths, amount of damage, maximum runup height, had a major impact on tsunami science or policy, etc. As a result, descriptions will include some of the most costly (2011 Tohoku, Japan), the most deadly (2004 Sumatra, 1883 Krakatau), and the highest runup ever observed (1958 Lituya Bay, Alaska). The discovery of the Cascadia subduction zone as the source of the 1700 Japanese "Orphan" tsunami and a future tsunami threat to the U.S. northwest coast, contributed to the decision to form the U.S. National Tsunami Hazard Mitigation Program. The great Lisbon earthquake of 1755 marked the beginning of the modern era of seismology. Knowledge gained from the 1964 Alaska earthquake and tsunami helped confirm the theory of plate tectonics. The 1946 Alaska, 1952 Kuril Islands, 1960 Chile, 1964 Alaska, and the 2004 Banda Aceh, tsunamis all resulted in warning centers or systems being established.The data descriptions on this poster were extracted from NOAA's National Geophysical Data Center (NGDC) global historical tsunami database. Additional information about these tsunamis, as well as water level data can be found by accessing the NGDC website www.ngdc.noaa.gov/hazard/

Ganoderma lucidum Polysaccharide Peptide (GLPP for the Cancer Treatment

Directory of Open Access Journals (Sweden)

Imam Rasjidi

2015-06-01

Full Text Available Ganoderma lucidum mushroom (also known as Ling Zhi in China, Mannetake /Reishi in Japan has been widely used for thousands of years to prevent and treat various diseases, such as heart disease, diabetes mellitus, viral infection, and cancer. Polysaccharides from Ganoderma lucidum has been extensively investigated for free radical scavenging activity. Both in vivo and in vitro studies suggest that G. lucidum have anti-tumor effects, which mediated by its immunomodulatory, anti-angiogenesis, and cytotoxic effects. Ganoderma lucidum polysaccharide peptide (GLPP which extracted from Ganoderma lucidum mycelium tissue culture, give the best quality of β-D-Glucans bioactive compounds. These biologically active glucans interact with receptors on the surface of immune cells such as macrophage and natural killer cell (NK cell to induce immunomodulatory and tumoricidal effects. However, many studies still need to answer those mechanisms.

Modelling vocal anatomy's significant effect on speech

NARCIS (Netherlands)

de Boer, B.

2010-01-01

This paper investigates the effect of larynx position on the articulatory abilities of a humanlike vocal tract. Previous work has investigated models that were built to resemble the anatomy of existing species or fossil ancestors. This has led to conflicting conclusions about the relation between

Flipped Classroom in Organic Chemistry Has Significant Effect on Students’ Grades

Directory of Open Access Journals (Sweden)

Caroline Cormier

2018-01-01

Full Text Available The flipped classroom as a form of active pedagogy in postsecondary chemistry has been developed during the last 10 years and has been gaining popularity with instructors and students ever since. In the current paradigm in science, technology, engineering, and mathematics education, it is widely recognized that active learning has significant positive effects on students’ grades. Postsecondary organic chemistry is a difficult course for students, and the traditional way of teaching does not foster students’ active involvement. Implementation of active pedagogy could increase students’ achievement in this course. However, few quantitative data are available on the impact of active pedagogy in general, or flipped classrooms in particular, on learning in organic chemistry at a postsecondary level. Thus, in this study, we evaluated the gain on final grade scores in organic chemistry after implementing a flipped classroom approach to promote active learning in this course. We encouraged students to be active by having them watch educational videos before each class and then having them work during class time on problems that focused on applying the concepts presented in the videos. Exams were the same as those completed by students in the traditional classrooms of our college. In an a posteriori analysis of our students’ grades, we compared final grades in traditional classrooms (control group, N = 66 and in flipped classrooms (experimental group, N = 151. The sample was stratified in three categories depending on students’ academic ability in college, from low-achieving to high-achieving students. Our results show that students in the experimental group have significantly higher final grades in organic chemistry than those in the control group, that is, 77% for students in the active classroom vs. 73% in the traditional classroom (p < 0.05. The effect was the greatest for low-achieving students, with final scores of 70% in

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

Science.gov (United States)

Crocker, Melissa K; Kaplowitz, Paul

2010-12-01

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

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

Science.gov (United States)

Crocker, Melissa K.; Kaplowitz, Paul

2010-01-01

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

Use of significance thresholds to integrate cumulative effects into project-level socio-economic impact assessment in Canada

International Nuclear Information System (INIS)

Joseph, Chris; Zeeg, Taylor; Angus, David; Usborne, Anna; Mutrie, Erin

2017-01-01

A longstanding critique of project-level environmental assessment is that it is weak at addressing cumulative effects, and because of this many argue that cumulative effects are best managed at a regional scale. However, in the absence of regional management it is important that project-level assessment supports cumulative effects management as best as possible. In this paper we present case study socio-economic impact assessments of liquefied natural gas development on Aboriginal groups on Canada's west coast. The case studies use an analytical structure modified from typical Canadian practice including unambiguous and non-arbitrary significance thresholds grounded in stakeholder values to focus baselines, impact assessment, and significance determination on cumulative effects. This approach is found to be more capable of informing decision-makers on cumulative effects as well as more rigorous and transparent than typical assessments. Much of this approach is not conceptually new, but at least in western Canada such an approach is not typically used or meaningfully implemented by practitioners. As such, the case studies serve to illustrate how practice can bolster project-level assessment. - Highlights: •Typical project assessment is weak with respect to cumulative effects. •Modified analysis structure and thresholds enable a focus on cumulative effects. •Clear, value-based thresholds make analysis rigorous, transparent, and democratic.

Significance of radiation effects in solid radioactive waste

International Nuclear Information System (INIS)

Permar, P.H.; McDonell, W.R.

1980-01-01

Proposed NRC criteria for disposal of high-level nuclear waste require development of waste packages to contain radionuclide for at least 1000 years, and design of repositories to prevent radionuclide release at an annual rate greater than 1 part in 100,000 of the total activity. The high-level wastes that are now temporarily stored as aqueous salts, sludges, and calcines must be converted to high-integrity solid forms that resist deterioration from radiation and other effects of long-term storage. Spent fuel may be encapsulated for similar long-term storage. Candidate waste forms beside the spent fuel elements themselves, include borosilicate and related glasses, mineral-like crystalline ceramics, concrete formulations, and metal-matrix glass or ceramic composites. these waste forms will sustain damage produced by beta-gamma radiation up to 10 12 rads, by alpha radiation up to 10 19 particles/g, by internal helium generation greater than about 0.1 atom percent, and by the atom transmutations accompanying radioactive decay. Current data indicate that under these conditions the glass forms suffer only minor volume changes, stored energy deposition, and leachability effects. The crystalline ceramics appear susceptible to the potentially more severe alterations accompanying metamictization and natural analogs of candidate materials are being examined to establish their suitability as waste forms. Helium concentrations in the waste forms are generally below thresholds for severe damage in either glass or crystalline ceramics at low temperatures, but microstructural effects are not well characterized. Transmutation effects remain to be established

[Different aluminum adjuvants significantly enhances the effect of immunization on Brucella Omp31].

Science.gov (United States)

Qing, Rui; Xiang, Qingke; Liu, Zhongqi; Xiao, Fei; Yang, Fan

2018-02-01

Objective To investigate the effect of aluminum phosphate (AP) and aluminum hydroxide (AH) as adjuvants on Brucella outer membrane protein 31 (Omp31) in inducing humoral and cellular immune responses and immune protection. Methods AP and AH adjuvants were prepared and separately mixed with Brucella Omp31 protein to measure the adsorption rates. The AP- and AH-absorbed Omp31 protein were intraperitoneally injected into BLAB/c mice at 0, 2, and 4 weeks, and meanwhile, unabsorbed Omp31 protein and PBS were used as controls. The levels of serum IgG, IgG1, IgG2a and genital tract secretion sIgA were determined by ELISA at 0, 2, 4 and 6 weeks. Spleen cells were collected for culture at 6 weeks, and the cells were stimulated by Omp31 for 48 hours followed by the analysis of IFN-γ and IL-10 levels in the supernatants by ELISA, and the determination of lymphocyte proliferation by CCK-8 assay. The mice were challenged with Brucella at 6 weeks, and bacterial content in spleen tissue was determined 1 and 2 weeks later. Results AP and AH could absorb over 70% and 85% of the Omp31 protein, respectively, for solutions at all the tested concentrations. ELISA suggested that serum IgG, IgG1, IgG2a and genital tract sIgA levels peaked 2 weeks after the last immunization for both AP and AH groups, and antibody level was higher in the AP and AH groups than the control groups, and higher in the AH group than in the AP group. CCK-8 assay showed that the proliferating rate of lymphocytes induced by the AH group was significantly higher than that by the AP group, and the AH group also showed significantly higher IFN-γ level in the supernatant than the AP group, but no significant difference in IL-10 level. The AH group had remarkably lower bacterial load in the spleen than the AP group 2 weeks after challenged by Brucella 16M strain. Conclusion Both AP and AH adjuvants effectively enhanced immunogenicity and immune protection of the Brucella Omp31 protein, and AH was superior to AP in

Stereotaxic intracavitary irradiation for cystic craniopharyngiomas

International Nuclear Information System (INIS)

Pollack, I.F.; Lunsford, L.D.; Slamovits, T.L.; Gumerman, L.W.; Levine, G.; Robinson, A.G.

1988-01-01

Stereotaxic intracavitary irradiation with instillation of phosphorus-32 ( 32 P) colloidal chromic phosphate was performed in nine patients with cystic craniopharyngiomas. Serial neurological, ophthalmological, neuroendocrinological, and radiological examinations were performed before and after treatment. Dosimetry was determined based on a computerized tomography (CT) estimation of tumor volume, and was calculated to provide a tumoricidal dose (200 to 300 Gy) to the cyst wall. The follow-up period ranged from 14 to 45 months (mean 27 months). After treatment, all nine patients showed improvement of symptoms and radiological evidence of cyst regression. Because of an expanding solid component producing recurrent symptoms, one patient required a craniotomy 14 months after isotope instillation. Three of five patients with impaired visual acuity before surgery had significant improvement in acuity after treatment. Preoperative visual field defects in eight patients improved in four after 32 P therapy. Of seven patients with preoperative endocrine abnormalities, one individual showed almost complete normalization and another had improvement in endocrine function. Patients who exhibited residual neuroendocrine function before isotope instillation developed no significant deterioration in endocrine status during the follow-up period. The findings suggest that stereotaxic intracavitary irradiation is a safe and effective treatment which should be considered as the initial surgery for cystic craniopharyngiomas

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

DEFF Research Database (Denmark)

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

2015-01-01

of Eimeria bovis and Eimeria zuernii. Three commercial herds and a total of 71 calves, aged 48 – 135 days, were included. Treatment with a single oral dose of toltrazuril (15 mg/kg) was given after relocation to common pens and one week before expected outbreak of eimeriosis. The effect of treatment...... was followed by weekly faecal sampling and weighing initially and at the end of a study period of 8 weeks. In Herd 2 and 3 toltrazuril treated calves gained on average 7.95 kg more than placebo treated calves (p = 0.007), and both oocyst excretion and prevalence of Eimeria spp. were significantly reduced...

Nanocarriers for Nitric Oxide Delivery

Directory of Open Access Journals (Sweden)

Juliana Saraiva

2011-01-01

Full Text Available Nitric oxide (NO is a promising pharmaceutical agent that has vasodilative, antibacterial, and tumoricidal effects. To study the complex and wide-ranging roles of NO and to facilitate its therapeutic use, a great number of synthetic compounds (e.g., nitrosothiols, nitrosohydroxyamines, N-diazeniumdiolates, and nitrosyl metal complexes have been developed to chemically stabilize and release NO in a controlled manner. Although NO is currently being exploited in many biomedical applications, its use is limited by several factors, including a short half-life, instability during storage, and potential toxicity. Additionally, efficient methods of both localized and systemic in vivo delivery and dose control are needed. One strategy for addressing these limitations and thus increasing the utility of NO donors is based on nanotechnology.

The thresholds for statistical and clinical significance

DEFF Research Database (Denmark)

Jakobsen, Janus Christian; Gluud, Christian; Winkel, Per

2014-01-01

BACKGROUND: Thresholds for statistical significance are insufficiently demonstrated by 95% confidence intervals or P-values when assessing results from randomised clinical trials. First, a P-value only shows the probability of getting a result assuming that the null hypothesis is true and does...... not reflect the probability of getting a result assuming an alternative hypothesis to the null hypothesis is true. Second, a confidence interval or a P-value showing significance may be caused by multiplicity. Third, statistical significance does not necessarily result in clinical significance. Therefore...... of the probability that a given trial result is compatible with a 'null' effect (corresponding to the P-value) divided by the probability that the trial result is compatible with the intervention effect hypothesised in the sample size calculation; (3) adjust the confidence intervals and the statistical significance...

Significance of radiation-induced bystander effects in radiation therapy

International Nuclear Information System (INIS)

Suzuki, Masao

2014-01-01

Since 1994, a Phase I/II clinical study and radiotherapy have carried out using carbon-ion beams produced with the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences. Now we constructed the new treatment facility for the advanced carbon-ion therapy at HIMAC applying a 3D fast spot scanning system with pencil beams. In the field of fundamental biological studies for high-LET heavy ions, there are some reports regarding bystander effects after exposure to alpha particles derived from 238 Pu or He-ion microbeams. However, only limited sets of studies have examined bystander effects after exposure to different ion species heavier than helium, such as carbon ions. We have been investigating bystander cellular responses in both normal human and human tumor cells irradiated with the HIMAC carbon ions. Bystander cell-killing effect was observed in the cells harboring wild-type P53 gene, but not in the P53-mutated cells. Moreover, observed bystander effect was suppressed by treating with a specific inhibitor of gap-junction mediated cell-cell communication. There is clear evidence that the carbon-ion irradiation enables the enhanced cell killing in cells with wild-type P53 gene via gap-junction mediated bystander effect. (author)

EFFECT SIGNIFICANCE ASSESSMENT OF THE THERMODYNAMICAL FACTORS ON THE SOLID OXIDE FUEL CELL OPERATION

Directory of Open Access Journals (Sweden)

V. A. Sednin

2015-01-01

Full Text Available Technologies of direct conversion of the fuel energy into electrical power are an upcoming trend in power economy. Over the last decades a number of countries have created industrial prototypes of power plants on fuel elements (cells, while fuel cells themselves became a commercial product on the world energy market. High electrical efficiency of the fuel cells allows predictting their further spread as part of hybrid installations jointly with gas and steam turbines which specifically enables achieving the electrical efficiency greater than 70 %. Nevertheless, investigations in the area of increasing efficiency and reliability of the fuel cells continue. Inter alia, research into the effects of oxidizing reaction thermodynamic parameters, fuel composition and oxidation reaction products on effectiveness of the solid oxide fuel cells (SOFC is of specific scientific interest. The article presents a concise analysis of the fuel type effects on the SOFC efficiency. Based on the open publications experimental data and the data of numerical model studies, the authors adduce results of the statistical analysis of the SOFC thermodynamic parameters effect on the effectiveness of its functioning as well as of the reciprocative factors of these parameters and gas composition at the inlet and at the outlet of the cell. The presented diagrams reflect dimension of the indicated parameters on the SOFC operation effectiveness. The significance levels of the above listed factors are ascertained. Statistical analysis of the effects of the SOFC functionning process thermodynamical, consumption and concentration parameters demonstrates quintessential influence of the reciprocative factors (temperature – flow-rate and pressure – flow-rate and the nitrogen N2 and oxygen O2 concentrations on the operation efficiency in the researched range of its functioning. These are the parameters to be considered on a first-priority basis while developing mathematical models

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

Science.gov (United States)

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

2011-05-01

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

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

Science.gov (United States)

Imbir, Kamil K

2016-01-01

Activation mechanisms such as arousal are known to be responsible for slowdown observed in the Emotional Stroop and modified Stroop tasks. Using the duality of mind perspective, we may conclude that both ways of processing information (automatic or controlled) should have their own mechanisms of activation, namely, arousal for an experiential mind, and subjective significance for a rational mind. To investigate the consequences of both, factorial manipulation was prepared. Other factors that influence Stroop task processing such as valence, concreteness, frequency, and word length were controlled. Subjective significance was expected to influence arousal effects. In the first study, the task was to name the color of font for activation charged words. In the second study, activation charged words were, at the same time, combined with an incongruent condition of the classical Stroop task around a fixation point. The task was to indicate the font color for color-meaning words. In both studies, subjective significance was found to shape the arousal impact on performance in terms of the slowdown reduction for words charged with subjective significance.

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

Directory of Open Access Journals (Sweden)

Kamil Konrad Imbir

2016-02-01

Full Text Available Activation mechanisms such as arousal are known to be responsible for slowdown observed in the Emotional Stroop (EST and modified Stroop tasks. Using the duality of mind perspective, we may conclude that both ways of processing information (automatic or controlled should have their own mechanisms of activation, namely, arousal for an experiential mind, and subjective significance for a rational mind. To investigate the consequences of both, factorial manipulation was prepared. Other factors that influence Stroop task processing such as valence, concreteness, frequency and word length were controlled. Subjective significance was expected to influence arousal effects. In the first study, the task was to name the color of font for activation charged words. In the second study, activation charged words were, at the same time, combined with an incongruent condition of the classical Stroop task around a fixation point. The task was to indicate the font color for color-meaning words. In both studies, subjective significance was found to shape the arousal impact on performance in terms of the slowdown reduction for words charged with subjective significance.

Beyond the Effects of Comprehensive Sexuality Education: The Significant Prospective Effects of Youth Assets on Contraceptive Behaviors.

Science.gov (United States)

Green, Jennifer; Oman, Roy F; Vesely, Sara K; Cheney, Marshall; Carroll, Leslie

2017-12-01

The purpose of the study was to prospectively determine if youth assets were significantly associated with contraception use after accounting for the effects of youths' exposure to comprehensive sexuality education programming. Prospective associations between youth asset scores, comprehensive sexuality education topics received, type of contraceptive used, and consistent contraceptive use were analyzed using multinomial and binomial logistic regression in a sample of 757 sexually active youth. Higher youth asset scores were associated with condom use (adjusted odds ratio [AOR] = 1.51, 95% CI = 1.01-2.28), hormonal birth control use (AOR = 2.71, 95% CI = 1.69-4.35), dual method use (AOR = 2.35, 95% CI = 1.44-3.82), and consistent contraceptive use (AOR = 1.97, 95% CI = 1.38-2.82). After controlling for youths' experience with comprehensive sexuality education, higher youth asset scores remained a significant predictor of hormonal birth control use (AOR = 2.09, 95% CI = 1.28-3.42), dual method use (AOR = 2.58, 95% CI = 1.61-4.15), and consistent contraceptive use (AOR = 1.95, 95% CI = 1.36-2.80). Youth serving organizations that are interested in preventing teen pregnancy should consider widespread implementation of evidence-based youth development programs that focus on building and strengthening specific youth assets. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

A Cloud Greenhouse Effect on Mars: Significant Climate Change in the Recent Past

Science.gov (United States)

Haberle, Robert M.; Kahre, Melinda A.; Schaeffer, James R.; Montmessin, Frank; Phillips, R J.

2012-01-01

The large variations in Mars orbit parameters are known to be significant drivers of climate change on the Red planet. The recent discovery of buried CO2 ice at the South Pole adds another dimension to climate change studies. In this paper we present results from the Ames GCM that show within the past million years it is possible that clouds from a greatly intensified Martian hydrological cycle may have produced a greenhouse effect strong enough to raise global mean surface temperatures by several tens of degrees Kelvin. It is made possible by the ability of the Martian atmosphere to transport water to high altitudes where cold clouds form, reduce the outgoing longwave radiation, and drive up surface temperatures to maintain global energy balance.

No significant effect of prefrontal tDCS on working memory performance in older adults

Directory of Open Access Journals (Sweden)

Jonna eNilsson

2015-12-01

Full Text Available Transcranial direct current stimulation (tDCS has been put forward as a non-pharmacological alternative for alleviating cognitive decline in old age. Although results have shown some promise, little is known about the optimal stimulation parameters for modulation in the cognitive domain. In this study, the effects of tDCS over the dorsolateral prefrontal cortex (dlPFC on working memory performance were investigated in thirty older adults. An N-back task assessed working memory before, during and after anodal tDCS at a current strength of 1mA and 2mA, in addition to sham stimulation. The study used a single-blind, cross-over design. The results revealed no significant effect of tDCS on accuracy or response times during or after stimulation, for any of the current strengths. These results suggest that a single session of tDCS over the dlPFC is unlikely to improve working memory, as assessed by an N-back task, in old age.

Use of an oncolytic virus secreting GM-CSF as combined oncolytic and immunotherapy for treatment of colorectal and hepatic adenocarcinomas.

Science.gov (United States)

Malhotra, Sandeep; Kim, Teresa; Zager, Jonathan; Bennett, Joseph; Ebright, Michael; D'Angelica, Michael; Fong, Yuman

2007-04-01

Oncolytic cancer therapy using herpes simplex viruses (HSV) that have direct tumoricidal effects and cancer immunotherapy using the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) have each been effective in preclinical testing. NV1034 is a multimutated oncolytic HSV carrying the gene for murine GM-CSF that attempts to combine these 2 anticancer strategies. The purpose of this study was to compare NV1034 to NV1023, the parent HSV mutants lacking GM-CSF, to determine if such combined oncolytic and immunotherapy using a single vector has advantages over oncolytic therapy alone. Expression GM-CSF in vitro did not alter the infectivity, cytotoxicity, or replication of NV1034 compared to the noncytokine-secreting control. Tumors infected with NV1034 produced GM-CSF in picogram quantities. In vivo efficacy of the viruses against murine colorectal carcinoma CT26 and murine hepatoma Hepa l-6 was then tested in subcutaneous tumors in syngeneic Balb/c and C57 L/J mice, respectively. In these immune-competent models, NV1034 and NV1023 each demonstrated potent antitumor activity. Treatment with NV1034 had significantly better antitumor effect compared to treatment with NV1023. Furthermore, there was no difference in the antitumor efficacy of these viruses in mice depleted of CD4+ and CD8+ T lymphocytes. Viral vectors combining oncolytic and immunotherapy are promising agents in treatment of colorectal carcinoma and hepatoma.

Significant effect of Ca2+ on improving the heat resistance of lactic acid bacteria.

Science.gov (United States)

Huang, Song; Chen, Xiao Dong

2013-07-01

The heat resistance of lactic acid bacteria (LAB) has been extensively investigated due to its highly practical significance. Reconstituted skim milk (RSM) has been found to be one of the most effective protectant wall materials for microencapsulating microorganisms during convective drying, such as spray drying. In addition to proteins and carbohydrate, RSM is rich in calcium. It is not clear which component is critical in the RSM protection mechanism. This study investigated the independent effect of calcium. Ca(2+) was added to lactose solution to examine its influence on the heat resistance of Lactobacillus rhamnosus ZY, Lactobacillus casei Zhang, Lactobacillus plantarum P8 and Streptococcus thermophilus ND03. The results showed that certain Ca(2+) concentrations enhanced the heat resistance of the LAB strains to different extents, that is produced higher survival and shorter regrowth lag times of the bacterial cells. In some cases, the improvements were dramatic. More scientifically insightful and more intensive instrumental study of the Ca(2+) behavior around and in the cells should be carried out in the near future. In the meantime, this work may lead to the development of more cost-effective wall materials with Ca(2+) added as a prime factor. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Confidence Intervals for Effect Sizes: Compliance and Clinical Significance in the "Journal of Consulting and Clinical Psychology"

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Odgaard, Eric C.; Fowler, Robert L.

2010-01-01

Objective: In 2005, the "Journal of Consulting and Clinical Psychology" ("JCCP") became the first American Psychological Association (APA) journal to require statistical measures of clinical significance, plus effect sizes (ESs) and associated confidence intervals (CIs), for primary outcomes (La Greca, 2005). As this represents the single largest…

The somatically significant dose, SSD, and analog of the GSD, the genetically significant dose

International Nuclear Information System (INIS)

Beentjes, L.B.; Duijsings, J.H.

1992-01-01

The medical applications of radiation comprise three main fields namely: Diagnostic Radiology, Radiotherapy and Nuclear Medicine. With the new weighting factors of ICRP (IC91a) the effective dose due to medical applications can be established. I is common to separate the effective dose into the genetic part and the somatic part, SED. In dealing with gonad doses it is important to account for the age of the person at the time of exposure as this will influence the number of children still to be expected from that person. The resulting dose will then be called the genetically significant dose, GSD. In a similar fashion this age factor will be important in considering the chance of tumor induction. The age of patients differs considerably from the average age of the general population. This age difference has to be accounted for if a comparison is to be made with other sources of radiation. This justifies establishing a somatically significant dose, SSD. The reduction of the SED value to a SSD for the medical field due to this phenomenon is .6 for diagnostic radiology, .5 for nuclear medicine and .3 for radiotherapy. Also the extension to more organs at risk, which result in a larger number of weighting factors published by ICRP (IC91a) tends to lower the calculated effective doses. (author)

Analysis of surface and build up region dose for motorized wedge and omni wedge

International Nuclear Information System (INIS)

Panta, Raj Kumar; Sundarum, T.

2008-01-01

Megavoltage x-ray beam exhibits the well known phenomenon of dose build-up within the first few millimeters of incident phantom surface or skin. The skin sparing effect of high energy gamma or x-ray photon may be reduced or even lost, if the beam is contaminated with electron or low energy photons. Since skin dose in the treatment of deeply seated tumor may be a limiting factor in the delivery of tumoricidal dose due to possible complications such as erythema, desquamation, fibrosis, necrosis and epilation, the dose distribution in the build up region should be known. The objective of this study was to measure and investigate the surface and build-up region dose for 6 MV and 15 MV photon beam for Motorized wedge and Omni wedge in Precise Digital Linear Accelerator (Elekta)

Evolution of sarcoma 180 (ascitic tumor in mice infected with Schistosoma mansoni

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Fausto Edmundo Lima Pereira

1986-03-01

Full Text Available Mice infected with 60 cercariae of Schistosoma mansoni were more resistant to the sarcoma 180 ascites tumor. Tumor inoculation was performed 50 days after schistosoma infection and the animals were observed and weighed at 48 hours intervals for development and progression of malignancy. In infected mice the weight gain (ascites formation started later and was shorter than in uninfected Controls. Also, the number of tumor cells into the peritoneal cavity 72h after tumor implantation was shorter in infected group than incontrols. This in creased resistance against a transplantable tumor probably is related to the effect of endotoxin on tumoricidal activity of macrophages activated by the infection. The immunodepression induced by Schistosoma mansoni infection enhances the proliferation of endogenous bacteria increasing the amount of endotoxin absorbed from the gut.

Present clinical status of hyperthermia associated with radiotherapy

International Nuclear Information System (INIS)

Jaulerry, C.; Bataini, J.P.; Brunin, F.; Gaboriaud, G.

1981-01-01

Improved techniques for inducing heat: ultrasound, microwaves, diathermy with different application modalities, capable of producing localized superficial or deep, regional or total body hyperthermia have been responsible for the multiplication of clinical trials. These studies have confirmed the tumoricidal effect of hyperthermia alone, or more especially when combined with radiotherapy, and the good tolerance of normal tissues to localized temperatures of 42 to 43.5 0 C even in previously irradiated cases. Localized heating does not seem to increase the incidence of metastasis. Enhancement ratios and therapeutic gain with respect to normal tissues are not yet well documented. Many problems, including the heterogenicity of tissues to be heated, difficulties with temperature monitoring, and selection of appropriate sequential scheduling of radiation and hyperthermia remain unsolved and further investigationss are required [fr

Space radiation-induced bystander effect: kinetics of biologic responses, mechanisms, and significance of secondary radiations

International Nuclear Information System (INIS)

Gonon, Geraldine

2011-01-01

Widespread evidence indicates that exposure of cell cultures to a particles results in significant biological changes in both the irradiated and non-irradiated bystander cells in the population. The induction of non-targeted biological responses in cell cultures exposed to low fluences of high charge (Z) and high energy (E) particles is relevant to estimates of the health risks of space radiation and to radiotherapy. Here, we investigated the mechanisms underlying the induction of stressful effects in confluent normal human fibroblast cultures exposed to low fluences of 1000 MeV/u iron ions (linear energy transfer (LET) 151 keV/μm), 600 MeV/u silicon ions (LET 50 keV/μm) or 290 MeV/u carbon ions (LET 13 keV/μm). We compared the results with those obtained in cell cultures exposed, in parallel, to low fluences of 0.92 MeV/u a particles (LET 109 keV/μm). Induction of DNA damage, changes in gene expression, protein carbonylation and lipid peroxidation during 24 h after exposure of confluent cultures to mean doses as low as 0.2 cGy of iron or silicon ions strongly supported the propagation of stressful effects from irradiated to bystander cells. At a mean dose of 0.2 cGy, only 1 and 3 % of the cells would be targeted through the nucleus by an iron or silicon ion, respectively. Within 24 h post-irradiation, immunoblot analyses revealed significant increases in the levels of phospho-TP53 (serine 15), p21Waf1 (also known as CDKN1A), HDM2, phospho-ERK1/2, protein carbonylation and lipid peroxidation. The magnitude of the responses suggested participation of non-targeted cells in the response. Furthermore, when the irradiated cell populations were subcultured in fresh medium shortly after irradiation, greater than expected increases in the levels of these markers were also observed during 24 h. Together, the results imply a rapidly propagated and persistent bystander effect. In situ analyses in confluent cultures showed 53BP1 foci formation, a marker of DNA damage, in

The significance of domino effect in chemical accidents

OpenAIRE

Hemmatian, Behrouz; Abdolhamidzadeh, B; Darbra Roman, Rosa Maria; Casal Fàbrega, Joaquim

2014-01-01

A historical survey was performed on 330 accidents involving domino effect, occurred in process/storage plants and in the transportation of hazardous materials; only accidents occurred after 1st-January-1961 have been considered. The main features – geographical location, type of accident, materials involved, origin and causes, consequences, domino sequences – were analyzed, with special consideration to the situation in the developing countries and compared to those from other previous surve...

Antitumor activity of the Korean mistletoe lectin is attributed to activation of macrophages and NK cells.

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Yoon, Taek Joon; Yoo, Yung Choon; Kang, Tae Bong; Song, Seong Kyu; Lee, Kyung Bok; Her, Erk; Song, Kyung Sik; Kim, Jong Bae

2003-10-01

Inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum) on tumor metastases produced by murine tumor cells (B16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 lymphoma cells) was investigated in syngeneic mice. An intravenous (i.v.) administration of KML-C (20-50 ng/mouse) 2 days before tumor inoculation significantly inhibited lung metastases of both B16-BL6 and colon 26-M3.1 cells. The prophylactic effect of 50 ng/mouse of KML-C on lung metastasis was almost the same with that of 100 microg/mouse of KM. Treatment with KML-C 1 day after tumor inoculation induced a significant inhibition of not only the experimental lung metastasis induced by B16-BL6 and colon 26-M3.1 cells but also the liver and spleen metastasis of L5178Y-ML25 cells. Furthermore, multiple administration of KML-C given at 3 day-intervals after tumor inoculation led to a significant reduction of lung metastasis and suppression of the growth of B16-BL6 melanoma cells in a spontaneous metastasis model. In an assay for natural killer (NK) cell activity, i.v. administration of KML-C (50 ng/mouse) significantly augmented NK cytotoxicity against Yac-1 tumor cells 2 days after KML-C treatment. In addition, treatment with KML-C (50 ng/mouse) induced tumoricidal activity of peritoneal macrophages against B16-BL6 and 3LL cells. These results suggest that KML-C has an immunomodulating activity to enhance the host defense system against tumors, and that its prophylactic and therapeutic effect on tumor metastasis is associated with the activation of NK cells and macrophages.

Toward better assessment of tornado potential in typhoons: Significance of considering entrainment effects for CAPE

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Sueki, Kenta; Niino, Hiroshi

2016-12-01

The characteristics of typhoons that spawned tornadoes (tornadic typhoons: TTs) in Japan from 1991 to 2013 were investigated by composite analysis using the Japanese 55 year Reanalysis and compared with those of typhoons that did not spawn tornadoes (nontornadic typhoons: NTs). We found that convective available potential energy (CAPE), which considers the effects of entrainment (entraining CAPE: E-CAPE), and storm-relative environmental helicity (SREH) are significantly large in the northeast quadrant of TTs where tornadoes frequently occur and that E-CAPE and SREH in that quadrant for TTs are larger than those for NTs. On the other hand, ordinary CAPE without entrainment does not account for the spatial distribution of tornado occurrences nor does it distinguish TTs from NTs. E-CAPE is sensitive to humidity in the midtroposphere; thus, it is effective for detecting a conditionally unstable layer up to about 550 hPa, which is distinctive of TTs.

Lipopolysaccharide (LPS)-mediated macrophage activation: the role of calcium in the generation of tumoricidal activity

International Nuclear Information System (INIS)

Drysdale, B.E.; Shin, H.S.

1986-01-01

As the authors reported, calcium ionophore, A23187, activates macrophages (M theta) for tumor cell killing and the activated M theta produce a soluble cytotoxic factor (M theta-CF) that is similar if not identical to tumor necrosis factor. Based on these observations they have investigated whether calcium is involved in the activation mediated by another potent M theta activator, LPS. The authors have shown that A23187 caused uptake of extracellular 45 Ca ++ but LPS did not. They have examined the effect of depleting extracellular calcium by using medium containing no added calcium containing 1.0 mM EGTA. In no case did depletion result in decreased M theta-CF production by the M theta activated with LPS. Measurements using the fluorescent, intracellular calcium indicator, Quin 2 have also been performed. While ionomycin, caused a rapid change in the Quin-2 signal, LPS at a concentration even in excess of that required to activate the M theta caused no change in the signal. When high doses of Quin 2 or another intracellular chelator, 8-(diethylaminol-octyl-3,4,5-trimethoxybenzoate, were used to treat M theta, M theta-CF production decreased and cytotoxic activity was impaired. These data indicate that one or more of the processes involved in M theta-CF production does require calcium, but that activation mediated by LPS occurs without the influx of extracellular calcium or redistribution of intracellular calcium

A Note on Testing Mediated Effects in Structural Equation Models: Reconciling Past and Current Research on the Performance of the Test of Joint Significance

Science.gov (United States)

Valente, Matthew J.; Gonzalez, Oscar; Miocevic, Milica; MacKinnon, David P.

2016-01-01

Methods to assess the significance of mediated effects in education and the social sciences are well studied and fall into two categories: single sample methods and computer-intensive methods. A popular single sample method to detect the significance of the mediated effect is the test of joint significance, and a popular computer-intensive method…

HAMLET treatment delays bladder cancer development.

Science.gov (United States)

Mossberg, Ann-Kristin; Hou, Yuchuan; Svensson, Majlis; Holmqvist, Bo; Svanborg, Catharina

2010-04-01

HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model. Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue. HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin. Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Protective and recuperative effects of 3-bromopyruvate on immunological, hepatic and renal homeostasis in a murine host bearing ascitic lymphoma: Implication of niche dependent differential roles of macrophages.

Science.gov (United States)

Yadav, Saveg; Pandey, Shrish Kumar; Goel, Yugal; Kujur, Praveen Kumar; Maurya, Babu Nandan; Verma, Ashish; Kumar, Ajay; Singh, Rana Pratap; Singh, Sukh Mahendra

2018-03-01

3-bromopyruvate (3-BP) possesses promising antineoplastic potential, however, its effects on immunological homeostasis vis a vis hepatic and renal functions in a tumor bearing host remain unclear. Therefore, the effect of 3-BP administration to a murine host bearing a progressively growing tumor of thymoma origin, designated as Dalton's lymphoma (DL), on immunological, renal and hepatic homeostasis was investigated. Administration of 3-BP (4 mg/kg) to the tumor bearing host reversed tumor growth associated thymic atrophy and splenomegaly, accompanied by altered cell survival and repertoire of splenic, bone marrow and tumor associated macrophages (TAM). TAM displayed augmented phagocytic, tumoricidal activities and production of IL-1 and TNF-α. 3-BP-induced activation of TAM was of indirect nature, mediated by IFN-γ. Blood count of T lymphocytes (CD4 + & CD8 + ) and NK cells showed a rise in 3-BP administered tumor bearing mice. Moreover, 3-BP administration triggered modulation of immunomodulatory cytokines in serum along with refurbished hepatic and renal functions. The study indicates the role of altered cytokines balance, site specific differential macrophage functions and myelopoiesis in restoration of lymphoid organ homeostasis in 3-BP administered tumor bearing host. These observations will have long lasting impact in understanding of alternate mechanisms underlying the antitumor action of 3-BP accompanying appraisal of safety issues for optimizing its antineoplastic actions. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Modified Cross Feedback Control for a Magnetically Suspended Flywheel Rotor with Significant Gyroscopic Effects

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Yuan Ren

2014-01-01

Full Text Available For magnetically suspended rigid rotors (MSRs with significant gyroscopic effects, phase lag of the control channel is the main factor influencing the system nutation stability and decoupling performance. At first, this paper proves that the phase lag of the cross channel instead of the decentralized channel is often the main factor influencing the system nutation stability at high speeds. Then a modified cross feedback control strategy based on the phase compensation of cross channel is proposed to improve the stability and decoupling performances. The common issues associated with the traditional control methods have been successfully resolved by this method. Analysis, simulation, and experimental results are presented to demonstrate the feasibility and superiority of the proposed control method.

The significance of some methodological effects on filtration and ingestion rates of the rotifer Brachionus plicatilis

Science.gov (United States)

Schlosser, H. J.; Anger, K.

1982-06-01

Filtration rate (F) and ingestion rate (I) were measured in the rotifer Brachionus plicatilis feeding on the flagellate Dunaliella spec. and on yeast cells (Saccharomyces cerevisiae). 60-min experiments in rotating bottles served as a standard for testing methodological effects on levels of F and I. A lack of rotation reduced F values by 40 %, and a rise in temperature from 18° to 23.5 °C increased them by 42 %. Ingestion rates increased significantly up to a particle (yeast) concentration of ca. 600-800 cells · μl-1; then they remained constant, whereas filtration rates decreased beyond this threshold. Rotifer density (up to 1000 ind · ml-1) and previous starvation (up to 40 h) did not significantly influence food uptake rates. The duration of the experiment proved to have the most significant effect on F and I values: in 240-min experiments, these values were on the average more than 90 % lower than in 15-min experiments. From this finding it is concluded that ingestion rates obtained from short-term experiments (60 min or less) cannot be used in energy budgets, because they severely overestimate the actual long-term feeding capacity of the rotifers. At the lower end of the particle size spectrum (2 to 3 µm) there are not only food cells, but apparently also contaminating faecal particles. Their number increased with increasing duration of experiments and lead to an underestimation of F and I. Elemental analyses of rotifers and their food suggest that B. plicatilis can ingest up to 0.6 mJ or ca. 14 % of its own body carbon within 15 min. The long term average was estimated as 3.4 mJ · ind-1 · d-1 or ca. 75 % of body carbon · d-1.

Effects of ADMA upon gene expression: an insight into the pathophysiological significance of raised plasma ADMA.

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Caroline L Smith

2005-10-01

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

The Significance of Loyalty on Consumer Credit Profitability

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Aditya Galih Prihartono

2012-04-01

Full Text Available The purpose of this research is to analyze and test the effect of customer loyalty on consumer credit profitability. Loyalty Index Score was developed to determine the level of customers’ loyalty level through 4 main variables; Longevity, Depth, Breadth and Referrals. The effect of Loyalty Index Score on profitability was further tested by path analysis to find out the significance direct relationship between loyalty and profitablity and the indirect relationship between the two variable through bucket. The result showed that loyalty has a significant effect on profitability either directly or indirectly. It was concluded that direct loyalty effect on profitability is lower than that of the indirect effect through bucket. The conclusion could be made by analyzing the available data from personal loan customers in one of the biggest multinational bank in indonesia during October 2010 until March 2011.

Sibling Competition & Growth Tradeoffs. Biological vs. Statistical Significance.

Science.gov (United States)

Kramer, Karen L; Veile, Amanda; Otárola-Castillo, Erik

2016-01-01

Early childhood growth has many downstream effects on future health and reproduction and is an important measure of offspring quality. While a tradeoff between family size and child growth outcomes is theoretically predicted in high-fertility societies, empirical evidence is mixed. This is often attributed to phenotypic variation in parental condition. However, inconsistent study results may also arise because family size confounds the potentially differential effects that older and younger siblings can have on young children's growth. Additionally, inconsistent results might reflect that the biological significance associated with different growth trajectories is poorly understood. This paper addresses these concerns by tracking children's monthly gains in height and weight from weaning to age five in a high fertility Maya community. We predict that: 1) as an aggregate measure family size will not have a major impact on child growth during the post weaning period; 2) competition from young siblings will negatively impact child growth during the post weaning period; 3) however because of their economic value, older siblings will have a negligible effect on young children's growth. Accounting for parental condition, we use linear mixed models to evaluate the effects that family size, younger and older siblings have on children's growth. Congruent with our expectations, it is younger siblings who have the most detrimental effect on children's growth. While we find statistical evidence of a quantity/quality tradeoff effect, the biological significance of these results is negligible in early childhood. Our findings help to resolve why quantity/quality studies have had inconsistent results by showing that sibling competition varies with sibling age composition, not just family size, and that biological significance is distinct from statistical significance.

Sibling Competition & Growth Tradeoffs. Biological vs. Statistical Significance.

Directory of Open Access Journals (Sweden)

Karen L Kramer

Full Text Available Early childhood growth has many downstream effects on future health and reproduction and is an important measure of offspring quality. While a tradeoff between family size and child growth outcomes is theoretically predicted in high-fertility societies, empirical evidence is mixed. This is often attributed to phenotypic variation in parental condition. However, inconsistent study results may also arise because family size confounds the potentially differential effects that older and younger siblings can have on young children's growth. Additionally, inconsistent results might reflect that the biological significance associated with different growth trajectories is poorly understood. This paper addresses these concerns by tracking children's monthly gains in height and weight from weaning to age five in a high fertility Maya community. We predict that: 1 as an aggregate measure family size will not have a major impact on child growth during the post weaning period; 2 competition from young siblings will negatively impact child growth during the post weaning period; 3 however because of their economic value, older siblings will have a negligible effect on young children's growth. Accounting for parental condition, we use linear mixed models to evaluate the effects that family size, younger and older siblings have on children's growth. Congruent with our expectations, it is younger siblings who have the most detrimental effect on children's growth. While we find statistical evidence of a quantity/quality tradeoff effect, the biological significance of these results is negligible in early childhood. Our findings help to resolve why quantity/quality studies have had inconsistent results by showing that sibling competition varies with sibling age composition, not just family size, and that biological significance is distinct from statistical significance.

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

Science.gov (United States)

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

2012-09-01

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

Learning from Clostridium novyi-NT: How to defeat cancer

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Li Wang

2018-01-01

Full Text Available Side effects associated with conventional anticancer therapies have prompted the new idea of solid tumor treatment strategy. One of them is using bacteria explored as potential antitumor agents over more than one century. Notably, the ideal therapy is a specifical target to tumors with limited toxicity. Here, we take “Clostridium novyi” for the search keyword in the PubMed from 2000 to 2015 and describe that C. novyi-NT spores act as “Trojan horse” for bacteriolytic therapy. This therapy is based on the fact that the live and attenuated obligate anaerobic bacteria are capable of binary fission selectively in anoxic areas of solid tumors and direct tumoricidal effects. Our succinct review mainly concentrates on the potential mechanisms of combination bacteriolytic therapy, an effective and safe tumor therapy with the help of C. novyi-NT. Importantly, C. novyi-NT spores were shown to induce solid tumor regression and exhibit the property to initiate an immune response. Therefore, C. novyi-NT spores should be an effective and safe tumor therapy.

Multifunctional Nanocarpets for Cancer Theranostics: Remotely Controlled Graphene Nanoheaters for Thermo-Chemosensitisation and Magnetic Resonance Imaging

Science.gov (United States)

Ramachandra Kurup Sasikala, Arathyram; Thomas, Reju George; Unnithan, Afeesh Rajan; Saravanakumar, Balasubramaniam; Jeong, Yong Yeon; Park, Chan Hee; Kim, Cheol Sang

2016-02-01

A new paradigm in cancer theranostics is enabled by safe multifunctional nanoplatform that can be applied for therapeutic functions together with imaging capabilities. Herein, we develop a multifunctional nanocomposite consisting of Graphene Oxide-Iron Oxide -Doxorubicin (GO-IO-DOX) as a theranostic cancer platform. The smart magnetic nanoplatform acts both as a hyperthermic agent that delivers heat when an alternating magnetic field is applied and a chemotherapeutic agent in a cancer environment by providing a pH-dependent drug release to administer a synergistic anticancer treatment with an enhanced T2 contrast for MRI. The novel GO-IO-DOX nanocomposites were tested in vitro and were observed to exhibit an enhanced tumoricidal effect through both hyperthermia and cancer cell-specific DOX release along with an excellent MRI performance, enabling a versatile theranostic platform for cancer. Moreover the localized antitumor effects of GO-IO-DOX increased substantially as a result of the drug sensitization through repeated application of hyperthermia.

The reoxygenation of hypoxia and the reduction of glucose metabolism in head and neck cancer by fractionated radiotherapy with intensity-modulated radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Okamoto, Shozo; Shiga, Tohru; Watanabe, Shiro; Hirata, Kenji; Magota, Keiichi; Kasai, Katsuhiko; Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Hokkaido (Japan); Yasuda, Koichi; Onimaru, Rikiya; Tuchiya, Kazuhiko; Shirato, Hiroki [Hokkaido University Graduate School of Medicine, Department of Radiology, Hokkaido (Japan); Nishijima, Ken-ichi; Kuge, Yuji [Hokkaido University, Central Institute of Isotope Science, Hokkaido (Japan)

2016-11-15

The purpose of this study was to prospectively investigate reoxygenation in the early phase of fractionated radiotherapy and serial changes of tumoricidal effects associated with intensity-modulated radiation therapy (IMRT) in patients with head and neck cancer (HNC) using F-18 fluoromisonidazole (FMISO) PET and F-18 fluorodeoxyglucose (FDG) PET. Patients with untreated HNC underwent FMISO-PET and FDG-PET studies prospectively. A PET evaluation was conducted before each IMRT (Pre-IMRT), during IMRT (at 30 Gy/15 fr) (Inter-IMRT), and after completion of IMRT (70 Gy/35 fr) (Post-IMRT). FMISO-PET images were scanned by a PET/CT scanner at 4 h after the FMISO injection. We quantitatively analyzed the FMISO-PET images of the primary lesion using the maximum standardized uptake (SUVmax) and tumor-to-muscle ratio (TMR). The hypoxic volume (HV) was calculated as an index of tumor hypoxia, and was defined as the volume when the TMR was ≥ 1.25. Each FDG-PET scan was started 1 h after injection. The SUVmax and metabolic tumor volume (MTV) values obtained by FDG-PET were analyzed. Twenty patients finished the complete PET study protocol. At Pre-IMRT, 19 patients had tumor hypoxia in the primary tumor. In ten patients, the tumor hypoxia disappeared at Inter-IMRT. Another seven patients showed the disappearance of tumor hypoxia at Post-IMRT. Two patients showed tumor hypoxia at Post-IMRT. The FMISO-PET results showed that the reduction rates of both SUVmax and TMR from Pre-IMRT to Inter-IMRT were significantly higher than the corresponding reductions from Inter-IMRT to Post-IMRT (SUVmax: 27 % vs. 10 %, p = 0.025; TMR: 26 % vs. 12 %, p = 0.048). The reduction rate of SUVmax in FDG-PET from Pre-IMRT to Inter-IMRT was similar to that from Inter-IMRT to Post-IMRT (47 % vs. 48 %, p = 0.778). The reduction rate of the HV in FMISO-PET from Pre-IMRT to Inter-IMRT tended to be larger than that from Inter-IMRT to Post-IMRT (63 % vs. 40 %, p = 0.490). Conversely, the reduction rate of

The reoxygenation of hypoxia and the reduction of glucose metabolism in head and neck cancer by fractionated radiotherapy with intensity-modulated radiation therapy

International Nuclear Information System (INIS)

Okamoto, Shozo; Shiga, Tohru; Watanabe, Shiro; Hirata, Kenji; Magota, Keiichi; Kasai, Katsuhiko; Tamaki, Nagara; Yasuda, Koichi; Onimaru, Rikiya; Tuchiya, Kazuhiko; Shirato, Hiroki; Nishijima, Ken-ichi; Kuge, Yuji

2016-01-01

The purpose of this study was to prospectively investigate reoxygenation in the early phase of fractionated radiotherapy and serial changes of tumoricidal effects associated with intensity-modulated radiation therapy (IMRT) in patients with head and neck cancer (HNC) using F-18 fluoromisonidazole (FMISO) PET and F-18 fluorodeoxyglucose (FDG) PET. Patients with untreated HNC underwent FMISO-PET and FDG-PET studies prospectively. A PET evaluation was conducted before each IMRT (Pre-IMRT), during IMRT (at 30 Gy/15 fr) (Inter-IMRT), and after completion of IMRT (70 Gy/35 fr) (Post-IMRT). FMISO-PET images were scanned by a PET/CT scanner at 4 h after the FMISO injection. We quantitatively analyzed the FMISO-PET images of the primary lesion using the maximum standardized uptake (SUVmax) and tumor-to-muscle ratio (TMR). The hypoxic volume (HV) was calculated as an index of tumor hypoxia, and was defined as the volume when the TMR was ≥ 1.25. Each FDG-PET scan was started 1 h after injection. The SUVmax and metabolic tumor volume (MTV) values obtained by FDG-PET were analyzed. Twenty patients finished the complete PET study protocol. At Pre-IMRT, 19 patients had tumor hypoxia in the primary tumor. In ten patients, the tumor hypoxia disappeared at Inter-IMRT. Another seven patients showed the disappearance of tumor hypoxia at Post-IMRT. Two patients showed tumor hypoxia at Post-IMRT. The FMISO-PET results showed that the reduction rates of both SUVmax and TMR from Pre-IMRT to Inter-IMRT were significantly higher than the corresponding reductions from Inter-IMRT to Post-IMRT (SUVmax: 27 % vs. 10 %, p = 0.025; TMR: 26 % vs. 12 %, p = 0.048). The reduction rate of SUVmax in FDG-PET from Pre-IMRT to Inter-IMRT was similar to that from Inter-IMRT to Post-IMRT (47 % vs. 48 %, p = 0.778). The reduction rate of the HV in FMISO-PET from Pre-IMRT to Inter-IMRT tended to be larger than that from Inter-IMRT to Post-IMRT (63 % vs. 40 %, p = 0.490). Conversely, the reduction rate of

Low-dose vaporized cannabis significantly improves neuropathic pain.

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Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-02-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

Parent socialization effects in different cultures: significance of directive parenting.

Science.gov (United States)

Sorkhabi, Nadia

2012-06-01

In this article, the controversy of divergent findings in research on parental socialization effects in different cultures is addressed. Three explanations intended to address divergent findings of socialization effects in different cultures, as advanced by researchers who emphasize cultural differences, are discussed. These include cultural differences in socialization values and goals of parents, parental emotional and cognitive characteristics associated with parenting styles, and adolescents' interpretations or evaluations of their parents' parenting styles. The empirical evidence for and against each of these arguments is examined and an alternative paradigm for understanding and empirical study of developmental outcomes associated with parenting styles in different cultures is suggested. Baumrind's directive parenting style is presented as an alternative to the authoritarian parenting style in understanding the positive developmental effects associated with "strict" parenting in cultures said to have a collectivist orientation. Directions for research on the three explanations are mentioned.

Confidence intervals for effect sizes: compliance and clinical significance in the Journal of Consulting and clinical Psychology.

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Odgaard, Eric C; Fowler, Robert L

2010-06-01

In 2005, the Journal of Consulting and Clinical Psychology (JCCP) became the first American Psychological Association (APA) journal to require statistical measures of clinical significance, plus effect sizes (ESs) and associated confidence intervals (CIs), for primary outcomes (La Greca, 2005). As this represents the single largest editorial effort to improve statistical reporting practices in any APA journal in at least a decade, in this article we investigate the efficacy of that change. All intervention studies published in JCCP in 2003, 2004, 2007, and 2008 were reviewed. Each article was coded for method of clinical significance, type of ES, and type of associated CI, broken down by statistical test (F, t, chi-square, r/R(2), and multivariate modeling). By 2008, clinical significance compliance was 75% (up from 31%), with 94% of studies reporting some measure of ES (reporting improved for individual statistical tests ranging from eta(2) = .05 to .17, with reasonable CIs). Reporting of CIs for ESs also improved, although only to 40%. Also, the vast majority of reported CIs used approximations, which become progressively less accurate for smaller sample sizes and larger ESs (cf. Algina & Kessleman, 2003). Changes are near asymptote for ESs and clinical significance, but CIs lag behind. As CIs for ESs are required for primary outcomes, we show how to compute CIs for the vast majority of ESs reported in JCCP, with an example of how to use CIs for ESs as a method to assess clinical significance.

Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM) and GBM Stem Cells.

Science.gov (United States)

Mukherjee, Sumit; Baidoo, Juliet N E; Sampat, Samay; Mancuso, Andrew; David, Lovena; Cohen, Leah S; Zhou, Shuiqin; Banerjee, Probal

2018-01-18

Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12-15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R (μM): 32:8:100 (termed 32 μM+ TriCurin). We have now prepared liposomal TriCurin (TrLp) and demonstrated that TrLp boosts activated p53 in cultured GL261 mouse GBM cells to trigger apoptosis of GBM and GBM stem cells in vitro. TrLp administration into mice yielded a stable plasma concentration of 210 nM C for 60 min, which, though sub-lethal for cultured GL261 cells, was able to cause repolarization of M2-like tumor (GBM)-associated microglia/macrophages to the tumoricidal M1-like phenotype and intra-GBM recruitment of activated natural killer cells. The intratumor presence of such tumoricidal immune cells was associated with concomitant suppression of tumor-load, and apoptosis of GBM and GBM stem cells. Thus, TrLp is a potential onco-immunotherapeutic agent against GBM tumors.

Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM and GBM Stem Cells

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Sumit Mukherjee

2018-01-01

Full Text Available Glioblastoma (GBM is a deadly brain tumor with a current mean survival of 12–15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E from green tea and resveratrol (R from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin to achieve superior potency against HPV+ tumors than C alone at C:E:R (μM: 32:8:100 (termed 32 μM+ TriCurin. We have now prepared liposomal TriCurin (TrLp and demonstrated that TrLp boosts activated p53 in cultured GL261 mouse GBM cells to trigger apoptosis of GBM and GBM stem cells in vitro. TrLp administration into mice yielded a stable plasma concentration of 210 nM C for 60 min, which, though sub-lethal for cultured GL261 cells, was able to cause repolarization of M2-like tumor (GBM-associated microglia/macrophages to the tumoricidal M1-like phenotype and intra-GBM recruitment of activated natural killer cells. The intratumor presence of such tumoricidal immune cells was associated with concomitant suppression of tumor-load, and apoptosis of GBM and GBM stem cells. Thus, TrLp is a potential onco-immunotherapeutic agent against GBM tumors.

Significance tests to determine the direction of effects in linear regression models.

Science.gov (United States)

Wiedermann, Wolfgang; Hagmann, Michael; von Eye, Alexander

2015-02-01

Previous studies have discussed asymmetric interpretations of the Pearson correlation coefficient and have shown that higher moments can be used to decide on the direction of dependence in the bivariate linear regression setting. The current study extends this approach by illustrating that the third moment of regression residuals may also be used to derive conclusions concerning the direction of effects. Assuming non-normally distributed variables, it is shown that the distribution of residuals of the correctly specified regression model (e.g., Y is regressed on X) is more symmetric than the distribution of residuals of the competing model (i.e., X is regressed on Y). Based on this result, 4 one-sample tests are discussed which can be used to decide which variable is more likely to be the response and which one is more likely to be the explanatory variable. A fifth significance test is proposed based on the differences of skewness estimates, which leads to a more direct test of a hypothesis that is compatible with direction of dependence. A Monte Carlo simulation study was performed to examine the behaviour of the procedures under various degrees of associations, sample sizes, and distributional properties of the underlying population. An empirical example is given which illustrates the application of the tests in practice. © 2014 The British Psychological Society.

Monosodium Urate Crystals Induce Upregulation of NK1.1-Dependent Killing by Macrophages and Support Tumor-Resident NK1.1+ Monocyte/Macrophage Populations in Antitumor Therapy.

Science.gov (United States)

Steiger, Stefanie; Kuhn, Sabine; Ronchese, Franca; Harper, Jacquie L

2015-12-01

Macrophages display phenotypic and functional heterogeneity dependent on the changing inflammatory microenvironment. Under some conditions, macrophages can acquire effector functions commonly associated with NK cells. In the current study, we investigated how the endogenous danger signal monosodium urate (MSU) crystals can alter macrophage functions. We report that naive, primary peritoneal macrophages rapidly upregulate the expression of the NK cell-surface marker NK1.1 in response to MSU crystals but not in response to LPS or other urate crystals. NK1.1 upregulation by macrophages was associated with mechanisms including phagocytosis of crystals, NLRP3 inflammasome activation, and autocrine proinflammatory cytokine signaling. Further analysis demonstrated that MSU crystal-activated macrophages exhibited NK cell-like cytotoxic activity against target cells in a perforin/granzyme B-dependent manner. Furthermore, analysis of tumor hemopoietic cell populations showed that effective, MSU-mediated antitumor activity required coadministration with Mycobacterium smegmatis to induce IL-1β production and significant accumulation of monocytes and macrophages (but not granulocytes or dendritic cells) expressing elevated levels of NK1.1. Our findings provide evidence that MSU crystal-activated macrophages have the potential to develop tumoricidal NK cell-like functions that may be exploited to boost antitumor activity in vivo. Copyright © 2015 by The American Association of Immunologists, Inc.

Effects of bovine pregnancy on the fatty acid composition of milk: the significance for humans needs.

Science.gov (United States)

Barreiro, R; Regal, P; Díaz-Bao, M; Vázquez, B I; Cepeda, A

2017-04-01

Milk from 40 Holstein dairy cows was collected from two different farms in Galicia (Spain). The differences in the fatty acid composition of two groups of cows, 20 pregnant and 20 non-pregnant, was studied to determine whether pregnancy status is a determinant factor that can alter the fatty acid profile of milk. Gas-chromatography (GC) coupled to flame ionisation detection (FID) was used for the determination of the fatty acids. Differences in the milk fatty acids between pregnant and non-pregnant cows were pronounced showing statistically significant differences for some fatty acids and the total saturated and monounsaturated fatty acids. Milk from non-pregnant cows was lower in saturated fatty acids and higher in monounsaturated fatty acids (unlike milk from pregnant cows). The effects of the consumption of bovine milk, particularly milk fat, on human health have been studied in depth and sometimes are associated with negative effects, but milk has also several beneficial characteristics linked to some fatty acids.

Rapamycin potentiates cytotoxicity by docetaxel possibly through downregulation of Survivin in lung cancer cells

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Li Hui

2011-03-01

Full Text Available Abstract Background To elucidate whether rapamycin, the inhibitor of mTOR (mammalian target of rapamycin, can potentiate the cytotoxic effect of docetaxel in lung cancer cells and to probe the mechanism underlying such enhancement. Methods Lung cancer cells were treated with docetaxel and rapamycin. The effect on the proliferation of lung cancer cells was evaluated using the MTT method, and cell apoptosis was measured by flow cytometry. Protein expression and level of phosphorylation were assayed using Western Blot method. Results Co-treatment of rapamycin and docetaxel was found to favorably enhance the cytotoxic effect of docetaxel in four lung cancer cell lines. This tumoricidal boost is associated with a reduction in the expression and phosphorylation levels of Survivin and ERK1/2, respectively. Conclusion The combined application of mTOR inhibitor and docetaxel led to a greater degree of cancer cell killing than that by either compound used alone. Therefore, this combination warrants further investigation in its suitability of serving as a novel therapeutic scheme for treating advanced and recurrent lung cancer patients.

Molecular imaging of tumor photoimmunotherapy: Evidence of photosensitized tumor necrosis and hemodynamic changes

DEFF Research Database (Denmark)

Kishimoto, Shun; Oshima, Nobu; Yamamoto, Kazutoshi

2018-01-01

Near-infrared photoimmunotherapy (NIR PIT) employs the photoabsorbing dye IR700 conjugated to antibodies specific for cell surface epidermal growth factor receptor (EGFR). NIR PIT has shown highly selective cytotoxicity in vitro and in vivo. Cell necrosis is thought to be the main mode of cytotox......Near-infrared photoimmunotherapy (NIR PIT) employs the photoabsorbing dye IR700 conjugated to antibodies specific for cell surface epidermal growth factor receptor (EGFR). NIR PIT has shown highly selective cytotoxicity in vitro and in vivo. Cell necrosis is thought to be the main mode...... of cytotoxicity based mainly on in vitro studies. To better understand the acute effects of NIR PIT, molecular imaging studies were performed to assess its cellular and vascular effects.In addition to in vitro studies for cytotoxicity of NIR PIT, the in vivo tumoricidal effects and hemodynamic changes induced....... Following NIR PIT, metabolic MRI using hyperpolarized fumarate showed the production of malate in EGFR-expressing A431 tumor xenografts, providing direct evidence for photosensitized tumor necrosis induced by NIR PIT. R2* mapping studies showed temporal changes in oxygenation, with an accompanying increase...

[Effects of long-term isolation and anticipation of significant event on sleep: results of the project "Mars-520"].

Science.gov (United States)

Zavalko, I M; Rasskazova, E I; Gordeev, S A; Palatov, S Iu; Kovrov, G V

2013-01-01

The purpose of the research was to study effect of long-term isolation on night sleep. The data were collected during international ground simulation of an interplanetary manned flight--"Mars-500". The polysomnographic recordings of six healthy men were performed before, four times during and after 520-days confinement. During the isolation sleep efficiency and delta-latency decreased, while sleep latency increased. Post-hoc analysis demonstrate significant differences between background and the last (1.5 months before the end of the experiment) measure during isolation. Frequency of nights with low sleep efficiency rose on the eve of the important for the crew events (simulation of Mars landing and the end of the confinement). Two weeks after the landing simulation, amount of the nights with a low sleep efficiency significantly decreased. Therefore, anticipation of significant event under condition of long-term isolation might result in sleep worsening in previously healthy men, predominantly difficulties getting to sleep.

[Induction of glutathione and activation of immune functions by low-dose, whole-body irradiation with gamma-rays].

Science.gov (United States)

Kojima, Shuji

2006-10-01

We first examined the relation between the induction of glutathione and immune functions in mice after low-dose gamma-ray irradiation. Thereafter, inhibition of tumor growth by radiation was confirmed in Ehrlich solid tumor (EST)-bearing mice. The total glutathione level of the splenocytes transiently increased soon after irradiation and reached a maximum at around 4 h postirradiation. Thereafter, the level reverted to the 0 h value by 24 h postirradiation. A significantly high splenocyte proliferative response was also recognized 4 h postirradiation. Natural killer (NK) activity was also increased significantly in a similar manner. The time at which the response reached the maximum coincided well with that of maximum total glutathione levels of the splenocytes in the gamma-ray-irradiated mice. Reduced glutathione exogenously added to splenocytes obtained from normal mice enhanced the proliferative response and NK activity in a dose-dependent manner. The inhibitory effects of radiation on tumor growth was then examined in EST-bearing mice. Repeated low-dose irradiation (0.5 Gy, four times, before and within an early time after inoculation) significantly delayed the tumor growth. Finally, the effect of single low-dose (0.5 Gy), whole-body gamma-ray irradiation on immune balance was examined to elucidate the mechanism underlying the antitumor immunity. The percentage of B cells in blood lymphocytes was selectively decreased after radiation, concomitant with an increase in that of the helper T cell population. The IFN-gamma level in splenocyte culture prepared from EST-bearing mice was significantly increased 48 h after radiation, although the level of IL-4 was unchanged. IL-12 secretion from macrophages was also enhanced by radiation. These results suggest that low-dose gamma-rays induce Th1 polarization and enhance the activities of tumoricidal effector cells, leading to an inhibition of tumor growth.

A novel STAT inhibitor, OPB-31121, has a significant antitumor effect on leukemia with STAT-addictive oncokinases

International Nuclear Information System (INIS)

Hayakawa, F; Sugimoto, K; Harada, Y; Hashimoto, N; Ohi, N; Kurahashi, S; Naoe, T

2013-01-01

Signal transduction and activator of transcription (STAT) proteins are extracellular ligand-responsive transcription factors that mediate cell proliferation, apoptosis, differentiation, development and the immune response. Aberrant signals of STAT induce uncontrolled cell proliferation and apoptosis resistance and are strongly involved in cancer. STAT has been identified as a promising target for antitumor drugs, but to date most trials have not been successful. Here, we demonstrated that a novel STAT inhibitor, OPB-31121, strongly inhibited STAT3 and STAT5 phosphorylation without upstream kinase inhibition, and induced significant growth inhibition in various hematopoietic malignant cells. Investigation of various cell lines suggested that OPB-31121 is particularly effective against multiple myeloma, Burkitt lymphoma and leukemia harboring BCR–ABL, FLT3/ITD and JAK2 V617F, oncokinases with their oncogenicities dependent on STAT3/5. Using an immunodeficient mouse transplantation system, we showed the significant antitumor effect of OPB-31121 against primary human leukemia cells harboring these aberrant kinases and its safety for normal human cord blood cells. Finally, we demonstrated a model to overcome drug resistance to upstream kinase inhibitors with a STAT inhibitor. These results suggested that OPB-31121 is a promising antitumor drug. Phase I trials have been performed in Korea and Hong Kong, and a phase I/II trial is underway in Japan

What if there were no significance tests?

CERN Document Server

Harlow, Lisa L; Steiger, James H

2013-01-01

This book is the result of a spirited debate stimulated by a recent meeting of the Society of Multivariate Experimental Psychology. Although the viewpoints span a range of perspectives, the overriding theme that emerges states that significance testing may still be useful if supplemented with some or all of the following -- Bayesian logic, caution, confidence intervals, effect sizes and power, other goodness of approximation measures, replication and meta-analysis, sound reasoning, and theory appraisal and corroboration. The book is organized into five general areas. The first presents an overview of significance testing issues that sythesizes the highlights of the remainder of the book. The next discusses the debate in which significance testing should be rejected or retained. The third outlines various methods that may supplement current significance testing procedures. The fourth discusses Bayesian approaches and methods and the use of confidence intervals versus significance tests. The last presents the p...

The cumulative effect of small dietary changes may significantly improve nutritional intakes in free-living children and adults

OpenAIRE

Bornet , Francis; Paineau , Damien; Beaufils , François; Boulier , Alain; Cassuto , Dominique-Adèle; Chwalow , Judith; Combris , Pierre; Couet , Charles; Jouret , Béatrice; Lafay , Lionel; Laville , Martine; Mahé , Sylvain; Ricour , Claude; Romon , Monique; Simon , Chantal

2010-01-01

Abstract Background/Objectives: The ELPAS study was an 8-month randomized controlled dietary modification trial designed to test the hypothesis that family dietary coaching would improve nutritional intakes and weight control in 2026 free-living children and parents (Paineau et al., 2008). It resulted in significant nutritional changes, with beneficial effects on body mass index in adults. In these ancillary analyses, we investigated dietary changes throughout the intervention. ...

Kefir exhibits anti‑proliferative and pro‑apoptotic effects on colon adenocarcinoma cells with no significant effects on cell migration and invasion.

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Khoury, Nathalie; El-Hayek, Stephany; Tarras, Omayr; El-Sabban, Marwan; El-Sibai, Mirvat; Rizk, Sandra

2014-11-01

Kefir, a fermented milk product, exhibits anti‑tumoral activity in vivo; yet its mechanism of action remains elusive. Recent studies have focused on the mechanism of action of kefir on cancer cells in vitro. The current study aims at examining the effect of kefir on cell survival, proliferation, and motility of colorectal cancer (CRC) cells. Kefir's anti‑cancer potential was tested on CRC cell lines, Caco‑2 and HT‑29, through cytotoxicity, proliferation, and apoptotic assays. The expression of certain genes involved in proliferation and apoptosis was measured using reverse transcriptase‑polymerase chain reaction (RT‑PCR) and western blotting. To assess the effect of kefir on cancer metastasis, wound‑healing and time‑lapse movies, in addition to collagen‑based invasion assay, were used. The results show that cell‑free fractions of kefir exhibit an anti‑proliferative effect on Caco‑2 and HT‑29 cells. Analysis of DNA content by flow cytometry revealed the ability of kefir to induce cell cycle arrest at the G1 phase. Kefir was also found to induce apoptosis, as seen by cell death ELISA. Results from RT‑PCR showed that kefir decreases the expression of transforming growth factor α (TGF‑α); and transforming growth factor‑β1 (TGF‑β1) in HT‑29 cells. Western blotting results revealed an upregulation in Bax:Bcl‑2 ratio, confirming the pro‑apoptotic effect of kefir, and an increase in p53 independent‑p21 expression upon kefir treatment. MMP expression was not altered by kefir treatment. Furthermore, results from time‑lapse motility movies, wound‑healing, and invasion assays showed no effect on the motility of colorectal as well as breast (MCF‑7 and MB‑MDA‑231) cancer cells upon kefir treatment. Our data suggest that kefir is able to inhibit the proliferation and induce apoptosis in HT‑29 and Caco‑2 CRC cells, yet it does not exhibit a significant effect on the motility and invasion of these cells in vitro.

Health significance and statistical uncertainty. The value of P-value.

Science.gov (United States)

Consonni, Dario; Bertazzi, Pier Alberto

2017-10-27

The P-value is widely used as a summary statistics of scientific results. Unfortunately, there is a widespread tendency to dichotomize its value in "P0.05" ("statistically not significant"), with the former implying a "positive" result and the latter a "negative" one. To show the unsuitability of such an approach when evaluating the effects of environmental and occupational risk factors. We provide examples of distorted use of P-value and of the negative consequences for science and public health of such a black-and-white vision. The rigid interpretation of P-value as a dichotomy favors the confusion between health relevance and statistical significance, discourages thoughtful thinking, and distorts attention from what really matters, the health significance. A much better way to express and communicate scientific results involves reporting effect estimates (e.g., risks, risks ratios or risk differences) and their confidence intervals (CI), which summarize and convey both health significance and statistical uncertainty. Unfortunately, many researchers do not usually consider the whole interval of CI but only examine if it includes the null-value, therefore degrading this procedure to the same P-value dichotomy (statistical significance or not). In reporting statistical results of scientific research present effects estimates with their confidence intervals and do not qualify the P-value as "significant" or "not significant".

Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology

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Mashhood Ahmed Sheikh

2017-08-01

Full Text Available The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support. The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study (N = 4,530, a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV, and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V. Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (% of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71 in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18, and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood (p < 0.001. Smoking in adulthood did not significantly

Neutrophils and Granulocytic MDSC: The Janus God of Cancer Immunotherapy

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Serena Zilio

2016-09-01

Full Text Available Neutrophils are the most abundant circulating blood cell type in humans, and are the first white blood cells recruited at the inflammation site where they orchestrate the initial immune response. Although their presence at the tumor site was recognized in the 1970s, until recently these cells have been neglected and considered to play just a neutral role in tumor progression. Indeed, in recent years neutrophils have been recognized to play a dual role in tumor development by either assisting the growth, angiogenesis, invasion, and metastasis or by exerting tumoricidal action directly via the secretion of antitumoral compounds, or indirectly via the orchestration of antitumor immunity. Understanding the biology of these cells and influencing their polarization in the tumor micro- and macro-environment may be the key for the development of new therapeutic strategies, which may finally hold the promise of an effective immunotherapy for cancer.

Clinical significance of adiponectin expression in colon cancer patients

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Mustafa Canhoroz

2014-01-01

Conclusion: Adiponectin, which is secreted by adipose tissue, may have a role in the development and progression of cancer via its pro-apoptotic and/or anti-proliferative effects. Adiponectin expression in tumor tissues is likely to have a negative effect on disease - free survival in patients with stage II/III colon cancer; however, no statistically significant effect was demonstrated.

An Analysis of Patient Perceptions and Expectations to Dental Implants: Is There a Significant Effect on Long-Term Satisfaction Levels?

Science.gov (United States)

2017-01-01

Here we present an analysis of patient perceptions and expectations to dental implant placement and their prosthetic reconstruction, to then consider whether they have an effect on long-term satisfaction levels. A Post-Treatment Completion Questionnaire was designed to analyse whether patient satisfaction is influenced by age and/or gender; has an effect on patient-reported self-confidence levels; contributes to increased levels of oral hygiene; provides further insight into the average pain levels during and after the surgical intervention; or influences further acceptance of dental implant surgery. And then whether relationships exist between any of these factors. 182 consecutive patients completed the survey: 68 males and 114 females (age mean 64.68 years ± 11.23 SD); the average number of months since treatment completion was 37.4 (males) and 62.6 (females). There is a significant relationship between comfort rating and “how well informed” the patient was (p = 0.015). A significantly positive relationship exists between “considering dental implants in the future” and “overall experience” (p = 0.001). A significantly positive relationship exists between “overall satisfaction with appearance” and “satisfaction with comfort” (p = 0.011). A significant relationship exists between “overall satisfaction with appearance,” “satisfaction with comfort,” and “overall satisfaction with experience” (p = 0.001). The results amplify the need to transmit logical, truthful information to patients when dental implant treatment is being considered. The “fully informed” patient will have realistic expectations that lead to high degrees of satisfaction. PMID:28928771

THRESHOLD OF SIGNIFICANCE IN STRESS MANAGEMENT

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Elena RUSE

2015-12-01

Full Text Available Stress management is the individual's ability to handle any situation, external conditions, to match the demands of the external environment. The researchers revealed several stages in the stress response. A first phase was called ‘‘alert reaction'' or ‘‘immediate reaction to stress‘‘, phase in which there are physiological modifications and manifestations that occur under psychological aspect. Adaptation phase is the phase in which the reactions from the first phase diminishes or disappears. Exhaustion phase is related to the diversity of stress factors and time and may exceed the resources of the human body to adapt. Influencing factors may be: limited, cognitive, perceptual, and a priori. But there is a threshold of significance in stress management. Once the reaction to external stimuli occurs, awareness is needed. The capability effect occurs, any side effect goes away and comes out the ''I AM'' effect.

Myeloma Cell Dynamics in Response to Treatment Supports a Model of Hierarchical Differentiation and Clonal Evolution.

Science.gov (United States)

Tang, Min; Zhao, Rui; van de Velde, Helgi; Tross, Jennifer G; Mitsiades, Constantine; Viselli, Suzanne; Neuwirth, Rachel; Esseltine, Dixie-Lee; Anderson, Kenneth; Ghobrial, Irene M; San Miguel, Jesús F; Richardson, Paul G; Tomasson, Michael H; Michor, Franziska

2016-08-15

Since the pioneering work of Salmon and Durie, quantitative measures of tumor burden in multiple myeloma have been used to make clinical predictions and model tumor growth. However, such quantitative analyses have not yet been performed on large datasets from trials using modern chemotherapy regimens. We analyzed a large set of tumor response data from three randomized controlled trials of bortezomib-based chemotherapy regimens (total sample size n = 1,469 patients) to establish and validate a novel mathematical model of multiple myeloma cell dynamics. Treatment dynamics in newly diagnosed patients were most consistent with a model postulating two tumor cell subpopulations, "progenitor cells" and "differentiated cells." Differential treatment responses were observed with significant tumoricidal effects on differentiated cells and less clear effects on progenitor cells. We validated this model using a second trial of newly diagnosed patients and a third trial of refractory patients. When applying our model to data of relapsed patients, we found that a hybrid model incorporating both a differentiation hierarchy and clonal evolution best explains the response patterns. The clinical data, together with mathematical modeling, suggest that bortezomib-based therapy exerts a selection pressure on myeloma cells that can shape the disease phenotype, thereby generating further inter-patient variability. This model may be a useful tool for improving our understanding of disease biology and the response to chemotherapy regimens. Clin Cancer Res; 22(16); 4206-14. ©2016 AACR. ©2016 American Association for Cancer Research.

Metastatic breast cancer - age has a significant effect on survival ...

African Journals Online (AJOL)

The data on 217 elderly (aged ≥ 65 years) and 209 middleaged postmenopausal patients with metastatic breast cancer treated in the Department of Medical Oncology, University of Pretoria, from 1976 to 1985 were analysed to determine the effect of age on survival. When considered as a group, the elderly have a more ...

[False positive results or what's the probability that a significant P-value indicates a true effect?

Science.gov (United States)

Cucherat, Michel; Laporte, Silvy

2017-09-01

The use of statistical test is central in the clinical trial. At the statistical level, obtaining a Pinformation about the plausibility of the existence of treatment effect. With "Pfalse positive is very high. This is the case if the power is low, if there is an inflation of the alpha risk or if the result is exploratory or chance discoveries. This possibility is important to take into consideration when interpreting the results of clinical trials in order to avoid pushing ahead significant results in appearance, but which are likely to be actually false positive results. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Erroneous analyses of interactions in neuroscience: a problem of significance

NARCIS (Netherlands)

Nieuwenhuis, S.; Forstmann, B.U.; Wagenmakers, E.-J.

2011-01-01

In theory, a comparison of two experimental effects requires a statistical test on their difference. In practice, this comparison is often based on an incorrect procedure involving two separate tests in which researchers conclude that effects differ when one effect is significant (P < 0.05) but the

Radio frequency induction of intracellular ferromagnetic particles: Potential for therapy

International Nuclear Information System (INIS)

Lerch, I.A.; Pizzarello, D.J.

1986-01-01

The authors have been studying the therapeutic potential of ferromagnetic or paramagnetic particles as mediators for depositing tumoricidal doses of radio frequency (RF) energy. Ferric oxide suspended in dextrose or polyvinylpyrrolidone was administered to retired female rat breeders with spontaneous mammary tumors. The rats were then exposed to an intense 100-kHz RF field. Tumor doubling times were increased from 23 days for controls to 62 days for rats irradiated 6 days after the administration of the particle suspensions. There was no conclusive evidence of organ damage caused by treatment. They conclude that the treatment modality merits further investigation

A new survival model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing rats in the treatment of peritoneal carcinomatosis

International Nuclear Information System (INIS)

Pelz, Joerg OW; Doerfer, Joerg; Hohenberger, Werner; Meyer, Thomas

2005-01-01

Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with peritoneal carcinomatosis of colorectal origin. Animal models are important in the evaluation of new treatment modalities. The purpose of this study was to devise an experimental setting which can be routinely used for the investigation of HIPEC in peritoneal carcinomatosis. A new peritoneal perfusion system in tumor bearing rats were tested. For this purpose CC531 colon carcinoma cells were implanted intraperitoneally in Wag/Rija rats. After 10 days of tumor growth the animals were randomized into three groups of six animals each: group 1: control (n = 6), group 2: HIPEC with mitomycin C in a concentration of 15 mg/m 2 (n = 6), group III: mitomycin C i.p. as monotherapy in a concentration of 10 mg/m 2 (n = 6). After 10 days, total tumor weight and the extent of tumor spread, as classified by the modified Peritoneal Cancer Index (PCI), were assessed by autopsy of the animals. No postoperative deaths were observed. Conjunctivitis, lethargy and loss of appetite were the main side effects in the HIPEC group. No severe locoregional or systemic toxity was observed. All control animals developed massive tumor growth. Tumor load was significantly reduced in the treatment group and was lowest in group II. The combination of hyperthermia with MMC resulted in an increased tumoricidal effect in the rat model. The presented model provides an opportunity to study the mechanism and effect of hyperthermic intraperitoneal chemotherapy and new drugs for this treatment modality

The Significance of Loyalty on Consumer Credit Profitability

OpenAIRE

Aditya Galih Prihartono; Ujang Sumarwan; Noer Azam Achsani; Kirbrandoko

2012-01-01

The purpose of this research is to analyze and test the effect of customer loyalty on consumer credit profitability. Loyalty Index Score was developed to determine the level of customers’ loyalty level through 4 main variables; Longevity, Depth, Breadth and Referrals. The effect of Loyalty Index Score on profitability was further tested by path analysis to find out the significance direct relationship between loyalty and profitablity and the indirect relationship between the two variable th...

Commonly used bowel preparations have significant and different effects upon cell proliferation in the colon: a pilot study

Directory of Open Access Journals (Sweden)

Riley Stuart A

2008-11-01

Full Text Available Abstract Background Markers of crypt cell proliferation are frequently employed in studies of the impact of genetic and exogenous factors on human colonic physiology. Human studies often rely on the assessment of tissue acquired at endoscopy. Modulation of cell proliferation by bowel preparation with oral laxatives may confound the findings of such studies, but there is little data on the impact of commonly used bowel preparations on markers of cell proliferation. Methods Crypt length, crypt cellularity and crypt cell proliferation were assessed in biopsies acquired after preparation with either Klean-Prep or Picolax. Crypt cell proliferation was assessed by whole-mount mitotic figure count, and by two different immunohistochemical (IHC labelling methods (Ki-67 and pHH3. Subsequent biopsies were obtained from the same patients without bowel preparation and similarly assessed. Parameters were compared between groups using analysis of variance and paired t-tests. Results There were significant differences in labelling indices (LI between biopsies taken after Klean-prep and those taken after Picolax preparation, for both Ki67 (p = 0.019 and pHH3 (p = 0.017. A similar trend was seen for whole-mount mitotic figure counts. Suppression or elevation of proliferation parameters by bowel preparation may mask any effect due to an intervention or disease. Conclusion Commonly used bowel preparations may have significant and different effects on crypt cell proliferation. This should be taken into account when designing studies and when considering the findings of existing studies.

Protein receptor-independent plasma membrane remodeling by HAMLET: a tumoricidal protein-lipid complex.

Science.gov (United States)

Nadeem, Aftab; Sanborn, Jeremy; Gettel, Douglas L; James, Ho C S; Rydström, Anna; Ngassam, Viviane N; Klausen, Thomas Kjær; Pedersen, Stine Falsig; Lam, Matti; Parikh, Atul N; Svanborg, Catharina

2015-11-12

A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This ''protein-centric" view is increasingly challenged by evidence for the involvement of specialized membrane domains in signal transduction. Here, we propose that membrane perturbation may serve as an alternative mechanism to activate a conserved cell-death program in cancer cells. This view emerges from the extraordinary manner in which HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills a wide range of tumor cells in vitro and demonstrates therapeutic efficacy and selectivity in cancer models and clinical studies. We identify a ''receptor independent" transformation of vesicular motifs in model membranes, which is paralleled by gross remodeling of tumor cell membranes. Furthermore, we find that HAMLET accumulates within these de novo membrane conformations and define membrane blebs as cellular compartments for direct interactions of HAMLET with essential target proteins such as the Ras family of GTPases. Finally, we demonstrate lower sensitivity of healthy cell membranes to HAMLET challenge. These features suggest that HAMLET-induced curvature-dependent membrane conformations serve as surrogate receptors for initiating signal transduction cascades, ultimately leading to cell death.

Geomorphic Effects, Chronologies, and Archaeological Significance of El Nino Floods in Southern Peru

Science.gov (United States)

Magilligan, F. J.; Manners, R.; Goldstein, P.

2003-12-01

The catastrophic effects of large floods have been well documented, on both contemporary and paleo-timecales, especially for the conterminous U.S. Less is known, however, about extreme events in hyper-arid sub-tropical climates where synoptic scale meteorological causes, such as El Nino-Southern Oscillation events, are the driving atmospheric mechanism. This research documents the geomorphic effects of extreme floods in the Moquegua River valley of southern Peru, in the core of the Atacama Desert. Using a combination of geomorphic mapping, hydrolologic modeling, aerial photography, ASTER satellite imagery, and GIS, we document the geomorphic signature of large contemporary floods within the mid-valley section (1500 masl) of the Rio Moquegua. Stratigraphic evidence and paleostage indicators of paleofloods, such as slackwater deposits and preserved high level flood gravels, are used to evidence late Holocene paleoflood magnitude-frequency relationships. On contemporary timescales, channel belt expansion by lateral erosion during large floods, such as the recent '97 and '98 floods, correspond to as much as 30-40 hectares of floodplain loss along the 20 km study reach. Sixty years of repeat aerial photography indicates that channel belt expansion and floodplain erosion commonly occurs along the Rio Moquegua. The frequent resetting of floodplain alluvium conditioned by these large floods is supported by radiocarbon dating of floodplain exposures. These dates indicate that most of the contemporary floodplain alluvium is younger that 560 14C yrs BP. The highest terrace remnants date to 3250 14C yrs BP and record a series of overbank flood gravels. Evidence for the regionally extensive Miraflores ENSO flood, ca. 1300 AD, exists in tributary and along mainstem sections. This flood has been documented along the coasts of Northern Chile to northern Peru, and has been evoked to explain significant social collapse. Our field evidence indicates that it catastrophically affected

Risk control and the minimum significant risk

International Nuclear Information System (INIS)

Seiler, F.A.; Alvarez, J.L.

1996-01-01

Risk management implies that the risk manager can, by his actions, exercise at least a modicum of control over the risk in question. In the terminology of control theory, a management action is a control signal imposed as feedback on the system to bring about a desired change in the state of the system. In the terminology of risk management, an action is taken to bring a predicted risk to lower values. Even if it is assumed that the management action taken is 100% effective and that the projected risk reduction is infinitely well known, there is a lower limit to the desired effects that can be achieved. It is based on the fact that all risks, such as the incidence of cancer, exhibit a degree of variability due to a number of extraneous factors such as age at exposure, sex, location, and some lifestyle parameters such as smoking or the consumption of alcohol. If the control signal is much smaller than the variability of the risk, the signal is lost in the noise and control is lost. This defines a minimum controllable risk based on the variability of the risk over the population considered. This quantity is the counterpart of the minimum significant risk which is defined by the uncertainties of the risk model. Both the minimum controllable risk and the minimum significant risk are evaluated for radiation carcinogenesis and are shown to be of the same order of magnitude. For a realistic management action, the assumptions of perfectly effective action and perfect model prediction made above have to be dropped, resulting in an effective minimum controllable risk which is determined by both risk limits. Any action below that effective limit is futile, but it is also unethical due to the ethical requirement of doing more good than harm. Finally, some implications of the effective minimum controllable risk on the use of the ALARA principle and on the evaluation of remedial action goals are presented

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

Science.gov (United States)

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

2016-06-01

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

Significance of the double-layer capacitor effect in polar rubbery dielectrics and exceptionally stable low-voltage high transconductance organic transistors.

Science.gov (United States)

Wang, Chao; Lee, Wen-Ya; Kong, Desheng; Pfattner, Raphael; Schweicher, Guillaume; Nakajima, Reina; Lu, Chien; Mei, Jianguo; Lee, Tae Hoon; Wu, Hung-Chin; Lopez, Jeffery; Diao, Ying; Gu, Xiaodan; Himmelberger, Scott; Niu, Weijun; Matthews, James R; He, Mingqian; Salleo, Alberto; Nishi, Yoshio; Bao, Zhenan

2015-12-14

Both high gain and transconductance at low operating voltages are essential for practical applications of organic field-effect transistors (OFETs). Here, we describe the significance of the double-layer capacitance effect in polar rubbery dielectrics, even when present in a very low ion concentration and conductivity. We observed that this effect can greatly enhance the OFET transconductance when driven at low voltages. Specifically, when the polar elastomer poly(vinylidene fluoride-co-hexafluoropropylene) (e-PVDF-HFP) was used as the dielectric layer, despite a thickness of several micrometers, we obtained a transconductance per channel width 30 times higher than that measured for the same organic semiconductors fabricated on a semicrystalline PVDF-HFP with a similar thickness. After a series of detailed experimental investigations, we attribute the above observation to the double-layer capacitance effect, even though the ionic conductivity is as low as 10(-10) S/cm. Different from previously reported OFETs with double-layer capacitance effects, our devices showed unprecedented high bias-stress stability in air and even in water.

Significance of the double-layer capacitor effect in polar rubbery dielectrics and exceptionally stable low-voltage high transconductance organic transistors

Science.gov (United States)

Wang, Chao; Lee, Wen-Ya; Kong, Desheng; Pfattner, Raphael; Schweicher, Guillaume; Nakajima, Reina; Lu, Chien; Mei, Jianguo; Lee, Tae Hoon; Wu, Hung-Chin; Lopez, Jeffery; Diao, Ying; Gu, Xiaodan; Himmelberger, Scott; Niu, Weijun; Matthews, James R.; He, Mingqian; Salleo, Alberto; Nishi, Yoshio; Bao, Zhenan

2015-01-01

Both high gain and transconductance at low operating voltages are essential for practical applications of organic field-effect transistors (OFETs). Here, we describe the significance of the double-layer capacitance effect in polar rubbery dielectrics, even when present in a very low ion concentration and conductivity. We observed that this effect can greatly enhance the OFET transconductance when driven at low voltages. Specifically, when the polar elastomer poly(vinylidene fluoride-co-hexafluoropropylene) (e-PVDF-HFP) was used as the dielectric layer, despite a thickness of several micrometers, we obtained a transconductance per channel width 30 times higher than that measured for the same organic semiconductors fabricated on a semicrystalline PVDF-HFP with a similar thickness. After a series of detailed experimental investigations, we attribute the above observation to the double-layer capacitance effect, even though the ionic conductivity is as low as 10–10 S/cm. Different from previously reported OFETs with double-layer capacitance effects, our devices showed unprecedented high bias-stress stability in air and even in water. PMID:26658331

The energetic significance of cooking.

Science.gov (United States)

Carmody, Rachel N; Wrangham, Richard W

2009-10-01

While cooking has long been argued to improve the diet, the nature of the improvement has not been well defined. As a result, the evolutionary significance of cooking has variously been proposed as being substantial or relatively trivial. In this paper, we evaluate the hypothesis that an important and consistent effect of cooking food is a rise in its net energy value. The pathways by which cooking influences net energy value differ for starch, protein, and lipid, and we therefore consider plant and animal foods separately. Evidence of compromised physiological performance among individuals on raw diets supports the hypothesis that cooked diets tend to provide energy. Mechanisms contributing to energy being gained from cooking include increased digestibility of starch and protein, reduced costs of digestion for cooked versus raw meat, and reduced energetic costs of detoxification and defence against pathogens. If cooking consistently improves the energetic value of foods through such mechanisms, its evolutionary impact depends partly on the relative energetic benefits of non-thermal processing methods used prior to cooking. We suggest that if non-thermal processing methods such as pounding were used by Lower Palaeolithic Homo, they likely provided an important increase in energy gain over unprocessed raw diets. However, cooking has critical effects not easily achievable by non-thermal processing, including the relatively complete gelatinisation of starch, efficient denaturing of proteins, and killing of food borne pathogens. This means that however sophisticated the non-thermal processing methods were, cooking would have conferred incremental energetic benefits. While much remains to be discovered, we conclude that the adoption of cooking would have led to an important rise in energy availability. For this reason, we predict that cooking had substantial evolutionary significance.

Uncertainty from the choice of microphysics scheme in convection-permitting models significantly exceeds aerosol effects

Directory of Open Access Journals (Sweden)

B. White

2017-10-01

Full Text Available This study investigates the hydrometeor development and response to cloud droplet number concentration (CDNC perturbations in convection-permitting model configurations. We present results from a real-data simulation of deep convection in the Congo basin, an idealised supercell case, and a warm-rain large-eddy simulation (LES. In each case we compare two frequently used double-moment bulk microphysics schemes and investigate the response to CDNC perturbations. We find that the variability among the two schemes, including the response to aerosol, differs widely between these cases. In all cases, differences in the simulated cloud morphology and precipitation are found to be significantly greater between the microphysics schemes than due to CDNC perturbations within each scheme. Further, we show that the response of the hydrometeors to CDNC perturbations differs strongly not only between microphysics schemes, but the inter-scheme variability also differs between cases of convection. Sensitivity tests show that the representation of autoconversion is the dominant factor that drives differences in rain production between the microphysics schemes in the idealised precipitating shallow cumulus case and in a subregion of the Congo basin simulations dominated by liquid-phase processes. In this region, rain mass is also shown to be relatively insensitive to the radiative effects of an overlying layer of ice-phase cloud. The conversion of cloud ice to snow is the process responsible for differences in cold cloud bias between the schemes in the Congo. In the idealised supercell case, thermodynamic impacts on the storm system using different microphysics parameterisations can equal those due to aerosol effects. These results highlight the large uncertainty in cloud and precipitation responses to aerosol in convection-permitting simulations and have important implications not only for process studies of aerosol–convection interaction, but also for

Tumor significant dose

International Nuclear Information System (INIS)

Supe, S.J.; Nagalaxmi, K.V.; Meenakshi, L.

1983-01-01

In the practice of radiotherapy, various concepts like NSD, CRE, TDF, and BIR are being used to evaluate the biological effectiveness of the treatment schedules on the normal tissues. This has been accepted as the tolerance of the normal tissue is the limiting factor in the treatment of cancers. At present when various schedules are tried, attention is therefore paid to the biological damage of the normal tissues only and it is expected that the damage to the cancerous tissues would be extensive enough to control the cancer. Attempt is made in the present work to evaluate the concent of tumor significant dose (TSD) which will represent the damage to the cancerous tissue. Strandquist in the analysis of a large number of cases of squamous cell carcinoma found that for the 5 fraction/week treatment, the total dose required to bring about the same damage for the cancerous tissue is proportional to T/sup -0.22/, where T is the overall time over which the dose is delivered. Using this finding the TSD was defined as DxN/sup -p/xT/sup -q/, where D is the total dose, N the number of fractions, T the overall time p and q are the exponents to be suitably chosen. The values of p and q are adjusted such that p+q< or =0.24, and p varies from 0.0 to 0.24 and q varies from 0.0 to 0.22. Cases of cancer of cervix uteri treated between 1978 and 1980 in the V. N. Cancer Centre, Kuppuswamy Naidu Memorial Hospital, Coimbatore, India were analyzed on the basis of these formulations. These data, coupled with the clinical experience, were used for choice of a formula for the TSD. Further, the dose schedules used in the British Institute of Radiology fraction- ation studies were also used to propose that the tumor significant dose is represented by DxN/sup -0.18/xT/sup -0.06/

How significant is the ‘significant other’? Associations between significant others’ health behaviors and attitudes and young adults’ health outcomes

Directory of Open Access Journals (Sweden)

Berge Jerica M

2012-04-01

Full Text Available Abstract Background Having a significant other has been shown to be protective against physical and psychological health conditions for adults. Less is known about the period of emerging young adulthood and associations between significant others’ weight and weight-related health behaviors (e.g. healthy dietary intake, the frequency of physical activity, weight status. This study examined the association between significant others’ health attitudes and behaviors regarding eating and physical activity and young adults’ weight status, dietary intake, and physical activity. Methods This study uses data from Project EAT-III, a population-based cohort study with emerging young adults from diverse ethnic and socioeconomic backgrounds (n = 1212. Logistic regression models examining cross-sectional associations, adjusted for sociodemographics and health behaviors five years earlier, were used to estimate predicted probabilities and calculate prevalence differences. Results Young adult women whose significant others had health promoting attitudes/behaviors were significantly less likely to be overweight/obese and were more likely to eat ≥ 5 fruits/vegetables per day and engage in ≥ 3.5 hours/week of physical activity, compared to women whose significant others did not have health promoting behaviors/attitudes. Young adult men whose significant other had health promoting behaviors/attitudes were more likely to engage in ≥ 3.5 hours/week of physical activity compared to men whose significant others did not have health promoting behaviors/attitudes. Conclusions Findings suggest the protective nature of the significant other with regard to weight-related health behaviors of young adults, particularly for young adult women. Obesity prevention efforts should consider the importance of including the significant other in intervention efforts with young adult women and potentially men.

The multikinase inhibitor Sorafenib displays significant antiproliferative effects and induces apoptosis via caspase 3, 7 and PARP in B- and T-lymphoblastic cells

International Nuclear Information System (INIS)

Schult, Catrin; Boldt, Sonja; Wolkenhauer, Olaf; Neri, Luca Maria; Freund, Mathias; Junghanss, Christian; Dahlhaus, Meike; Ruck, Sabine; Sawitzky, Mandy; Amoroso, Francesca; Lange, Sandra; Etro, Daniela; Glass, Aenne; Fuellen, Georg

2010-01-01

Targeted therapy approaches have been successfully introduced into the treatment of several cancers. The multikinase inhibitor Sorafenib has antitumor activity in solid tumors and its effects on acute lymphoblastic leukemia (ALL) cells are still unclear. ALL cell lines (SEM, RS4;11 and Jurkat) were treated with Sorafenib alone or in combination with cytarabine, doxorubicin or RAD001. Cell count, apoptosis and necrosis rates, cell cycle distribution, protein phosphorylation and metabolic activity were determined. Sorafenib inhibited the proliferation of ALL cells by cell cycle arrest accompanied by down-regulation of CyclinD3 and CDK4. Furthermore, Sorafenib initiated apoptosis by cleavage of caspases 3, 7 and PARP. Apoptosis and necrosis rates increased significantly with most pronounced effects after 96 h. Antiproliferative effects of Sorafenib were associated with a decreased phosphorylation of Akt (Ser473 and Thr308), FoxO3A (Thr32) and 4EBP-1 (Ser65 and Thr70) as early as 0.5 h after treatment. Synergistic effects were seen when Sorafenib was combined with other cytotoxic drugs or a mTOR inhibitor emphasizing the Sorafenib effect. Sorafenib displays significant antileukemic activity in vitro by inducing cell cycle arrest and apoptosis. Furthermore, it influences PI3K/Akt/mTOR signaling in ALL cells

Structural characterization of more potent alternatives to HAMLET, a tumoricidal complex of α-lactalbumin and oleic acid.

Science.gov (United States)

Nemashkalova, Ekaterina L; Kazakov, Alexei S; Khasanova, Leysan M; Permyakov, Eugene A; Permyakov, Sergei E

2013-09-10

HAMLET is a complex of human α-lactalbumin (hLA) with oleic acid (OA) that kills various tumor cells and strains of Streptococcus pneumoniae. More potent protein-OA complexes were previously reported for bovine α-lactalbumin (bLA) and β-lactoglobulin (bLG), and pike parvalbumin (pPA), and here we explore their structural features. The concentration dependencies of the tryptophan fluorescence of hLA, bLA, and bLG complexes with OA reveal their disintegration at protein concentrations below the micromolar level. Chemical cross-linking experiments provide evidence that association with OA shifts the distribution of oligomeric forms of hLA, bLA, bLG, and pPA toward higher-order oligomers. This effect is confirmed for bLA and bLG using the dynamic light scattering method, while pPA is shown to associate with OA vesicles. Like hLA binding, OA binding increases the affinity of bLG for small unilamellar dipalmitoylphosphatidylcholine vesicles, while pPA efficiently binds to the vesicles irrespective of OA binding. The association of OA with bLG and pPA increases their α-helix and cross-β-sheet content and resistance to enzymatic proteolysis, which is indicative of OA-induced protein structuring. The lack of excess heat sorption during melting of bLG and pPA in complex with OA and the presence of a cooperative thermal transition at the level of their secondary structure suggest that the OA-bound forms of bLG and pPA lack a fixed tertiary structure but exhibit a continuous thermal transition. Overall, despite marked differences, the HAMLET-like complexes that were studied exhibit a common feature: a tendency toward protein oligomerization. Because OA-induced oligomerization has been reported for other proteins, this phenomenon is inherent to many proteins.

Barnacle geese achieve significant energetic savings by changing posture.

Science.gov (United States)

Tickle, Peter G; Nudds, Robert L; Codd, Jonathan R

2012-01-01

Here we report the resting metabolic rate in barnacle geese (Branta leucopsis) and provide evidence for the significant energetic effect of posture. Under laboratory conditions flow-through respirometry together with synchronous recording of behaviour enabled a calculation of how metabolic rate varies with posture. Our principal finding is that standing bipedally incurs a 25% increase in metabolic rate compared to birds sitting on the ground. In addition to the expected decrease in energy consumption of hindlimb postural muscles when sitting, we hypothesise that a change in breathing mechanics represents one potential mechanism for at least part of the observed difference in energetic cost. Due to the significant effect of posture, future studies of resting metabolic rates need to take into account and/or report differences in posture.

Orthognathic Surgery Has a Significant Effect on Perceived Personality Traits and Emotional Expressions.

Science.gov (United States)

Mazzaferro, Daniel M; Wes, Ari M; Naran, Sanjay; Pearl, Rebecca; Bartlett, Scott P; Taylor, Jesse A

2017-11-01

The effects of orthognathic surgery go beyond objective cephalometric correction of facial and dental disproportion and malocclusion, respectively. The authors hypothesized that there is tangible improvement following surgery that alters publicly perceived personality traits and emotions. The authors used Amazon.com's Mechanical Turk (MTurk), a crowdsourcing tool, to determine how preoperative and postoperative images of orthognathic surgery patients were perceived on six personality traits and six emotional expressions based on posteroanterior and lateral photographs. Blinded respondents provided demographic information and were randomly assigned to one of two sets of 20 photographs (10 subjects before and after surgery). Data on 20 orthognathic surgery patients were collected from 476 individuals. The majority of participants were female (52.6 percent), 18 to 39 years old (67.9 percent), Caucasian (76.6 percent), had some college or technical training or graduated college (72.7 percent), and had an annual income between $20,000 and $99,999 (74.6 percent). A paired t test analysis found that subjects were perceived significantly more favorably after orthognathic surgery in 12 countenance categories: more dominant, trustworthy, friendly, intelligent, attractive, and happy; and also less threatening, angry, surprised, sad, afraid, and disgusted (p surgery than those earning less (p orthognathic surgery, with both perceived personality traits and emotions deemed more favorable. Additional work is needed to better understand the physiologic underpinnings of such findings. Crowdsourcing technology offers a unique opportunity for surgeons to gather data regarding laypeople's perceptions of surgical outcomes in areas such as orthognathic surgery.

Detecting significant changes in protein abundance

Directory of Open Access Journals (Sweden)

Kai Kammers

2015-06-01

Full Text Available We review and demonstrate how an empirical Bayes method, shrinking a protein's sample variance towards a pooled estimate, leads to far more powerful and stable inference to detect significant changes in protein abundance compared to ordinary t-tests. Using examples from isobaric mass labelled proteomic experiments we show how to analyze data from multiple experiments simultaneously, and discuss the effects of missing data on the inference. We also present easy to use open source software for normalization of mass spectrometry data and inference based on moderated test statistics.

Effect modification of air pollution on Urinary 8-Hydroxy-2'-Deoxyguanosine by genotypes: an application of the multiple testing procedure to identify significant SNP interactions

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Christiani David C

2010-12-01

Full Text Available Abstract Background Air pollution is associated with adverse human health, but mechanisms through which pollution exerts effects remain to be clarified. One suggested pathway is that pollution causes oxidative stress. If so, oxidative stress-related genotypes may modify the oxidative response defenses to pollution exposure. Methods We explored the potential pathway by examining whether an array of oxidative stress-related genes (twenty single nucleotide polymorphisms, SNPs in nine genes modified associations of pollutants (organic carbon (OC, ozone and sulfate with urinary 8-hydroxy-2-deoxygunosine (8-OHdG, a biomarker of oxidative stress among the 320 aging men. We used a Multiple Testing Procedure in R modified by our team to identify the significance of the candidate genes adjusting for a priori covariates. Results We found that glutathione S-tranferase P1 (GSTP1, rs1799811, M1 and catalase (rs2284367 and group-specific component (GC, rs2282679, rs1155563 significantly or marginally significantly modified effects of OC and/or sulfate with larger effects among those carrying the wild type of GSTP1, catalase, non-wild type of GC and the non-null of GSTM1. Conclusions Polymorphisms of oxidative stress-related genes modified effects of OC and/or sulfate on 8-OHdG, suggesting that effects of OC or sulfate on 8-OHdG and other endpoints may be through the oxidative stress pathway.

Significance of the Capacity Recovery Effect in Pouch Lithium-Sulfur Battery Cells

DEFF Research Database (Denmark)

Knap, Vaclav; Zhang, Teng; Stroe, Daniel Loan

2016-01-01

Lithium-Sulfur (Li-S) batteries are an emerging energy storage technology, which is technically-attractive due to its high theoretical limits; practically, it is expected that Li-S batteries will result into lighter energy storage devices with higher capacities than traditional Lithium-ion...... batteries. One of the actual disadvantages for this technology is the highly pronounced rate capacity effect, which reduces the available capacity to be discharged when high currents are used. This drawback might be addressed by the use of the capacity recovery effect, which by introducing relaxation...... periods between consecutive pulse discharges of the battery, increases the available discharge capacity of the cell. The capacity recovery effect of the Li-S cell is studied in this paper using the pulse discharge technique, considering its dependence on the applied current, discharge step length...

Hydrologic effects of large southwestern USA wildfires significantly increase regional water supply: fact or fiction?

Science.gov (United States)

Wine, M. L.; Cadol, D.

2016-08-01

In recent years climate change and historic fire suppression have increased the frequency of large wildfires in the southwestern USA, motivating study of the hydrological consequences of these wildfires at point and watershed scales, typically over short periods of time. These studies have revealed that reduced soil infiltration capacity and reduced transpiration due to tree canopy combustion increase streamflow at the watershed scale. However, the degree to which these local increases in runoff propagate to larger scales—relevant to urban and agricultural water supply—remains largely unknown, particularly in semi-arid mountainous watersheds co-dominated by winter snowmelt and the North American monsoon. To address this question, we selected three New Mexico watersheds—the Jemez (1223 km2), Mogollon (191 km2), and Gila (4807 km2)—that together have been affected by over 100 wildfires since 1982. We then applied climate-driven linear models to test for effects of fire on streamflow metrics after controlling for climatic variability. Here we show that, after controlling for climatic and snowpack variability, significantly more streamflow discharged from the Gila watershed for three to five years following wildfires, consistent with increased regional water yield due to enhanced infiltration-excess overland flow and groundwater recharge at the large watershed scale. In contrast, we observed no such increase in discharge from the Jemez watershed following wildfires. Fire regimes represent a key difference between the contrasting responses of the Jemez and Gila watersheds with the latter experiencing more frequent wildfires, many caused by lightning strikes. While hydrologic dynamics at the scale of large watersheds were previously thought to be climatically dominated, these results suggest that if one fifth or more of a large watershed has been burned in the previous three to five years, significant increases in water yield can be expected.

Treatment with pioglitazone induced significant, reversible mitral regurgitation.

Science.gov (United States)

Dorkhan, Mozhgan; Dencker, Magnus; Frid, Anders

2008-04-30

There has in recent years been great concern about possible cardiac side effects of thiazolidinediones (TZDs). We present a case-report of a 60 year-old male who developed significant mitral regurgitation during six months treatment with pioglitazone in parallel with laboratory indications of fluid retention. Echocardiography six months after discontinuation of medication showed regression of mitral regurgitation and the laboratory parameters were also normalized. It is noteworthy that six months treatment with pioglitazone could induce significant valve dysfunction, which was reversible, and this underlines the importance of carefully monitoring patients when placing them on treatment with TZDs.

Treatment with pioglitazone induced significant, reversible mitral regurgitation

Directory of Open Access Journals (Sweden)

Frid Anders

2008-04-01

Full Text Available Abstract There has in recent years been great concern about possible cardiac side effects of thiazolidinediones (TZDs. We present a case-report of a 60 year-old male who developed significant mitral regurgitation during six months treatment with pioglitazone in parallel with laboratory indications of fluid retention. Echocardiography six months after discontinuation of medication showed regression of mitral regurgitation and the laboratory parameters were also normalized. It is noteworthy that six months treatment with pioglitazone could induce significant valve dysfunction, which was reversible, and this underlines the importance of carefully monitoring patients when placing them on treatment with TZDs.

Rumen-protected choline: A significance effect on dairy cattle nutrition.

Science.gov (United States)

Jayaprakash, G; Sathiyabarathi, M; Robert, M Arokia; Tamilmani, T

2016-08-01

Choline is a vitamin-like substance it has multi-function in animal production, reproduction, and health. The transition period is most crucial stage in lactation cycle of dairy cows due to its association with negative hormonal and energy balances. Unfortunately, unprotected choline easily degrades in the rumen; therefore, choline added to the diet in a rumen-protected form. The use of rumen-protected choline (RPC) is a preventive measurement for the fatty liver syndrome and ketosis; may improve milk production as well as milk composition and reproduction parameters. This review summarizes the effectiveness of RPC on animal production, health, and reproduction.

Barnacle geese achieve significant energetic savings by changing posture.

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Peter G Tickle

Full Text Available Here we report the resting metabolic rate in barnacle geese (Branta leucopsis and provide evidence for the significant energetic effect of posture. Under laboratory conditions flow-through respirometry together with synchronous recording of behaviour enabled a calculation of how metabolic rate varies with posture. Our principal finding is that standing bipedally incurs a 25% increase in metabolic rate compared to birds sitting on the ground. In addition to the expected decrease in energy consumption of hindlimb postural muscles when sitting, we hypothesise that a change in breathing mechanics represents one potential mechanism for at least part of the observed difference in energetic cost. Due to the significant effect of posture, future studies of resting metabolic rates need to take into account and/or report differences in posture.

Positive detection of exfoliated colon cancer cells on linear stapler cartridges was associated with depth of tumor invasion and preoperative bowel preparation in colon cancer.

Science.gov (United States)

Ikehara, Kishiko; Endo, Shungo; Kumamoto, Kensuke; Hidaka, Eiji; Ishida, Fumio; Tanaka, Jun-Ichi; Kudo, Shin-Ei

2016-08-31

The aim of this study was to investigate exfoliated cancer cells (ECCs) on linear stapler cartridges used for anastomotic sites in colon cancer. We prospectively analyzed ECCs on linear stapler cartridges used for anastomosis in 100 colon cancer patients who underwent colectomy. Having completed the functional end-to-end anastomosis, the linear stapler cartridges were irrigated with saline, which was collected for cytological examination and cytological diagnoses were made by board-certified pathologists based on Papanicolaou staining. The detection rate of ECCs on the linear stapler cartridges was 20 %. Positive detection of ECCs was significantly associated with depth of tumor invasion (p = 0.012) and preoperative bowel preparation (p = 0.003). There were no marked differences between ECC-positive and ECC-negative groups in terms of the operation methods, tumor location, histopathological classification, and surgical margins. Since ECCs were identified on the cartridge of the linear stapler used for anastomosis, preoperative mechanical bowel preparation using polyethylene glycol solution and cleansing at anastomotic sites using tumoricidal agents before anastomosis may be necessary to decrease ECCs in advanced colon cancer.

Exosomes in Cancer Nanomedicine and Immunotherapy: Prospects and Challenges.

Science.gov (United States)

Syn, Nicholas L; Wang, Lingzhi; Chow, Edward Kai-Hua; Lim, Chwee Teck; Goh, Boon-Cher

2017-07-01

Exosomes (versatile, cell-derived nanovesicles naturally endowed with exquisite target-homing specificity and the ability to surmount in vivo biological barriers) hold substantial promise for developing exciting approaches in drug delivery and cancer immunotherapy. Specifically, bioengineered exosomes are being successfully deployed to deliver potent tumoricidal drugs (siRNAs and chemotherapeutic compounds) preferentially to cancer cells, while a new generation of exosome-based therapeutic cancer vaccines has produced enticing results in early-phase clinical trials. Here, we review the state-of-the-art technologies and protocols, and discuss the prospects and challenges for the clinical development of this emerging class of therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preliminary report of a new treatment strategy for advanced pelvic malignancy: surgical resection and radiation therapy using afterloading catheters plus an inflatable displacement prosthesis in the treatment of advanced primary and recurrent rectal cancer

International Nuclear Information System (INIS)

Edington, H.D.; Hancock, S.; Coe, F.L.; Sugarbaker, P.H.

1986-01-01

An unsolved problem in colon and rectal surgery involves the treatment of locally invasive primary and recurrent rectal cancer. An approach is described that uses intracavitary iridium-192 sources in combination with a pelvic displacement prosthesis to augment external beam radiation doses to sites of residual disease identified at surgery. This approach should permit administration of tumoricidal doses of radiation to positive surgical margins minimizing radiation toxicity to the small bowel. The radiation source and all prosthetic materials are removed at the bedside within 2 weeks of surgery, ensuring accurate radiation dosimetry, minimizing infectious complications, and sparing the patient the need for full high-dose pelvic irradiation

Effects of Domestic Violence on Children and Significance of Psychosocial Support

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Neslihan Lok

2016-06-01

Full Text Available Nowadays increasing complexity of living conditions of children influence every aspect of family atmosphere, parent-child relationships and child rearing practices. These are significant factors in development of childrens personality and sustaining their mental health. Although family environment is considered to be safest environment for children, many parents grind them consciously or unconsciously on the grounds of edification which might cause problems in their physical, spiritual, mental and affective growth leading them to be unhealthy individuals. Therefore, children exposed to violence by their family members should be determined by a multidisciplinary team to make a psychosocial support available. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(2: 156-161

Bedtime Blood Pressure Chronotherapy Significantly Improves Hypertension Management.

Science.gov (United States)

Hermida, Ramón C; Ayala, Diana E; Fernández, José R; Mojón, Artemio; Crespo, Juan J; Ríos, María T; Smolensky, Michael H

2017-10-01

Consistent evidence of numerous studies substantiates the asleep blood pressure (BP) mean derived from ambulatory BP monitoring (ABPM) is both an independent and a stronger predictor of cardiovascular disease (CVD) risk than are daytime clinic BP measurements or the ABPM-determined awake or 24-hour BP means. Hence, cost-effective adequate control of sleep-time BP is of marked clinical relevance. Ingestion time, according to circadian rhythms, of hypertension medications of 6 different classes and their combinations significantly improves BP control, particularly sleep-time BP, and reduces adverse effects. Copyright © 2017 Elsevier Inc. All rights reserved.

A home education program for older adults with hearing impairment and their significant others: a randomized trial evaluating short- and long-term effects

NARCIS (Netherlands)

Kramer, S.E.; Allessie, G.H.; Dondorp, A.W.; Zekveld, A.A.; Kapteyn, T.S.

2005-01-01

This paper addresses the development and effectiveness of a home education program. The program, designed for hearing-impaired elders and their significant others (SO), deals with communication strategies and speech reading. Participants were randomly assigned to a training group (hearing aid

Reevaluating the Concept of Treating Experimental Tumors with a Mixed Bacterial Vaccine: Coley’s Toxin

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C. Maletzki

2012-01-01

Full Text Available Several decades after Coley’s initial work, we here systematically analyzed tumoricidal as well as immunostimulatory effects of the historical preparation Coley’s Toxin (CT, a safe vaccine made of heat-inactivated S. pyogenes and S. marcescens. First, by performing in vitro analysis, established human pancreatic carcinoma cell lines responded with dose- and time-dependent growth inhibition. Effects were attributed to necrotic as well as apoptotic cell death as determined by increased Caspase 3/7 levels, raised numbers of cells with sub-G1-DNA, and induced p expression, indicative for cell cycle arrest. Besides, CT effectively stimulated human peripheral blood leukocytes (huPBL from healthy volunteers. Quantitative gene expression analysis revealed upregulated mRNA levels of selected Toll-like receptors. Flow cytometric phenotyping of CT-stimulated huPBLs identified raised numbers of CD25+-activated leukocytes. In vivo, repetitive, local CT application was well tolerated by animals and induced considerable delay of Panc02 tumors. However, systemic treatment failed to affect tumor growth. Antitumoral effects following local therapy were primarily accompanied by stimulation of innate immune mechanisms. Data presented herein prove that the historical approach of using killed bacteria as active immunotherapeutic agents still holds promise, and further careful preclinical analyses may pave the way back into clinical applications.

The Addition of Manganese Porphyrins during Radiation Inhibits Prostate Cancer Growth and Simultaneously Protects Normal Prostate Tissue from Radiation Damage

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Arpita Chatterjee

2018-01-01

Full Text Available Radiation therapy is commonly used for prostate cancer treatment; however, normal tissues can be damaged from the reactive oxygen species (ROS produced by radiation. In separate reports, we and others have shown that manganese porphyrins (MnPs, ROS scavengers, protect normal cells from radiation-induced damage but inhibit prostate cancer cell growth. However, there have been no studies demonstrating that MnPs protect normal tissues, while inhibiting tumor growth in the same model. LNCaP or PC3 cells were orthotopically implanted into athymic mice and treated with radiation (2 Gy, for 5 consecutive days in the presence or absence of MnPs. With radiation, MnPs enhanced overall life expectancy and significantly decreased the average tumor volume, as compared to the radiated alone group. MnPs enhanced lipid oxidation in tumor cells but reduced oxidative damage to normal prostate tissue adjacent to the prostate tumor in combination with radiation. Mechanistically, MnPs behave as pro-oxidants or antioxidants depending on the level of oxidative stress inside the treated cell. We found that MnPs act as pro-oxidants in prostate cancer cells, while in normal cells and tissues the MnPs act as antioxidants. For the first time, in the same in vivo model, this study reveals that MnPs enhance the tumoricidal effect of radiation and reduce oxidative damage to normal prostate tissue adjacent to the prostate tumor in the presence of radiation. This study suggests that MnPs are effective radio-protectors for radiation-mediated prostate cancer treatment.

The Significance of the Bystander Effect: Modeling, Experiments, and More Modeling

Energy Technology Data Exchange (ETDEWEB)

Brenner, David J.

2009-07-22

Non-targeted (bystander) effects of ionizing radiation are caused by intercellular signaling; they include production of DNA damage and alterations in cell fate (i.e. apoptosis, differentiation, senescence or proliferation). Biophysical models capable of quantifying these effects may improve cancer risk estimation at radiation doses below the epidemiological detection threshold. Understanding the spatial patterns of bystander responses is important, because it provides estimates of how many bystander cells are affected per irradiated cell. In a first approach to modeling of bystander spatial effects in a three-dimensional artificial tissue, we assumed the following: (1) The bystander phenomenon results from signaling molecules (S) that rapidly propagate from irradiated cells and decrease in concentration (exponentially in the case of planar symmetry) as distance increases. (2) These signals can convert cells to a long-lived epigenetically activated state, e.g. a state of oxidative stress; cells in this state are more prone to DNA damage and behavior alterations than normal and therefore exhibit an increased response (R) for many end points (e.g. apoptosis, differentiation, micronucleation). These assumptions were implemented by a mathematical formalism and computational algorithms. The model adequately described data on bystander responses in the 3D system using a small number of adjustable parameters. Mathematical models of radiation carcinogenesis are important for understanding mechanisms and for interpreting or extrapolating risk. There are two classes of such models: (1) long-term formalisms that track pre-malignant cell numbers throughout an entire lifetime but treat initial radiation dose-response simplistically and (2) short-term formalisms that provide a detailed initial dose-response even for complicated radiation protocols, but address its modulation during the subsequent cancer latency period only indirectly. We argue that integrating short- and long

Antitumor effect of vitamin D-binding protein-derived macrophage activating factor on Ehrlich ascites tumor-bearing mice.

Science.gov (United States)

Koga, Y; Naraparaju, V R; Yamamoto, N

1999-01-01

Cancerous cells secrete alpha-N-acetylgalactosaminidase (NaGalase) into the blood stream, resulting in deglycosylation of serum vitamin D3-binding protein (known as Gc protein), which is a precursor for macrophage activating factor (MAF). Incubation of Gc protein with immobilized beta-galactosidase and sialidase generates the most potent macrophage activating factor (designated GcMAF). Administration of GcMAF to cancer-bearing hosts can bypass the inactivated MAF precursor and act directly on macrophages for efficient activation. Therapeutic effects of GcMAF on Ehrlich ascites tumor-bearing mice were assessed by survival time and serum NaGalase activity, because serum NaGalase activity was proportional to tumor burden. A single administration of GcMAF (100 pg/mouse) to eight mice on the same day after transplantation of the tumor (5 x 10(5) cells) showed a mean survival time of 21 +/- 3 days for seven mice, with one mouse surviving more than 60 days, whereas tumor-bearing controls had a mean survival time of 13 +/- 2 days. Six of the eight mice that received two GcMAF administrations, at Day 0 and Day 4 after transplantation, survived up to 31 +/- 4 days whereas, the remaining two mice survived for more than 60 days. Further, six of the eight mice that received three GcMAF administrations with 4-day intervals showed an extended survival of at least 60 days, and serum NaGalase levels were as low as those of control mice throughout the survival period. The cure with subthreshold GcMAF-treatments (administered once or twice) of tumor-bearing mice appeared to be a consequence of sustained macrophage activation by inflammation resulting from the macrophage-mediated tumoricidal process. Therefore, a protracted macrophage activation induced by a few administrations of minute amounts of GcMAF eradicated the murine ascites tumor.

Extracts of Crinum latifolium inhibit the cell viability of mouse lymphoma cell line EL4 and induce activation of anti-tumour activity of macrophages in vitro.

Science.gov (United States)

Nguyen, Hoang-Yen T; Vo, Bach-Hue T; Nguyen, Lac-Thuy H; Bernad, Jose; Alaeddine, Mohamad; Coste, Agnes; Reybier, Karine; Pipy, Bernard; Nepveu, Françoise

2013-08-26

Crinum latifolium L. (CL) leaf extracts have been traditionally used in Vietnam and are now used all over the world for the treatment of prostate cancer. However, the precise cellular mechanisms of the action of CL extracts remain unclear. To examine the effects of CL samples on the anti-tumour activity of peritoneal murine macrophages. The properties of three extracts (aqueous, flavonoid, alkaloid), one fraction (alkaloid), and one pure compound (6-hydroxycrinamidine) obtained from CL, were studied (i) for redox capacities (DPPH and bleaching beta-carotene assays), (ii) on murine peritoneal macrophages (MTT assay) and on lymphoma EL4-luc2 cells (luciferine assay) for cytotoxicity, (iii) on macrophage polarization (production of ROS and gene expression by PCR), and (iv) on the tumoricidal functions of murine peritoneal macrophages (lymphoma cytotoxicity by co-culture with syngeneic macrophages). The total flavonoid extract with a high antioxidant activity (IC50=107.36 mg/L, DPPH assay) showed an inhibitory action on cancer cells. Alkaloid extracts inhibited the proliferation of lymphoma cells either by directly acting on tumour cells or by activating of the tumoricidal functions of syngeneic macrophages. The aqueous extract induced mRNA expression of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin 6 (IL-6) indicating differentiation of macrophages into pro-inflammatory M1 polarized macrophages. The total flavonoid, alkaloid extracts and an alkaloid fraction induced the expression of the formyl peptide receptor (FPR) on the surface of the polarized macrophages that could lead to the activation of macrophages towards the M1 phenotype. Aqueous and flavonoid extracts enhanced NADPH quinine oxido-reductase 1 (NQO1) mRNA expression in polarized macrophages which could play an important role in cancer chemoprevention. All the samples studied were non-toxic to normal living cells and the pure alkaloid tested, 6-hydroxycrinamidine, was not

Significant enhancement of metal heat dissipation from mechanically exfoliated graphene nanosheets through thermal radiation effect

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Junxiong Hu

2017-05-01

Full Text Available We demonstrate a facile approach to significantly enhance the heat dissipation potential of conventional aluminum (Al heat sinks by mechanically coating graphene nanosheets. For Al and graphene-coated Al heat sinks, the change in temperature with change in coating coverage, coating thickness and heat flux are studied. It is found that with the increase in coating coverage from 0 to 100%, the steady-state temperature is decreased by 5 °C at a heat flux of 1.8 W cm-1. By increasing the average thickness of graphene coating from 480 nm to 1900 nm, a remarkable temperature reduction up to 7 °C can be observed. Moreover, with the increase in heat flux from 1.2 W cm-1 to 2.4 W cm-1, the temperature difference between uncoated and graphene-coated samples increases from 1 °C to 6 °C. The thermal analysis and finite element simulation reveal that the thermal radiation plays a key role in enhancing the heat dissipation performance. The effect of heat convection remains weak owing to the low air velocity at surface-air boundary. This work provides a technological innovation in improving metal heat dissipation using graphene nanosheets.

Sucralfate significantly reduces ciprofloxacin concentrations in serum.

OpenAIRE

Garrelts, J C; Godley, P J; Peterie, J D; Gerlach, E H; Yakshe, C C

1990-01-01

The effect of sucralfate on the bioavailability of ciprofloxacin was evaluated in eight healthy subjects utilizing a randomized, crossover design. The area under the concentration-time curve from 0 to 12 h was reduced from 8.8 to 1.1 micrograms.h/ml by sucralfate (P less than 0.005). Similarly, the maximum concentration of ciprofloxacin in serum was reduced from 2.0 to 0.2 micrograms/ml (P less than 0.005). We conclude that concurrent ingestion of sucralfate significantly reduces the concentr...

Dosimetric aspects of the treatment of metastatic bone pain with radiopharmaceuticals

International Nuclear Information System (INIS)

Garcia, T.; Marti, J. F.; Olivas, C.; Vercher, J. L.; Repetto, R.; Bello, P.

2014-01-01

Within the context of treatment of metastatic bone pain with bone seeking radiopharmaceuticals, this paper expounds the results of an analysis of available molecules (both approved for clinical use or still under study) intended to obtain a detailed comparison of their dosimetric characteristics. These can be used to supplement the list of already know differences between them, such as efficacy, appearance and length of the palliative effect, eventual tumoricidal effect, myelotoxicity, sale price and availability. Seven radiopharmaceuticals have been analysed, five of them are based on beta emission radionuclides: 3 2P, 1 53Sm, 1 86Re and 1 88Re and the other two ones are based on high Linear energy Transference emission radionuclides: 1 17mSn and 2 23Ra a series of estimates of the main dosimetric parameters for each radiopharmaceutical analysed have been obtained. The values obtained might be worth being incorporated to the risk/benefit analysis that precedes every choice of the specific radiopharmaceutical to be used with an individual patient. In this way, we hope these results will be of some help for those Nuclear Medicine specialists interested in the treatment of oncological bone pathologies. (Author)

Post-operative high dose rate brachytherapy in patients with low to intermediate risk endometrial cancer

International Nuclear Information System (INIS)

Pearcey, R.G.; Petereit, D.G.

2000-01-01

This paper investigates the outcome using different dose/fractionation schedules in high dose rate (HDR) post-operative vaginal vault radiotherapy in patients with low to intermediate risk endometrial cancer. The world literature was reviewed and thirteen series were analyzed representing 1800 cases. A total of 12 vaginal vault recurrences were identified representing an overall vaginal control rate of 99.3%. A wide range of dose fractionation schedules and techniques have been reported. In order to analyze a dose response relationship for tumor control and complications, the biologically effective doses to the tumor and late responding tissues were calculated using the linear quadratic model. A threshold was identified for complications, but not vaginal control. While dose fractionation schedules that delivered a biologically effective dose to the late responding tissues in excess of 100 Gy 3 (LQED = 60 Gy) predicted for late complications, dose fractionation schedules that delivered a modest dose to the vaginal surface (50 Gy 10 or LQED = 30 Gy) appeared tumoricidal with vaginal control rates of at least 98%. By using convenient, modest dose fractionation schedules, HDR vaginal vault - brachytherapy yields very high local control and extremely low morbidity rates. (author)

Significant Revisions to OSHA 29 CFR 1910.269.

Science.gov (United States)

Neitzel, Dennis K

2015-06-01

The updated OSHA 29 CFR 1910.269 requirements are significant for assisting employers in their efforts to protect their employees from electrical hazards. In addition, OSHA based these revisions on the latest consensus standards and improvements in electrical safety technology. Together, the updated regulation creates a unified and up-to-date set of requirements to help employers more effectively establish safe work practices to protect their workers.

Hygienic significance of radiostability as measures of adaptive feasibilities

International Nuclear Information System (INIS)

Kudritskij, Yu.K.

1987-01-01

An attempt is made to substantiate hygienic significance of radiostability analysis as measures of adaptive feasibilities variation under the low dose ionizing radiation effect (IR). Examples of this substantiation are presented. Not only biological radiation effects but social adaptivity problems may be analysed. With more information adaptive feasibilities of human body to radiation factor are extended, its radiostability increases. Analysis of the state of adaptive feasibilities and their development estimation are vital problems of radiation hygiene, the basis for regulation and normalization of radiation factor

Tumor-Targeting Salmonella typhimurium A1-R Promotes Tumoricidal CD8+ T Cell Tumor Infiltration and Arrests Growth and Metastasis in a Syngeneic Pancreatic-Cancer Orthotopic Mouse Model.

Science.gov (United States)

Murakami, Takashi; Hiroshima, Yukihiko; Zhang, Yong; Zhao, Ming; Kiyuna, Tasuku; Hwang, Ho Kyoung; Miyake, Kentaro; Homma, Yuki; Mori, Ryutaro; Matsuyama, Ryusei; Chishima, Takashi; Ichikawa, Yasushi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

2018-01-01

The present study determined the effect of the tumor-targeting strain Salmonella typhimurium A1-R (S. typhimurium A1-R) on CD8 + tumor-infiltrating lymphocytes (TILs) in a syngeneic pancreatic-cancer orthotopic mouse model. The effect of tumor-targeting S. typhimurium A1-R on CD8 + TILs was determined on the Pan02 murine pancreatic-adenocarcinoma implanted orthotopically in the pancreatic tail of C57BL/6 immunocompromised mice. Three weeks after orthotopic implantation, mice were randomized as follows G1: untreated control group (n = 8); and G2: S. typhimurium A1-R-treatment group (n = 8, 1 × 10 7 colony forming units [CFU]/body, iv, weekly, 3 weeks). On the 22nd day from initial treatment, all mice were sacrificed and tumors were harvested. The tumor-volume ratio was defined as ratio of tumor volume on the 22nd day relative to the 1st day. The tumor volume ratio was significantly lower in the S. typhimurium A1-R-treated group (G2) (3.0 ± 2.8) than the untreated control (G1) (39.9 ± 30.7, P R-treated mice (G2). Six mice in G1 had peritoneal dissemination, whereas no mice showed peritoneal dissemination in G2 (P R promotes CD8 + T cell infiltration and inhibition of tumor growth and metastasis. J. Cell. Biochem. 119: 634-639, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Significance of abolishing British National Oil Corporation

Energy Technology Data Exchange (ETDEWEB)

Mabro, R

1985-04-01

The decision to abolish British National Oil Corporation has greater significance than any commentator, so far, has cared to admit. Mr. Mabro says the Government has done much more than get rid of an institution it had previously weakened and emasculated; in effect, it had abdicated its responsibilities for the pricing of North Sea oil. He further observes that these moves may be consistent with the tenets of a simplistic free-market ideology: they betray, however, a lack of understanding of the economics of oil, and of the UK economic interest in oil.

Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

Science.gov (United States)

Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-01-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

The UK's Levy Control Framework for renewable electricity support: Effects and significance

International Nuclear Information System (INIS)

Lockwood, Matthew

2016-01-01

There is a long-standing debate over price vs. quantity approaches to supporting the deployment of renewable electricity technologies. In the context of a recent shift from quantity to price-based support, the UK has also introduced a new form of budgetary framework, the Levy Control Framework (LCF). The introduction of the LCF has been very important for investors but has received relatively little attention in the academic literature. The paper gives an overview of the LCF, explores its effects on renewables policy, on consumers and on investor confidence arguing that an unintended consequence of its introduction has been to increase uncertainty, through interactions with underlying support mechanisms. A number of problems with the current scope and design of the LCF are noted. It is argued that the LCF is best understood as aimed at avoiding a political backlash against renewable support policy in a context where the benefits of such policy are concentrated economically and socially. The paper concludes by placing the LCF within a wider context of a shift towards greater budgetary control over renewable energy support policy across European countries. - Highlights: • Gives an description of the Levy Control Framework. • Analyses the effects of the LCF on UK renewable policy. • Reviews possible purposes of the LCF. • Evaluates the effects of the LCF on consumers and investors. • Places the LCF in context of greater cost control over renewables across the EU.

Prognostic significance of kynurenine 3-monooxygenase and effects on proliferation, migration, and invasion of human hepatocellular carcinoma.

Science.gov (United States)

Jin, Haojie; Zhang, Yurong; You, Haiyan; Tao, Xuemei; Wang, Cun; Jin, Guangzhi; Wang, Ning; Ruan, Haoyu; Gu, Dishui; Huo, Xisong; Cong, Wenming; Qin, Wenxin

2015-06-23

Kynurenine 3-monooxygenase (KMO) is a pivotal enzyme in the kynurenine pathway of tryptophan degradation and plays a critical role in Huntington's and Alzheimer's diseases. This study aimed to examine the expression of KMO in human hepatocellular carcinoma (HCC) and investigate the relationship between its expression and prognosis of HCC patients. We first analyzed KMO expression in 120 paired HCC samples (HCC tissues vs matched adjacent non-cancerous liver tissues), and 205 clinical HCC specimens using immunohistochemistry (IHC). Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of HCC. The results of IHC analysis showed that KMO expression was significantly higher in HCC tissues than that in normal liver tissues (all p KMO was an independent prognostic factor for overall survival (OS) and time to recurrence (TTR) (both pKMO positively regulated proliferation, migration, and invasion of HCC cells. These results suggest that KMO exhibits tumor-promoting effects towards HCC and it may serve as a novel prognostic marker in HCC.

Enhancing the Effectiveness of Significant Event Analysis: Exploring Personal Impact and Applying Systems Thinking in Primary Care.

Science.gov (United States)

Bowie, Paul; McNaughton, Elaine; Bruce, David; Holly, Deirdre; Forrest, Eleanor; Macleod, Marion; Kennedy, Susan; Power, Ailsa; Toppin, Denis; Black, Irene; Pooley, Janet; Taylor, Audrey; Swanson, Vivien; Kelly, Moya; Ferguson, Julie; Stirling, Suzanne; Wakeling, Judy; Inglis, Angela; McKay, John; Sargeant, Joan

2016-01-01

Significant event analysis (SEA) is well established in many primary care settings but can be poorly implemented. Reasons include the emotional impact on clinicians and limited knowledge of systems thinking in establishing why events happen and formulating improvements. To enhance SEA effectiveness, we developed and tested "guiding tools" based on human factors principles. Mixed-methods development of guiding tools (Personal Booklet-to help with emotional demands and apply a human factors analysis at the individual level; Desk Pad-to guide a team-based systems analysis; and a written Report Format) by a multiprofessional "expert" group and testing with Scottish primary care practitioners who submitted completed enhanced SEA reports. Evaluation data were collected through questionnaire, telephone interviews, and thematic analysis of SEA reports. Overall, 149/240 care practitioners tested the guiding tools and submitted completed SEA reports (62.1%). Reported understanding of how to undertake SEA improved postintervention (P systems issues (85/123, 69.1%), while most found the Report Format clear (94/123, 76.4%) and would recommend it (88/123, 71.5%). Most SEA reports adopted a systems approach to analyses (125/149, 83.9%), care improvement (74/149, 49.7), or planned actions (42/149, 28.2%). Applying human factors principles to SEA potentially enables care teams to gain a systems-based understanding of why things go wrong, which may help with related emotional demands and with more effective learning and improvement.

A Novel Least Significant Bit First Processing Parallel CRC Circuit

Directory of Open Access Journals (Sweden)

Xiujie Qu

2013-01-01

Full Text Available In HDLC serial communication protocol, CRC calculation can first process the most or least significant bit of data. Nowadays most CRC calculation is based on the most significant bit (MSB first processing. An algorithm of the least significant bit (LSB first processing parallel CRC is proposed in this paper. Based on the general expression of the least significant bit first processing serial CRC, using state equation method of linear system, we derive a recursive formula by the mathematical deduction. The recursive formula is applicable to any number of bits processed in parallel and any series of generator polynomial. According to the formula, we present the parallel circuit of CRC calculation and implement it with VHDL on FPGA. The results verify the accuracy and effectiveness of this method.

A novel multi-drug metronomic chemotherapy significantly delays tumor growth in mice.

Science.gov (United States)

Tagliamonte, Maria; Petrizzo, Annacarmen; Napolitano, Maria; Luciano, Antonio; Rea, Domenica; Barbieri, Antonio; Arra, Claudio; Maiolino, Piera; Tornesello, Marialina; Ciliberto, Gennaro; Buonaguro, Franco M; Buonaguro, Luigi

2016-02-24

The tumor immunosuppressive microenvironment represents a major obstacle to an effective tumor-specific cellular immune response. In the present study, the counterbalance effect of a novel metronomic chemotherapy protocol on such an immunosuppressive microenvironment was evaluated in a mouse model upon sub-cutaneous ectopic implantation of B16 melanoma cells. The chemotherapy consisted of a novel multi-drug cocktail including taxanes and alkylating agents, administered in a daily metronomic fashion. The newly designed strategy was shown to be safe, well tolerated and significantly efficacious. Treated animals showed a remarkable delay in tumor growth and prolonged survival as compared to control group. Such an effect was directly correlated with CD4(+) T cell reduction and CD8(+) T cell increase. Furthermore, a significant reduction in the percentage of both CD25(+)FoxP3(+) and CD25(+)CD127(low) regulatory T cell population was found both in the spleens and in the tumor lesions. Finally, the metronomic chemotherapy induced an intrinsic CD8(+) T cell response specific to B16 naturally expressed Trp2 TAA. The novel multi-drug daily metronomic chemotherapy evaluated in the present study was very effective in counterbalancing the immunosuppressive tumor microenvironment. Consequently, the intrinsic anti-tumor T cell immunity could exert its function, targeting specific TAA and significantly containing tumor growth. Overall, the results show that this represents a promising adjuvant approach to significantly enhance efficacy of intrinsic or vaccine-elicited tumor-specific cellular immunity.

A unifying mechanism for cancer cell death through ion channel activation by HAMLET.

Science.gov (United States)

Storm, Petter; Klausen, Thomas Kjaer; Trulsson, Maria; Ho C S, James; Dosnon, Marion; Westergren, Tomas; Chao, Yinxia; Rydström, Anna; Yang, Henry; Pedersen, Stine Falsig; Svanborg, Catharina

2013-01-01

Ion channels and ion fluxes control many aspects of tissue homeostasis. During oncogenic transformation, critical ion channel functions may be perturbed but conserved tumor specific ion fluxes remain to be defined. Here we used the tumoricidal protein-lipid complex HAMLET as a probe to identify ion fluxes involved in tumor cell death. We show that HAMLET activates a non-selective cation current, which reached a magnitude of 2.74±0.88 nA within 1.43±0.13 min from HAMLET application. Rapid ion fluxes were essential for HAMLET-induced carcinoma cell death as inhibitors (amiloride, BaCl2), preventing the changes in free cellular Na(+) and K(+) concentrations also prevented essential steps accompanying carcinoma cell death, including changes in morphology, uptake, global transcription, and MAP kinase activation. Through global transcriptional analysis and phosphorylation arrays, a strong ion flux dependent p38 MAPK response was detected and inhibition of p38 signaling delayed HAMLET-induced death. Healthy, differentiated cells were resistant to HAMLET challenge, which was accompanied by innate immunity rather than p38-activation. The results suggest, for the first time, a unifying mechanism for the initiation of HAMLET's broad and rapid lethal effect on tumor cells. These findings are particularly significant in view of HAMLET's documented therapeutic efficacy in human studies and animal models. The results also suggest that HAMLET offers a two-tiered therapeutic approach, killing cancer cells while stimulating an innate immune response in surrounding healthy tissues.

Significant effect of grain size distribution on compaction rates in granular aggregates

NARCIS (Netherlands)

Niemeijer, André|info:eu-repo/dai/nl/370832132; Elsworth, Derek; Marone, Chris

2009-01-01

We investigate the role of pressure solution in deformation of upper- to mid-crustal rocks using aggregates of halite as a room temperature analog for fluid-assisted deformation processes in the Earth's crust. Experiments evaluate the effects of initial grain size distribution on macroscopic

No significant effect of the SLCO1B1 polymorphism on the pharmacokinetics of ursodeoxycholic acid.

Science.gov (United States)

Xiang, Xiaoqiang; Vakkilainen, Juha; Backman, Janne T; Neuvonen, Pertti J; Niemi, Mikko

2011-11-01

To investigate possible effects of the SLCO1B1 polymorphism on the pharmacokinetics of ursodeoxycholic acid (UDCA) and its metabolites in healthy volunteers. In a crossover study with two phases, 15 healthy volunteers with the SLCO1B1*1A/*1A genotype, seven with the *1B/*1B genotype, and five with the *15/*15 or *5/*15 genotype ingested placebo or a single 150-mg dose of UDCA. Plasma concentrations of bile acids and their biosynthesis marker were determined up to 24 h post-ingestion by liquid chromatography-tandem mass spectrometry. The SLCO1B1 genotype had no significant effect on the pharmacokinetics of UDCA. The geometric mean ratios (95% confidence interval) of UDCA area under the plasma concentration-time curve from 0 to 12 h (AUC(0-12)) in subjects with the SLCO1B1*1B/*1B genotype and in subjects with the SLCO1B1*15/*15 or *5/*15 genotype to the AUC(0-12) in subjects with the SLCO1B1*1A/*1A genotype were 1.07 (0.85, 1.35; P = 0.459) and 0.93 (0.75, 1.15; P = 0.563), respectively. In addition, following either placebo or UDCA administration, the SLCO1B1 polymorphism showed no association with the AUC(0-24) of the glycine and taurine conjugates of UDCA, with endogenous bile acids, or with the incremental AUC(0-24) of a bile acid synthesis marker. Compared with placebo, UDCA ingestion increased the AUC(0-24) of cholic acid, glycochenodeoxycholic acid, glycocholic acid, and glycodeoxycholic acid by 1.5-, 1.1-, 1.2-, and 1.2- fold (P acids.

Adverse effects of anticoagulation treatment: clinically significant upper gastrointestinal hemorrhage

Directory of Open Access Journals (Sweden)

Pavel Skok

2006-12-01

Full Text Available Background: Over the last years, the use of oral anticoagulant treatment has increased dramatically, principally for the prevention of venous thrombosis and thrombembolic events. This treatment is demanding, especially among the elderly with concommitant diseases and different medication. Aim of the study to evaluate the rate of serious complications, clinically significant hemorrhage from upper gastointestinal tract in patients treated with oral antiocoagulants in a prospective cohort study.Patients and methods: Included were patients admitted to our institution between January 1, 1994 and December 31, 2003 due to gastrointestinal hemorrhage. Emergency endoscopy and laboratory testing was performed in all patients.Results: 6416 patients were investigated: 2452 women (38.2 % and 3964 men (61.8 %, mean age 59.1 years, SD 17.2. Among our patients, 55 % were aged over 60 years. In 86.4 % of patients the source of bleeding was confirmed in the upper gastrointestinal tract. In the last week prior to bleeding, 20.4 % (1309/6416 of all patients were regularly taking nonsteroidal anti-inflammatory drugs, anticoagulant therapy or antiplatelet agents in single daily doses at least. 6.3 % of patients (82/1309 with abundant hemorrhage from upper gastrointestinal tract were using oral anticoagulant therapy and had INR > 5 at admission, 25.6 % of them had INR > 10. The mortality of patients using oral anticoagulants and INR > 5 was 17.1 %.Conclusions: Upper gastrointestinal hemorrhage is a serious complication of different medications, particularly in elderly patients. Safe use of anticoagulant therapy is based on careful selection of patients and correct intake of the prescribed drugs.

Thresholds for statistical and clinical significance in systematic reviews with meta-analytic methods

DEFF Research Database (Denmark)

Jakobsen, Janus Christian; Wetterslev, Jorn; Winkel, Per

2014-01-01

BACKGROUND: Thresholds for statistical significance when assessing meta-analysis results are being insufficiently demonstrated by traditional 95% confidence intervals and P-values. Assessment of intervention effects in systematic reviews with meta-analysis deserves greater rigour. METHODS......: Methodologies for assessing statistical and clinical significance of intervention effects in systematic reviews were considered. Balancing simplicity and comprehensiveness, an operational procedure was developed, based mainly on The Cochrane Collaboration methodology and the Grading of Recommendations...... Assessment, Development, and Evaluation (GRADE) guidelines. RESULTS: We propose an eight-step procedure for better validation of meta-analytic results in systematic reviews (1) Obtain the 95% confidence intervals and the P-values from both fixed-effect and random-effects meta-analyses and report the most...

Uranium chemistry: significant advances

International Nuclear Information System (INIS)

Mazzanti, M.

2011-01-01

The author reviews recent progress in uranium chemistry achieved in CEA laboratories. Like its neighbors in the Mendeleev chart uranium undergoes hydrolysis, oxidation and disproportionation reactions which make the chemistry of these species in water highly complex. The study of the chemistry of uranium in an anhydrous medium has led to correlate the structural and electronic differences observed in the interaction of uranium(III) and the lanthanides(III) with nitrogen or sulfur molecules and the effectiveness of these molecules in An(III)/Ln(III) separation via liquid-liquid extraction. Recent work on the redox reactivity of trivalent uranium U(III) in an organic medium with molecules such as water or an azide ion (N 3 - ) in stoichiometric quantities, led to extremely interesting uranium aggregates particular those involved in actinide migration in the environment or in aggregation problems in the fuel processing cycle. Another significant advance was the discovery of a compound containing the uranyl ion with a degree of oxidation (V) UO 2 + , obtained by oxidation of uranium(III). Recently chemists have succeeded in blocking the disproportionation reaction of uranyl(V) and in stabilizing polymetallic complexes of uranyl(V), opening the way to to a systematic study of the reactivity and the electronic and magnetic properties of uranyl(V) compounds. (A.C.)

Radiation-induced autologous in situ tumor vaccines

International Nuclear Information System (INIS)

Guha, Chandan

2014-01-01

Radiation therapy (RT) has been used as a definitive treatment for many solid tumors. While tumoricidal properties of RT are instrumental for standard clinical application, irradiated tumors can potentially serve as a source of tumor antigens in vivo, where dying tumor cells would release tumor antigens and danger signals and serve as autologous in situ tumor vaccines. Using murine tumor models of prostate, metastatic lung cancer and melanoma, we have demonstrated evidence of radiation-enhanced tumor-specific immune response that resulted in improved primary tumor control and reduction in systemic metastasis and cure. We will discuss the immunogenic properties of RT and determine how immunotherapeutic approaches can synergize with RT in boosting immune cells cell function. (author)

The dream-lag effect: selective processing of personally significant events during Rapid Eye Movement sleep, but not during Slow Wave Sleep

OpenAIRE

van Rijn, E.; Eichenlaub, J.-B.; Lewis, Penelope A.; Walker, M.P.; Gaskell, M.G.; Malinowski, J.E.; Blagrove, M.

2015-01-01

Incorporation of details from waking life events into Rapid Eye Movement (REM) sleep dreams has been found to be highest on the night after, and then 5-7 nights after events (termed, respectively, the day-residue and dream-lag effects). In experiment 1, 44 participants kept a daily log for 10. days, reporting major daily activities (MDAs), personally significant events (PSEs), and major concerns (MCs). Dream reports were collected from REM and Slow Wave Sleep (SWS) in the laboratory, or from ...

The radioecological significance of semi-natural ecosystems

International Nuclear Information System (INIS)

Howard, B.J.; Howard, D.C.

1997-01-01

The transfer of radiocaesium to many food products either produced in or harvested from semi-natural ecosystems is high compared with intensive agricultural areas. Radiocaesium contamination levels in semi-natural foods are highly variable and difficult to predict. Spatial analysis may help to explain some of the variability and give improved estimates of the total output of radiocaesium in food products produced or harvested from semi-natural ecosystems. Consumption of foodstuffs from semi-natural ecosystems can contribute significantly to radiocaesium ingestion by humans. The long effective half-lives that occur for some semi-natural products lead to an increase with time in their importance compared with agricultural products. In determining the importance of semi-natural food products, the diet needs to be considered for both the average population and for special groups who utilize these environments to a greater extent than normal. Effective countermeasures have been developed to reduce radiocaesium levels in some semi-natural products. (author)

TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy.

Science.gov (United States)

Akalu, Yemsratch T; Rothlin, Carla V; Ghosh, Sourav

2017-03-01

Cancer immunotherapy utilizing T-cell checkpoint inhibitors has shown tremendous clinical success. Yet, this mode of treatment is effective in only a subset of patients. Unresponsive patients tend to have non-T-cell-inflamed tumors that lack markers associated with the activation of adaptive anti-tumor immune responses. Notably, elimination of cancer cells by T cells is critically dependent on the optimal activity of innate immune cells. Therefore, identifying new targets that regulate innate immune cell function and promote the engagement of adaptive tumoricidal responses is likely to lead to the development of improved therapies against cancer. Here, we review the TAM receptor tyrosine kinases-TYRO3, AXL, and MERTK-as an emerging class of innate immune checkpoints that participate in key steps of anti-tumoral immunity. Namely, TAM-mediated efferocytosis, negative regulation of dendritic cell activity, and dysregulated production of chemokines collectively favor the escape of malignant cells. Hence, disabling TAM signaling may promote engagement of adaptive immunity and complement T-cell checkpoint blockade. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Radithor and the era of mild radium therapy

International Nuclear Information System (INIS)

Macklis, R.M.

1990-01-01

Soon after the discovery of radium, a school of practitioners arose who were interested primarily in the physiological rather than the tumoricidal powers of this new radioactive element. This treatment philosophy was called mild radium therapy and involved the oral or parenteral administration of microgram quantities of radium and its daughter isotopes, often as cures for rheumatic diseases, hypertension, and metabolic disorders. Manufacturers of patent medicines responded to this market by producing a variety of over-the-counter radioactive preparations including pills, elixirs, and salves. One such nostrum was Radithor, a popular and expensive mixture of radium 226 and radium 228 in distilled water. Radithor was advertised as an effective treatment for over 150 endocrinologic diseases, especially lassitude and sexual impotence. Over 400,000 bottles, each containing over 2 muCi (74 kBq) of radium, were apparently marketed and sold worldwide between 1925 and 1930. The death of the Pittsburgh millionaire sportsman Eben M. Byers, who was an avid Radithor user, by radium poisoning in 1932 brought an end to this era and prompted the development of regulatory controls for all radiopharmaceuticals

The Quantification of the Significance of EATR Determinants: Evidence for EU Countries

Directory of Open Access Journals (Sweden)

Jan Široký

2017-01-01

Full Text Available At present, corporate tax is applied in all EU Member States with the exception of Estonia. Nevertheless, the nominal corporate tax rate does not reflect the real tax burden. For determination of the effective tax burden for corporations, there are used effective corporate tax rates. The aim of the paper is to quantify the relation between the effective average corporate tax rate and nominal corporate tax rates, depreciations, loss compensation and selected investment incentives and to identify the significance of these factors based on the panel analysis. Based on the panel analysis it was found that effective average tax rate is only statistically dependant on nominal corporate tax rate, on tax loss compensation and on the depreciation tax rate of movable property, while in case of other factors, such as depreciation of immovable property, tax holidays and R&D incentives, the dependence is not statistically significant.

Mesoporous silica nanoparticle supported PdIr bimetal catalyst for selective hydrogenation, and the significant promotional effect of Ir

Energy Technology Data Exchange (ETDEWEB)

Yang, Hui; Huang, Chao; Yang, Fan [The Key Laboratory of Fuel Cell Technology of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641 (China); Yang, Xu [Key Laboratory of Renewable Energy, Guangzhou Institute of Energy Conversion, Chinese Academy of Sciences, Guangzhou (China); Du, Li [The Key Laboratory of Fuel Cell Technology of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641 (China); Key Laboratory of Renewable Energy, Guangzhou Institute of Energy Conversion, Chinese Academy of Sciences, Guangzhou (China); Liao, Shijun, E-mail: chsjliao@scut.edu.cn [The Key Laboratory of Fuel Cell Technology of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641 (China); Key Laboratory of Renewable Energy, Guangzhou Institute of Energy Conversion, Chinese Academy of Sciences, Guangzhou (China)

2015-12-01

Graphical abstract: A mesoporous silica nanoparticle (MSN) supported bimetal catalyst, PdIr/MSN, was prepared by a facile impregnation and hydrogen reduction method. The strong promotional effect of Ir was observed and thoroughly investigated. At the optimal molar ratio of Ir to Pd (N{sub Ir}/N{sub Pd} = 0.1), the activity of PdIr{sub 0.1}/MSN was up to eight times and 28 times higher than that of monometallic Pd/MSN and Ir/MSN, respectively. The catalysts were characterized comprehensively by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, and hydrogen temperature programmed reduction, which revealed that the promotional effect of Ir may be due to the enhanced dispersion of active components on the MSN, and to the intensified Pd–Ir electronic interaction caused by the addition of Ir. - Highlights: • Mesoporous nanoparticles were synthesized and used as support for metal catalyst. • PdIr bimetallic catalyst exhibited significantly improved hydrogenation activity. • The strong promotion of Ir was recognized firstly and investigated intensively. • PdIr exhibits 18 times higher activity than Pd to the hydrogenation of nitrobenzene. - Abstract: A mesoporous silica nanoparticle (MSN) supported bimetal catalyst, PdIr/MSN, was prepared by a facile impregnation and hydrogen reduction method. The strong promotional effect of Ir was observed and thoroughly investigated. At the optimal molar ratio of Ir to Pd (N{sub Ir}/N{sub Pd} = 0.1), the activity of PdIr{sub 0.1}/MSN was up to eight times and 28 times higher than that of monometallic Pd/MSN and Ir/MSN, respectively. The catalysts were characterized comprehensively by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, and hydrogen temperature programmed reduction, which revealed that the promotional effect of Ir may be due to the enhanced dispersion of active components on the MSN, and to the intensified Pd–Ir electronic interaction

Significance of Operating Environment in Condition Monitoring of Large Civil Structures

OpenAIRE

Alampalli, Sreenivas

1999-01-01

Success of remote long-term condition monitoring of large civil structures and developing calibrated analytical models for damage detection, depend significantly on establishing accurate baseline signatures and their sensitivity. Most studies reported in the literature concentrated on the effect of structural damage on modal parameters without emphasis on reliability of modal parameters. Thus, a field bridge structure was studied for the significance of operating conditions in relation to bas...

Chronic administration of ethanol leaf extract of Moringa oleifera Lam. (Moringaceae) may compromise glycaemic efficacy of Sitagliptin with no significant effect in retinopathy in a diabetic rat model.

Science.gov (United States)

Olurishe, Comfort; Kwanashie, Helen; Zezi, Abdulkadiri; Danjuma, Nuhu; Mohammed, Bisalla

2016-12-24

Moringa oleifera Lam. (Moringaceae) has gained awareness for its antidiabetic effect, and is used as alternative therapy or concurrently with orthodox medicines such as sitagliptin in diabetes mellitus. This is without ascertaining the possibility of drug-herb interactions, which could either lead to enhanced antidiabetic efficacy, increased toxicity, or compromised glycaemic control with negative consequence in diabetic retinopathy. To investigate the effect, of sitagliptin (50mg/kg), Moringa oleifera (300mg/kg) leaf extract, and a combination of both on glycaemic control parameters, lenticular opacity and changes in retinal microvasculature in alloxan (150mg/kg i.p) induced diabetic rat model. Seven groups of eight rats per group were used, with groups I, II and VII as normal (NC), diabetic (DC) and post-prandial controls (PPC). Groups III to VI were diabetic rats on sitagliptin (III), M. oleifera (IV), sitagliptin and M. oleifera (SM) (V), for 42 days with 2 weeks delayed treatment in a post-prandial hyperglycaemic group (PPSM) (VI). Glycaemic control parameters, insulin levels, body weights, and effects of retinal microvasculature on lenticular opacity/morphology were investigated. A significant decrease in fasting blood glucose (FBG) levels was displayed in SM group from day 14(60%) (p<0.01) to day 28 (38%) (p<0.01) of treatment, compared to day 1. Thereafter, a steady increase of up to 57% on day 42 compared to day 28 was observed. A significant decrease in random blood glucose (RBG) levels, were demonstrated on day 42 (24%) (p<0.001), compared to day 1. No significant difference was seen in mean serum levels of insulin across groups. No significant changes in body weights. Evidence of mild lenticular opacity was observed, with no significant effect in pathologic lesions in the retina. The chronic co-administration of sitagliptin and M. oleifera showed a progressive decrease in anti-hyperglycaemic effect of sitagliptin, and although it delayed the onset of

The significance of the grasshopper effect on the atmospheric distribution of persistent organic substances

Science.gov (United States)

Semeena, V. S.; Lammel, Gerhard

2005-04-01

Slowly degradable, semivolatile organic compounds (SOCs) may undergo more than one volatilization-transport-deposition cycle through the atmosphere (multi-hopping). The significance of this process for the potential for long-range transport (LRT) is addressed for the first time. We use a multicompartment model which in turn is based on a general circulation model. The results suggest that both transport by single-hopping and multi-hopping contribute significantly to LRT of DDT and γ-HCH (lindane) and to accumulation in high latitudes. A larger fraction of the molecules transported by multi-hopping than of the molecules transported by single-hopping is deposited to the world's oceans. Multi-hopping prevails in the boundary layer far from the source regions. However, single-hopping contributes an almost equal amount to the deposition of DDT and γ-HCH in the Arctic.

Clinical Significance of Resistin Expression in Osteoarthritis: A Meta-Analysis

Directory of Open Access Journals (Sweden)

Xiao-Chuan Li

2014-01-01

Full Text Available Background. The objective of this study was to conduct a systematic review of literature evaluating human resistin expression as a diagnostic factor in osteoarthritis development and to quantify the overall diagnostic effect. Method. Relevant studies were identified and evaluated for quality through multiple search strategies. Studies analyzing resistin expression in the development of OA were eligible for inclusion. Data from eligible studies were extracted and included into the meta-analysis using a random-effects model. Results. Four case-control studies consisting of a total of 375 OA patients and 214 controls as well as three sex-stratified analyses composed of 53 males and 104 females were incorporated into our meta-analysis. Our results revealed that resistin levels were significantly higher in male OA subjects and OA patients overall. Country-stratified analysis yielded significantly different estimates in resistin levels between male OA subjects and female OA subjects in the Canadian subgroup but not among the French and USA subgroups. Based on the resistin levels in OA cases and controls, resistin levels were heightened in OA patients in the Dutch population. Conclusion. These results support the hypothesis that high expression of resistin represents a significant and reproducible marker of poor progression in OA patients, especially in males.

III. Cellular ultrastructures in situ as key to understanding tumor energy metabolism: biological significance of the Warburg effect.

Science.gov (United States)

Witkiewicz, Halina; Oh, Phil; Schnitzer, Jan E

2013-01-01

cell cycle through mitosis, indicated that Warburg effect had a fundamental biological significance extending to non-malignant tissues. The approach used here could facilitate integration of accumulated cyber knowledge on cancer metabolism into predictive science.

Neighbourhood effects as indirect effects: evidence from a Dutch case study on the significance of neighbourhood for employment trajectories

NARCIS (Netherlands)

Pinkster, F.M.

2014-01-01

One of the key challenges in the study of neighbourhood effects on work is to understand the pathways through which disadvantaged neighbourhoods impact the employment opportunities of residents. Endogenous explanations for neighbourhood effects focus on social life in these neighbourhoods,

Distinguishing between statistical significance and practical/clinical meaningfulness using statistical inference.

Science.gov (United States)

Wilkinson, Michael

2014-03-01

Decisions about support for predictions of theories in light of data are made using statistical inference. The dominant approach in sport and exercise science is the Neyman-Pearson (N-P) significance-testing approach. When applied correctly it provides a reliable procedure for making dichotomous decisions for accepting or rejecting zero-effect null hypotheses with known and controlled long-run error rates. Type I and type II error rates must be specified in advance and the latter controlled by conducting an a priori sample size calculation. The N-P approach does not provide the probability of hypotheses or indicate the strength of support for hypotheses in light of data, yet many scientists believe it does. Outcomes of analyses allow conclusions only about the existence of non-zero effects, and provide no information about the likely size of true effects or their practical/clinical value. Bayesian inference can show how much support data provide for different hypotheses, and how personal convictions should be altered in light of data, but the approach is complicated by formulating probability distributions about prior subjective estimates of population effects. A pragmatic solution is magnitude-based inference, which allows scientists to estimate the true magnitude of population effects and how likely they are to exceed an effect magnitude of practical/clinical importance, thereby integrating elements of subjective Bayesian-style thinking. While this approach is gaining acceptance, progress might be hastened if scientists appreciate the shortcomings of traditional N-P null hypothesis significance testing.

Treatment Planning for Pulsed Reduced Dose-Rate Radiotherapy in Helical Tomotherapy

International Nuclear Information System (INIS)

Rong Yi; Paliwal, Bhudatt; Howard, Steven P.; Welsh, James

2011-01-01

Purpose: Pulsed reduced dose-rate radiotherapy (PRDR) is a valuable method of reirradiation because of its potential to reduce late normal tissue toxicity while still yielding significant tumoricidal effect. A typical method using a conventional linear accelerator (linac) is to deliver a series of 20-cGy pulses separated by 3-min intervals to give an effective dose-rate of just under 7 cGy/min. Such a strategy is fraught with difficulties when attempted on a helical tomotherapy unit. We investigated various means to overcome this limitation. Methods and Materials: Phantom and patient cases were studied. Plans were generated with varying combinations of field width (FW), pitch, and modulation factor (MF) to administer 200 cGy per fraction to the planning target in eight subfractions, thereby mimicking the technique used on conventional linacs. Plans were compared using dose-volume histograms, homogeneity indices, conformation numbers, and treatment time. Plan delivery quality assurance was performed to assess deliverability. Results: It was observed that for helical tomotherapy, intrinsic limitations in leaf open time in the multileaf collimator deteriorate plan quality and deliverability substantially when attempting to deliver very low doses such as 20-40 cGy. The various permutations evaluated revealed that the combination of small FW (1.0 cm), small MF (1.3-1.5), and large pitch (∼0.86), along with the half-gantry-angle-blocked scheme, can generate clinically acceptable plans with acceptable delivery accuracy (±3%). Conclusion: Pulsed reduced dose-rate radiotherapy can be accurately delivered using helical tomotherapy for tumor reirradiation when the appropriate combination of FW, MF, and pitch is used.

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

Science.gov (United States)

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

2015-05-15

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

Identification of sequence motifs significantly associated with antisense activity

Directory of Open Access Journals (Sweden)

Peek Andrew S

2007-06-01

Full Text Available Abstract Background Predicting the suppression activity of antisense oligonucleotide sequences is the main goal of the rational design of nucleic acids. To create an effective predictive model, it is important to know what properties of an oligonucleotide sequence associate significantly with antisense activity. Also, for the model to be efficient we must know what properties do not associate significantly and can be omitted from the model. This paper will discuss the results of a randomization procedure to find motifs that associate significantly with either high or low antisense suppression activity, analysis of their properties, as well as the results of support vector machine modelling using these significant motifs as features. Results We discovered 155 motifs that associate significantly with high antisense suppression activity and 202 motifs that associate significantly with low suppression activity. The motifs range in length from 2 to 5 bases, contain several motifs that have been previously discovered as associating highly with antisense activity, and have thermodynamic properties consistent with previous work associating thermodynamic properties of sequences with their antisense activity. Statistical analysis revealed no correlation between a motif's position within an antisense sequence and that sequences antisense activity. Also, many significant motifs existed as subwords of other significant motifs. Support vector regression experiments indicated that the feature set of significant motifs increased correlation compared to all possible motifs as well as several subsets of the significant motifs. Conclusion The thermodynamic properties of the significantly associated motifs support existing data correlating the thermodynamic properties of the antisense oligonucleotide with antisense efficiency, reinforcing our hypothesis that antisense suppression is strongly associated with probe/target thermodynamics, as there are no enzymatic

Impact significance determination-Back to basics

International Nuclear Information System (INIS)

Lawrence, David P.

2007-01-01

Impact significance determination is widely recognized as a vital and critical EIA activity. But impact significance related concepts are poorly understood. And the quality of approaches for impact significance determination in EIA practice remains highly variable. This article seeks to help establish a sound and practical conceptual foundation for formulating and evaluating impact significance determination approaches. It addresses the nature (what is impact significance?), the core characteristics (what are the major properties of significance determination?), the rationale (why are impact significance determinations necessary?), the procedural and substantive objectives (what do impact significance determinations seek to achieve?), and the process for making impact significance judgments (how is impact significance determination conducted?). By identifying fundamental attributes and key distinctions associated with impact significance determinations, a basis is provided for designing and evaluating impact significance determination procedures at both the regulatory and applied levels

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

Science.gov (United States)

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

2018-04-22

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

Significance of heel pad confinement for the shock absorption at heel strike.

Science.gov (United States)

Jørgensen, U; Ekstrand, J

1988-12-01

Shock absorption (SA) is a simple way to reduce the body load and can be used in the prevention and treatment of injuries. The heel pad is the most important shock absorber in the shoe heel complex. The purpose of this study was to investigate whether the SA at heel strike can be increased by heel support in people and shoes with high or low SA. The impact forces at heel strike were measured on an AMTI (R) force platform. Fourteen legs were tested in seven persons (nine with normal and five with low heel pad SA) in gait analysis and in human drop tests. The tests were performed barefooted, and in a soccer and a running shoe (selected by shoe drop test), with and without the distal 2 cm of the heel counter. The heel pad confinement produced by the heel counter (the heel counter effect) increased the SA in both shoe types significantly in both impact situations. The mean increase in SA was 8.8% (range 5.8%-15.5%). The heel counter effect was in all situations significantly higher in persons with low heel pad shock absorbency (LHPSA) than in those with normal heel pads. The barefoot impact peak force per kg body weight was significantly higher (6% mean) on the side with LHPSA. The running shoe provided the significantly greatest SA compared with the soccer shoe. It is concluded that the shock absorbency at heel strike can be increased significantly by heel support, with highest effect in persons with LHPSA, both in shoes with high and low SA.(ABSTRACT TRUNCATED AT 250 WORDS)

Significant Effect of a Pre-Exercise High-Fat Meal after a 3-Day High-Carbohydrate Diet on Endurance Performance

Directory of Open Access Journals (Sweden)

Ikuma Murakami

2012-06-01

Full Text Available We investigated the effect of macronutrient composition of pre-exercise meals on endurance performance. Subjects consumed a high-carbohydrate diet at each meal for 3 days, followed by a high-fat meal (HFM; 1007 ± 21 kcal, 30% CHO, 55% F and 15% P or high-carbohydrate meal (HCM; 1007 ± 21 kcal, 71% CHO, 20% F and 9% P 4 h before exercise. Furthermore, just prior to the test, subjects in the HFM group ingested either maltodextrin jelly (M or a placebo jelly (P, while subjects in the HCM ingested a placebo jelly. Endurance performance was measured as running time until exhaustion at a speed between lactate threshold and the onset of blood lactate accumulation. All subjects participated in each trial, randomly assigned at weekly intervals. We observed that the time until exhaustion was significantly longer in the HFM + M (p < 0.05 than in HFM + P and HCM + P conditions. Furthermore, the total amount of fat oxidation during exercise was significantly higher in HFM + M and HFM + P than in HCM + P (p < 0.05. These results suggest that ingestion of a HFM prior to exercise is more favorable for endurance performance than HCM. In addition, HFM and maltodextrin ingestion following 3 days of carbohydrate loading enhances endurance running performance.

Bacterial Carriers for Glioblastoma Therapy

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Nalini Mehta

2017-03-01

Full Text Available Treatment of aggressive glioblastoma brain tumors is challenging, largely due to diffusion barriers preventing efficient drug dosing to tumors. To overcome these barriers, bacterial carriers that are actively motile and programmed to migrate and localize to tumor zones were designed. These carriers can induce apoptosis via hypoxia-controlled expression of a tumor suppressor protein p53 and a pro-apoptotic drug, Azurin. In a xenograft model of human glioblastoma in rats, bacterial carrier therapy conferred a significant survival benefit with 19% overall long-term survival of >100 days in treated animals relative to a median survival of 26 days in control untreated animals. Histological and proteomic analyses were performed to elucidate the safety and efficacy of these carriers, showing an absence of systemic toxicity and a restored neural environment in treated responders. In the treated non-responders, proteomic analysis revealed competing mechanisms of pro-apoptotic and drug-resistant activity. This bacterial carrier opens a versatile avenue to overcome diffusion barriers in glioblastoma by virtue of its active motility in extracellular space and can lead to tailored therapies via tumor-specific expression of tumoricidal proteins.

Germ cell toxicity: significance in genetic and fertility effects of radiation and chemicals

International Nuclear Information System (INIS)

Oakberg, E.F.

1983-01-01

The response of the male and female to radiation and chemicals is different. Any loss of oocytes in the female cannot be replaced, and if severe enough, will result in a shortening of the reproductive span. In the male, a temporary sterile period may be induced owing to destruction of the differentiating spermatogonia, but the stem cells are the most resistant spermatogonial type, are capable of repopulating the seminiferous epithelium, and fertility usually returns. The response of both the male and female changes with development of the embryonic to the adult gonad, and with differentiation and maturation in the adult. The primordial germ cells, early oocytes, and differentiating spermatogonia of the adult male are unusually sensitive to the cytotoxic action of noxious agents, but each agent elicits a specific response owing to the intricate biochemical and physiological changes associated with development and maturation of the gametes. The relationship of germ cell killing to fertility is direct, and long-term fertility effects can be predicted from histological analysis of the gonads. The relationship to genetic effects, on the other hand, is indirect, and acts primarily by limiting the cell stages available for testing, by affecting the distribution of mitotically active stem cells among the different stages of the mitotic cycle, and thereby, changing both the type and frequency of genetic effects observed. 100 references, 38 figures, 7 tables

An integrated PRA module for fast determination of risk significance and improvement effectiveness

International Nuclear Information System (INIS)

Chao, Chun-Chang; Lin, Jyh-Der

2004-01-01

With the widely use of PRA technology in risk-informed applications, to predict the changes of CDF and LERF becomes a standard process for risk-informed applications. This paper describes an integrated PRA module prepared for risk-informed applications. The module contains a super risk engine, a super fault tree engine, an advanced PRA model and a tool for data base maintenance. The individual element of the module also works well for purpose other than risk-informed applications. The module has been verified and validated through a series of scrupulous benchmark tests with similar software. The results of the benchmark tests showed that the module has remarkable accuracy and speed even for an extremely large-size top-logic fault tree as well as for the case in which large amount of MCSs may be generated. The risk monitor for nuclear power plants in Taiwan is the first application to adopt the module. The results predicted by the risk monitor are now accepted by the regulatory agency. A tool to determine the risk significance according to the inspection findings will be the next application to adopt the module in the near future. This tool classified the risk significance into four different color codes according to the level of increase on CDF. Experience of application showed that the flexibility, the accuracy and speed of the module make it useful in any risk-informed applications when risk indexes must be determined by resolving a PRA model. (author)

Leukocyte-reduction filters and radiation do not cause significant changes in platelet function

International Nuclear Information System (INIS)

Nagura, Yutaka; Tsuno, Hirokazu; Shibata, Yoichi; Takahashi, Koki

2003-01-01

In the present study, we investigated the effects of radiation and leukocyte-reduction filters on platelet function. Platelet aggregation in response to collagen and ADP were measured prior to and after irradiation and filtration, as were the platelet recovery rate and complement factor C3. Four types of leukocyte-reduction filter were used, namely positively-, negatively-, and non-charged filters (all of polyester composition), as well as a polyurethane filter. Radiation itself did not significantly affect either the platelet recovery rate, platelet function, or C3 value. On the other hand, filtration through polyester leukocyte-reduction filters resulted in a significant reduction in the platelet recovery rate, an effect not observed with the polyurethane filter. However, none of the filters caused significant changes in platelet function or in C3 value. We concluded that radiation and filtration do not cause significant changes in platelet function, but polyurethane filters are superior to polyester filters in relation to platelet recovery. (author)

Meaning and significance of

Directory of Open Access Journals (Sweden)

Ph D Student Roman Mihaela

2011-05-01

Full Text Available The concept of "public accountability" is a challenge for political science as a new concept in this area in full debate and developement ,both in theory and practice. This paper is a theoretical approach of displaying some definitions, relevant meanings and significance odf the concept in political science. The importance of this concept is that although originally it was used as a tool to improve effectiveness and eficiency of public governance, it has gradually become a purpose it itself. "Accountability" has become an image of good governance first in the United States of America then in the European Union.Nevertheless,the concept is vaguely defined and provides ambiguous images of good governance.This paper begins with the presentation of some general meanings of the concept as they emerge from specialized dictionaries and ancyclopaedies and continues with the meanings developed in political science. The concept of "public accontability" is rooted in economics and management literature,becoming increasingly relevant in today's political science both in theory and discourse as well as in practice in formulating and evaluating public policies. A first conclusin that emerges from, the analysis of the evolution of this term is that it requires a conceptual clarification in political science. A clear definition will then enable an appropriate model of proving the system of public accountability in formulating and assessing public policies, in order to implement a system of assessment and monitoring thereof.

A philosophical taxonomy of ethically significant moral distress.

Science.gov (United States)

Thomas, Tessy A; McCullough, Laurence B

2015-02-01

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

Korean Red Ginseng exhibits no significant adverse effect on disease activity in patients with rheumatoid arthritis: a randomized, double-blind, crossover study

Directory of Open Access Journals (Sweden)

Soo-Kyung Cho

2018-04-01

Full Text Available Background: Panax ginseng is a well-known immune modulator, and there is concern that its immune-enhancing effects may negatively affect patients with rheumatoid arthritis (RA by worsening symptoms or increasing the risk of adverse effects from other drugs. In this randomized, crossover clinical trial, we evaluated the impact of Korean Red Ginseng (KRG on disease activity and safety in RA patients. Methods: A total of 80 female RA patients were randomly assigned to either the KRG (2 g/d, n = 40 treatment or placebo (n = 40 groups for 8 wk, followed by crossover to the other treatment group for an additional 8 wk. The primary outcome was the disease flare rate, defined as worsening disease activity according to the disease activity score 28 joints-erythrocyte sedimentation rate (DAS28-ESR. The secondary outcomes were development of adverse events (AEs and patient reported outcomes. Outcomes were evaluated at baseline and 8 wk and 16 wk. The outcomes were compared using the Chi-square test. Results: Of the 80 patients, 70 completed the full study. Their mean age was 51.9 yr, and most exhibited low disease activity (mean DAS28-ESR 3.5 ± 1.0 at enrollment. After intervention, the flare rate was 3.7% in each group. During KRG treatment, 10 AEs were reported, while five AEs were developed with placebo; however, this difference was not statistically significant (p = 0.16. Gastrointestinal- and nervous system-related symptoms were frequent in the KRG group. Conclusion: KRG is not significantly associated with either disease flare rate or the rate of AE development in RA patients. Keywords: effect, Korean Red Ginseng, rheumatoid arthritis, safety

Meta-analyses triggered by previous (false-)significant findings : Problems and solutions

NARCIS (Netherlands)

Schuit, Ewoud; Roes, Kit C B; Mol, Ben W J; Kwee, Anneke; Moons, Karel G M; Groenwold, Rolf H H

2015-01-01

BACKGROUND: Meta-analyses are typically triggered by a (potentially false-significant) finding in one of the preceding primary studies. We studied consequences of meta-analysis investigating effects when primary studies that triggered such meta-analysis are also included. METHODS: We analytically

Barnacle Geese Achieve Significant Energetic Savings by Changing Posture

OpenAIRE

Tickle, Peter G.; Nudds, Robert L.; Codd, Jonathan R.

2012-01-01

Here we report the resting metabolic rate in barnacle geese (Branta leucopsis) and provide evidence for the significant energetic effect of posture. Under laboratory conditions flow-through respirometry together with synchronous recording of behaviour enabled a calculation of how metabolic rate varies with posture. Our principal finding is that standing bipedally incurs a 25% increase in metabolic rate compared to birds sitting on the ground. In addition to the expected decrease in energy con...

Concept of malignant significant factor and its applicability for and occupational exposures

International Nuclear Information System (INIS)

Hashizume, Tadashi; Maruyama, Takashi; Tateno, Yukio

1980-01-01

In the medical and occupational exposures, there is a tradition to use the genetically significant dose as an index of harm to the population although it only includes the genetical effects from ionizing radiations. A similar significant dose for somatic effects such as radiation leukemogenesis and carcinogenesis should be added to the genetically significant dose in order to approach an index of total harm to the population from medical and occupational exposures. For this purpose, leukemia and malignant significant factors were determined based on the induction of malignant diseases including leukemia for the atomic bombs in Hiroshima and Nagasaki and the life expectancy of individuals subject to medical examinations or treatments as well as radiation workers, taking account of the possibility of their deaths due to other diseases or accidents during a latent period of malignant diseases. The resultant significant factors were tabulated as a function of life expectancy for their application to medical and occupational exposures. For an example, the malignant significant factor for a person having the life expectancy of 60, 40 and 20 years was about 0.87, 0.45 and 0.10, respectively. This paper will discuss the applicability of the leukemia and malignant significant factors to the risk estimation of medical and occupational exposures; namely (1) the risk estimation for an individual in the population; (2) the risk estimation for individuals in a given age group who were continuously irradiated with natural radiations or received occupational exposures; (3) the risk estimation for the pupulation in a given age distribution and (4) the risk estimation for individuals after retirement of radiation works. (author)

Surface renewal as a significant mechanism for dust emission

Directory of Open Access Journals (Sweden)

J. Zhang

2016-12-01

Full Text Available Wind tunnel experiments of dust emissions from different soil surfaces are carried out to better understand dust emission mechanisms. The effects of surface renewal on aerodynamic entrainment and saltation bombardment are analyzed in detail. It is found that flow conditions, surface particle motions (saltation and creep, soil dust content and ground obstacles all strongly affect dust emission, causing its rate to vary over orders of magnitude. Aerodynamic entrainment is highly effective, if dust supply is unlimited, as in the first 2–3 min of our wind tunnel runs. While aerodynamic entrainment is suppressed by dust supply limits, surface renewal through the motion of surface particles appears to be an effective pathway to remove the supply limit. Surface renewal is also found to be important to the efficiency of saltation bombardment. We demonstrate that surface renewal is a significant mechanism affecting dust emission and recommend that this mechanism be included in future dust models.

The dream-lag effect: Selective processing of personally significant events during Rapid Eye Movement sleep, but not during Slow Wave Sleep.

Science.gov (United States)

van Rijn, E; Eichenlaub, J-B; Lewis, P A; Walker, M P; Gaskell, M G; Malinowski, J E; Blagrove, M

2015-07-01

Incorporation of details from waking life events into Rapid Eye Movement (REM) sleep dreams has been found to be highest on the night after, and then 5-7 nights after events (termed, respectively, the day-residue and dream-lag effects). In experiment 1, 44 participants kept a daily log for 10 days, reporting major daily activities (MDAs), personally significant events (PSEs), and major concerns (MCs). Dream reports were collected from REM and Slow Wave Sleep (SWS) in the laboratory, or from REM sleep at home. The dream-lag effect was found for the incorporation of PSEs into REM dreams collected at home, but not for MDAs or MCs. No dream-lag effect was found for SWS dreams, or for REM dreams collected in the lab after SWS awakenings earlier in the night. In experiment 2, the 44 participants recorded reports of their spontaneously recalled home dreams over the 10 nights following the instrumental awakenings night, which thus acted as a controlled stimulus with two salience levels, high (sleep lab) and low (home awakenings). The dream-lag effect was found for the incorporation into home dreams of references to the experience of being in the sleep laboratory, but only for participants who had reported concerns beforehand about being in the sleep laboratory. The delayed incorporation of events from daily life into dreams has been proposed to reflect REM sleep-dependent memory consolidation. However, an alternative emotion processing or emotional impact of events account, distinct from memory consolidation, is supported by the finding that SWS dreams do not evidence the dream-lag effect. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Quality of life and adolescents' communication with their significant others (mother, father, and best friend): the mediating effect of attachment to pets.

Science.gov (United States)

Marsa-Sambola, Ferran; Williams, Joanne; Muldoon, Janine; Lawrence, Alistair; Connor, Melanie; Currie, Candace

2017-06-01

The relationship between adolescents' communication with their significant others (mother, father, and best friend) and quality of life (KIDSCREEN) was investigated in 2262 Scottish adolescent pet owners. The variable attachment to pets was also tested and assessed as a mediator of this relationship. A positive relationship between adolescents' communication with their significant other (mother, father, and best friend) and quality of life decreased when controlling for attachment to dogs. In cat owners, a positive relationship between communication with a best friend and quality of life decreased when controlling for attachment to cats. In cat and dog owners, attachment to these pets predicted higher levels of quality of life. Higher attachment to dogs and cats was explained by good best friend (IV) and attachment to pets (DV) and best friends. Mediation effects of attachment to dogs and cats might be explained in terms of the caring activities associated with these types of pets.

Teaching physical activities to students with significant disabilities using video modeling.

Science.gov (United States)

Cannella-Malone, Helen I; Mizrachi, Sharona V; Sabielny, Linsey M; Jimenez, Eliseo D

2013-06-01

The objective of this study was to examine the effectiveness of video modeling on teaching physical activities to three adolescents with significant disabilities. The study implemented a multiple baseline across six physical activities (three per student): jumping rope, scooter board with cones, ladder drill (i.e., feet going in and out), ladder design (i.e., multiple steps), shuttle run, and disc ride. Additional prompt procedures (i.e., verbal, gestural, visual cues, and modeling) were implemented within the study. After the students mastered the physical activities, we tested to see if they would link the skills together (i.e., complete an obstacle course). All three students made progress learning the physical activities, but only one learned them with video modeling alone (i.e., without error correction). Video modeling can be an effective tool for teaching students with significant disabilities various physical activities, though additional prompting procedures may be needed.

Dosimetric aspects of the treatment of metastatic bone pain with radiopharmaceuticals; Aspectos dosimetricos de los tratamientos del dolor oseo metastasico con radiofarmacos

Energy Technology Data Exchange (ETDEWEB)

Garcia, T.; Marti, J. F.; Olivas, C.; Vercher, J. L.; Repetto, R.; Bello, P.

2014-02-01

Within the context of treatment of metastatic bone pain with bone seeking radiopharmaceuticals, this paper expounds the results of an analysis of available molecules (both approved for clinical use or still under study) intended to obtain a detailed comparison of their dosimetric characteristics. These can be used to supplement the list of already know differences between them, such as efficacy, appearance and length of the palliative effect, eventual tumoricidal effect, myelotoxicity, sale price and availability. Seven radiopharmaceuticals have been analysed, five of them are based on beta emission radionuclides: {sup 3}2P, {sup 1}53Sm, {sup 1}86Re and {sup 1}88Re and the other two ones are based on high Linear energy Transference emission radionuclides: {sup 1}17mSn and {sup 2}23Ra a series of estimates of the main dosimetric parameters for each radiopharmaceutical analysed have been obtained. The values obtained might be worth being incorporated to the risk/benefit analysis that precedes every choice of the specific radiopharmaceutical to be used with an individual patient. In this way, we hope these results will be of some help for those Nuclear Medicine specialists interested in the treatment of oncological bone pathologies. (Author)

The role of stereotactic radiation therapy in the management of children with brain tumors.

Science.gov (United States)

Lew, C M; LaVally, B

1995-10-01

Conventional radiation therapy plays an important role in the management of intracranial tumors in children. For certain tumors radiation therapy serves as the primary mode of treatment, and for others it plays an adjuvant role with surgery and/or chemotherapy. Improvements in long-term survival rates have focused attention on the long-term sequelae of brain tumors and their treatment, and the sequelae, in turn, have become important targets for clinical investigation. Long-term side effects of particular concern in children include cranial nerve damage, memory and intellectual deficits, pituitary-hypothalamic dysfunction, demyelinization of brain tissue, and secondary malignancies. A new form of radiation therapy, stereotactic radiotherapy (SRT), merges the technologies of stereotactic surgery and conventional fractionated radiotherapy. The intent is to deliver maximum tumoricidal doses to the target while limiting the dose to normal surrounding brain tissue. The key feature of SRT is a noninvasive, relocatable immobilization system to assure accurate and reproducible positioning during planning and treatment. The headframes used for children have been modified to address their specific needs. The complexities of this process require careful preparation of patients and their families and the participation of many disciplines. Long-term follow-up will be essential to evaluate the effectiveness of this innovative treatment.

Photocoagulation treatment for clinically significant radiation macular oedema

Energy Technology Data Exchange (ETDEWEB)

Kinyoun, J.L.; Zamber, R.W.; Lawrence, B.S.; Barlow, W.E.; Arnold, A.M. [Washington Univ., Seattle, WA (United States)

1995-02-01

Macular oedema is a leading cause of vision loss in patients with radiation retinopathy. In an effort to find an effective treatment for this vision threatening complication, 12 eyes (eight patients) were treated with photocoagulation for clinically significant radiation macular oedema (CSRMO) defined as central macular thickening, exudates threatening the macular centre, or one disc area of thickening in the macula. Median visual acuity improved from 20/100 pre-operatively to 20/90 at the initial post-operative examination (mean follow up 5 months) and to 20/75 at the final post-operative examination (mean follow up 39 months). At the final post-operative examination, visual acuity had improved in eight (67%) eyes and six (50%) eyes had complete resolution of the CSRMO; two (17%) other eyes had improved anatomically in that fewer CSRMO criteria were present. These results suggest that macular photocoagulation is effective in decreasing macular oedema and improving vision in eyes with CSRMO. (author).

Photocoagulation treatment for clinically significant radiation macular oedema

International Nuclear Information System (INIS)

Kinyoun, J.L.; Zamber, R.W.; Lawrence, B.S.; Barlow, W.E.; Arnold, A.M.

1995-01-01

Macular oedema is a leading cause of vision loss in patients with radiation retinopathy. In an effort to find an effective treatment for this vision threatening complication, 12 eyes (eight patients) were treated with photocoagulation for clinically significant radiation macular oedema (CSRMO) defined as central macular thickening, exudates threatening the macular centre, or one disc area of thickening in the macula. Median visual acuity improved from 20/100 pre-operatively to 20/90 at the initial post-operative examination (mean follow up 5 months) and to 20/75 at the final post-operative examination (mean follow up 39 months). At the final post-operative examination, visual acuity had improved in eight (67%) eyes and six (50%) eyes had complete resolution of the CSRMO; two (17%) other eyes had improved anatomically in that fewer CSRMO criteria were present. These results suggest that macular photocoagulation is effective in decreasing macular oedema and improving vision in eyes with CSRMO. (author)

Effect of posture on the diurnal variation in clinically significant diabetic macular edema.

Science.gov (United States)

Polito, Antonio; Polini, Giovanni; Chiodini, Raffaella Gortana; Isola, Miriam; Soldano, Franca; Bandello, Francesco

2007-07-01

To investigate the role of posture and other systemic factors in the diurnal variation of clinically significant diabetic macular edema (CSDME). Ten eyes of 10 diabetic subjects with CSDME underwent four OCT foveal thickness measurements with StratusOCT at 9 AM and 12, 3, and 6 PM consecutively on two different days, with the subject in an upright position on one and in a recumbent position on the other. For the "recumbent-position" measurements, the patients were admitted the night before and remained in bed during the entire day of testing. Clinical laboratory results at baseline included HbA1c, urinary albumin, and serum creatinine. Refraction and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity were also measured before each OCT measurement was taken. Variations in blood pressure, body temperature, plasma glucose, renin, aldosterone, and cortisol levels were measured and then correlated with macular thickness. Foveal thickening decreased in all cases over the course of the day. The decrease, however, was significantly greater for the upright-position measurements (relative mean +/- SD decrease of 20.6% +/- 6.5% in the upright position and 6.2% +/- 4.6% in the recumbent position). Visual acuity improved by at least 1 ETDRS line in three eyes in the upright position as opposed to only one eye in the recumbent position. There seemed to be no association between any of the systemic factors studied and foveal thickening, with the exception of cortisol. The results support the hypothesis that posture and hydrostatic pressure play a major role in determining time-related shifts in CSDME and suggest that the forces of Starling's law can in part, account for CSDME formation.

Significance of agricultural row structure on the microwave emissivity of soils

Science.gov (United States)

Promes, P. M.; Jackson, T. J.; O'Neill, P. E.

1987-01-01

A series of field experiments was carried out to extend the data base available for verifying agricultural row effect models of emissivity. The row effects model was used to simulate a data base from which an algorithm could be developed to account for row effects when the scene dielectric constant and small-scale roughness are unknown. One objective of the study was to quantify the significance of row structure and to develop a practical procedure for removing the effects of periodic row structure on the microwave emissivity of a soil in order to use the emissivity values to estimate the soil moisture. A second objective was to expand the data set available for model verification through field observations using a truck-mounted 1.4-GHz microwave radiometer.

77 FR 48858 - Significant New Use Rules on Certain Chemical Substances

Science.gov (United States)

2012-08-15

... adverse chronic effects from the presumed degradation product of this PMN substance on humans and wildlife...) human exposure to the substance and its potential degradation products. To protect against these risks... may be significant (or substantial) human exposure to the substances and their potential degradation...

The significance test controversy revisited the fiducial Bayesian alternative

CERN Document Server

Lecoutre, Bruno

2014-01-01

The purpose of this book is not only to revisit the “significance test controversy,”but also to provide a conceptually sounder alternative. As such, it presents a Bayesian framework for a new approach to analyzing and interpreting experimental data. It also prepares students and researchers for reporting on experimental results. Normative aspects: The main views of statistical tests are revisited and the philosophies of Fisher, Neyman-Pearson and Jeffrey are discussed in detail. Descriptive aspects: The misuses of Null Hypothesis Significance Tests are reconsidered in light of Jeffreys’ Bayesian conceptions concerning the role of statistical inference in experimental investigations. Prescriptive aspects: The current effect size and confidence interval reporting practices are presented and seriously questioned. Methodological aspects are carefully discussed and fiducial Bayesian methods are proposed as a more suitable alternative for reporting on experimental results. In closing, basic routine procedures...

Impact significance determination-Pushing the boundaries

International Nuclear Information System (INIS)

Lawrence, David P.

2007-01-01

Impact significance determination practice tends to be highly variable. Too often insufficient consideration is given to good practice insights. Also, impact significance determinations are frequently narrowly defined addressing, for example, only individual, negative impacts, focusing on bio-physical impacts, and not seeking to integrate either the Precautionary Principle or sustainability. This article seeks to extend the boundaries of impact significance determination practice by providing an overview of good general impact significance practices, together with stakeholder roles and potential methods for addressing significance determination challenges. Relevant thresholds, criteria, contextual considerations and support methods are also highlighted. The analysis is then extended to address how impact significance determination practices change for positive as compared with negative impacts, for cumulative as compared with individual impacts, for socio-economic as compared with bio-physical impacts, when the Precautionary Principle is integrated into the process, and when sustainability contributions drive the EIA process and related impact significance determinations. These refinements can assist EIA practitioners in ensuring that the scope and nature of impact significance determinations reflect the broadened scope of emerging EIA requirements and practices. Suggestions are included for further refining and testing of the proposed changes to impact significance determination practice

Prognostic significance of XRCC4 expression in hepatocellular carcinoma

Science.gov (United States)

Huang, Xiao-Ying; Yao, Jin-Guang; Wang, Chao; Wei, Zhong-Hong; Ma, Yun; Wu, Xue-Min; Luo, Chun-Ying; Xia, Qiang; Long, Xi-Dai

2017-01-01

Background Our previous investigations have shown that the variants of X-ray repair complementing 4 (XRCC4) may be involved in hepatocellular carcinoma (hepatocarcinoma) tumorigenesis. This study aimed to investigate the possible prognostic significance of XRCC4 expression for hepatocarcinoma patients and possible value for the selection of transarterial chemoembolization (TACE) treatment. Materials and Methods We conducted a hospital-based retrospective analysis (including 421 hepatocarcinoma cases) to analyze the effects of XRCC4 on hepatocarcinoma prognosis and TACE. The levels of XRCC4 expression were tested using immunohistochemistry. The sensitivity of cancer cells to anti-cancer drug doxorubicin was evaluated using the half-maximal inhibitory concentration (IC50). Results XRCC4 expression was significantly correlated with pathological features including tumor stage, liver cirrhosis, and micro-vessel density. XRCC4 expression was an independent prognostic factor of hepatocarcinoma, and TACE treatments had no effects on prognosis of hepatocarcinoma patients with high XRCC4 expression. More intriguingly, TACE improved the prognosis of hepatocarcinoma patients with low XRCC4 expression. Functionally, XRCC4 overexpression increased while XRCC4 knockdown reduced the IC50 of cancer cells to doxorubicin. Conclusions These results suggest that XRCC4 may be an independent prognostic factor for hepatocarcinoma patients, and that decreasing XRCC4 expression may be beneficial for post-operative adjuvant TACE treatment in hepatocarcinoma. PMID:29152133

Engaging Youth with and without Significant Disabilities in Inclusive Service Learning

Science.gov (United States)

Carter, Erik W.; Swedeen, Beth; Moss, Colleen K.

2012-01-01

Service learning is an effective curricular approach to increase instructional relevance and engagement for all students. For students with significant disabilities in transition, meaningful service can be an especially useful avenue for exploring career interests, gaining and practicing important life skills, and connecting to the community in…

Significance of the S100A4 protein in psoriasis

DEFF Research Database (Denmark)

Zibert, John R; Skov, Lone; Thyssen, Jacob P

2010-01-01

the expression and significance of S100A4 in psoriasis. We found significant upregulation of S100A4 in the dermis of psoriatic skin compared with normal skin. This pattern of S100A4 expression differs considerably from that of other S100 proteins, S100A7 and S100A8/9, with predominant expression in the epidermis...... of psoriasis. Furthermore, we revealed a massive release of the biologically active forms of S100A4 from psoriatic skin. Interestingly, we found stabilization (increase) of p53 in the basal layer of epidermis in close proximity to cells expressing S100A4. To examine the possible implication of S100A4...... in the pathogenesis of psoriasis, we analyzed the effect of S100A4 blocking antibodies in a human psoriasis xenograft SCID mouse model and observed a significant reduction of the epidermal thickness and impairment in cell proliferation and dermal vascularization. In conclusion, we showed strong upregulation...

The significance of recruiting underrepresented minorities in medicine: an examination of the need for effective approaches used in admissions by higher education institutions

Directory of Open Access Journals (Sweden)

Obed Figueroa

2014-09-01

Full Text Available The purpose of this paper is to examine the significance of recruiting underrepresented minorities in medicine (URM. This would include African Americans, Hispanics, and Native Americans. The research findings support the belief that URMs, upon graduating, are more likely to become practitioners in underserved communities, thereby becoming a resource that prompts us to find effective ways to help increase their college enrollments statewide. This paper analyzes the recruitment challenges for institutions, followed by a review of creative and effective approaches used by organizations and universities. The results have shown positive outcomes averaging a 50% increase in minority enrollments and retention. In other areas, such as cognitive development, modest gains were achieved in programs that were shorter in duration. The results nevertheless indicated steps in the right direction inspiring further program developments.

Effect of postmortem sampling technique on the clinical significance of autopsy blood cultures.

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Hove, M; Pencil, S D

1998-02-01

Our objective was to investigate the value of postmortem autopsy blood cultures performed with an iodine-subclavian technique relative to the classical method of atrial heat searing and antemortem blood cultures. The study consisted of a prospective autopsy series with each case serving as its own control relative to subsequent testing, and a retrospective survey of patients coming to autopsy who had both autopsy blood cultures and premortem blood cultures. A busy academic autopsy service (600 cases per year) at University of Texas Medical Branch Hospitals, Galveston, Texas, served as the setting for this work. The incidence of non-clinically relevant (false-positive) culture results were compared using different methods for collecting blood samples in a prospective series of 38 adult autopsy specimens. One hundred eleven adult autopsy specimens in which both postmortem and antemortem blood cultures were obtained were studied retrospectively. For both studies, positive culture results were scored as either clinically relevant or false positives based on analysis of the autopsy findings and the clinical summary. The rate of false-positive culture results obtained by an iodine-subclavian technique from blood drawn soon after death were statistically significantly lower (13%) than using the classical method of obtaining blood through the atrium after heat searing at the time of the autopsy (34%) in the same set of autopsy subjects. When autopsy results were compared with subjects' antemortem blood culture results, there was no significant difference in the rate of non-clinically relevant culture results in a paired retrospective series of antemortem blood cultures and postmortem blood cultures using the iodine-subclavian postmortem method (11.7% v 13.5%). The results indicate that autopsy blood cultures obtained using the iodine-subclavian technique have reliability equivalent to that of antemortem blood cultures.

Psychological distress of female caregivers of significant others with cancer

Directory of Open Access Journals (Sweden)

Tony Cassidy

2015-12-01

Full Text Available This study explored the role of time since diagnosis and whether the care recipient was a child, a parent, or a spouse, on caregiver’s perceptions of the caring role, with a group of 269 female cancer caregivers. Questionnaire measures were used to explore psychological and social resources and psychological distress. Analysis of variance and hierarchical multiple regression were used and identified significant effects of time since diagnosis and care recipient. This study concludes that a more tailored approach to understanding the needs of caregivers is required particularly in terms of time since diagnosis and care recipient, in order to provide more effective support.

Emulsion oil droplet size significantly affects satiety: A pre-ingestive approach.

Science.gov (United States)

Lett, Aaron M; Norton, Jennifer E; Yeomans, Martin R

2016-01-01

Previous research has demonstrated that the manipulation of oil droplet size within oil-in-water emulsions significantly affects sensory characteristics, hedonics and expectations of food intake, independently of energy content. Smaller oil droplets enhanced perceived creaminess, increased Liking and generated greater expectations of satiation and satiety, indicating that creaminess is a satiety-relevant sensory cue within these systems. This paper extends these findings by investigating the effect of oil droplet size (d4,3: 2 and 50 μm) on food intake and appetite. Male participants (n = 34 aged 18-37; BMI of 22.7 ± 1.6 kg/m(2); DEBQ restricted eating score of 1.8 ± 0.1.) completed two test days, where they visited the laboratory to consume a fixed-portion breakfast, returning 3 h later for a "drink", which was the emulsion preload containing either 2 or 50 μm oil droplets. This was followed 20 min later with an ad libitum pasta lunch. Participants consumed significantly less at the ad libitum lunch after the preload containing 2 μm oil droplets than after the 50 μm preload, with an average reduction of 12% (62.4 kcal). Despite the significant differences in intake, no significant differences in sensory characteristics were noted. The findings show that the impact that an emulsion has on satiety can be enhanced without producing significantly perceivable differences in sensory properties. Therefore, by introducing a processing step which results in a smaller droplets, emulsion based liquid food products can be produced that enhance satiety, allowing covert functional redesign. Future work should consider the mechanism responsible for this effect. Copyright © 2015 Elsevier Ltd. All rights reserved.

Significant effect of NSP-ase enzyme supplementation in sunflower meal-based diet on the growth and nutrient digestibility in broilers.

Science.gov (United States)

Bilal, M; Mirza, M A; Kaleem, M; Saeed, M; Reyad-Ul-Ferdous, Md; Abd El-Hack, M E

2017-04-01

The response of broiler chickens to 3 levels of sunflower meal and 2 levels of NSP-ase enzyme combination (with and without) was investigated in 3 × 2 factorial arrangement under complete randomized design (CRD). A total of 240 Hubbard broiler chicks were fed on practical mash diets having 2950 kcal of ME and 21% CP from 1 to 42 days of age. The BW gain was not significantly reduced when 25% SFM was added in the diets during 1 to 42 days of age. Supplementation of NSP-ase in broiler diets (day 1-42 overall) demonstrated non-significant differences (p Replacement of SBM with SFM or inclusion of SFM at higher level (25%) increased/deteriorated FCR. The addition of exogenous NSP-ase showed a significant improvement (p < 0.01) in feed:gain. The improvement was clearly demonstrated when SFM was added to the experimental diet at 15% or even 20%. Supplementation of NSP-ase at the 25% inclusion level could not, however, sustain the beneficial effect, which was possibly due to excessively high dietary CF. No difference was noted across the treatments regarding carcass response. Relative gizzard weight and intestinal weight were observed to be improved in birds consuming higher levels of SFM (p = 0.00). The digestibility of CF was observed to improve when SFM was used at 20% and 25% in the diets. No improvement in the digestibility of CF was observed with NSP-ase supplementation, which meant other factors were clearly involved. Supplementation of NSP-ase improved FCR up to 20% SFM. At 25% SFM, no improvement in the digestibility of CF was observed with NSP-ase supplementation. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Traditional Indian spices and their health significance.

Science.gov (United States)

Krishnaswamy, Kamala

2008-01-01

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

Response to a spill of national significance

International Nuclear Information System (INIS)

Jensen, D.S.; Pond, R.; Johnson, M.H.

1993-01-01

Responding to a spill of national significance (SONS), such as the 1989 Exxon Valdez spill, requires an augmenting organization to support the local response organization. The US Coast Guard has developed SONS protocol to be better prepared to respond to these infrequent catastrophic spills. A flag-level Coast Guard officer assumes the role of national incident commander (NIC) and federal on-scene coordinator (OSC), and is supported by a national incident task force (NITF). The major role of the NITF is to develop a national response strategy, acquire response resources and allocate them efficiently, and effectively deal with many peripheral national issues. Unified command concepts have been incorporated into the NITF and its primary organizational elements. In addition, frequent training and exercising is essential to keep the SONS protocol's preparedness at an acceptable level

Motivationally Significant Stimuli Show Visual Prior Entry: Evidence for Attentional Capture

Science.gov (United States)

West, Greg L.; Anderson, Adam A. K.; Pratt, Jay

2009-01-01

Previous studies that have found attentional capture effects for stimuli of motivational significance do not directly measure initial attentional deployment, leaving it unclear to what extent these items produce attentional capture. Visual prior entry, as measured by temporal order judgments (TOJs), rests on the premise that allocated attention…

Are studies reporting significant results more likely to be published?

Science.gov (United States)

Koletsi, Despina; Karagianni, Anthi; Pandis, Nikolaos; Makou, Margarita; Polychronopoulou, Argy; Eliades, Theodore

2009-11-01

Our objective was to assess the hypothesis that there are variations of the proportion of articles reporting a significant effect, with a higher percentage of those articles published in journals with impact factors. The contents of 5 orthodontic journals (American Journal of Orthodontics and Dentofacial Orthopedics, Angle Orthodontist, European Journal of Orthodontics, Journal of Orthodontics, and Orthodontics and Craniofacial Research), published between 2004 and 2008, were hand-searched. Articles with statistical analysis of data were included in the study and classified into 4 categories: behavior and psychology, biomaterials and biomechanics, diagnostic procedures and treatment, and craniofacial growth, morphology, and genetics. In total, 2622 articles were examined, with 1785 included in the analysis. Univariate and multivariate logistic regression analyses were applied with statistical significance as the dependent variable, and whether the journal had an impact factor, the subject, and the year were the independent predictors. A higher percentage of articles showed significant results relative to those without significant associations (on average, 88% vs 12%) for those journals. Overall, these journals published significantly more studies with significant results, ranging from 75% to 90% (P = 0.02). Multivariate modeling showed that journals with impact factors had a 100% increased probability of publishing a statistically significant result compared with journals with no impact factor (odds ratio [OR], 1.99; 95% CI, 1.19-3.31). Compared with articles on biomaterials and biomechanics, all other subject categories showed lower probabilities of significant results. Nonsignificant findings in behavior and psychology and diagnosis and treatment were 1.8 (OR, 1.75; 95% CI, 1.51-2.67) and 3.5 (OR, 3.50; 95% CI, 2.27-5.37) times more likely to be published, respectively. Journals seem to prefer reporting significant results; this might be because of authors

Sixteen-Day Bedrest Significantly Increases Plasma Colloid Osmotic Pressure

Science.gov (United States)

Hargens, Alan R.; Hsieh, S. T.; Murthy, G.; Ballard, R. E.; Convertino, V. A.; Wade, Charles E. (Technical Monitor)

1994-01-01

Upon exposure to microgravity, astronauts lose up to 10% of their total plasma volume, which may contribute to orthostatic intolerance after space flight. Because plasma colloid osmotic pressure (COP) is a primary factor maintaining plasma volume, our objective was to measure time course changes in COP during microgravity simulated by 6 deg. head-down tilt (HDT). Seven healthy male subjects (30-55 years of age) were placed in HDT for 16 days. For the purpose of another study, three of the seven subjects were chosen to exercise on a cycle ergometer on day 16. Blood samples were drawn immediately before bedrest on day 14 of bedrest, 18-24 hours following exercise while all subjects were still in HDT and 1 hour following bedrest termination. Plasma COP was measured in all 20 microliter EDTA-treated samples using an osmometer fitted with a PM 30 membrane. Data were analyzed with paired and unpaired t-tests. Plasma COP on day 14 of bedrest (29.9 +/- 0.69 mmHg) was significantly higher (p less than 0.005) than the control, pre-bedrest value (23.1 +/- 0.76 mmHg). At one hour of upright recovery after HDT, plasma COP remained significantly elevated (exercise: 26.9 +/- 0.87 mmHg; no exercise: 26.3 +/- 0.85 mmHg). Additionally, exercise had no significant effect on plasma COP 18-24 hours following exercise (exercise: 27.8 +/- 1.09 mmHg; no exercise: 27.1 +/- 0.78 mmHg). Our results demonstrate that plasma COP increases significantly with microgravity simulated by HDT. However, preliminary results indicate exercise during HDT does not significantly affect plasma COP.

Assessment of tumoricidal efficacy and response to treatment with 18F-FDG PET/CT after intraarterial infusion with the antiglycolytic agent 3-bromopyruvate in the VX2 model of liver tumor.

Science.gov (United States)

Liapi, Eleni; Geschwind, Jean-Francois H; Vali, Mustafa; Khwaja, Afsheen A; Prieto-Ventura, Veronica; Buijs, Manon; Vossen, Josephina A; Ganapathy-Kanniappan, Shanmugasudaram; Ganapathy, Shanmugasudaram; Wahl, Richard L

2011-02-01

The purpose of this study was to determine the effects of 3-bromopyruvate (3-BrPA) on tumor glucose metabolism as imaged with (18)F-FDG PET/CT at multiple time points after treatment and compare them with those after intraarterial control injections of saline. Twenty-three New Zealand White rabbits implanted intrahepatically with VX2 tumors were assigned to 1 of 2 groups: 14 rabbits were assigned to the treatment group (TG) and 9 to the saline control group (SG). All animals were infused with 25 mL of either 1.75 mM 3-BrPA or saline over 1 h via a 2-French catheter, which was secured in the hepatic artery. For PET/CT, the animals were injected with 37 MBq of (18)F-FDG at 1 d before treatment and 2 h, 24 h, and 1 wk after treatment. Tumor size, tumor and liver maximal standardized uptake value (SUV(max)), and tumor-to-background ratios were calculated for all studies. Seven TG and 5 SG animals were sacrificed at 1 wk after treatment for histopathologic analysis. Intense (18)F-FDG uptake was seen in untreated tumors. A significant reduction in tumor SUV(max) was noted in TG animals, when compared with SG animals, at 1 wk after treatment (P = 0.006). The tumor-to-liver background ratio in the TG animals, compared with the SG animals, was significantly reduced as early as 24 h after treatment (P = 0.01) and remained reduced at 1 wk (P = 0.003). Tumor SUV(max) increased from the baseline levels at 7 d in controls (P = 0.05). The histopathologic analysis of explanted livers revealed increased tumor necrosis in all TG samples. There was a significant inverse correlation (r(2) = 0.538, P = 0.005) between the percentage of tumor necrosis on histopathology and tumor SUV(max) on (18)F-FDG PET at 7 d after treatment with 3-BrPA. Intraarterial injection of 3-BrPA resulted in markedly decreased (18)F-FDG uptake as imaged by PET/CT and increased tumor necrosis on histopathology at 1 wk after treatment in the VX2 rabbit liver tumor. PET/CT appears to be a useful means to follow

Significant NRC Enforcement Actions

Data.gov (United States)

Nuclear Regulatory Commission — This dataset provides a list of Nuclear Regulartory Commission (NRC) issued significant enforcement actions. These actions, referred to as "escalated", are issued by...

Experimental evidence concerning the significant information depth of electron backscatter diffraction (EBSD)

Energy Technology Data Exchange (ETDEWEB)

Wisniewski, Wolfgang, E-mail: wolfgang.w@uni-jena.de [Otto-Schott-Institut, Jena University, Fraunhoferstr. 6, 07743 Jena (Germany); Saager, Stefan [Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstraße 28, 01277 Dresden (Germany); Böbenroth, Andrea [Fraunhofer Institute for the Microstructure of Materials and Systems IMWS, Walter-Huelse-Straße 1, 06120 Halle (Saale) (Germany); Rüssel, Christian [Otto-Schott-Institut, Jena University, Fraunhoferstr. 6, 07743 Jena (Germany)

2017-02-15

Experiments concerning the information depth of electron backscatter diffraction (EBSD) are performed on samples featuring an amorphous wedge on a crystalline substrate and a crystalline wedge on an amorphous substrate. The effects of the acceleration voltage and exemplary software settings on the ability to measure through an amorphous layer are presented. Changes in the EBSD-signal could be detected through a ≈142 nm thick layer of amorphous Si while orientation measurements could be performed through a ≈116 nm thick layer when using a voltage of 30 kV. The complexity of the information depth significant to a given EBSD-pattern and the multiple parameters influencing it are discussed. It is suggested that a “core information depth” is significant to high quality patterns while a larger “maximum information depth” becomes relevant when the pattern quality decreases or the sample is inhomogeneous within the information volume, i.e. in the form of partially crystalline materials or crystal layers in the nm scale. - Highlights: • Experimental evidence of the significant information depth of EBSD is presented. • Effects of the voltage and exemplary software settings are discussed. • Dependence of the significant information depth on the pattern quality is proposed. • The information depth may reach up to 142 nm in Si when using a voltage of 30 kV. • The information depth depends on the available technology.

A human intervention study with foods containing natural Ah-receptor agonists does not significantly show AhR-mediated effects as measured in blood cells and urine.

Science.gov (United States)

de Waard, Pim W J; Peijnenburg, Ad A C M; Baykus, Hakan; Aarts, Jac M M J G; Hoogenboom, Ron L A P; van Schooten, Frederik J; de Kok, Theo M C M

2008-10-22

Binding and activation of the aryl hydrocarbon receptor (AhR) is thought to be an essential step in the toxicity of the environmental pollutants dioxins and dioxin-like PCBs. However, also a number of natural compounds, referred to as NAhRAs (natural Ah-receptor agonists), which are present in, for example, fruits and vegetables, can bind and activate this receptor. To study their potential effects in humans, we first investigated the effect of the prototypical AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression in ex vivo exposed freshly isolated human lymphocytes, and compared the resulting gene expression profile with those caused by the well-known NAhRA indolo[3,2-b]carbazole (ICZ), originating from cruciferous vegetables, and by a hexane extract of NAhRA-containing grapefruit juice (GJE). Only ICZ induced a gene expression profile similar to TCDD in the lymphocytes, and both significantly up-regulated CYP1B1 and TIPARP (TCDD-inducible poly (ADP-ribose) polymerase) mRNA. Next, we performed a human intervention study with NAhRA-containing cruciferous vegetables and grapefruit juice. The expression of the prototypical AhR-responsive genes CYP1A1, CYP1B1 and NQO1 in whole blood cells and in freshly isolated lymphocytes was not significantly affected. Also enzyme activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO), as judged by caffeine metabolites in urine, were unaffected, except for a small down-regulation of NAT2 activity by grapefruit juice. Examination of blood plasma with DR CALUX showed a 12% increased AhR agonist activity 3 and 24 h after consumption of cruciferous vegetables, but did not show a significant effect of grapefruit juice consumption. We conclude that intake of NAhRAs from food may result in minor AhR-related effects measurable in human blood and urine.

Hypoxia: Exposure Time Until Significant Performance Effects

Science.gov (United States)

2016-03-07

three alcoholic beverages per day (on average), or were taking any prescription medication (besides oral contraceptives). Likewise, those who were...or tested positively for pregnancy were disqualified from the study, as the risks of hypoxia to a human fetus are currently unknown. Also, those...that could impact inclusion in the study. After the questionnaire, all female participants provided a urine sample for pregnancy testing. Participants

Fabrication of CoZn alloy nanowire arrays: Significant improvement in magnetic properties by annealing process

International Nuclear Information System (INIS)

Koohbor, M.; Soltanian, S.; Najafi, M.; Servati, P.

2012-01-01

Highlights: ► Increasing the Zn concentration changes the structure of NWs from hcp to amorphous. ► Increasing the Zn concentration significantly reduces the Hc value of NWs. ► Magnetic properties of CoZn NWs can be significantly enhanced by appropriate annealing. ► The pH of electrolyte has no significant effect on the properties of the NW arrays. ► Deposition frequency has considerable effects on the magnetic properties of NWs. - Abstract: Highly ordered arrays of Co 1−x Zn x (0 ≤ x ≤ 0.74) nanowires (NWs) with diameters of ∼35 nm and high length-to-diameter ratios (up to 150) were fabricated by co-electrodeposition of Co and Zn into pores of anodized aluminum oxide (AAO) templates. The Co and Zn contents of the NWs were adjusted by varying the ratio of Zn and Co ion concentrations in the electrolyte. The effect of the Zn content, electrodeposition conditions (frequency and pH) and annealing on the structural and magnetic properties (e.g., coercivity (Hc) and squareness (Sq)) of NW arrays were investigated using X-ray diffraction (XRD), scanning electron microscopy, electron diffraction, and alternating gradient force magnetometer (AGFM). XRD patterns reveal that an increase in the concentration of Zn ions of the electrolyte forces the hcp crystal structure of Co NWs to change into an amorphous phase, resulting in a significant reduction in Hc. It was found that the magnetic properties of NWs can be significantly improved by appropriate annealing process. The highest values for Hc (2050 Oe) and Sq (0.98) were obtained for NWs electrodeposited using 0.95/0.05 Co:Zn concentrations at 200 Hz and annealed at 575 °C. While the pH of electrolyte is found to have no significant effect on the structural and magnetic properties of the NW arrays, the electrodeposition frequency has considerable effects on the magnetic properties of the NW arrays. The changes in magnetic property of NWs are rooted in a competition between shape anisotropy and

Significant Returns in Engagement and Performance with a Free Teaching App

Science.gov (United States)

Green, Alan

2016-01-01

Pedagogical research shows that teaching methods other than traditional lectures may result in better outcomes. However, lecture remains the dominant method in economics, likely due to high implementation costs of methods shown to be effective in the literature. In this article, the author shows significant benefits of using a teaching app for…

Significant questions in thin liquid film heat transfer

International Nuclear Information System (INIS)

Bankoff, S.G.

1994-01-01

Thin liquid films appear in many contexts, such as the cooling of gas turbine blade tips, rocket engines, microelectronics arrays, and hot fuel element surfaces in hypothetical nuclear reactor accidents. Apart from these direct cooling applications of thin liquid layers, thin films form a crucial element in determining the allowable heat flux limits in boiling. This is because the last stages of dryout almost invariably involve the rupture of a residual liquid film, either as a microlayer underneath the bubbles, or a thin annular layer in a high-quality burnout scenario. The destabilization of these thin films under the combined actions of shear stress, evaporation, and thermocapillary effects is quite complex. The later stages of actual rupture to form dry regions, which then expand, resulting in possible overheating, are even more complex and less well understood. However, significant progress has been made in understanding the behavior of these thin films, which are subject to competing instabilities prior to actual rupture. This will be reviewed briefly. Recent work on the advance, or recession, of contact lines will also be described briefly, and significant questions that still remain to be answered will be discussed. 68 refs., 7 figs

Climate change and vector-borne diseases of public health significance.

Science.gov (United States)

Ogden, Nicholas H

2017-10-16

There has been much debate as to whether or not climate change will have, or has had, any significant effect on risk from vector-borne diseases. The debate on the former has focused on the degree to which occurrence and levels of risk of vector-borne diseases are determined by climate-dependent or independent factors, while the debate on the latter has focused on whether changes in disease incidence are due to climate at all, and/or are attributable to recent climate change. Here I review possible effects of climate change on vector-borne diseases, methods used to predict these effects and the evidence to date of changes in vector-borne disease risks that can be attributed to recent climate change. Predictions have both over- and underestimated the effects of climate change. Mostly under-estimations of effects are due to a focus only on direct effects of climate on disease ecology while more distal effects on society's capacity to control and prevent vector-borne disease are ignored. There is increasing evidence for possible impacts of recent climate change on some vector-borne diseases but for the most part, observed data series are too short (or non-existent), and impacts of climate-independent factors too great, to confidently attribute changing risk to climate change. © Crown copyright 2017.

Melatonin: a chemical photoperiodic signal with clinical significance in humans.

Science.gov (United States)

Pang, S F; Pang, C S; Poon, A M; Lee, P P; Liu, Z M; Shiu, S Y

1998-03-01

Secretion of pineal melatonin exhibits a diumal rhythm and a seasonal rhythm in humans. Night-time melatonin is high at 3-5 year-old and decreases with age. Many drugs and pathological conditions also change melatonin levels in the circulation. Melatonin has a mild sedative effect and has been used effectively in synchronizing the sleep-wake cycle of patients with sleep disorders. Immunoenhancing, anti-cancer, anti-aging and anti-oxidant effects of melatonin have been proposed. Recent studies suggest that melatonin receptors are present in central and peripheral tissues. The importance of melatonin receptors on the nervous, reproductive, immune and renal functions is implicated. Studies on the molecular biology, physiology and pathology of melatonin receptors in different tissues are progressing rapidly. The physiological and pathological changes in melatonin secretion, multifarious melatonin actions, and diverse melatonin receptors reported suggest that melatonin is a photoperiodic signal with clinical significance in humans.

Intensive inpatient treatment for bulimia nervosa: Statistical and clinical significance of symptom changes.

Science.gov (United States)

Diedrich, Alice; Schlegl, Sandra; Greetfeld, Martin; Fumi, Markus; Voderholzer, Ulrich

2018-03-01

This study examines the statistical and clinical significance of symptom changes during an intensive inpatient treatment program with a strong psychotherapeutic focus for individuals with severe bulimia nervosa. 295 consecutively admitted bulimic patients were administered the Structured Interview for Anorexic and Bulimic Syndromes-Self-Rating (SIAB-S), the Eating Disorder Inventory-2 (EDI-2), the Brief Symptom Inventory (BSI), and the Beck Depression Inventory-II (BDI-II) at treatment intake and discharge. Results indicated statistically significant symptom reductions with large effect sizes regarding severity of binge eating and compensatory behavior (SIAB-S), overall eating disorder symptom severity (EDI-2), overall psychopathology (BSI), and depressive symptom severity (BDI-II) even when controlling for antidepressant medication. The majority of patients showed either reliable (EDI-2: 33.7%, BSI: 34.8%, BDI-II: 18.1%) or even clinically significant symptom changes (EDI-2: 43.2%, BSI: 33.9%, BDI-II: 56.9%). Patients with clinically significant improvement were less distressed at intake and less likely to suffer from a comorbid borderline personality disorder when compared with those who did not improve to a clinically significant extent. Findings indicate that intensive psychotherapeutic inpatient treatment may be effective in about 75% of severely affected bulimic patients. For the remaining non-responding patients, inpatient treatment might be improved through an even stronger focus on the reduction of comorbid borderline personality traits.

Analysis of human error and organizational deficiency in events considering risk significance

International Nuclear Information System (INIS)

Lee, Yong Suk; Kim, Yoonik; Kim, Say Hyung; Kim, Chansoo; Chung, Chang Hyun; Jung, Won Dea

2004-01-01

In this study, we analyzed human and organizational deficiencies in the trip events of Korean nuclear power plants. K-HPES items were used in human error analysis, and the organizational factors by Jacobs and Haber were used for organizational deficiency analysis. We proposed the use of CCDP as a risk measure to consider risk information in prioritizing K-HPES items and organizational factors. Until now, the risk significance of events has not been considered in human error and organizational deficiency analysis. Considering the risk significance of events in the process of analysis is necessary for effective enhancement of nuclear power plant safety by focusing on causes of human error and organizational deficiencies that are associated with significant risk

Genetic variation and significance of hepatitis B surface antigen

Directory of Open Access Journals (Sweden)

ZHANG Zhenhua

2013-11-01

Full Text Available Hepatitis B virus (HBV is prone to genetic variation because there is reverse transcription in the process of HBV replication. The gene mutation of hepatitis B surface antigen may affect clinical diagnosis of HBV infection, viral replication, and vaccine effect. The current research and existing problems are discussed from the following aspects: the mechanism and biological and clinical significance of S gene mutation. Most previous studies focused on S gene alone, so S gene should be considered as part of HBV DNA in the future research on S gene mutation.

Significance evaluation in factor graphs

DEFF Research Database (Denmark)

Madsen, Tobias; Hobolth, Asger; Jensen, Jens Ledet

2017-01-01

in genomics and the multiple-testing issues accompanying them, accurate significance evaluation is of great importance. We here address the problem of evaluating statistical significance of observations from factor graph models. Results Two novel numerical approximations for evaluation of statistical...... significance are presented. First a method using importance sampling. Second a saddlepoint approximation based method. We develop algorithms to efficiently compute the approximations and compare them to naive sampling and the normal approximation. The individual merits of the methods are analysed both from....... Conclusions The applicability of saddlepoint approximation and importance sampling is demonstrated on known models in the factor graph framework. Using the two methods we can substantially improve computational cost without compromising accuracy. This contribution allows analyses of large datasets...

Significance of Operating Environment in Condition Monitoring of Large Civil Structures

Directory of Open Access Journals (Sweden)

Sreenivas Alampalli

1999-01-01

Full Text Available Success of remote long-term condition monitoring of large civil structures and developing calibrated analytical models for damage detection, depend significantly on establishing accurate baseline signatures and their sensitivity. Most studies reported in the literature concentrated on the effect of structural damage on modal parameters without emphasis on reliability of modal parameters. Thus, a field bridge structure was studied for the significance of operating conditions in relation to baseline signatures. Results indicate that in practice, civil structures should be monitored for at least one full cycle of in-service environmental changes before establishing baselines for condition monitoring or calibrating finite-element models. Boundary conditions deserve special attention.

23 CFR 630.1010 - Significant projects.

Science.gov (United States)

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Significant projects. 630.1010 Section 630.1010 Highways... PRECONSTRUCTION PROCEDURES Work Zone Safety and Mobility § 630.1010 Significant projects. (a) A significant project is one that, alone or in combination with other concurrent projects nearby is anticipated to cause...

Significant Improvement of Catalytic Efficiencies in Ionic Liquids

International Nuclear Information System (INIS)

Song, Choong Eui; Yoon, Mi Young; Choi, Doo Seong

2005-01-01

The use of ionic liquids as reaction media can confer many advantages upon catalytic reactions over reactions in organic solvents. In ionic liquids, catalysts having polar or ionic character can easily be immobilized without additional structural modification and thus the ionic solutions containing the catalyst can easily be separated from the reagents and reaction products, and then, be reused. More interestingly, switching from an organic solvent to an ionic liquid often results in a significant improvement in catalytic performance (e.g., rate acceleration, (enantio)selectivity improvement and an increase in catalyst stability). In this review, some recent interesting results which can nicely demonstrate these positive 'ionic liquid effect' on catalysis are discussed

Pharmacological significance of the interplay between angiotensin receptors: MAS receptors as putative final mediators of the effects elicited by angiotensin AT1 receptors antagonists.

Science.gov (United States)

Pernomian, Larissa; Pernomian, Laena; Gomes, Mayara S; da Silva, Carlos H T P

2015-12-15

The interplay between angiotensin AT1 receptors and MAS receptors relies on several inward regulatory mechanisms from renin-angiotensin system (RAS) including the functional crosstalk between angiotensin II and angiotensin-(1-7), the competitive AT1 antagonism exhibited by angiotensin-(1-7), the antagonist feature assigned to AT1/MAS heterodimerization on AT1 signaling and the AT1-mediated downregulation of angiotensin-converting enzyme 2 (ACE2). Recently, such interplay has acquired an important significance to RAS Pharmacology since a few studies have supporting strong evidences that MAS receptors mediate the effects elicited by AT1 antagonists. The present Perspective provides an overview of the regulatory mechanisms involving AT1 and MAS receptors, their significance to RAS Pharmacology and the future directions on the interplay between angiotensin receptors. Copyright © 2015 Elsevier B.V. All rights reserved.

Creating Significant Learning Experiences across Disciplines

Science.gov (United States)

Levine, Laura E.; Fallahi, Carolyn R.; Nicoll-Senft, Joan M.; Tessier, Jack T.; Watson, Cheryl L.; Wood, Rebecca M.

2008-01-01

The purpose of this study was to use Fink's (2003) taxonomy of significant learning to redesign courses and assess student learning. Significant improvements were found across the semester for students in the six courses, but there were differences in which taxa showed improvement in each course. The meta-analysis showed significant, positive…

The antiplatelet effects of nitrates: is it of clinical significance in patients with cardiovascular disease?

Science.gov (United States)

Zhou, Rui-Hai; Frishman, William H

2010-01-01

Organic nitrates have been used for over a century in cardiovascular therapy and are still widely used in the treatment of acute coronary syndromes, chronic angina pectoris, and congestive heart failure. Nitrates, together with sodium nitroprusside, generally referred to as nitrovasodilators, exert their biologic effects via the release of nitric oxide. They are also known as nitric oxide donors. The mechanism of action of these drugs is traditionally believed to lie in their arterial vasodilation and venodilation effects, resulting in an improvement of coronary artery blood supply and/or reduction of cardiac workload in the treatment of coronary artery disease and congestive heart failure. Recently it has been recognized that these drugs also have intrinsic antiplatelet and antithrombotic effects, demonstrated both in vitro and in vivo, which would add further rationale for the use of these drugs in atherothrombotic diseases. Research has shown that nitrovasodilators can nonselectively inhibit platelet aggregation induced by multiple stimuli. However, clinical trials have yielded conflicting results regarding clinical outcome, especially with long-term nitrate use. The potentially beneficial effects of nitrates could be negated by the development of tolerance and the generation of deleterious oxidative stress causing endothelial dysfunction during continuous nitrate administration. Much progress has been made in the development of new nitric oxide donors devoid of oxidant-generating properties. Novel combination therapies with nitrovasodilators plus antioxidants or agents with antioxidant properties have shown promise in reducing or reversing tolerance, potentiating antiplatelet effects, and improving clinical outcome. It is expected that clinical introduction of novel nitrovasodilator regimens will provide a new approach to the prevention and treatment of atherothrombotic diseases. Large-scale clinical trials will ultimately provide the evidence-based answers.

The significance of belief and expectancy within the spiritual healing encounter.

Science.gov (United States)

Wirth, D P

1995-07-01

Historically, traditional cultures recognized the importance of belief and expectancy within the healing encounter and created complex rituals and ceremonies designed to elicit or foster the expectancy and participation of both the healer and patient, as well as the community as a whole. This holistic approach to health care was a fundamental component in the spiritual healing rituals of virtually all traditional native cultures. The focus of the current study was to assess the impact of healer and patient expectations on mental and physical health parameters following a spiritual healing session. A pre-post methodological design which incorporated extensive psychophysiological health outcome measures along with independent medical diagnoses was utilized. The study was conducted in a northern California suburb of Marin County utilizing an American-born spiritual healer trained in the Philippines. The results indicated that there was a statistically significant difference between the pre-treatment and post-treatment scores for all fourteen dependent variables examined. The data also demonstrated a significant difference between the high versus low expectancy subjects for both patient and healer groups, as well as a significant relationship between high expectancy in patients and healer and the effectiveness of the spiritual healing encounter. The results of the study therefore suggest that high healer and patient expectancy may be important elements which can serve as both predictors as well as facilitators of the healing process. The degree of bonding or communication between the healer and patient was postulated as an important factor in this regard. Due to the fact that a majority of the conditions reported (75%) were organic disorders that would not commonly disappear within the 3 week time frame of the study, the significant results obtained suggest that spiritual healing in combination with traditional allopathic medicine may have the potential to be an

Significant promotion effect of carbon nanotubes on the electrocatalytic activity of supported Pd NPs for ethanol oxidation reaction of fuel cells: the role of inner tubes.

Science.gov (United States)

Zhang, Jin; Cheng, Yi; Lu, Shanfu; Jia, Lichao; Shen, Pei Kang; Jiang, San Ping

2014-11-18

The inner tubes of carbon nanotubes (CNTs) have a significant promotion effect on the electrocatalytic activity of Pd nanoparticles (NPs) for the ethanol oxidation of direct alcohol fuel cells (DAFCs) and Pd NPs supported on CNTs with 3-7 walls show a much higher activity as compared to that supported on typical single-walled and multi-walled CNTs.

Significant Effect of Pore Sizes on Energy Storage in Nanoporous Carbon Supercapacitors.

Science.gov (United States)

Young, Christine; Lin, Jianjian; Wang, Jie; Ding, Bing; Zhang, Xiaogang; Alshehri, Saad M; Ahamad, Tansir; Salunkhe, Rahul R; Hossain, Shahriar A; Khan, Junayet Hossain; Ide, Yusuke; Kim, Jeonghun; Henzie, Joel; Wu, Kevin C-W; Kobayashi, Naoya; Yamauchi, Yusuke

2018-04-20

Mesoporous carbon can be synthesized with good control of surface area, pore-size distribution, and porous architecture. Although the relationship between porosity and supercapacitor performance is well known, there are no thorough reports that compare the performance of numerous types of carbon samples side by side. In this manuscript, we describe the performance of 13 porous carbon samples in supercapacitor devices. We suggest that there is a "critical pore size" at which guest molecules can pass through the pores effectively. In this context, the specific surface area (SSA) and pore-size distribution (PSD) are used to show the point at which the pore size crosses the threshold of critical size. These measurements provide a guide for the development of new kinds of carbon materials for supercapacitor devices. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transarterial Re-188 labeled Lipiodol therapy in cases of inoperable hepatocellular carcinoma

International Nuclear Information System (INIS)

Kumar, Ajay; Pant, G.S.; Bandopadhyaya, G.P.; Bal, C.S.; Srivastava, D.N.; Acharya, S.K.; Pandey, G.K.; DattaGupta, S.; Sundaram, K.R.; Zanzonicog, Pat; Sundaram, Felix X.; Padhy, A.K.

2004-01-01

Full text: Most of the patients of hepatocellular carcinoma (HCC) present late with inoperable disease, cirrhosis of the liver and sometimes with portal vein thrombosis. In these circumstances, chemoembolisation is not possible. Similarly, if tumor is not accessible percutaneously, percutaneous ablative procedures are also ruled out. Such patients can be offered internal radionuclide therapy. In the internal radionuclide therapy, it is desirable to deliver the maximum possible radiation to the tumor, while protecting the critical organs such as normal liver parenchyma, lungs and the bone marrow (for which critical levels of radiation doses are predetermined as 30, 12 and 1.5 Gy, respectively). This is possible with individual dosimetry, by which radiation-absorbed dose/MBq to the various organs including the tumor is calculated and the 'maximum tolerated activity (MTA)', which can be safely administered to the patient, is estimated. However, this MTA should be able to deliver enough radiation to the tumor to ablate it completely (considered to be 80-100 Gy). We conducted trans-arterial Re-188 lipiodol therapy in patients with inoperable HCC after calculating MTA with individual dosimetry, in a multi-centric trial conducted by IAEA, and tried to evaluate whether calculated MTA could deliver tumoricidal radiation dose. With a transarterially injected scout dose (185 MBq) of Re-188, radiation absorbed dose to above mentioned organs including tumor were calculated in ten patients after acquiring planar gamma camera images, using conjugate view method (images taken up to 3 hrs post-injection along with a standard source) and performing first-order corrections for scatter (by taking images both in photopeak and scatter window) and attenuation (by taking a flood source and a transmission scan of the patents prior to the administration of Re-188). Images were acquired on gamma camera(Siemens-ORBITOR or GE- Millennium VG) with high/medium-energy collimator and radiation

Confidence Intervals: From tests of statistical significance to confidence intervals, range hypotheses and substantial effects

Directory of Open Access Journals (Sweden)

Dominic Beaulieu-Prévost

2006-03-01

Full Text Available For the last 50 years of research in quantitative social sciences, the empirical evaluation of scientific hypotheses has been based on the rejection or not of the null hypothesis. However, more than 300 articles demonstrated that this method was problematic. In summary, null hypothesis testing (NHT is unfalsifiable, its results depend directly on sample size and the null hypothesis is both improbable and not plausible. Consequently, alternatives to NHT such as confidence intervals (CI and measures of effect size are starting to be used in scientific publications. The purpose of this article is, first, to provide the conceptual tools necessary to implement an approach based on confidence intervals, and second, to briefly demonstrate why such an approach is an interesting alternative to an approach based on NHT. As demonstrated in the article, the proposed CI approach avoids most problems related to a NHT approach and can often improve the scientific and contextual relevance of the statistical interpretations by testing range hypotheses instead of a point hypothesis and by defining the minimal value of a substantial effect. The main advantage of such a CI approach is that it replaces the notion of statistical power by an easily interpretable three-value logic (probable presence of a substantial effect, probable absence of a substantial effect and probabilistic undetermination. The demonstration includes a complete example.

Fabrication of CoZn alloy nanowire arrays: Significant improvement in magnetic properties by annealing process

Energy Technology Data Exchange (ETDEWEB)

Koohbor, M. [Department of Physics, University of Kurdistan, Sanandaj (Iran, Islamic Republic of); Soltanian, S., E-mail: s.soltanian@gmail.com [Department of Physics, University of Kurdistan, Sanandaj (Iran, Islamic Republic of); Department of Electrical and Computer Engineering, University of British Columbia, Vancouver (Canada); Najafi, M. [Department of Physics, University of Kurdistan, Sanandaj (Iran, Islamic Republic of); Department of Physics, Hamadan University of Technology, Hamadan (Iran, Islamic Republic of); Servati, P. [Department of Electrical and Computer Engineering, University of British Columbia, Vancouver (Canada)

2012-01-05

Highlights: Black-Right-Pointing-Pointer Increasing the Zn concentration changes the structure of NWs from hcp to amorphous. Black-Right-Pointing-Pointer Increasing the Zn concentration significantly reduces the Hc value of NWs. Black-Right-Pointing-Pointer Magnetic properties of CoZn NWs can be significantly enhanced by appropriate annealing. Black-Right-Pointing-Pointer The pH of electrolyte has no significant effect on the properties of the NW arrays. Black-Right-Pointing-Pointer Deposition frequency has considerable effects on the magnetic properties of NWs. - Abstract: Highly ordered arrays of Co{sub 1-x}Zn{sub x} (0 {<=} x {<=} 0.74) nanowires (NWs) with diameters of {approx}35 nm and high length-to-diameter ratios (up to 150) were fabricated by co-electrodeposition of Co and Zn into pores of anodized aluminum oxide (AAO) templates. The Co and Zn contents of the NWs were adjusted by varying the ratio of Zn and Co ion concentrations in the electrolyte. The effect of the Zn content, electrodeposition conditions (frequency and pH) and annealing on the structural and magnetic properties (e.g., coercivity (Hc) and squareness (Sq)) of NW arrays were investigated using X-ray diffraction (XRD), scanning electron microscopy, electron diffraction, and alternating gradient force magnetometer (AGFM). XRD patterns reveal that an increase in the concentration of Zn ions of the electrolyte forces the hcp crystal structure of Co NWs to change into an amorphous phase, resulting in a significant reduction in Hc. It was found that the magnetic properties of NWs can be significantly improved by appropriate annealing process. The highest values for Hc (2050 Oe) and Sq (0.98) were obtained for NWs electrodeposited using 0.95/0.05 Co:Zn concentrations at 200 Hz and annealed at 575 Degree-Sign C. While the pH of electrolyte is found to have no significant effect on the structural and magnetic properties of the NW arrays, the electrodeposition frequency has considerable effects on

Significant-Loophole-Free Test of Bell's Theorem with Entangled Photons.

Science.gov (United States)

Giustina, Marissa; Versteegh, Marijn A M; Wengerowsky, Sören; Handsteiner, Johannes; Hochrainer, Armin; Phelan, Kevin; Steinlechner, Fabian; Kofler, Johannes; Larsson, Jan-Åke; Abellán, Carlos; Amaya, Waldimar; Pruneri, Valerio; Mitchell, Morgan W; Beyer, Jörn; Gerrits, Thomas; Lita, Adriana E; Shalm, Lynden K; Nam, Sae Woo; Scheidl, Thomas; Ursin, Rupert; Wittmann, Bernhard; Zeilinger, Anton

2015-12-18

Local realism is the worldview in which physical properties of objects exist independently of measurement and where physical influences cannot travel faster than the speed of light. Bell's theorem states that this worldview is incompatible with the predictions of quantum mechanics, as is expressed in Bell's inequalities. Previous experiments convincingly supported the quantum predictions. Yet, every experiment requires assumptions that provide loopholes for a local realist explanation. Here, we report a Bell test that closes the most significant of these loopholes simultaneously. Using a well-optimized source of entangled photons, rapid setting generation, and highly efficient superconducting detectors, we observe a violation of a Bell inequality with high statistical significance. The purely statistical probability of our results to occur under local realism does not exceed 3.74×10^{-31}, corresponding to an 11.5 standard deviation effect.

Chronic methamphetamine exposure significantly decreases microglia activation in the arcuate nucleus.

Science.gov (United States)

Lloyd, Steven A; Corkill, Beau; Bruster, Matthew C; Roberts, Rick L; Shanks, Ryan A

2017-07-01

Methamphetamine is a powerful psychostimulant drug and its use and abuse necessitates a better understanding of its neurobiobehavioral effects. The acute effects of binge dosing of methamphetamine on the neurons in the CNS are well studied. However, the long-term effects of chronic, low-dose methamphetamine are less well characterized, especially in other cell types and areas outside of the major dopamine pathways. Mice were administered 5mg/kg/day methamphetamine for ten days and brain tissue was analyzed using histochemistry and image analysis. Increased microglia activity in the striatum confirmed toxic effects of methamphetamine in this brain region using this dosing paradigm. A significant decrease in microglia activity in the arcuate nucleus of the hypothalamus was observed with no effect noted on dopamine neurons in the arcuate nucleus. Given the importance of this area in homeostatic and neuroendocrine regulation, the current study highlights the need to more fully understand the systemic effects of chronic, low-dose methamphetamine use. The novel finding of microglia downregulation after chronic methamphetamine could lead to advances in understanding neuroinflammatory responses towards addiction treatment and protection from psychostimulant-induced neurotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Significance of atmospheric effects of heat rejection from energy centers in the semi arid northwest

International Nuclear Information System (INIS)

Ramsdell, J.V.; Drake, R.L.; Young, J.R.

1976-01-01

The results presented in this paper have been obtained using simple atmospheric models in an attempt to optimize heat sink management in a conceptual nuclear energy center (NEC) at Hanford. The models have been designed to be conservatice in the sense that they are biased toward over prediction of the impact of cooling system effluents on humidity and fog. Thus the models are screening tools to be used to identify subjects for further, more realistic examination. Within this context the following conclusions have been reached: the evaluation of any atmospheric impact postulated for heat dissipation must be conducted in quantitative terms which can be used to determine the significance of the impact; of the potential atmospheric impacts of large heat releases from energy centers, the one most amenable to quantitative evaluation in meaningful terms as the increase in fog; a postulated increase in frequency of fog can be translated into terms of visibility and both can be evaluated statistically; the translation of a increase in fog to visibility terms permits economic evaluation of the impact; and the predicted impact of the HNEC on fog and visibility is statistically significant whether the energy center consists of 20 or 40 units

Initial experience with the NRC significance determination process

International Nuclear Information System (INIS)

Madison, A.L.

2001-01-01

The U.S. Nuclear Regulatory Commission (NRC) has revamped its inspection, assessment, and enforcement programs for commercial nuclear power plants. The new oversight process uses more objective, timely, and safety-significant criteria in assessing performance, while seeking to more effectively and efficiently regulate the industry. The NRC tested the new process at thirteen reactors at nine sites across the country on a pilot basis in 1999 to identify what things worked well and what improvements were called for before beginning Initial Implementation at all US nuclear power plants on April 2, 2000. After a year of experience has been gained with the new oversight process at all US plants, the NRC anticipates making further improvements based on this wider experience. (author)

Initial experience with the NRC significance determination process

Energy Technology Data Exchange (ETDEWEB)

Madison, A.L. [Office of Nuclear Reactor Regulation, US Nuclear Regulatory Commission (United States)

2001-07-01

The U.S. Nuclear Regulatory Commission (NRC) has revamped its inspection, assessment, and enforcement programs for commercial nuclear power plants. The new oversight process uses more objective, timely, and safety-significant criteria in assessing performance, while seeking to more effectively and efficiently regulate the industry. The NRC tested the new process at thirteen reactors at nine sites across the country on a pilot basis in 1999 to identify what things worked well and what improvements were called for before beginning Initial Implementation at all US nuclear power plants on April 2, 2000. After a year of experience has been gained with the new oversight process at all US plants, the NRC anticipates making further improvements based on this wider experience. (author)

Human-directed social behaviour in dogs shows significant heritability.

Science.gov (United States)

Persson, M E; Roth, L S V; Johnsson, M; Wright, D; Jensen, P

2015-04-01

Through domestication and co-evolution with humans, dogs have developed abilities to attract human attention, e.g. in a manner of seeking assistance when faced with a problem solving task. The aims of this study were to investigate within breed variation in human-directed contact seeking in dogs and to estimate its genetic basis. To do this, 498 research beagles, bred and kept under standardized conditions, were tested in an unsolvable problem task. Contact seeking behaviours recorded included both eye contact and physical interactions. Behavioural data was summarized through a principal component analysis, resulting in four components: test interactions, social interactions, eye contact and physical contact. Females scored significantly higher on social interactions and physical contact and age had an effect on eye contact scores. Narrow sense heritabilities (h(2) ) of the two largest components were estimated at 0.32 and 0.23 but were not significant for the last two components. These results show that within the studied dog population, behavioural variation in human-directed social behaviours was sex dependent and that the utilization of eye contact seeking increased with age and experience. Hence, heritability estimates indicate a significant genetic contribution to the variation found in human-directed social interactions, suggesting that social skills in dogs have a genetic basis, but can also be shaped and enhanced through individual experiences. This research gives the opportunity to further investigate the genetics behind dogs' social skills, which could also play a significant part into research on human social disorders such as autism. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

[Long-term effect of a cognitive intervention on learning and participation in a significant leisure activity in early dementia of Alzheimer type: a case study].

Science.gov (United States)

Provencher, Véronique; Bier, Nathalie; Audet, Thérèse; Gagnon, Lise

2009-06-01

Decreased ability to accomplish significant leisure activities often occurs in early stages of dementia of Alzheimer type (DAT). As a long term effect, it may eventually affect the quality of life of the patient as well as that of the caregiver's. In a previous study, a woman with early DAT (77 years old, MMSE: 24/30) improved her participation in 2 leisure activities (listening to music and praying in a group) following the learning of a few tasks (e.g. using a radio cassette, remembering the significance of an pre-programmed ring) as a result of a cognitive intervention. The present study presents the long term effect of this intervention on the retention of the learned tasks and on spontaneous participation in both leisure activities of her daily living. Measures of tasks' learning and spontaneous participation in activities have been obtained through direct observation (ex: ability to use the tasks learned without assistance) and telephone conversations with the caregiver. The measures were taken 9 to 15 months post-intervention. Nine months after the end of the intervention, the participant could no longer use the radio cassette, but was able to remember the significance of the pre-programmed ring. Similarly, she stopped listening to music, but still attended her prayer group. The intervention appears to maintain participation in a leisure activity for several months in a patient with early DAT, in spite of expected functional decline. This functional impact can be achieved through retention of specific learned tasks as well as by strong external cues (daily pre-programmed ring), and can increase the quality of life for patients with DAT.

Evidence of significant covalent bonding in Au(CN)(2)(-).

Science.gov (United States)

Wang, Xue-Bin; Wang, Yi-Lei; Yang, Jie; Xing, Xiao-Peng; Li, Jun; Wang, Lai-Sheng

2009-11-18

The Au(CN)(2)(-) ion is the most stable Au compound known for centuries, yet a detailed understanding of its chemical bonding is still lacking. Here we report direct experimental evidence of significant covalent bonding character in the Au-C bonds in Au(CN)(2)(-) using photoelectron spectroscopy and comparisons with its lighter congeners, Ag(CN)(2)(-) and Cu(CN)(2)(-). Vibrational progressions in the Au-C stretching mode were observed for all detachment transitions for Au(CN)(2)(-), in contrast to the atomic-like transitions for Cu(CN)(2)(-), revealing the Au-C covalent bonding character. In addition, rich electronic structural information was obtained for Au(CN)(2)(-) by employing 118 nm detachment photons. Density functional theory and high-level ab initio calculations were carried out to understand the photoelectron spectra and obtain insight into the nature of the chemical bonding in the M(CN)(2)(-) complexes. Significant covalent character in the Au-C bonding due to the strong relativistic effects was revealed in Au(CN)(2)(-), consistent with its high stability.

Clinical significance of MUC13 in pancreatic ductal adenocarcinoma.

Science.gov (United States)

Khan, Sheema; Zafar, Nadeem; Khan, Shabia S; Setua, Saini; Behrman, Stephen W; Stiles, Zachary E; Yallapu, Murali M; Sahay, Peeyush; Ghimire, Hemendra; Ise, Tomoko; Nagata, Satoshi; Wang, Lei; Wan, Jim Y; Pradhan, Prabhakar; Jaggi, Meena; Chauhan, Subhash C

2018-01-15

Poor prognosis of pancreatic cancer (PanCa) is associated with lack of an effective early diagnostic biomarker. This study elucidates significance of MUC13, as a diagnostic/prognostic marker of PanCa. MUC13 was assessed in tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT-PCR, computational and submicron scale mass-density fluctuation analyses, ROC and Kaplan Meir curve analyses. MUC13 expression was detected in 100% pancreatic intraepithelial neoplasia (PanIN) lesions (Mean composite score: MCS = 5.8; AUC >0.8, P 0.8; P artificial intelligence based algorithm analyses also elucidated association of MUC13 with greater morphological disorder (P < 0.001) and nuclear MUC13 as strong predictor for cancer aggressiveness and poor patient survival. This study provides significant information regarding MUC13 expression/subcellular localization in PanCa samples and supporting the use anti-MUC13 MAb for the development of PanCa diagnostic/prognostic test. Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Serious fighting-related injuries produce a significant reduction in intelligence.

Science.gov (United States)

Schwartz, Joseph A; Beaver, Kevin M

2013-10-01

Fighting-related injuries are common among adolescents within the United States, but how such injuries relate to subsequent cognitive functioning remains unclear. In particular, the long-term effect of fighting-related injuries suffered during important developmental periods, such as adolescence, on subsequent cognitive functioning has been overlooked by previous studies. The purpose of this study is to examine the association between sustaining serious fighting-related injuries and changes in verbal intelligence (IQ) over a 5- to 6-year time period. Longitudinal multivariate statistical models were used to analyze data from the National Longitudinal Study of Adolescent Health collected between 1994 and 2002 and analyzed in 2013. Even a single fighting-related injury resulted in a significant reduction in IQ over time even after controlling for age, race, sex, and changes in socioeconomic status (SES) over the study period. Additionally, females experienced a significantly greater reduction in IQ from each fighting-related injury than males. Fighting-related injuries have a significant impact on subsequent cognitive functioning and intelligence. The implications for future policies and research are discussed in more detail. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Significant Lactic Acidosis from Albuterol

Directory of Open Access Journals (Sweden)

Deborah Diercks

2018-03-01

Full Text Available Lactic acidosis is a clinical entity that demands rapid assessment and treatment to prevent significant morbidity and mortality. With increased lactate use across many clinical scenarios, lactate values themselves cannot be interpreted apart from their appropriate clinical picture. The significance of Type B lactic acidosis is likely understated in the emergency department (ED. Given the mortality that sepsis confers, a serum lactate is an important screening study. That said, it is with extreme caution that we should interpret and react to the resultant elevated value. We report a patient with a significant lactic acidosis. Though he had a high lactate value, he did not require aggressive resuscitation. A different classification scheme for lactic acidosis that focuses on the bifurcation of the “dangerous” and “not dangerous” causes of lactic acidosis may be of benefit. In addition, this case is demonstrative of the potential overuse of lactates in the ED.

Melatonin Distribution Reveals Clues to Its Biological Significance in Basal Metazoans

Science.gov (United States)

Roopin, Modi; Levy, Oren

2012-01-01

Although nearly ubiquitous in nature, the precise biological significance of endogenous melatonin is poorly understood in phylogenetically basal taxa. In the present work, we describe insights into the functional role of melatonin at the most “basal” level of metazoan evolution. Hitherto unknown morphological determinants of melatonin distribution were evaluated in Nematostella vectensis by detecting melatonin immunoreactivity and examining the spatial gene expression patterns of putative melatonin biosynthetic and receptor elements that are located at opposing ends of the melatonin signaling pathway. Immuno-melatonin profiling indicated an elaborate interaction with reproductive tissues, reinforcing previous conjectures of a melatonin-responsive component in anthozoan reproduction. In situ hybridization (ISH) to putative melatonin receptor elements highlighted the possibility that the bioregulatory effects of melatonin in anthozoan reproduction may be mediated by interactions with membrane receptors, as in higher vertebrates. Another intriguing finding of the present study pertains to the prevalence of melatonin in centralized nervous structures. This pattern may be of great significance given that it 1) identifies an ancestral association between melatonin and key neuronal components and 2) potentially implies that certain effects of melatonin in basal species may be spread widely by regionalized nerve centers. PMID:23300630

Origin of anti-tumor activity of the cysteine-containing GO peptides and further optimization of their cytotoxic properties

Science.gov (United States)

Tyuryaeva, Irina I.; Lyublinskaya, Olga G.; Podkorytov, Ivan S.; Skrynnikov, Nikolai R.

2017-01-01

Antitumor GO peptides have been designed as dimerization inhibitors of prominent oncoprotein mucin 1. In this study we demonstrate that activity of GO peptides is independent of the level of cellular expression of mucin 1. Furthermore, these peptides prove to be broadly cytotoxic, causing cell death also in normal cells such as dermal fibroblasts and endometrial mesenchymal stem cells. To explore molecular mechanism of their cytotoxicity, we have designed and tested a number of new peptide sequences containing the key CxC or CxxC motifs. Of note, these sequences bear no similarity to mucin 1 except that they also contain a pair of proximal cysteines. Several of the new peptides turned out to be significantly more potent than their GO prototypes. The results suggest that cytotoxicity of these peptides stems from their (moderate) activity as disulfide oxidoreductases. It is expected that such peptides, which we have termed DO peptides, are involved in disulfide-dithiol exchange reaction, resulting in formation of adventitious disulfide bridges in cell proteins. In turn, this leads to a partial loss of protein function and rapid onset of apoptosis. We anticipate that coupling DO sequences with tumor-homing transduction domains can create a potentially valuable new class of tumoricidal peptides.

The quest for significance model of radicalization: implications for the management of terrorist detainees.

Science.gov (United States)

Dugas, Michelle; Kruglanski, Arie W

2014-01-01

Radicalization and its culmination in terrorism represent a grave threat to the security and stability of the world. A related challenge is effective management of extremists who are detained in prison facilities. The major aim of this article is to review the significance quest model of radicalization and its implications for management of terrorist detainees. First, we review the significance quest model, which elaborates on the roles of motivation, ideology, and social processes in radicalization. Secondly, we explore the implications of the model in relation to the risks of prison radicalization. Finally, we analyze the model's implications for deradicalization strategies and review preliminary evidence for the effectiveness of a rehabilitation program targeting components of the significance quest. Based on this evidence, we argue that the psychology of radicalization provides compelling reason for the inclusion of deradicalization efforts as an essential component of the management of terrorist detainees. Copyright © 2014 John Wiley & Sons, Ltd.

Genome-wide identification of significant aberrations in cancer genome.

Science.gov (United States)

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

2012-07-27

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

Experimental study on the effect of ingested lead shot on Estuarine crocodiles: significance for Finniss River field studies

International Nuclear Information System (INIS)

Hammerton, K.M.

2002-01-01

Lead has long been recognised as a cumulative metabolic poison in humans, domestic animals and wildlife. Because of the many industrial activities that have brought about its widespread distribution, lead is ubiquitous in the environment. For example, uranium mining at the Rum Jungle site on the Finniss River, Northern Territory, resulted in contamination of river sediments with lead. Today, lead levels remain at about 250 mg kg-1 of wet river sediment within the immediate vicinity of the mine. Another potential source of lead poisoning in wildlife is the use of lead gunshot for hunting. Mortality in wild waterfowl caused by the ingestion of spent lead shot has been recognised in North America and Europe for over a century. An experimental study was undertaken to assess the above hypothesis on the effects of lead in the environs of crocodiles. The specific effects of lead intoxication arise mainly from the interaction of lead with the enzymatic processes in the haem biosynthetic pathway. One of these enzymes, δ-aminolevulinic acid dehydratase (ALAD), catalyses the condensation of two molecules of aminolevulinic acid to produce the pyrrole, porphobilinogen, the building block of the haem molecule. ALAD is a metalloenzyme requiring zinc for activity and is inhibited by lead displacing the essential zinc. This inhibition of ALAD by lead has been used as a specific biomarker for lead poisoning in fish, birds and mammals. An assay system was developed for the measurement of ALAD activity in crocodilian blood. It was found that ALAD was inhibited by up to 90% during the first week after exposure of the crocodiles to lead shot. There was an inverse correlation between BPb and ALAD activity throughout the 42 week experimental period. BPb concentrations greater than 100 mg dL-1 produced significant inhibition of ALAD. The results indicated that ALAD inhibition could be used as a specific biomarker of lead toxicity in crocodiles

Significant competitive advantage conferred by meiosis and syngamy in the yeast Saccharomyces cerevisiae.

Science.gov (United States)

Birdsell, J; Wills, C

1996-01-01

The presumed advantages of genetic recombinations are difficult to demonstrate directly. To investigate the effects of recombination and background heterozygosity on competitive ability, we have performed serial-transfer competition experiments between isogenic sexual and asexual strains of the yeast Saccharomyces cerevisiae. The members of these diploid pairs of strains differed only in being heterozygous (sexual) or homozygous (asexual) at the mating type or MAT locus. Competing pairs had either a completely homozygous or a heterozygous genetic background, the latter being heterozygous at many different loci throughout the genome. A round of meiotic recombination (automixis) conferred a large and statistically significant enhancement of competitive ability on sexual strains with a heterozygous genetic background. By contrast, in homozygous background competitions, meiosis decreased the sexual strains' initial relative competitive ability. In all cases, however, the sexual strains outcompeted their isogenic asexual counterparts, whether meiotic recombination had occurred or not. In some genetic backgrounds, this was due in part to an overdominance effect on competitive advantage of heterozygosity at the MAT locus. The advantage of the sexual strains also increased significantly during the course of the homozygous background competitions, particularly when meiosis had occurred. This latter effect either did not occur or was very weak in heterozygous background competitions. Overall, sexual strains with heterozygous genetic backgrounds had a significantly higher initial relative competitive ability than those with homozygous backgrounds. The advantage of mating type heterozygosity in this organism extends far beyond the ability to recombine meiotically. PMID:8570658

Unified Health Gamification can significantly improve well-being in corporate environments.

Science.gov (United States)

Shahrestani, Arash; Van Gorp, Pieter; Le Blanc, Pascale; Greidanus, Fabrizio; de Groot, Kristel; Leermakers, Jelle

2017-07-01

There is a multitude of mHealth applications that aim to solve societal health problems by stimulating specific types of physical activities via gamification. However, physical health activities cover just one of the three World Health Organization (WHO) dimensions of health. This paper introduces the novel notion of Unified Health Gamification (UHG), which covers besides physical health also social and cognitive health and well-being. Instead of rewarding activities in the three WHO dimensions using different mHealth competitions, UHG combines the scores for such activities on unified leaderboards and lets people interact in social circles beyond personal interests. This approach is promising in corporate environments since UHG can connect the employees with intrinsic motivation for physical health with those who have quite different interests. In order to evaluate this approach, we realized an app prototype and we evaluated it in two corporate pilot studies. In total, eighteen pilot users participated voluntarily for six weeks. Half of the participants were recruited from an occupational health setting and the other half from a treatment setting. Our results suggest that the UHG principles are worth more investigation: various positive health effects were found based on a validated survey. The mean mental health improved significantly at one pilot location and at the level of individual pilot participants, multiple other effects were found to be significant: among others, significant mental health improvements were found for 28% of the participants. Most participants intended to use the app beyond the pilot, especially if it would be further developed.

Significance of librarian’s self-concept in the communication process

Directory of Open Access Journals (Sweden)

Darja Kobal-Grum

2004-01-01

Full Text Available The article deals with the significance of the librarian’s self-concept in the communication process. First, it underlines the meaning of reference interviews, and second, it focuses on other micro and macro aspects of communication. The analysis shows that the librarian’s self-concept is hierarchically organised, structured, and therefore it consists of different areas. Each area equally contributes to the development and preservation of the appropriate librarian’s self-concept; although some areas have more direct influence than others. To attain a high self-concept, it is of fundamental importance, that the librarian develops all self-concept areas, from individual ones to social ones. It was found that a structured and positive specialist’s self-concept is highly significant for the contribution of effective reference interviews, and finally, the article offers some directions for a successful development of the communication process.

75 FR 27643 - Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NSR): Aggregation

Science.gov (United States)

2010-05-18

... once the delay is no longer necessary. ADDRESSES: Docket: The final rule, the petition for...): Aggregation AGENCY: Environmental Protection Agency (EPA). ACTION: Delay of effective date. SUMMARY: EPA is delaying the effective date of the final rule titled ``Prevention of Significant Deterioration (PSD) and...

Phenolic constituents of Pulicaria undulata (L. C.A. Mey. sub sp. undulata (Asteraceae: Antioxidant protective effects and chemosystematic significances

Directory of Open Access Journals (Sweden)

Sameh R. Hussein

2017-04-01

Full Text Available One new naturally isoflavone compound, 5,7,2′,3′,4′ penta hydroxyl isoflavone-4′-O-β-glucopyranoside (1 was isolated from the aqueous methanol extract (AME of Pulicaria undulata subsp. undulata, together with seven known compounds: kaempferol (2, kaempferol 3-O-β-glucoside (3, quercetin (4, quercetin 3-O-β-glucoside (5, quercetin 3-O-β-galactoside (6, quercetin 3,7-di OCH3 (7, and caffeic acid (8. Their structures were established through chemical (acid hydrolysis and spectral analysis (UV, NMR, and ESIM. The AME and some isolated compounds were evaluated as protective agents. Free radical scavenging using a microscaled 2,2-diphenyl-1-picrylhydrazyl assay was used to assess the direct antioxidant properties that were evaluated by the ability to protect murine Hepa1c1c7 liver cells against damage induced by the organic peroxide tert-butyl hydroperoxide. The neutral red uptake assay (NRU was used to record the activity. Results of the 2,2-diphenyl-1-picrylhydrazyl assay recorded differential scavenging properties in ascending order: 5,7,2′,3′,4′ penta hydroxyl isoflavone-4′-O-β-glucopyranoside>quercetin>quercetin 3-O-galactoside>caffeic acid>quercetin 3,7-di-OCH3>kaempferol with 50% inhibitory concentrations of 3.9 μM, 7.5 μM, 11.4 μM, 12.2 μM, 78.1 μM, and 252.3 μM, respectively. The antioxidative potential reveals the potency of AME, quercetin, and quercetin 3,7-di-OCH3. The latter compound showed full protection at 100 μM (33 μg/mL against the induced toxicant effect where the 50% effective concentration was calculated as 33.6±1.7 μM (11.1 μg/mL. In addition to quercetin, which was extensively shown previously as a cytoprotective agent, AME was less potent; it was capable of protecting 75% at 100 μg/mL with 50% effective concentration of 92.3±4 μg/mL. Moreover, the isolated flavonoids were found to be significantly chemosystematic markers.

The effects of radiation on the diseases of aging in experimental animals: gerontological significance

International Nuclear Information System (INIS)

Hollander, C.F.; Zwieten, M.J. van; Broerse, J.J.

1979-01-01

A study of the effect of different types and doses of ionizing radiation on the induction of mammary tumours in rats and the role of ovarian hormones in tumour indication is reported. The occurrence of other diseases in the irradiated animals is also studied and compared to those occurring in non-irradiated controls. (Auth.)

Omega-3 fatty acid therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation, however, did not significantly improve insulin sensitivity in patients with hypertriglyceridemia.

Science.gov (United States)

Oh, Pyung Chun; Koh, Kwang Kon; Sakuma, Ichiro; Lim, Soo; Lee, Yonghee; Lee, Seungik; Lee, Kyounghoon; Han, Seung Hwan; Shin, Eak Kyun

2014-10-20

Experimental studies demonstrate that higher intake of omega-3 fatty acids (n-3 FA) improves insulin sensitivity, however, we reported that n-3 FA 2g therapy, most commonly used dosage did not significantly improve insulin sensitivity despite reducing triglycerides by 21% in patients. Therefore, we investigated the effects of different dosages of n-3 FA in patients with hypertriglyceridemia. This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Forty-four patients (about 18 had metabolic syndrome/type 2 diabetes mellitus) in each group were given placebo, n-3 FA 1 (O1), 2 (O2), or 4 g (O4), respectively daily for 2 months. n-3 FA therapy dose-dependently and significantly decreased triglycerides and triglycerides/HDL cholesterol and improved flow-mediated dilation, compared with placebo (by ANOVA). However, each n-3 FA therapy did not significantly decrease high-sensitivity C-reactive protein and fibrinogen, compared with placebo. O1 significantly increased insulin levels and decreased insulin sensitivity (determined by QUICKI) and O2 significantly decreased plasma adiponectin levels relative to baseline measurements. Of note, when compared with placebo, each n-3 FA therapy did not significantly change insulin, glucose, adiponectin, glycated hemoglobin levels and insulin sensitivity (by ANOVA). We observed similar results in a subgroup of patients with the metabolic syndrome. n-3 FA therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation. Nonetheless, n-3 FA therapy did not significantly improve acute-phase reactants and insulin sensitivity in patients with hypertriglyceridemia, regardless of dosages. Copyright © 2014. Published by Elsevier Ireland Ltd.

A significantly joint effect between arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of urothelial carcinoma

International Nuclear Information System (INIS)

Wang, Y.-H.; Yeh, S.-D.; Shen, K.-H.; Shen, Cheng-Huang; Juang, G.-D.; Hsu, L.-I; Chiou, H.-Y.; Chen, C.-J.

2009-01-01

Cigarette smoking, arsenic and occupational exposures are well-known risk factors for the development of urothelial carcinoma (UC). Therefore, the aim of this study is to investigate whether the effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures on risk of UC could be modified by genetic polymorphisms of cytochrome P450 2E1 and glutathione S-transferase omega. A hospital-based case-control study consisted of 520 histologically confirmed UC cases, and 520 age- and gender-matched cancer-free controls were carried out from September 1998 to December 2007. Genotyping of CYP2E1, GSTO1 and GSTO2 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Subjects with both of cigarette smoking and alcohol consumption have a significantly increased UC risk (odds ratio [OR] = 2.9; 95% confidence interval [CI] = 1.9-4.4). Significantly increased UC risks of 1.5 and 1.9 were found for study subjects with high arsenic exposure and those who have been exposed to two or more occupational exposures, respectively. A significantly increased UC risk of 3.9 was observed in study subjects with H2-H2 diplotype of GSTO1 and GSTO2. The significantly highest UC risk of 9.0 was found for those with all environmental risk factors of cigarette smoking, alcohol consumption, arsenic and occupational exposures and two or more risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2. Our findings suggest that a significantly joint effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of UC was found.

Prognostic significance of macrophage invasion in hilar cholangiocarcinoma

International Nuclear Information System (INIS)

Atanasov, Georgi; Hau, Hans-Michael; Dietel, Corinna; Benzing, Christian; Krenzien, Felix; Brandl, Andreas; Wiltberger, Georg; Matia, Ivan; Prager, Isabel; Schierle, Katrin; Robson, Simon C.; Reutzel-Selke, Anja; Pratschke, Johann; Schmelzle, Moritz; Jonas, Sven

2015-01-01

Tumor-associated macrophages (TAMs) promote tumor progression and have an effect on survival in human cancer. However, little is known regarding their influence on tumor progression and prognosis in human hilar cholangiocarcinoma. We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution and localization of TAMs, as defined by expression of CD68. Abundance of TAMs was correlated with clinicopathologic characteristics, tumor recurrence and patients’ survival. Statistical analysis was performed using SPSS software. Patients with high density of TAMs in tumor invasive front (TIF) showed significantly higher local and overall tumor recurrence (both ρ < 0.05). Furthermore, high density of TAMs was associated with decreased overall (one-year 83.6 % vs. 75.1 %; three-year 61.3 % vs. 42.4 %; both ρ < 0.05) and recurrence-free survival (one-year 93.9 % vs. 57.4 %; three-year 59.8 % vs. 26.2 %; both ρ < 0.05). TAMs in TIF and tumor recurrence, were confirmed as the only independent prognostic variables in the multivariate survival analysis (all ρ < 0.05). Overall survival and recurrence free survival of patients with hilar cholangiocarcinoma significantly improved in patients with low levels of TAMs in the area of TIF, when compared to those with a high density of TAMs. These observations suggest their utilization as valuable prognostic markers in routine histopathologic evaluation, and might indicate future therapeutic approaches by targeting TAMs

Graphene oxide significantly inhibits cell growth at sublethal concentrations by causing extracellular iron deficiency.

Science.gov (United States)

Yu, Qilin; Zhang, Bing; Li, Jianrong; Du, Tingting; Yi, Xiao; Li, Mingchun; Chen, Wei; Alvarez, Pedro J J

Graphene oxide (GO)-based materials are increasingly being used in medical materials and consumer products. However, their sublethal effects on biological systems are poorly understood. Here, we report that GO (at 10 to 160 mg/L) induced significant inhibitory effects on the growth of different unicellular organisms, including eukaryotes (i.e. Saccharomyces cerevisiae, Candida albicans, and Komagataella pastoris) and prokaryotes (Pseudomonas fluorescens). Growth inhibition could not be explained by commonly reported cytotoxicity mechanisms such as plasma membrane damage or oxidative stress. Based on transcriptomic analysis and measurement of extra- and intracellular iron concentrations, we show that the inhibitory effect of GO was mainly attributable to iron deficiency caused by binding to the O-functional groups of GO, which sequestered iron and disrupted iron-related physiological and metabolic processes. This inhibitory mechanism was corroborated with supplementary experiments, where adding bathophenanthroline disulfonate-an iron chelating agent-to the culture medium exerted similar inhibition, whereas removing surface O-functional groups of GO decreased iron sequestration and significantly alleviated the inhibitory effect. These findings highlight a potential indirect detrimental effect of nanomaterials (i.e. scavenging of critical nutrients), and encourage research on potential biomedical applications of GO-based materials to sequester iron and enhance treatment of iron-dependent diseases such as cancer and some pathogenic infections.

Ethanol-drug absorption interaction: potential for a significant effect on the plasma pharmacokinetics of ethanol vulnerable formulations.

Science.gov (United States)

Lennernäs, Hans

2009-01-01

Generally, gastric emptying of a drug to the small intestine is controlled by gastric motor activity and is the main factor affecting the onset of absorption. Accordingly, the emptying rate from the stomach is mainly affected by the digestive state, the properties of the pharmaceutical formulation and the effect of drugs, posture and circadian rhythm. Variability in the gastric emptying of drugs is reflected in variability in the absorption rate and the shape of the plasma pharmacokinetic profile. When ethanol interacts with an oral controlled release product, such that the mechanism controlling drug release is impaired, the delivery of the dissolved dose into the small intestine and the consequent absorption may result in dangerously high plasma concentrations. For example, the maximal plasma concentration of hydromorphone has individually been shown to be increased as much as 16 times through in vivo testing as a result of this specific pharmacokinetic ethanol-drug formulation interaction. Thus, a pharmacokinetic ethanol-drug interaction is a very serious safety concern when substantially the entire dose from a controlled release product is rapidly emptied into the small intestine (dose dumping), having been largely dissolved in a strong alcoholic beverage in the stomach during a sufficient lag-time in gastric emptying. Based on the literature, a two hour time frame for screening the in vitro dissolution profile of a controlled release product in ethanol concentrations of up to 40% is strongly supported and may be considered as the absolute minimum standard. It is also evident that the dilution, absorption and metabolism of ethanol in the stomach are processes with a minor effect on the local ethanol concentration and that ethanol exposure will be highly dependent on the volume and ethanol concentration of the fluid ingested, together with the rate of intake and gastric emptying. When and in which patients a clinically significant dose dumping will happen is

Macrophage and NK-mediated killing of precursor-B acute lymphoblastic leukemia cells targeted with a-fucosylated anti-CD19 humanized antibodies.

Science.gov (United States)

Matlawska-Wasowska, K; Ward, E; Stevens, S; Wang, Y; Herbst, R; Winter, S S; Wilson, B S

2013-06-01

This work reports the tumoricidal effects of a novel investigational humanized anti-CD19 monoclonal antibody (Medi-551). An a-fucosylated antibody with increased affinity for human FcγRIIIA, Medi-551 is shown to mediate both antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Medi-551/CD19 complexes internalize slowly (>5 h) and thus remain accessible to effector cells for prolonged periods. We evaluated in vitro ADCC and ADCP activities of primary human natural killer (NK) cells and macrophages against precursor-B (pre-B) acute lymphoblastic leukemia (ALL) cell lines and pediatric patient blasts. Fluorescent imaging studies document immunological synapses formed between anti-CD19-bound target leukemia cells and effector cells and capture the kinetics of both NK-mediated killing and macrophage phagocytosis. Genetic polymorphisms in FcγRIIIA-158F/V modulate in vitro activities of effector cells, with FcγRIIIA-158V homozygotes or heterozygotes showing the strongest activity. Medi-551 treatment of severe combined immunodeficiency (SCID) mice engrafted with human pre-B cells led to prolonged animal survival and markedly reduced disease burden in blood, liver and bone marrow. These data show that anti-CD19 antibodies effectively recruit immune cells to pre-B ALL cells and support a move forward to early phase trials in this disease.

Affective picture modulation: valence, arousal, attention allocation and motivational significance.

Science.gov (United States)

Leite, Jorge; Carvalho, Sandra; Galdo-Alvarez, Santiago; Alves, Jorge; Sampaio, Adriana; Gonçalves, Oscar F

2012-03-01

The present study analyses the modulatory effects of affective pictures in the early posterior negativity (EPN), the late positive potential (LPP) and the human startle response on both the peripheral (eye blink EMG) and central neurophysiological levels (Probe P3), during passive affective pictures viewing. The affective pictures categories were balanced in terms of valence (pleasant; unpleasant) and arousal (high; low). The data shows that EPN may be sensitive to specific stimulus characteristics (affective relevant pictures versus neutral pictures) associated with early stages of attentional processing. In later stages, the heightened attentional resource allocation as well as the motivated significance of the affective stimuli was found to elicit enhanced amplitudes of slow wave processes thought to be related to enhanced encoding, namely LPP,. Although pleasant low arousing pictures were effective in engaging the resources involved in the slow wave processes, the highly arousing affective stimuli (pleasant and unpleasant) were found to produce the largest enhancement of the LPP, suggesting that high arousing stimuli may are associated with increased motivational significance. Additionally the response to high arousing stimuli may be suggestive of increased motivational attention, given the heightened attentional allocation, as expressed in the P3 probe, especially for the pleasant pictures. The hedonic valence may then serve as a mediator of the attentional inhibition to the affective priming, potentiating or inhibiting a shift towards defensive activation, as measured by the startle reflex. Copyright © 2011 Elsevier B.V. All rights reserved.

Biological significance of sperm whale responses to sonar: Comparison with anti-predator responses

NARCIS (Netherlands)

Curé, C.; Isojunno, S.; Visser, F.; Wensveen, P.J.; Sivle, L.D.; Kvadsheim, P.H.; Lam, F.A.; Miller, P.J.O.

2016-01-01

A key issue when investigating effects of anthropogenic noise on cetacean behavior is to identify the biological significance of the responses. Predator presence can be considered a natural high-level disturbance stimulus to which prey animals have evolved adaptive response strategies to reduce

No significant effect of transcranial direct current stimulation (tDCS) found on simple motor reaction time comparing 15 different simulation protocols.

Science.gov (United States)

Horvath, Jared Cooney; Carter, Olivia; Forte, Jason D

2016-10-01

Research exploring the behavioral impact of transcranial direct current stimulation (tDCS) over M1 has produced homogenous results. The most common explanations to address this homogeneity concerns the differential impact of varied tDCS parameters (such as stimulation intensity or electrode montage). To explore this, we systematically examined the effects of 15 different tDCS protocols on a well-elucidated neurobehavioral system: simple visual motor reaction time (smRT). For the initial phase of this study, 150 healthy participants were randomly assigned to one of 5 experimental groups (2mA anodal, 2mA cathodal, 1mA anodal, 1mA cathodal, or sham) across 3 different conditions (orbitofrontal, bilateral, or extracephalic reference electrode location). The active electrode was always placed over M1 and tDCS lasted for 20min. Starting ~5min prior to stimulation and running continuously for ~30min, participants were repeatedly presented with a visual cue centered on a computer monitor and asked to press a response button as quickly as possible at stimulus onset (stimuli number: 100 pre-, 400 during-, and 100-post stimulation - interstimulus interval: 1-3s). Ex-gaussian distribution curves, miss, and error rates were determined for each normalized batch of 100 RTs and compared using a two-way ANOVA. As the largest group differences were seen with 2mA anodal (compared to sham) stimulation using an orbitofrontal montage, an additional 60 healthy participants were recruited to further test for significance in this condition. No significant impact of tDCS was seen on any parameter of smRT distribution, error rate, or miss rate, regardless of polarity, stimulation intensity, electrode montage, or stimulation-to-task relationship. Our results suggest that tDCS over M1 might not have a predictable or reliable effect on short duration smRT. Our results raise interesting questions regarding the mechanisms by which tDCS might modulate more complex motor behaviors. Additional

Cultural significance of primary teeth for caregivers in Northeast Brazil.

Science.gov (United States)

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

2008-04-01

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

HVDC Transmission an Outlook and Significance for Pakistani Power Sector

Science.gov (United States)

Ahmad, Muhammad; Wang, Zhixin; Wang, Jinjian; Baloach, Mazhar H.; Longxin, Bao; Hua, Qing

2018-04-01

Recently a paradigm shift in the power sector is observed, i.e., countries across the globe have deviated their attention to distributed generation rather than conventional centralized bulk generation. Owing to the above narrative, distributed energy resources e.g., wind and PV have gained the adequate attention of governments and researchers courtesy to their eco-friendly nature. On the contrary, the increased infiltration of distributed generation to the power system has introduced many technical and economical glitches such as long-distance transmission, transmission lines efficiency, control capability and cost etc. To mitigate these complications, the utility of high voltage direct current (HVDC) transmission has emerged as a possible solution. In this context, this paper includes a brief discussion on the fundamentals HVDC and its significance in Pakistani power sector. Furthermore, the potential of distributed energy resources for Pakistan is also the subject matter of this paper, so that significance of HVDC transmission can effectively be deliberated.

Gadolinium neutron capture therapy for brain tumors. Biological aspects

International Nuclear Information System (INIS)

Takagaki, Masao; Oda, Yoshifumi; Matsumoto, Masato; Kikuchi, Haruhiko; Kobayashi, Tooru; Kanda, Keiji; Ujeno, Yowri.

1994-01-01

This study investigated the tumoricidal effect of gadolinium neutron capture therapy (Gd-NCT) in in vitro and in vivo systems using Gd-DTPA. In in vitro study, a certain amount of Gd-DTPA, yielding 5000 ppm Gd-n, was added to human glioma cells, T98G, upon which thermal neutrons were exposed. After irradiation, the cells were incubated and the colonies were counted 10 days later. In in vivo study, Fisher-344 rats with experimentally induced gliosarcoma cells (9L) were exposed to thermal neutrons at a fluence rate of 3E+9/s for 1 h immediately after iv injection of Gd-DTPA. Two weeks after irradiation, brain samples were histologically examined. Tumor clearance of Gd-DTPA was also determined. In vitro analysis showed that a 1% survival level was obtained at 3.75E+12 (n/cm 2 ) for the Gd (+) medium and 2.50E+13 (n/cm 2 ) for the Gd (-) medium. In in vivo analysis, the concentration of Gd in 9L-rat brain tumor after iv injection of 0.2 mg/kg Gd-DTPA was found to be less than 100 ppm, but Gd-NCT on 9L-rat brain tumor administered with a ten-fold dose showed a substantial killing effect on tumor without serious injury to the normal brain structure. The killing effect of Gd-NCT was confirmed in in vitro and in vivo systems. (N.K.)

Anatomic and functional leg-length inequality: A review and recommendation for clinical decision-making. Part I, anatomic leg-length inequality: prevalence, magnitude, effects and clinical significance

Directory of Open Access Journals (Sweden)

Knutson Gary A

2005-07-01

Full Text Available Abstract Background Leg-length inequality is most often divided into two groups: anatomic and functional. Part I of this review analyses data collected on anatomic leg-length inequality relative to prevalence, magnitude, effects and clinical significance. Part II examines the functional "short leg" including anatomic-functional relationships, and provides an outline for clinical decision-making. Methods Online database – Medline, CINAHL and MANTIS – and library searches for the time frame of 1970–2005 were done using the term "leg-length inequality". Results and Discussion Using data on leg-length inequality obtained by accurate and reliable x-ray methods, the prevalence of anatomic inequality was found to be 90%, the mean magnitude of anatomic inequality was 5.2 mm (SD 4.1. The evidence suggests that, for most people, anatomic leg-length inequality does not appear to be clinically significant until the magnitude reaches ~ 20 mm (~3/4". Conclusion Anatomic leg-length inequality is near universal, but the average magnitude is small and not likely to be clinically significant.

Diagnostic significance of hepatic venography and retrograde portography in portal hypertension

Energy Technology Data Exchange (ETDEWEB)

Fukunaga, Masaki

1987-07-01

In this series, we studied about diagnostic significance of hepatic venography and retrograde portography in portal hypertension by using stepwise discriminant analysis. The accuracy rate of the discrimination was 95 % in liver cirrhosis (LC), 86 % in B' type LC, 83 % in primary biliary cirrhosis (PBC) and 57 % in idiopathic portal hypertension (IPH). The difficulty in differential diagnosis of IPH from PBC was due to similarity of hepatic vascular changes in both diseases. Next we studied about the relationship between venographic findings and the causes of LC. The size of regenerated nodule in alcoholic LC was significantly smaller than the others, so venographic findings were different from others. It was concluded that hepatic venography was useful examination for differential diagnosis in portal hypertension, and was effective for considering about the causes of LC.

Diagnostic significance of hepatic venography and retrograde portography in portal hypertension

International Nuclear Information System (INIS)

Fukunaga, Masaki

1987-01-01

In this series, we studied about diagnostic significance of hepatic venography and retrograde portography in portal hypertension by using stepwise discriminant analysis. The accuracy rate of the discrimination was 95 % in liver cirrhosis (LC), 86 % in B' type LC, 83 % in primary biliary cirrhosis (PBC) and 57 % in idiopathic portal hypertension (IPH). The difficulty in differential diagnosis of IPH from PBC was due to similarity of hepatic vascular changes in both diseases. Next we studied about the relationship between venographic findings and the causes of LC. The size of regenerated nodule in alcoholic LC was significantly smaller than the others, so venographic findings were different from others. It was concluded that hepatic venography was useful examination for differential diagnosis in portal hypertension, and was effective for considering about the causes of LC. (author)

Significant components of service brand equity in healthcare sector.

Science.gov (United States)

Chahal, Hardeep; Bala, Madhu

2012-01-01

The purpose of the study is to examine three significant components of service brand equity--i.e. perceived service quality, brand loyalty, and brand image--and analyze relationships among the components of brand equity and also their relationship with brand equity, which is still to be theorized and developed in the healthcare literature. Effective responses were received from 206 respondents, selected conveniently from the localities of Jammu city. After scale item analysis, the data were analyzed using factor analysis, correlations, t-tests, multiple regression analysis and path modeling using SEM. The findings of the study support that service brand equity in the healthcare sector is greatly influenced by brand loyalty and perceived quality. However, brand image has an indirect effect on service brand equity through brand loyalty (mediating variable). The research can be criticized on the ground that data were selected conveniently from respondents residing in the city of Jammu, India. But at the same time the respondents were appropriate for the study as they have adequate knowledge about the hospitals, and were associated with the selected hospital for more than four years. Furthermore, the validity and reliability of the data are strong enough to take care of the limitations of the convenience sampling selection method. The study has unique value addition to the service marketing vis-à-vis healthcare literature, from both theoretical and managerial perspectives. The study establishes a direct and significant relationship between service brand equity and its two components, i.e. perceived service quality and brand loyalty in the healthcare sector. It also provides directions to healthcare service providers in creating, enhancing, and maintaining service brand equity through service quality and brand loyalty, to sustain competitive advantage.

The expression and clinical significance of HDGF in osteosarcoma

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Chen Z

2015-09-01

Full Text Available Zhiguo Chen,1 Shenghai Qiu,2 Xiaofei Lu31Department of Orthopedics, Linyi People’s Hospital, Linyi City, Shandong Province, People’s Republic of China; 2Department of Orthopedics, People’s Hospital of Taiyuan, Taiyuan City, Shanxi Province, People’s Republic of China; 3Department of General Surgery, Jinan Central Hospital affiliated to Shandong University, Jinan City, Shandong Province, People’s Republic of ChinaAim: To investigate the expression of hepatoma-derived growth factor (HDGF in osteosarcoma (OS and the correlation with clinicopathologic factors, prognosis, and tumor progression.Method: HDGF expression in OS tissues was detected by immunohistochemistry. The correlation between HDGF and clinicopathologic factors was analyzed by chi-square test, and the association between HDGF expression and the overall survival rates was evaluated by univariate analysis using Kaplan–Meier method. HDGF concentration in cell medium or cell lysates was detected by enzyme-linked immunosorbent assay method. The effect of extrinsic and intrinsic HDGF on OS cell proliferation was detected by MTT assay after recombinant HDGF stimulation or HDGF knockdown, respectively.Results: Proportion of HDGF high expression was 18.69% (20/107 in OS. HDGF high expression was significantly associated with larger tumor size (P=0.004. With experiments in vitro, we demonstrated that human recombinant HDGF could activate AKT and MAPK signaling pathway, resulting in OS cell proliferation. By knocking down HDGF expression, we proved that intrinsic HDGF was required in OS proliferation.Conclusion: High HDGF expression was significantly associated with larger OS tumor size and could promote OS cell proliferation, indicating that HDGF could be an effective biomarker and a potential drug target in OS treatment.Keywords: hepatoma-derived growth factor, osteosarcoma, tumor size, proliferation, overall survival rate

Recent Literature on Whether Statistical Significance Tests Should or Should Not Be Banned.

Science.gov (United States)

Deegear, James

This paper summarizes the literature regarding statistical significant testing with an emphasis on recent literature in various discipline and literature exploring why researchers have demonstrably failed to be influenced by the American Psychological Association publication manual's encouragement to report effect sizes. Also considered are…

The development and significance of vesicular-arbuscular mycorrhizas as influenced by agricultural practices

NARCIS (Netherlands)

Ruissen, M.A.

1982-01-01

The development and significance of vesicular- arbuscular mycorrhizas (VAM) in wheat and potatoes have been studied in relation to various farming systems and agricultural practices. The effects of farming systems on VAM have been observed on three neighbouring experimental farms in the vicinity of

Significance and occurrence of fumonisins from Aspergillus niger

DEFF Research Database (Denmark)

Mogensen, Jesper Mølgaard

Fumonisins is a well-studied group of mycotoxins, mainly produced in maize by Fusarium species. However with the recent discovery of a fumonisin production by Aspergillus niger, other food commodities are at risk, since A. niger is a ubiquitous contaminant of many food and feed products....... The objective of this thesis was to determine the significance and occurrence of fumonisins from Aspergillus niger in food, the frequency of fumonisin production in A. niger isolates, as well as studies of the effect of physiological factors affecting fumonisin production. Major findings in this context have...... been the ocumentation of the production of fumonisins in raisins and peanuts, and occurrence of A. niger derived fumonisins in retail wine and raisins. Physiological investigations have demonstrated that fumonisin production in A. niger occurs at temperatures between 20-37 °C. Three water activity...

Codon Deviation Coefficient: a novel measure for estimating codon usage bias and its statistical significance

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Zhang Zhang

2012-03-01

Full Text Available Abstract Background Genetic mutation, selective pressure for translational efficiency and accuracy, level of gene expression, and protein function through natural selection are all believed to lead to codon usage bias (CUB. Therefore, informative measurement of CUB is of fundamental importance to making inferences regarding gene function and genome evolution. However, extant measures of CUB have not fully accounted for the quantitative effect of background nucleotide composition and have not statistically evaluated the significance of CUB in sequence analysis. Results Here we propose a novel measure--Codon Deviation Coefficient (CDC--that provides an informative measurement of CUB and its statistical significance without requiring any prior knowledge. Unlike previous measures, CDC estimates CUB by accounting for background nucleotide compositions tailored to codon positions and adopts the bootstrapping to assess the statistical significance of CUB for any given sequence. We evaluate CDC by examining its effectiveness on simulated sequences and empirical data and show that CDC outperforms extant measures by achieving a more informative estimation of CUB and its statistical significance. Conclusions As validated by both simulated and empirical data, CDC provides a highly informative quantification of CUB and its statistical significance, useful for determining comparative magnitudes and patterns of biased codon usage for genes or genomes with diverse sequence compositions.

Determination of significance in Ecological Impact Assessment: Past change, current practice and future improvements

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Briggs, Sam; Hudson, Malcolm D., E-mail: mdh@soton.ac.uk

2013-01-15

Ecological Impact Assessment (EcIA) is an important tool for conservation and achieving sustainable development. 'Significant' impacts are those which disturb or alter the environment to a measurable degree. Significance is a crucial part of EcIA, our understanding of the concept in practice is vital if it is to be effective as a tool. This study employed three methods to assess how the determination of significance has changed through time, what current practice is, and what would lead to future improvements. Three data streams were collected: interviews with expert stakeholders, a review of 30 Environmental Statements and a broad-scale survey of the United Kingdom Institute of Ecology and Environmental Management (IEEM) members. The approach taken in the determination of significance has become more standardised and subjectivity has become constrained through a transparent framework. This has largely been driven by a set of guidelines produced by IEEM in 2006. The significance of impacts is now more clearly justified and the accuracy with which it is determined has improved. However, there are limitations to accuracy and effectiveness of the determination of significance. These are the quality of baseline survey data, our scientific understanding of ecological processes and the lack of monitoring and feedback of results. These in turn are restricted by the limited resources available in consultancies. The most notable recommendations for future practice are the implementation of monitoring and the publication of feedback, the creation of a central database for baseline survey data and the streamlining of guidance. - Highlights: Black-Right-Pointing-Pointer The assessment of significance has changed markedly through time. Black-Right-Pointing-Pointer The IEEM guidelines have driven a standardisation of practice. Black-Right-Pointing-Pointer Currently limited by quality of baseline data and scientific understanding. Black-Right-Pointing-Pointer Monitoring

Death, Catastrophe, and the Significance of Tragedy

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Jennifer Ballengee

2014-05-01

Full Text Available This NANO note will examine the tension between representation, memorial, and the catastrophe of death that emerges in the space of tragedy, as the problem arises in two quite different works: Oedipus at Colonus, a fairly typical fifth-century Greek tragedy, and Falling Man, Don DeLillo’s novel that, in its attempt to address the events of 9/11, reflects in form and subject matter many of Aristotle’s terms of tragic representation. It is not the intent of this note to engage with the recent proliferation of work in “performance theory.” Rather than being concerned with an imagined exchange between audience and actor, this study examines how the supplementary relationship of gesture and speech in tragedy disrupts the public/private distinction, and how this articulation effects and enables the public memorialization of death. Thus, this paper will consider the representation of death as an event whose catastrophic, and somewhat mysterious, collision of the public and the private lends it its tragic significance.

Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF.

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Yamamoto, Nobuto; Suyama, Hirofumi; Nakazato, Hiroaki; Yamamoto, Nobuyuki; Koga, Yoshihiko

2008-07-01

Serum vitamin D binding protein (Gc protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of colorectal cancer patients was lost or reduced because Gc protein is deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Deglycosylated Gc protein cannot be converted to MAF, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent macrophage-activating factor (GcMAF) ever discovered, but it produces no side effect in humans. Macrophages treated with GcMAF (100 microg/ml) develop an enormous variation of receptors and are highly tumoricidal to a variety of cancers indiscriminately. Administration of 100 nanogram (ng)/ human maximally activates systemic macrophages that can kill cancerous cells. Since the half-life of the activated macrophages is approximately 6 days, 100 ng GcMAF was administered weekly to eight nonanemic colorectal cancer patients who had previously received tumor-resection but still carried significant amounts of metastatic tumor cells. As GcMAF therapy progressed, the MAF precursor activities of all patients increased and conversely their serum Nagalase activities decreased. Since serum Nagalase is proportional to tumor burden, serum Nagalase activity was used as a prognostic index for time course analysis of GcMAF therapy. After 32-50 weekly administrations of 100 ng GcMAF, all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of metastatic tumor cells. During 7 years after the completion of GcMAF therapy, their serum Nagalase activity did not increase, indicating no recurrence of cancer, which was also supported by the annual CT scans of these patients.

Protective specific immunity induced by doxorubicin plus TNF-alpha combination treatment of EL4 lymphoma-bearing C57BL/6 mice.

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Ehrke, M J; Verstovsek, S; Maccubbin, D L; Ujházy, P; Zaleskis, G; Berleth, E; Mihich, E

2000-07-01

The therapeutic efficacy of a single (day 8), moderate dose (4 mg/kg, i.v.) of doxorubicin (DOX, Adriamycin) combined with recombinant human TNF-alpha (3 different doses and 5 different schedules, i.v.) was evaluated in C57BL/6 mice bearing an implant (s.c.) of the DOX-sensitive, TNF-alpha-resistant EL4 lymphoma. In parallel to monitoring survival, the levels of several host anti-tumor cytolytic effector functions of splenocytes and thymocytes were evaluated throughout the treatment period and in long-term survivors (LTS). DOX treatment alone resulted in a moderate (approx. 20%) increase in life span but no cures. TNF-alpha alone, at any tested dose or schedule, had little or no positive effect on survival. The combinations of DOX and TNF-alpha were only slightly better than DOX alone with respect to the time to death of mice that died (approx. 29% increase); however, each of the combinations involving 1,000 U TNF-alpha/injection produced a fraction (20% to 80%) of LTS. The host defense activities examined included those of splenic and thymic cytolytic T lymphocytes (CTL) and lymphokine-activated killer cells as well as splenic tumoricidal macrophages. Although most activities were modulated by tumor growth and/or treatment, only CTL responsiveness appeared to correlate with survival. CTL activity in the treated groups with LTS was significantly higher than in control groups late in the treatment period. Finally, ex vivo analyses of splenocytes and thymocytes together with the rejection of implanted tumor at 17 months established that LTS displayed specific long-term immune memory. Copyright 2000 Wiley-Liss, Inc.

Prognostic significance of adverse events in patients with hepatocellular carcinoma treated with sorafenib.

Science.gov (United States)

Granito, Alessandro; Marinelli, Sara; Negrini, Giulia; Menetti, Saverio; Benevento, Francesca; Bolondi, Luigi

2016-03-01

Sorafenib is the standard treatment for patients with hepatocellular carcinoma (HCC) with advanced stage disease. Although its effectiveness has been demonstrated by randomized clinical trials and confirmed by field practice studies, reliable markers predicting therapeutic response have not yet been identified. Like other tyrosine kinase inhibitors, treatment with sorafenib is burdened by the development of adverse effects, the most frequent being cutaneous toxicity, diarrhoea, arterial hypertension and fatigue. In recent years, several studies have analysed the correlation between off-target effects and sorafenib efficacy in patients with HCC. In this review, an overview of the studies assessing the prognostic significance of sorafenib-related adverse events is provided.

Significant interarm blood pressure difference predicts cardiovascular risk in hypertensive patients

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Kim, Su-A; Kim, Jang Young; Park, Jeong Bae

2016-01-01

Abstract There has been a rising interest in interarm blood pressure difference (IAD), due to its relationship with peripheral arterial disease and its possible relationship with cardiovascular disease. This study aimed to characterize hypertensive patients with a significant IAD in relation to cardiovascular risk. A total of 3699 patients (mean age, 61 ± 11 years) were prospectively enrolled in the study. Blood pressure (BP) was measured simultaneously in both arms 3 times using an automated cuff-oscillometric device. IAD was defined as the absolute difference in averaged BPs between the left and right arm, and an IAD ≥ 10 mm Hg was considered to be significant. The Framingham risk score was used to calculate the 10-year cardiovascular risk. The mean systolic IAD (sIAD) was 4.3 ± 4.1 mm Hg, and 285 (7.7%) patients showed significant sIAD. Patients with significant sIAD showed larger body mass index (P < 0.001), greater systolic BP (P = 0.050), more coronary artery disease (relative risk = 1.356, P = 0.034), and more cerebrovascular disease (relative risk = 1.521, P = 0.072). The mean 10-year cardiovascular risk was 9.3 ± 7.7%. By multiple regression, sIAD was significantly but weakly correlated with the 10-year cardiovascular risk (β = 0.135, P = 0.008). Patients with significant sIAD showed a higher prevalence of coronary artery disease, as well as an increase in 10-year cardiovascular risk. Therefore, accurate measurements of sIAD may serve as a simple and cost-effective tool for predicting cardiovascular risk in clinical settings. PMID:27310982

Vaccination with OK-432 followed by TC-1 tumor lysate leads to significant antitumor effects.

Science.gov (United States)

Chen, I-Ju; Yen, Chih-Feng; Lin, Kun-Ju; Lee, Chyi-Long; Soong, Yung-Kuei; Lai, Chyong-Huey; Lin, Cheng-Tao

2011-07-01

Human papillomavirus (HPV) infects large numbers of women worldwide and is present in more than 99% of all cervical cancer. TC-1 cell is a cell line with high expression of E7 antigen of HPV type 16 and its cell lysate has been demonstrated as an ideal inducer of E7-specific, antitumor immunity. OK-432 (Picibanil), a penicillin-killed Streptococcus pyogenes, has been reported with potent immunomodulation properties in cancer treatment by stimulating the maturation of dendritic cells (DCs) and secretion of Th-1 type cytokines. The current study demonstrated that a protocol to immunize the C57BL/6 mice with OK-432 followed by treatment with TC-1 lysate can generate markedly increased immune responses of E7-specific CD4(+) T cells and a moderate increase of natural killer (NK) cell, as well as a satisfactorily protective and therapeutic antitumor effect by triggering the DCs to prime T cells. Depletion of lymphocyte subset in vivo suggested that the antitumor effects could be dominantly executed by CD8+ T cells and followed by NK cells, and both of these reactions were induced by the generation of robust E7-specific CD4(+) T helper cell response. These findings warrant OK-432 combination with tumor-lysate as an effective and safe vaccine in future clinical application of cervical cancer.

Global warming: the significance of methane

International Nuclear Information System (INIS)

Dessus, B.; Le Treut, H.; Laponche, B.

2008-01-01

the concept of Global Warming Potential (GWP) indicates the relative contribution to global warming over a given period (for example 100 years) of a pulse emission at the start of the period of 1 kg of a specific greenhouse gas (GHG) in comparison to the contribution, over the same period, of an emission of 1 kg of CO 2 . The GWPs calculated for different time intervals take into account the differences in atmospheric lifetimes of the different GHGs. Using the '100-year GWP' to measure non CO 2 GHG emissions is not well suited to the case of permanent or long lifetime measures whose effectiveness is to be assessed at a given time horizon. In this context, it contributes to significantly playing down the importance of reducing emissions of GHGs with short atmospheric lifetimes. Thus, for example, methane which is not emitted over the period 2020- 2100 as a result of a landfill site being closed in 2020 will have an impact (as opposed to if the site remained in operation) that would be far greater towards 2100 compared to a CO 2 emission source that has also been stopped permanently and whose climate impact is measured in an equivalent manner. Using the GWP is only appropriate if applied year after year to time horizons considered to be of concern or decisive by climate studies, thus in particular 2050, 2100 and 2150. This is all the more significant as climate experts' current concerns lead them not only to advocate long-term stabilisation of GHG concentrations but also to avoid as far as possible intermediate excess of these concentrations over the coming century. Finally, it is noted that CH 4 prevention policies implemented in the short term may continue to have a long-term impact greater than merely taking into account the current GWP would imply. To more or less ignore the impact of CH 4 as it is unsuitable for accounting purposes affects the exclusive character of the link that may exist between the issue of GHGs and that of energy. Furthermore, if the

Human Body 3D Posture Estimation Using Significant Points and Two Cameras

Science.gov (United States)

Juang, Chia-Feng; Chen, Teng-Chang; Du, Wei-Chin

2014-01-01

This paper proposes a three-dimensional (3D) human posture estimation system that locates 3D significant body points based on 2D body contours extracted from two cameras without using any depth sensors. The 3D significant body points that are located by this system include the head, the center of the body, the tips of the feet, the tips of the hands, the elbows, and the knees. First, a linear support vector machine- (SVM-) based segmentation method is proposed to distinguish the human body from the background in red, green, and blue (RGB) color space. The SVM-based segmentation method uses not only normalized color differences but also included angle between pixels in the current frame and the background in order to reduce shadow influence. After segmentation, 2D significant points in each of the two extracted images are located. A significant point volume matching (SPVM) method is then proposed to reconstruct the 3D significant body point locations by using 2D posture estimation results. Experimental results show that the proposed SVM-based segmentation method shows better performance than other gray level- and RGB-based segmentation approaches. This paper also shows the effectiveness of the 3D posture estimation results in different postures. PMID:24883422

Genome-wide identification of significant aberrations in cancer genome

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Yuan Xiguo

2012-07-01

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

[Exosomes and Immune Cells].

Science.gov (United States)

Seo, Naohiro

2017-05-01

In addition to the cytokines and cytotoxic granules, exosomes have been known as the intercellular communicator and cytotoxic missile of immune cells for the past decade. It has been well known that mature dendritic cell(DC)-derived exosomes participate in the T cell and natural killer(NK)cell activation, while immature DCs secrete tolerogenic exosomes for regulatory T(Treg)cell generation. Treg cell-derived EVs act as a suppressor against pathogenic type-1 T helper(Th1)cell responses. CD8+ T cells produce tumoricidal exosomes for preventing tumor invasion and metastasis transiently after T cell receptor(TCR)-mediated stimulation. Thus, immune cells produce functional exosomes in the activation state- and/or differentiation stage-dependent manner. In this review, the role of immune cell-derived exosomes will be introduced, focusing mainly on immune reaction against tumor.

SICOD: modification system anatomophysiological relationship of organs and tumors in radiation therapy thoracic-abdominal; SICOD: sistema de modificacion de la relacion anatomofisiologica de organos tumores toracico-abdominales en radioterapia

Energy Technology Data Exchange (ETDEWEB)

Velazquez Miranda, S.; Gomez-Millan Barrachina, J.; Ortiz Seidel, M.; Bayo Lozano, E.

2011-07-01

In radiotherapy are used to pursue some distributions tumoricidal and tolerable while the surrounding organs. This is achieved using techniques normally for the modulation of the beams, but few do away shyly and mechanically critical organ tumor: Prone breast treatment or use of belly board. What we want here is more than a diaphragmatic compression or extracranial stereotactic, is a mechanical system to modify the relationship of chest-abdominal organs as proposed in surgery usually operating tables. Want to achieve for example a kidney that may move a synchronously with breathing more than 2 cm in their peri renal fat sack, moves only millimeters embedded in the most closed and close to the backbone of your bag, or we can reduce movement of the diaphragm only on the side of affected lung, making breathing tolerable for patients with low performance status.

Statistical significance of cis-regulatory modules

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Smith Andrew D

2007-01-01

Full Text Available Abstract Background It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. Results We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. Conclusion The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM and MODSTORM software.

[Current clinical significance of anaerobic bacteremia].

Science.gov (United States)

Jirsa, Roman; Marešová, Veronika; Brož, Zdeněk

2010-10-01

to estimate tje current clinical significance of anaerobic bacteremia in a group of Czech hospitals. this retrospective analysis comprised 8 444 anaerobic blood cultures in patients admitted to four Czech hospitals between 2004 and 2007. in 16 patients, blood cultures yielded significant anaerobic bacteria. Thus, anaerobic bacteremia accounted for less than 2 % of clinically significant bacteremia. Four patients (18 %) died but none of the deaths could be clearly attributable to anaerobic bacteria in the bloodstream. The most common comorbidities predisposing to anaerobic bacteremia and the most frequent sources of infection were similar to those reported by other authors. The majority of anaerobic bacteremia cases were due to gram-negative bacteria, followed by Clostridium perfringens and, surprisingly, Eubacterium spp. (particularly Eubacterium lentum). anaerobic bacteremia remains rare. The comparison of our data with those by other authors suggests that (despite the reported high mortality) the actual clinical significance of anaerobic bacteremia is rather controversial and that the anaerobic bacteremia might not correspond to more serious pathogenic role of the anaerobic bacteria as the source of infection.

40 CFR 1508.27 - Significantly.

Science.gov (United States)

2010-07-01

... Register of Historic Places or may cause loss or destruction of significant scientific, cultural, or... cultural resources, park lands, prime farmlands, wetlands, wild and scenic rivers, or ecologically critical...

Historical Significant Volcanic Eruption Locations

Data.gov (United States)

Department of Homeland Security — A significant eruption is classified as one that meets at least one of the following criteriacaused fatalities, caused moderate damage (approximately $1 million or...

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

Science.gov (United States)

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

2000-10-01

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

Staphylococcal Entertotoxins of the Enterotoxin Gene Cluster (egcSEs Induce Nitrous Oxide- and Cytokine Dependent Tumor Cell Apoptosis in a Broad Panel of Human Tumor Cells

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David eTerman

2013-08-01

Full Text Available The egcSEs comprise five genetically linked staphylococcal enterotoxins, SEG, SEI, SElM, SElN and SElO and two pseudotoxins which constitute an operon present in up to 80% of Staphylococcus aureus isolates. A preparation containing theses proteins was recently used to treat advanced lung cancer with pleural effusion. We investigated the hypothesis that egcSEs induce nitrous oxide (NO and associated cytokine production and that these agents may be involved in tumoricidal effects against a broad panel of clinically relevant human tumor cells. Preliminary studies showed that egcSEs and SEA activated T cells (range: 11-25% in a concentration dependent manner. Peripheral blood mononuclear cells (PBMCs stimulated with equimolar quantities of egcSEs expressed NO synthase and generated robust levels of nitrite (range: 200-250 µM, a breakdown product of NO; this reaction was inhibited by NG-monomethyl-L-arginine (L-NMMA (0.3 mM, an NO synthase antagonist. Cell free supernatants (CSFs of all egcSE-stimulated PBMCs were also equally effective in inducing concentration dependent tumor cell apoptosis in a broad panel of human tumor cells. The latter effect was due in part to the generation of NO and TNF-α since it was significantly abolished by L-NMMA, anti-TNF-α antibodies respectively and a combination thereof. A hierarchy of tumor cell sensitivity to these CFSs was as follows: lung carcinoma>osteogenic sarcoma>melanoma>breast carcinoma>neuroblastoma. Notably, SEG induced robust activation of NO/TNFα-dependent tumor cell apoptosis comparable to the other egcSEs and SEA despite TNF-α and IFN-γ levels that were 2 and 8 fold lower respectively than the other egcSEs and SEA. Thus, egcSEs produced by S. aureus induce NO synthase and the increased NO formation together with TNF-α appear to contribute to egcSE-mediated apoptosis against a broad panel of human tumor cells.

One arm exercise induces significant interarm diastolic blood pressure difference.

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Hong, Dezhi; Wang, Jiwei; Su, Hai; Xu, Jingsong; Liu, Yanna; Peng, Qiang; Wang, Lijuan

2011-06-01

This study is designed to investigate the inducing effect of one arm exercise on interarm difference (IAD) in the blood pressure (BP). Fifty healthy young participants were included in the study. Three-minute exercises of the right arm elbow flexion and extension were performed. The bilateral brachial BP was simultaneously measured with two automatic BP measurement devices before (basic) and immediately 0, 5, 10, 15, 20, and 30 min after exercise. The absolute difference in the systolic BP (SBP) and diastolic BP (DBP) between the left and right BP of at least 10 mmHg was recognized as sIAD and dIAD. The baseline data of the SBP and DBP in left and right arms revealed no significant difference (SBP: 110 ± 10 vs. 111 ± 11 mmHg; DBP: 66 ± 8 vs. 66 ± 9 mmHg, both not significant). The prevalence of dIAD was 2% at the baseline. However, this prevalence increased to 80% at 0 min, as right arm exercise induced the right DBP decrease and left DBP increase, and then the prevalence decreased gradually within a 30-min recovery period. The prevalence of sIAD was zero at the baseline and the maximal prevalence was 8% during the 20-min postexercise period. One arm exercise can lead to a significant IAD in DBP. Any arm exercise should be avoided before BP measurement.

Effect of Plasma Membrane Semipermeability in Making the Membrane Electric Double Layer Capacitances Significant.

Science.gov (United States)

Sinha, Shayandev; Sachar, Harnoor Singh; Das, Siddhartha

2018-01-30

Electric double layers (or EDLs) formed at the membrane-electrolyte interface (MEI) and membrane-cytosol interface (MCI) of a charged lipid bilayer plasma membrane develop finitely large capacitances. However, these EDL capacitances are often much larger than the intrinsic capacitance of the membrane, and all of these capacitances are in series. Consequently, the effect of these EDL capacitances in dictating the overall membrane-EDL effective capacitance C eff becomes negligible. In this paper, we challenge this conventional notion pertaining to the membrane-EDL capacitances. We demonstrate that, on the basis of the system parameters, the EDL capacitance for both the permeable and semipermeable membranes can be small enough to influence C eff . For the semipermeable membranes, however, this lowering of the EDL capacitance can be much larger, ensuring a reduction of C eff by more than 20-25%. Furthermore, for the semipermeable membranes, the reduction in C eff is witnessed over a much larger range of system parameters. We attribute such an occurrence to the highly nonintuitive electrostatic potential distribution associated with the recently discovered phenomena of charge-inversion-like electrostatics and the attainment of a positive zeta potential at the MCI for charged semipermeable membranes. We anticipate that our findings will impact the quantification and the identification of a large number of biophysical phenomena that are probed by measuring the plasma membrane capacitance.

Clinical significance of gamma camera renography in chronic renal insufficiency

International Nuclear Information System (INIS)

Dudczak, R.; Frischauf, H.; Kletter, K.

1980-01-01

Gamma camera renography allows, together with renal imaging, an evaluation of individual renal function. For these examinations, I 123 orthoiodohippurate is preferred and most widely used. The results on patients with chronic renal insufficiency, including urologic and posttransplantation patients, are reported. Whereas the method is of clinical significance in evaluating posttransplantation complications and in assessing individual kidney function preoperatively in urology, as well as in monitoring therapeutic effects in the early period of renal disease, it is of limited diagnostic value in chronic renal insufficiency. In this latter regard, clinical and laboratory examinations are of primary importance. (author)

Occult pneumothoraces in Chinese patients with significant blunt chest trauma: radiological classification and proposed clinical significance.

Science.gov (United States)

Lee, Ryan K L; Graham, Colin A; Yeung, Janice H H; Ahuja, Anil T; Rainer, Timothy H

2012-12-01

An occult pneumothorax (OP) is a pneumothorax not seen on a supine chest X-ray (CXR) but detected on abdominal or thoracic computed tomography (CT) scanning. With the increasing use of CT in the management of significantly injured trauma patients, more OPs are being detected. The aim of this study was to classify OPs diagnosed on thoracic CT (TCT) and correlate them with their clinical significance. Retrospective analysis of prospectively collected trauma registry data. Total 36 (N=36) consecutive significantly injured trauma patients admitted through the emergency department (ED) who sustained blunt chest trauma and underwent TCT between 1 January 2007 and 31 December 2008 were included. OP was defined as the identification (by a consultant radiologist) of a pneumothorax on TCT that had not been detected on supine CXR. OPs were classified by laterality (unilateral/bilateral) and location (apical, basal, non apical/basal). The size of pneumothoraces, severity of injury [including number of associated thoracic injuries and injury severity score (ISS)], length of hospital stay and mortality were compared between groups. The need for tube thoracostomy and clinical outcome were also analysed. Patients with bilateral OPs (N=8) had significantly more associated thoracic injuries (median: 2 vs. 1, p=0.01), higher ISS (median: 35 vs. 23, p=0.02) and longer hospital stay (median: 20 days vs. 11 days, p=0.01) than those with a unilateral OP (N=28). Basal OPs (N=7) were significantly larger than apical (N=10) and non-apical/basal Ops (N=11). Basal OPs were associated with significantly more associated thoracic injuries (median: 2 vs. 1, p=0.01), higher ISS (median: 35 vs. 25, p=0.04) and longer hospital stays (median: 23 days vs. 17 days, p=0.02) than apical Ops, which had higher ISS (median: 35 vs. 25, p=0.04) and longer hospital stays (median: 23 days vs. 15 days, p=0.02) than non-apical/basal OPs. Non-apical/basal OPs were associated with more related injuries (median: 2

Myelopotentiating effect of curcumin in tumor-bearing host: Role of bone marrow resident macrophages

Energy Technology Data Exchange (ETDEWEB)

Vishvakarma, Naveen Kumar; Kumar, Anjani; Kumar, Ajay; Kant, Shiva [School of Biotechnology, Banaras Hindu University, Varanasi-221 005, U.P. (India); Bharti, Alok Chandra [Division of Molecular Oncology, Institute of Cytology and Preventive Oncology, Noida, UP (India); Singh, Sukh Mahendra, E-mail: sukhmahendrasingh@yahoo.com [School of Biotechnology, Banaras Hindu University, Varanasi-221 005, U.P. (India)

2012-08-15

The present investigation was undertaken to study if curcumin, which is recognized for its potential as an antineoplastic and immunopotentiating agent, can also influence the process of myelopoiesis in a tumor-bearing host. Administration of curcumin to tumor-bearing host augmented count of bone marrow cell (BMC) accompanied by an up-regulated BMC survival and a declined induction of apoptosis. Curcumin administration modulated expression of cell survival regulatory molecules: Bcl2, p53, caspase-activated DNase (CAD) and p53-upregulated modulator of apoptosis (PUMA) along with enhanced expression of genes of receptors for M-CSF and GM-CSF in BMC. The BMC harvested from curcumin-administered hosts showed an up-regulated colony forming ability with predominant differentiation into bone marrow-derived macrophages (BMDM), responsive for activation to tumoricidal state. The number of F4/80 positive bone marrow resident macrophages (BMM), showing an augmented expression of M-CSF, was also augmented in the bone marrow of curcumin-administered host. In vitro reconstitution experiments indicated that only BMM of curcumin-administered hosts, but not in vitro curcumin-exposed BMM, augmented BMC survival. It suggests that curcumin-dependent modulation of BMM is of indirect nature. Such prosurvival action of curcumin is associated with altered T{sub H1}/T{sub H2} cytokine balance in serum. Augmented level of serum-borne IFN-γ was found to mediate modulation of BMM to produce enhanced amount of monokines (IL-1, IL-6, TNF-α), which are suggested to augment the BMC survival. Taken together the present investigation indicates that curcumin can potentiate myelopoiesis in a tumor-bearing host, which may have implications in its therapeutic utility. Highlights: ► Curcumin augments myelopoiesis in tumor-bearing host. ► Bone marrow resident macrophages mediate curcumin-dependent augmented myelopoiesis. ► Serum borne cytokine are implicated in modulation of bone marrow resident

Myelopotentiating effect of curcumin in tumor-bearing host: Role of bone marrow resident macrophages

International Nuclear Information System (INIS)

Vishvakarma, Naveen Kumar; Kumar, Anjani; Kumar, Ajay; Kant, Shiva; Bharti, Alok Chandra; Singh, Sukh Mahendra

2012-01-01

The present investigation was undertaken to study if curcumin, which is recognized for its potential as an antineoplastic and immunopotentiating agent, can also influence the process of myelopoiesis in a tumor-bearing host. Administration of curcumin to tumor-bearing host augmented count of bone marrow cell (BMC) accompanied by an up-regulated BMC survival and a declined induction of apoptosis. Curcumin administration modulated expression of cell survival regulatory molecules: Bcl2, p53, caspase-activated DNase (CAD) and p53-upregulated modulator of apoptosis (PUMA) along with enhanced expression of genes of receptors for M-CSF and GM-CSF in BMC. The BMC harvested from curcumin-administered hosts showed an up-regulated colony forming ability with predominant differentiation into bone marrow-derived macrophages (BMDM), responsive for activation to tumoricidal state. The number of F4/80 positive bone marrow resident macrophages (BMM), showing an augmented expression of M-CSF, was also augmented in the bone marrow of curcumin-administered host. In vitro reconstitution experiments indicated that only BMM of curcumin-administered hosts, but not in vitro curcumin-exposed BMM, augmented BMC survival. It suggests that curcumin-dependent modulation of BMM is of indirect nature. Such prosurvival action of curcumin is associated with altered T H1 /T H2 cytokine balance in serum. Augmented level of serum-borne IFN-γ was found to mediate modulation of BMM to produce enhanced amount of monokines (IL-1, IL-6, TNF-α), which are suggested to augment the BMC survival. Taken together the present investigation indicates that curcumin can potentiate myelopoiesis in a tumor-bearing host, which may have implications in its therapeutic utility. Highlights: ► Curcumin augments myelopoiesis in tumor-bearing host. ► Bone marrow resident macrophages mediate curcumin-dependent augmented myelopoiesis. ► Serum borne cytokine are implicated in modulation of bone marrow resident

Significance of perceptually relevant image decolorization for scene classification

Science.gov (United States)

Viswanathan, Sowmya; Divakaran, Govind; Soman, Kutti Padanyl

2017-11-01

Color images contain luminance and chrominance components representing the intensity and color information, respectively. The objective of this paper is to show the significance of incorporating chrominance information to the task of scene classification. An improved color-to-grayscale image conversion algorithm that effectively incorporates chrominance information is proposed using the color-to-gray structure similarity index and singular value decomposition to improve the perceptual quality of the converted grayscale images. The experimental results based on an image quality assessment for image decolorization and its success rate (using the Cadik and COLOR250 datasets) show that the proposed image decolorization technique performs better than eight existing benchmark algorithms for image decolorization. In the second part of the paper, the effectiveness of incorporating the chrominance component for scene classification tasks is demonstrated using a deep belief network-based image classification system developed using dense scale-invariant feature transforms. The amount of chrominance information incorporated into the proposed image decolorization technique is confirmed with the improvement to the overall scene classification accuracy. Moreover, the overall scene classification performance improved by combining the models obtained using the proposed method and conventional decolorization methods.

Pulmonary spheral tuberculosis: features and clinical significance of spiral dynamic CT

International Nuclear Information System (INIS)

Xie Ruming; Ma Daqing; Li Tieyi; Chen Yi; Lu Fudong; Zhou Xinhua

2001-01-01

Objective: To assess the features and clinical significance of spiral dynamic CT in patients with pulmonary spheral tuberculosis. Methods: The 54 foci in 42 patients with pulmonary spheral tuberculosis were studied. Thin-sections at 2 mm thickness and 2 mm interval through the nodular center were obtained before and after administration of contrast material. Results: In 54 pulmonary spheral tuberculosis, maximum enhanced CT value in 51 (94.4%, 51/54) foci was less than 20 HU, and more than 20 HU in the other 3(5.6%, 3/54) foci. 27(50.0%, 27/54) foci showed no any enhancement, 24, (44%, 24/54) foci showed capsular enhancement, 1(1.9%, 1/54) focus showed peripheral enhancement and 2(3.7%, 2/54) foci showed extensive enhancement. The accuracy of the correct diagnosis was 25.9% in terms of plain CT and 94.4% in terms of enhanced CT scanning. The difference was significant (x 2 = 50.1, P < 0.05). The curative effect of extensive enhanced foci and peripheral enhanced foci was optimal, capsular enhanced foci was second, and non-enhanced foci was barely satisfactory. Conclusion: Spiral dynamic CT technique may improve the accuracy of diagnosing pulmonary spheral tuberculosis. No enhancement and/or capsular enhancement were suggestive of tuberculosis. The enhancing character of foci might contribute to assess the curative effect of anti-tuberculosis

Significance of insulin for glucose metabolism in skeletal muscle during contractions

DEFF Research Database (Denmark)

Hespel, P; Vergauwen, Lieven; Vandenberghe, K

1996-01-01

is essentially effected via increased blood flow, significantly contributes to stimulate glucose uptake. Again, however, increased glucose delivery appears to be a more potent stimulus of muscle glucose uptake as the circulating insulin level is increased. Furthermore, contractions and elevated flow prove...... is effected primarily via mechanisms exerted within the muscle cell related to the contractile activity per se. Yet contractions become a more potent stimulus of muscle glucose uptake as the plasma insulin level is increased. In addition, enhanced glucose delivery to muscle, which during exercise...... to be additive stimuli of muscle glucose uptake at any plasma insulin level. In conclusion, the extent to which muscle glucose uptake is stimulated during exercise depends on various factors, including 1) the intensity of the contractile activity, 2) the magnitude of the exercise-associated increase in muscle...

Codon Deviation Coefficient: A novel measure for estimating codon usage bias and its statistical significance

KAUST Repository

Zhang, Zhang

2012-03-22

Background: Genetic mutation, selective pressure for translational efficiency and accuracy, level of gene expression, and protein function through natural selection are all believed to lead to codon usage bias (CUB). Therefore, informative measurement of CUB is of fundamental importance to making inferences regarding gene function and genome evolution. However, extant measures of CUB have not fully accounted for the quantitative effect of background nucleotide composition and have not statistically evaluated the significance of CUB in sequence analysis.Results: Here we propose a novel measure--Codon Deviation Coefficient (CDC)--that provides an informative measurement of CUB and its statistical significance without requiring any prior knowledge. Unlike previous measures, CDC estimates CUB by accounting for background nucleotide compositions tailored to codon positions and adopts the bootstrapping to assess the statistical significance of CUB for any given sequence. We evaluate CDC by examining its effectiveness on simulated sequences and empirical data and show that CDC outperforms extant measures by achieving a more informative estimation of CUB and its statistical significance.Conclusions: As validated by both simulated and empirical data, CDC provides a highly informative quantification of CUB and its statistical significance, useful for determining comparative magnitudes and patterns of biased codon usage for genes or genomes with diverse sequence compositions. 2012 Zhang et al; licensee BioMed Central Ltd.

Evolutionarily significant units of the critically endangered leaf frog Pithecopus ayeaye (Anura, Phyllomedusidae) are not effectively preserved by the Brazilian protected areas network.

Science.gov (United States)

de Magalhães, Rafael Félix; Lemes, Priscila; Camargo, Arley; Oliveira, Ubirajara; Brandão, Reuber Albuquerque; Thomassen, Hans; Garcia, Paulo Christiano de Anchietta; Leite, Felipe Sá Fortes; Santos, Fabrício Rodrigues

2017-11-01

Protected areas (PAs) are essential for biodiversity conservation, but their coverage is considered inefficient for the preservation of all species. Many species are subdivided into evolutionarily significant units (ESUs) and the effectiveness of PAs in protecting them needs to be investigated. We evaluated the usefulness of the Brazilian PAs network in protecting ESUs of the critically endangered Pithecopus ayeaye through ongoing climate change. This species occurs in a threatened mountaintop ecosystem known as campos rupestres . We used multilocus DNA sequences to delimit geographic clusters, which were further validated as ESUs with a coalescent approach. Ecological niche modeling was used to estimate spatial changes in ESUs' potential distributions, and a gap analysis was carried out to evaluate the effectiveness of the Brazilian PAs network to protect P. ayeaye in the face of climate changes. We tested the niche overlap between ESUs to gain insights for potential management alternatives for the species. Pithecopus ayeaye contains at least three ESUs isolated in distinct mountain regions, and one of them is not protected by any PA. There are no climatic niche differences between the units, and only 4% of the suitable potential area of the species is protected in present and future projections. The current PAs are not effective in preserving the intraspecific diversity of P. ayeaye in its present and future range distributions. The genetic structure of P. ayeaye could represent a typical pattern in campos rupestres endemics, which should be considered for evaluating its conservation status.

[Self-relaxation techniques for glaucoma patients. Significance of autogenic training, hypnosis and music therapy].

Science.gov (United States)

Bertelmann, T; Strempel, I

2016-02-01

Glaucoma is currently the second most common cause of severe visual impairment and blindness worldwide. Standard pharmaceutical and surgical interventions often fail to prevent progression of glaucomatous optic neuropathy. To evaluate whether adjuvantly applied self-relaxation techniques can significantly impact intraocular pressure, ocular perfusion and the overall mental state of affected patients. A search of the literature was carried out and a comprehensive overview of currently available data is presented. Autogenic training, hypnosis and music therapy can significantly impact intraocular pressure, ocular perfusion and overall mental state of patients suffering from glaucoma. As all of these adjuvant therapeutic options are cost-effective, available almost everywhere and at anytime as well as without any known side effects, they can be useful additional techniques in the overall concept for treating glaucoma patients. Regular ocular examinations by an ophthalmologist are, however, mandatory.

Inpatient Treatment for Adolescents with Anorexia Nervosa: Clinical Significance and Predictors of Treatment Outcome.

Science.gov (United States)

Schlegl, Sandra; Diedrich, Alice; Neumayr, Christina; Fumi, Markus; Naab, Silke; Voderholzer, Ulrich

2016-05-01

This study evaluated the clinical significance as well as predictors of outcome for adolescents with severe anorexia nervosa (AN) treated in an inpatient setting. Body mass index (BMI), eating disorder (ED) symptoms [Eating Disorder Inventory-2 (EDI-2)], general psychopathology and depression were assessed in 238 patients at admission and discharge. BMI increased from 14.8 + 1.2 to 17.3 + 1.4 kg/m(2). Almost a fourth (23.6%) of the patients showed reliable changes, and 44.7% showed clinically significant changes (EDI-2). BMI change did not significantly differ between those with reliable or clinically significant change or no reliable change in EDI-2. Length of stay, depression and body dissatisfaction were negative predictors of a clinically significant change. Inpatient treatment is effective in about two thirds of adolescents with AN and should be considered when outpatient treatment fails. About one third of patients showed significant weight gain, but did not improve regarding overall ED symptomatology. Future studies should focus on treatment strategies for non-responders. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Relative significance of surgery and radiotherapy in treatment of brain metastases of lung cancer

International Nuclear Information System (INIS)

Yamashita, Junkoh; Ohtsuka, Sinichi; Yamasaki, Toshiki; Gi, Hidefuku; Ha, Young-Soo; Handa, Hajime

1983-01-01

One hundred and sixteen cases of brain metastases of lung cancer were retrospectively analysed with special reference to the relative significance of surgery and radiotherapy. The median survival time from diagnosis of brain metastases was 1.2 months in 27 cases without treatment, 2.5 months in 51 cases treated by surgery alone, 4.2 months in 31 cases treated by radiotherapy alone and 6.5 months in 7 cases treated by surgery and radiotherapy. The survival rate in patients treated by radiotherapy was significantly better than in those not treated by radiotherapy. However, the effect of surgery was not significant in prolongation of survival time. On the other hand, the rate of improvement in neurological symptoms assessed at one month after the initiation of treatment was 80.9% in 47 cases treated by surgery and 19.4 % in 31 cases treated by radiotherapy. The result suggested that surgery is superior to radiotherapy in alleviating neurological symptoms. It is important to understand the nature of effect of each treatment. A better result will be anticipated by proper selection or combination of these treatments. (author)

Efficacy of a Word- and Text-Based Intervention for Students With Significant Reading Difficulties.

Science.gov (United States)

Vaughn, Sharon; Roberts, Garrett J; Miciak, Jeremy; Taylor, Pat; Fletcher, Jack M

2018-05-01

We examine the efficacy of an intervention to improve word reading and reading comprehension in fourth- and fifth-grade students with significant reading problems. Using a randomized control trial design, we compare the fourth- and fifth-grade reading outcomes of students with severe reading difficulties who were provided a researcher-developed treatment with reading outcomes of students in a business-as-usual (BAU) comparison condition. A total of 280 fourth- and fifth-grade students were randomly assigned within school in a 1:1 ratio to either the BAU comparison condition ( n = 139) or the treatment condition ( n = 141). Treatment students were provided small-group tutoring for 30 to 45 minutes for an average of 68 lessons (mean hours of instruction = 44.4, SD = 11.2). Treatment students performed statistically significantly higher than BAU students on a word reading measure (effect size [ES] = 0. 58) and a measure of reading fluency (ES = 0.46). Though not statistically significant, effect sizes for students in the treatment condition were consistently higher than BAU students for decoding measures (ES = 0.06, 0.08), and mixed for comprehension (ES = -0.02, 0.14).

Asymptomatic bacteriuria. Clinical significance and management.

Science.gov (United States)

Raz, Raul

2003-10-01

The clinical significance and management of asymptomatic bacteriuria (ASB) differs according to different groups of patients. ASB requires antibiotic treatment in pregnant women, children aged 5-6 years and prior to invasive genitourinary procedures. However, there is a consensus that ASB in the elderly, healthy school girls and young women, diabetic women and patients with indwelling catheters or intermittent catheterization has no clinical significance and antibiotic prescription is not indicated.

Significance of Hemispheric Security for Mexico

Science.gov (United States)

2003-04-07

La Seguridad Internacional, la Nueva Geopolitica Continental y Mexico ,” Seminario Internacional sobre Misiones de Paz, Seguridad y Defensa, Rio de...USAWC STRATEGY RESEARCH PROJECT SIGNIFICANCE OF HEMISPHERIC SECURITY FOR MEXICO by LTC Enrique Garcia Jaramillo Cavalry, Mexican Army COL Joseph R...xx-xx-2002 to xx-xx-2003 4. TITLE AND SUBTITLE Significance of Hemispheric Security for Mexico Unclassified 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c

15 CFR 970.701 - Significant adverse environmental effects.

Science.gov (United States)

2010-01-01

... under a license of scale-model mining systems which simulate commercial recovery could adversely affect... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES... Service or another Federal agency; (5) Meteorological observations and measurements, including the setting...

The earth is flat (p > 0.05): significance thresholds and the crisis of unreplicable research.

Science.gov (United States)

Amrhein, Valentin; Korner-Nievergelt, Fränzi; Roth, Tobias

2017-01-01

The widespread use of 'statistical significance' as a license for making a claim of a scientific finding leads to considerable distortion of the scientific process (according to the American Statistical Association). We review why degrading p -values into 'significant' and 'nonsignificant' contributes to making studies irreproducible, or to making them seem irreproducible. A major problem is that we tend to take small p -values at face value, but mistrust results with larger p -values. In either case, p -values tell little about reliability of research, because they are hardly replicable even if an alternative hypothesis is true. Also significance ( p  ≤ 0.05) is hardly replicable: at a good statistical power of 80%, two studies will be 'conflicting', meaning that one is significant and the other is not, in one third of the cases if there is a true effect. A replication can therefore not be interpreted as having failed only because it is nonsignificant. Many apparent replication failures may thus reflect faulty judgment based on significance thresholds rather than a crisis of unreplicable research. Reliable conclusions on replicability and practical importance of a finding can only be drawn using cumulative evidence from multiple independent studies. However, applying significance thresholds makes cumulative knowledge unreliable. One reason is that with anything but ideal statistical power, significant effect sizes will be biased upwards. Interpreting inflated significant results while ignoring nonsignificant results will thus lead to wrong conclusions. But current incentives to hunt for significance lead to selective reporting and to publication bias against nonsignificant findings. Data dredging, p -hacking, and publication bias should be addressed by removing fixed significance thresholds. Consistent with the recommendations of the late Ronald Fisher, p -values should be interpreted as graded measures of the strength of evidence against the null hypothesis

Personal significance is encoded automatically by the human brain: an event-related potential study with ringtones.

Science.gov (United States)

Roye, Anja; Jacobsen, Thomas; Schröger, Erich

2007-08-01

In this human event-related brain potential (ERP) study, we have used one's personal--relative to another person's--ringtone presented in a two-deviant passive oddball paradigm to investigate the long-term memory effects of self-selected personal significance of a sound on the automatic deviance detection and involuntary attention system. Our findings extend the knowledge of long-term effects usually reported in group-approaches in the domains of speech, music and environmental sounds. In addition to the usual mismatch negativity (MMN) and P3a component elicited by deviants in contrast to standard stimuli, we observed a posterior ERP deflection directly following the MMN for the personally significant deviant only. This specific impact of personal significance started around 200 ms after sound onset and involved neural generators that were different from the mere physical deviance detection mechanism. Whereas the early part of the P3a component was unaffected by personal significance, the late P3a was enhanced for the ERPs to the personal significant deviant suggesting that this stimulus was more powerful in attracting attention involuntarily. Following the involuntary attention switch, the personally significant stimulus elicited a widely-distributed negative deflection, probably reflecting further analysis of the significant sound involving evaluation of relevance or reorienting to the primary task. Our data show, that the personal significance of mobile phone and text message technology, which have developed as a major medium of communication in our modern world, prompts the formation of individual memory representations, which affect the processing of sounds that are not in the focus of attention.

The potential significance of microbial activity in radioactive waste disposal

International Nuclear Information System (INIS)

McCabe, A.M.

1987-12-01

The aim of this report is to assess the potential significance of microbial activity in radioactive waste disposal. It outlines the major factors which need to be considered in order to evaluate the importance of microbiological action. These include water and nutritional sources (particularly carbon) hostile conditions (particularly the effects of radiation and pH), the establishment of pH micro-environments and the degradative effect of microbial metabolic by-products on the disposed waste forms. Before an active microbial population can develop there are certain basic requirements for life. These are outlined and the possibility of colonisation occurring within the chemical, radiological and nutritional constraints of a repository are considered. Once colonisation is assumed, the effect of microbial activity is discussed under five headings, i.e. (i) direct attack, (ii) physical disruption (which includes consideration of fissuring processes and void formation), (iii) gas generation (which may be of particular importance), (iv) radionuclide uptake and finally (v) alteration of groundwater chemistry. Particular attention is paid to the possibility of environments becoming established both within the waste form itself (allowing microbes to attack from the inside of the repository outward) or attack on the encapsulant materials (microbes attacking from the outside inward). (author)

Intraoperative Sensorcaine significantly improves postoperative pain management in outpatient reduction mammaplasty.

Science.gov (United States)

Culliford, Alfred T; Spector, Jason A; Flores, Roberto L; Louie, Otway; Choi, Mihye; Karp, Nolan S

2007-09-15

Breast reduction is one of the most frequently performed plastic surgical procedures in the United States; more than 160,500 patients underwent the procedure in 2005. Many outpatient reduction mammaplasty patients report the greatest postoperative discomfort in the first 48 hours. The authors' investigated the effect of intraoperative topical application of the long-acting local anesthetic agent bupivacaine (Sensorcaine or Marcaine) on postoperative pain, time to postanesthesia care unit discharge, and postoperative use of narcotic medication. In a prospective, randomized, single-blind trial, intraoperative use of Sensorcaine versus placebo (normal saline) was compared. Postoperative pain was quantified using the visual analogue scale, and time to discharge from the postanesthesia care unit was recorded. Patients documented their outpatient pain medication usage. Of the 37 patients enrolled in the study, 20 were treated with intraoperative topical Sensorcaine and 17 received placebo. Patients treated with Sensorcaine were discharged home significantly faster (2.9 hours versus 3.8 hours, p = 0.002). The control arm consistently had higher pain scores in the postanesthesia care unit (although not statistically significant) than the Sensorcaine group using the visual analogue scale system. Furthermore, patients receiving Sensorcaine required significantly less narcotic medication while recovering at home (mean, 3.5 tablets of Vicodin) than the control group (mean, 6.4 tablets; p = 0.001). There were no complications resulting from Sensorcaine usage. This prospective, randomized, single-blind study demonstrates that a single dose of intraoperative Sensorcaine provides a safe, inexpensive, and efficacious way to significantly shorten the length of postanesthesia care unit stay and significantly decrease postoperative opioid analgesic use in patients undergoing ambulatory reduction mammaplasty.

Discovery of potent and selective cytotoxic activity of new quinazoline-ureas against TMZ-resistant glioblastoma multiforme (GBM).

Science.gov (United States)

Elkamhawy, Ahmed; Viswanath, Ambily Nath Indu; Pae, Ae Nim; Kim, Hyeon Young; Heo, Jin-Chul; Park, Woo-Kyu; Lee, Chong-Ock; Yang, Heekyoung; Kim, Kang Ho; Nam, Do-Hyun; Seol, Ho Jun; Cho, Heeyeong; Roh, Eun Joo

2015-10-20

Herein, we report new quinazoline-urea based compounds with potent cytotoxic activities against TMZ-resistant glioblastoma multiforme (GBM) cells. Low micromolar IC₅₀ values were exhibited over a panel of three primary GBM patient-derived cell cultures belonging to proneural (GBM-1), mesenchymal (GBM-2), and classical (GBM-3) subtypes. Eight compounds showed excellent selectivity indices for GBM cells comparing to a normal astrocyte cell line. In JC-1 assay, analogues 11, 12, 20, 22, and 24 exerted promising rates of mPTP opening induction towards proneural GBM subtype. Compounds 11, 20, and 24 bound to the translocator protein 18 kDa (TSPO) in submicromolar range using [(3)H] PK-11195 binding affinity assay. A homology model was built and docked models of 11, 12, 20, 22 and 24 were generated for describing their plausible binding modes in TSPO. In 3D clonogenic assay, compound 20 manifested potent tumoricidal effects on TMZ-resistant GBM cells even at submicromolar concentrations. In addition, CYP450 and hERG assays presented a safe toxicity profile of 20. Taken as a whole, this report presents compound 20 as a potent, selective and safe GBM cytotoxic agent which constitutes a promising direction against TMZ-resistant GBM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Stress and Systemic Inflammation: Yin-Yang Dynamics in Health and Diseases.

Science.gov (United States)

Yan, Qing

2018-01-01

Studies in psychoneuroimmunology (PNI) would provide better insights into the "whole mind-body system." Systems biology models of the complex adaptive systems (CASs), such as a conceptual framework of "Yin-Yang dynamics," may be helpful for identifying systems-based biomarkers and targets for more effective prevention and treatment. The disturbances in the Yin-Yang dynamical balance may result in stress, inflammation, and various disorders including insomnia, Alzheimer's disease, obesity, diabetes, cardiovascular diseases, skin disorders, and cancer. At the molecular and cellular levels, the imbalances in the cytokine pathways, mitochondria networks, redox systems, and various signaling pathways may contribute to systemic inflammation. In the nervous system, Yin and Yang may represent the dynamical associations between the progressive and regressive processes in aging and neurodegenerative diseases. In response to the damages to the heart, the Yin-Yang dynamical balance between proinflammatory and anti-inflammatory cytokine networks is crucial. The studies of cancer have revealed the importance of the Yin-Yang dynamics in the tumoricidal and tumorigenic activities of the immune system. Stress-induced neuroimmune imbalances are also essential in chronic skin disorders including atopic dermatitis and psoriasis. With the integrative framework, the restoration of the Yin-Yang dynamics can become the objective of dynamical systems medicine.

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF.

Science.gov (United States)

Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki

2008-07-01

Serum Gc protein (known as vitamin D(3)-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Therefore, macrophages of prostate cancer patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent MAF (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages activated by GcMAF develop a considerable variation of receptors that recognize the abnormality in malignant cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer patients received weekly administration of 100 ng of GcMAF. As the MAF precursor activity increased, their serum Nagalase activity decreased. Because serum Nagalase activity is proportional to tumor burden, the entire time course analysis for GcMAF therapy was monitored by measuring the serum Nagalase activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16 patients had very low serum Nagalase levels equivalent to those of healthy control values, indicating that these patients are tumor-free. No recurrence occurred for 7 years.

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF1

Science.gov (United States)

Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki

2008-01-01

Serum Gc protein (known as vitamin D3-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Therefore, macrophages of prostate cancer patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized β-galactosidase and sialidase generated the most potent MAF (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages activated by GcMAF develop a considerable variation of receptors that recognize the abnormality in malignant cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer patients received weekly administration of 100 ng of GcMAF. As the MAF precursor activity increased, their serum Nagalase activity decreased. Because serum Nagalase activity is proportional to tumor burden, the entire time course analysis for GcMAF therapy was monitored by measuring the serum Nagalase activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16 patients had very low serum Nagalase levels equivalent to those of healthy control values, indicating that these patients are tumor-free. No recurrence occurred for 7 years. PMID:18633461

Clinical significance of anismus in encopresis.

Science.gov (United States)

Catto-Smith, A G; Nolan, T M; Coffey, C M

1998-09-01

Treatments designed to relieve paradoxical contraction of the anal sphincters during defecation (anismus) have had limited success in children with encopresis. This has raised doubts as to the clinical relevance of this diagnosis in childhood as anorectal dysfunction. Our aim was to determine whether, in patients who had treatment-resistant encopresis, the presence of electromyographic anismus was associated with increased faecal retention. Sixty-eight children with soiling (mean age 8.7+/-2.06 years) were assessed by clinical examination, abdominal radiography and then with anorectal manometry. Patients with electromyographic anismus (n=32; 47%) had significantly increased radiographic rectal faecal retention and were significantly less likely to be able to defecate water-filled balloons. There were no significant differences in response to prior therapy, history of primary encopresis, behavioural adjustment or in sociodemographic data. Our results suggest that electromyographic anismus is associated with obstructed defecation and faecal retention.

Testing Significance Testing

Directory of Open Access Journals (Sweden)

Joachim I. Krueger

2018-04-01

Full Text Available The practice of Significance Testing (ST remains widespread in psychological science despite continual criticism of its flaws and abuses. Using simulation experiments, we address four concerns about ST and for two of these we compare ST’s performance with prominent alternatives. We find the following: First, the 'p' values delivered by ST predict the posterior probability of the tested hypothesis well under many research conditions. Second, low 'p' values support inductive inferences because they are most likely to occur when the tested hypothesis is false. Third, 'p' values track likelihood ratios without raising the uncertainties of relative inference. Fourth, 'p' values predict the replicability of research findings better than confidence intervals do. Given these results, we conclude that 'p' values may be used judiciously as a heuristic tool for inductive inference. Yet, 'p' values cannot bear the full burden of inference. We encourage researchers to be flexible in their selection and use of statistical methods.

Demonstrating the benefits of fuel cells: further significant progress towards commercialisation

Energy Technology Data Exchange (ETDEWEB)

Anon,

1995-01-01

The fourteenth Fuel Cell Seminar held in San Diego, California in 1994 is reported. The phosphoric acid fuel cell (PAFC) is the closest to widespread commercialization. PAFC cogeneration plants have to be shown to compare favourable in reliability with current mature natural gas-fuelled engine and turbine technologies. Although highly efficient, further development is necessary to produce cost effective generators. Progress is being made on proton exchange membrane fuel cell (PEMFC) stationary power plants, too, which may prove to be cost effective. In view of its lower operating temperature, at below 100[sup o]C compared with about 200[sup o]C for the PAFC, the principal use of the PEMFC has been identified as powering vehicles. Fuel cells have significant environmental advantages but further capital cost reductions are necessary if they are to compete with established technologies. (UK)

Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial.

Directory of Open Access Journals (Sweden)

Akhirunnesa Mily

Full Text Available Development of new tuberculosis (TB drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D3 (vitD3 and 4-phenyl butyrate (PBA are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects.To examine if oral adjunctive therapy with 5,000IU vitD3 or 2x500 mg PBA or PBA+vitD3 to standard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients.Adult TB patients (n = 288 were enrolled in a randomized, double-blind, placebo-controlled trial conducted in Bangladesh. Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8. Clinical assessments and sputum smear microscopy were performed weekly up to week 4, fortnightly up to week 12 and at week 24; TB culture was performed at week 0, 4 and 8; concentrations of LL-37 in cells, 25-hydroxyvitamin D3 (25(OHD3 in plasma and ex vivo bactericidal function of monocyte-derived macrophages (MDM were determined at week 0, 4, 8, 12 and additionally at week 24 for plasma 25(OHD3.At week 4, 71% (46/65 of the patients in the PBA+vitD3-group (p = 0.001 and 61.3% (38/62 in the vitD3-group (p = 0.032 were culture negative compared to 42.2% (27/64 in the placebo-group. The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD3-group (p = 0.001 and 2.2 times higher in vitD3-group (p = 0.032 compared to placebo. The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 (p = 0.034. Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo (log rank 11.38, p = 0.01.Adjunct therapy with PBA+vitD3 or vitD3 or PBA to standard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host-directed-therapy in the treatment of TB

The significance of translation regulation in the stress response

Science.gov (United States)

2013-01-01

Background The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation. Results A genome-scale study of the translational response to nutritional limitation was performed in the model bacterium Lactococcus lactis. Two measures were used to assess the translational status of each individual mRNA: the fraction engaged in translation (ribosome occupancy) and ribosome density (number of ribosomes per 100 nucleotides). Under isoleucine starvation, half of the mRNAs considered were translationally down-regulated mainly due to decreased ribosome density. This pattern concerned genes involved in growth-related functions such as translation, transcription, and the metabolism of fatty acids, phospholipids and bases, contributing to the slowdown of growth. Only 4% of the mRNAs were translationally up-regulated, mostly related to prophagic expression in response to stress. The remaining genes exhibited antagonistic regulations of the two markers of translation. Ribosome occupancy increased significantly for all the genes involved in the biosynthesis of isoleucine, although their ribosome density had decreased. The results revealed complex translational regulation of this pathway, essential to cope with isoleucine starvation. To elucidate the regulation of global gene expression more generally, translational regulation was compared to transcriptional regulation under isoleucine starvation and to other post-transcriptional regulations related to mRNA degradation and mRNA dilution by growth. Translational regulation appeared to accentuate the effects of transcriptional changes for down-regulated growth-related functions under isoleucine starvation although m

32 CFR 651.39 - Significance.

Science.gov (United States)

2010-07-01

... existing pollution standards; cause water, air, noise, soil, or underground pollution; impair visibility... Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) ENVIRONMENTAL QUALITY ENVIRONMENTAL ANALYSIS OF ARMY ACTIONS (AR 200-2) Environmental Assessment § 651.39 Significance. (a) If the...

Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions

Science.gov (United States)

Ming, Guo-li; Song, Hongjun

2011-01-01

Summary Adult neurogenesis, a process of generating functional neurons from adult neural precursors, occurs throughout life in restricted brain regions in mammals. The past decade has witnessed tremendous progress in addressing questions related to almost every aspect of adult neurogenesis in the mammalian brain. Here we review major advances in our understanding of adult mammalian neurogenesis in the dentate gyrus of the hippocampus and from the subventricular zone of the lateral ventricle, the rostral migratory stream to the olfactory bulb. We highlight emerging principles that have significant implications for stem cell biology, developmental neurobiology, neural plasticity, and disease mechanisms. We also discuss remaining questions related to adult neural stem cells and their niches, underlying regulatory mechanisms and potential functions of newborn neurons in the adult brain. Building upon the recent progress and aided by new technologies, the adult neurogenesis field is poised to leap forward in the next decade. PMID:21609825

Factoring local sequence composition in motif significance analysis.

Science.gov (United States)

Ng, Patrick; Keich, Uri

2008-01-01

We recently introduced a biologically realistic and reliable significance analysis of the output of a popular class of motif finders. In this paper we further improve our significance analysis by incorporating local base composition information. Relying on realistic biological data simulation, as well as on FDR analysis applied to real data, we show that our method is significantly better than the increasingly popular practice of using the normal approximation to estimate the significance of a finder's output. Finally we turn to leveraging our reliable significance analysis to improve the actual motif finding task. Specifically, endowing a variant of the Gibbs Sampler with our improved significance analysis we demonstrate that de novo finders can perform better than has been perceived. Significantly, our new variant outperforms all the finders reviewed in a recently published comprehensive analysis of the Harbison genome-wide binding location data. Interestingly, many of these finders incorporate additional information such as nucleosome positioning and the significance of binding data.

Knowledge-fused differential dependency network models for detecting significant rewiring in biological networks.

Science.gov (United States)

Tian, Ye; Zhang, Bai; Hoffman, Eric P; Clarke, Robert; Zhang, Zhen; Shih, Ie-Ming; Xuan, Jianhua; Herrington, David M; Wang, Yue

2014-07-24

Modeling biological networks serves as both a major goal and an effective tool of systems biology in studying mechanisms that orchestrate the activities of gene products in cells. Biological networks are context-specific and dynamic in nature. To systematically characterize the selectively activated regulatory components and mechanisms, modeling tools must be able to effectively distinguish significant rewiring from random background fluctuations. While differential networks cannot be constructed by existing knowledge alone, novel incorporation of prior knowledge into data-driven approaches can improve the robustness and biological relevance of network inference. However, the major unresolved roadblocks include: big solution space but a small sample size; highly complex networks; imperfect prior knowledge; missing significance assessment; and heuristic structural parameter learning. To address these challenges, we formulated the inference of differential dependency networks that incorporate both conditional data and prior knowledge as a convex optimization problem, and developed an efficient learning algorithm to jointly infer the conserved biological network and the significant rewiring across different conditions. We used a novel sampling scheme to estimate the expected error rate due to "random" knowledge. Based on that scheme, we developed a strategy that fully exploits the benefit of this data-knowledge integrated approach. We demonstrated and validated the principle and performance of our method using synthetic datasets. We then applied our method to yeast cell line and breast cancer microarray data and obtained biologically plausible results. The open-source R software package and the experimental data are freely available at http://www.cbil.ece.vt.edu/software.htm. Experiments on both synthetic and real data demonstrate the effectiveness of the knowledge-fused differential dependency network in revealing the statistically significant rewiring in biological

Reporting instructions significantly impact false positive rates when reading chest radiographs

Energy Technology Data Exchange (ETDEWEB)

Robinson, John W.; Brennan, Patrick C.; Mello-Thoms, Claudia; Lewis, Sarah J. [The University of Sydney, Medical Image Optimisation and Perception Group, Discipline of Medical Radiation Sciences, Faculty of Health Sciences, Lidcombe, NSW (Australia)

2016-10-15

To determine the impact of specific reporting tasks on the performance of radiologists when reading chest radiographs. Ten experienced radiologists read a set of 40 postero-anterior (PA) chest radiographs: 21 nodule free and 19 with a proven solitary nodule. There were two reporting conditions: an unframed task (UFT) to report any abnormality and a framed task (FT) reporting only lung nodule/s. Jackknife free-response operating characteristic (JAFROC) figure of merit (FOM), specificity, location sensitivity and number of true positive (TP), false positive (FP), true negative (TN) and false negative (FN) decisions were used for analysis. JAFROC FOM for tasks showed a significant reduction in performance for framed tasks (P = 0.006) and an associated decrease in specificity (P = 0.011) but no alteration to the location sensitivity score. There was a significant increase in number of FP decisions made during framed versus unframed tasks for nodule-containing (P = 0.005) and nodule-free (P = 0.011) chest radiographs. No significant differences in TP were recorded. Radiologists report more FP decisions when given specific reporting instructions to search for nodules on chest radiographs. The relevance of clinical history supplied to radiologists is called into question and may induce a negative effect. (orig.)

Reporting instructions significantly impact false positive rates when reading chest radiographs

International Nuclear Information System (INIS)

Robinson, John W.; Brennan, Patrick C.; Mello-Thoms, Claudia; Lewis, Sarah J.

2016-01-01

To determine the impact of specific reporting tasks on the performance of radiologists when reading chest radiographs. Ten experienced radiologists read a set of 40 postero-anterior (PA) chest radiographs: 21 nodule free and 19 with a proven solitary nodule. There were two reporting conditions: an unframed task (UFT) to report any abnormality and a framed task (FT) reporting only lung nodule/s. Jackknife free-response operating characteristic (JAFROC) figure of merit (FOM), specificity, location sensitivity and number of true positive (TP), false positive (FP), true negative (TN) and false negative (FN) decisions were used for analysis. JAFROC FOM for tasks showed a significant reduction in performance for framed tasks (P = 0.006) and an associated decrease in specificity (P = 0.011) but no alteration to the location sensitivity score. There was a significant increase in number of FP decisions made during framed versus unframed tasks for nodule-containing (P = 0.005) and nodule-free (P = 0.011) chest radiographs. No significant differences in TP were recorded. Radiologists report more FP decisions when given specific reporting instructions to search for nodules on chest radiographs. The relevance of clinical history supplied to radiologists is called into question and may induce a negative effect. (orig.)

77 FR 43520 - Significant New Use Rules on a Certain Chemical Substance; Removal of Significant New Use Rules

Science.gov (United States)

2012-07-25

... April 27, 2012 (77 FR 25236) (FRL-9343-4). If you have questions regarding the applicability of this... (77 FR 25236). If you have questions, consult the technical person listed under FOR FURTHER... 2070-AB27 Significant New Use Rules on a Certain Chemical Substance; Removal of Significant New Use...

The manic phase of Bipolar disorder significantly impairs theory of mind decoding.

Science.gov (United States)

Hawken, Emily R; Harkness, Kate L; Lazowski, Lauren K; Summers, David; Khoja, Nida; Gregory, James Gardner; Milev, Roumen

2016-05-30

Bipolar disorder is associated with significant deficits in the decoding of others' mental states in comparison to healthy participants. However, differences in theory of mind decoding ability among patients in manic, depressed, and euthymic phases of bipolar disorder is currently unknown. Fifty-nine patients with bipolar I or II disorder (13 manic, 25 depressed, 20 euthymic) completed the "Reading the Mind in the Eyes" Task (Eyes task) and the Animals Task developed to control for non-mentalistic response demands of the Eyes Task. Patients also completed self-report and clinician-rated measures of depression, mania, and anxiety symptoms. Patients in the manic phase were significantly less accurate than those in the depressed and euthymic phases at decoding mental states in the Eyes task, and this effect was strongest for eyes of a positive or neutral valence. Further Eyes task performance was negatively correlated with the symptoms of language/thought disorder, pressured speech, and disorganized thoughts and appearance. These effects held when controlling for accuracy on the Animals task, response times, and relevant demographic and clinical covariates. Results suggest that the state of mania, and particularly psychotic symptoms that may overlap with the schizophrenia spectrum, are most strongly related to social cognitive deficits in bipolar disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Significant plant growth stimulation by composted as opposed to untreated Biochar

Science.gov (United States)

Kammann, Claudia; Messerschmidt, Nicole; Müller, Christoph; Steffens, Diedrich; Schmidt, Hans-Peter; Koyro, Hans-Werner

2013-04-01

The application of production-fresh, untreated biochar does not always result in yield improvements, in particular in temperate or boreal soils. Therefore the use of biochar for soil C sequestration, although desirable from a global change mitigation point of view, may never be implemented without proven and economically feasible pathways for biochar effects in agriculture. To investigate earlier reports of the beneficial effects of composting biochar (e.g. Fischer & Glaser, 2012) we conducted a fully replicated (n=3, +/- biochar) large-scale composting study at the Delinat Institute in Arbaz, Switzerland. The materials were manures (bovine, horse and chicken), straw, stone meal and composting was performed with our without +20 vol.% of a woody biochar (German Charcoal GmbH). Interestingly, the rotting temperature was significantly higher in the biochar-compost while C and N were retained to a certain extent. To investigate the effect of composting ("ageing") on biochar effects, a completely randomized full-factorial pot study was carried out in the greenhouse using the pseudo-cereal Chenopodium quinoa. The three factors used in the study were (I) type of biochar addition ("aged", "fresh", or zero BC), (II) addition of compost and (III) low and high application rates of a full NPK-fertilizer (equivalent to 28 and 140 kg N ha-1, NPK + micronutrients) in several doses. The growth medium was a poor loamy sand. Biochars and compost were all added at a rate of 2% (w/w) to the soil. From the start there was a considerable difference between the growth of Quinoa with the fresh compared to the aged biochar. The fresh biochar produced the well-known reduction in plant growth compared to the unamended control. This reduction was alleviated to a certain extent by the addition of either compost and/or increased fertilization. In contrast the co-composted biochar always resulted in a highly significant stimulation of the Quinoa yield (roots, shoots, inflorescences). This

Tundra permafrost thaw causes significant shifts in energy partitioning

Directory of Open Access Journals (Sweden)

Christian Stiegler

2016-04-01

Full Text Available Permafrost, a key component of the arctic and global climate system, is highly sensitive to climate change. Observed and ongoing permafrost degradation influences arctic hydrology, ecology and biogeochemistry, and models predict that rapid warming is expected to significantly reduce near-surface permafrost and seasonally frozen ground during the 21st century. These changes raise concern of how permafrost thaw affects the exchange of water and energy with the atmosphere. However, associated impacts of permafrost thaw on the surface energy balance and possible feedbacks on the climate system are largely unknown. In this study, we show that in northern subarctic Sweden, permafrost thaw and related degradation of peat plateaus significantly change the surface energy balance of three peatland complexes by enhancing latent heat flux and, to less degree, also ground heat flux at the cost of sensible heat flux. This effect is valid at all radiation levels but more pronounced at higher radiation levels. The observed differences in flux partitioning mainly result from the strong coupling between soil moisture availability, vegetation composition, albedo and surface structure. Our results suggest that ongoing and predicted permafrost degradation in northern subarctic Sweden ultimately result in changes in land–atmosphere coupling due to changes in the partitioning between latent and sensible heat fluxes. This in turn has crucial implications for how predictive climate models for the Arctic are further developed.

Small changes in meal patterns lead to significant changes in total caloric intake. Effects of diet and social status on food intake in female rhesus monkeys.

Science.gov (United States)

Moore, Carla J; Lowe, Jonathan; Michopoulos, Vasiliki; Ulam, Patrick; Toufexis, Donna; Wilson, Mark E; Johnson, Zachary

2013-03-01

Social subordination in macaques is a well-established model to study the adverse effects of psychosocial stress on a number of health outcomes, including stress-induced eating. The present analysis was conducted to empirically define a meal among free-feeding female rhesus monkeys and to examine the roles of meal patterning (e.g., meal size, meal frequency, and snacking patterns) in findings from a previous study demonstrating that psychosocial stress increases overall caloric intake among subordinate animals with access to a highly palatable diet. Results indicate that all animals, regardless of social status, consumed more frequent meals, larger meals, and more calories in the form of snacks when a highly palatable diet was available. Additional findings suggest that subordinate animals consumed significantly larger meals compared to their dominant counterparts regardless of the dietary environment. Additionally, subordinate females with a history of exposure to the palatable diet consumed significantly more snack calories than both dominant and subordinate animals without previous exposure to the palatable diet when these females were returned to a standard laboratory diet. These findings illustrate how small changes in meal patterns can lead to significant increases in total caloric intake, which if prolonged, could promote the emergence of an obese phenotype. Copyright © 2012 Elsevier Ltd. All rights reserved.

Significant enhancement by biochar of caproate production via chain elongation.

Science.gov (United States)

Liu, Yuhao; He, Pinjing; Shao, Liming; Zhang, Hua; Lü, Fan

2017-08-01

In this study, biochar was introduced into a chain elongation system to enhance the bioproduction of caproate and caprylate. The concentration of caproate increased to 21.1 g/L upon the addition of biochar, which is the highest level of caproate reported for such a system to date when ethanol was used as electron donor. The addition of biochar created a tougher system with more stable microorganism community structure for chain elongation, in which no obvious inhibition by products or substrates was observed, moreover, the lag phase was reduced 2.3-fold compared to the system without biochar. These reinforcement effect of biochar are attributed to the enhanced conductivity due to the significant enrichment of functional microorganisms via the microbial network surrounding smaller biochar particles, and via the adsorption on the rough surfaces or pores of larger particles, which facilitated electron transfer. Higher amounts of extracellular polymer substances and higher conductivity induced by biochar could contribute to the reinforcement effect in chain elongation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integration of biomimicry and nanotechnology for significantly improved detection of circulating tumor cells (CTCs).

Science.gov (United States)

Myung, Ja Hye; Park, Sin-Jung; Wang, Andrew Z; Hong, Seungpyo

2017-12-13

Circulating tumor cells (CTCs) have received a great deal of scientific and clinical attention as a biomarker for diagnosis and prognosis of many types of cancer. Given their potential significance in clinics, a variety of detection methods, utilizing the recent advances in nanotechnology and microfluidics, have been introduced in an effort of achieving clinically significant detection of CTCs. However, effective detection and isolation of CTCs still remain a tremendous challenge due to their extreme rarity and phenotypic heterogeneity. Among many approaches that are currently under development, this review paper focuses on a unique, promising approach that takes advantages of naturally occurring processes achievable through application of nanotechnology to realize significant improvement in sensitivity and specificity of CTC capture. We provide an overview of successful outcome of this biomimetic CTC capture system in detection of tumor cells from in vitro, in vivo, and clinical pilot studies. We also emphasize the clinical impact of CTCs as biomarkers in cancer diagnosis and predictive prognosis, which provides a cost-effective, minimally invasive method that potentially replaces or supplements existing methods such as imaging technologies and solid tissue biopsy. In addition, their potential prognostic values as treatment guidelines and that ultimately help to realize personalized therapy are discussed. Copyright © 2017. Published by Elsevier B.V.

Strategies for Testing Statistical and Practical Significance in Detecting DIF with Logistic Regression Models

Science.gov (United States)

Fidalgo, Angel M.; Alavi, Seyed Mohammad; Amirian, Seyed Mohammad Reza

2014-01-01

This study examines three controversial aspects in differential item functioning (DIF) detection by logistic regression (LR) models: first, the relative effectiveness of different analytical strategies for detecting DIF; second, the suitability of the Wald statistic for determining the statistical significance of the parameters of interest; and…

Biphasic electrical targeting plays a significant role in schwann cell activation.

Science.gov (United States)

Kim, In Sook; Song, Yun Mi; Cho, Tae Hyung; Pan, Hui; Lee, Tae Hyung; Kim, Sung June; Hwang, Soon Jung

2011-05-01

Electrical stimulation (ES) is a promising technique for axonal regeneration of peripheral nerve injuries. However, long-term, continuous ES in the form of biphasic electric current (BEC) to stimulate axonal regeneration has rarely been attempted and the effects of BEC on Schwann cells are unknown. We hypothesized that long-term, continuous ES would trigger the activation of Schwann cells, and we therefore investigated the effect of BEC on the functional differentiation of primary human mesenchymal stromal cells (hMSCs) into Schwann cells, as well as the activity of primary Schwann cells. Differentiation of hMSCs into Schwann cells was determined by coculture with rat pheochromocytoma cells (PC12 cell line). We also investigated the in vivo effects of long-term ES (4 weeks) on axonal outgrowth of a severed sciatic nerve with a 7-mm gap after retraction of the nerve ends in rats by implanting an electronic device to serve as a neural conduit. PC12 cells cocultured with hMSCs electrically stimulated during culture in Schwann cell differentiation medium (Group I) had longer neurites and a greater percentage of PC12 cells were neurite-sprouting than when cocultured with hMSCs cultured in growth medium (control group) or unstimulated hMSCs in the same culture conditions as used for Group I (Group II). Group I cells showed significant upregulation of Schwann cell-related neurotrophic factors such as nerve growth factor and glial-derived neurotrophic factor compared to Group II cells at both the mRNA and protein levels. Primary Schwann cells responded to continuous BEC with increased proliferation and the induction of nerve growth factor and glial-derived neurotrophic factor, similar to Group I cells, and in addition, induction of brain-derived neurotrophic factor was observed. Immunohistochemical investigation of sciatic nerve regenerates revealed that BEC increased axonal outgrowth significantly. These results demonstrate that BEC enhanced the functional activity of

Clinically significant cardiopulmonary events and the effect of definition standardization on apnea of prematurity management.

Science.gov (United States)

Powell, M B F; Ahlers-Schmidt, C R; Engel, M; Bloom, B T

2017-01-01

To define the impact of care standardization on caffeine and cardiorespiratory monitoring at neonatal intensive care unit (NICU) discharge. Electronic records were abstracted for infants aged 24-36 weeks gestation with birth weights appropriate for gestational age. Infants who died, transferred prior to discharge, had major pulmonary anomalies, required a home monitor for mechanical ventilation or had a family history of sudden infant death syndrome were excluded. Data and records were used to indicate when the new definition of clinically significant cardiopulmonary events (CSCPEs) and concurrent education was implemented. Preimplementation and postimplementation cohorts were compared. Incidence fell from 74% diagnosed with apnea of prematurity at baseline to 49% diagnosed with CSCPE postimplementation (Pdefinitions and treatments reduced the use of caffeine and cardiorespiratory monitors upon NICU dismissal.

Building stones can be of geoheritage significance

Science.gov (United States)

Brocx, Margaret; Semeniuk, Vic

2017-04-01

Building stones have generally been assigned values according to their cultural, aesthetic, and rarity significance, amongst other criteria, but they also may have geoheritage significance. This is akin to the geoheritage significance ascribed to minerals and fossils housed as ex situ specimens in museums. We proffer the notion that building stones can be of geoheritage value particularly where they comprise permanent buildings, they illustrate significant windows into the history of the Earth, and they can be visited as an ex situ museum locality (e.g., the "Blue Granite" of Iceland) for education as part of building-stone tours. For some rocks the quarries that supplied the building stone are no longer in existence and hence the building stones provide the only record of that type of material; for other rocks, the building stone may illustrate features in the lithology no longer present in the quarry itself (e.g., rare and large xenoliths). Building stones are particularly significant as they are often polished and manifest structures, fabrics, and textures not evident in outcrop. We illustrate here examples of building stone of geoheritage significance using Australian and International examples. Australian designated stones could include the "Sydney Sandstone" or "Victorian Bluestone". For international examples, there is the famous "Carrara Marble" in Italy and the widely known "Portland Limestone" from southern England, the latter having been utilized for St Pauls Cathedral in London and the UN building in New York City.

Brain metastases from breast cancer: prognostic significance of HER-2 overexpression, effect of trastuzumab and cause of death

International Nuclear Information System (INIS)

Le Scodan, Romuald; Jouanneau, Ludivine; Massard, Christophe; Gutierrez, Maya; Kirova, Youlia; Cherel, Pascal; Gachet, Julie; Labib, Alain; Mouret-Fourme, Emmanuelle

2011-01-01

To access the prognostic significance of HER-2 overexpression, the effect of trastuzumab and the cause of death in patients with brain metastases (BM) from breast cancer (BC). We analyzed the outcome of 130 patients with BM from BC who received whole-brain radiotherapy (WBRT) (without surgery or radiosurgery) between January 1998 and April 2006. Demographic data, tumor characteristics, and treatments were prospectively recorded. The impact of HER-2 overexpression and trastuzumab-based therapy on overall survival (OS) and the cause of death were evaluated. The median follow-up for the whole population was 6.25 months (mean: 9.15; range: 0.23-53). The median survival time and 1-year survival rates after BM diagnosis were 7.43 months and 35.8% (95% CI: 28-45.7) respectively. The median survival time for HER-2 negative patients (n = 78), HER-2 positive patients not treated with trastuzumab (n = 20) and HER-2 positive patients treated with trastuzumab (n = 32) were 5.9 months, 5.6 months and 19.53 months, respectively. The 1-year survival rates were 26.1%, 29.2% and 62.6% respectively, (p < 0.004). Among the 18 HER-2 positive patients treated with trastuzumab who died, 11 (61%) apparently succumbed from CNS progression, in the face of stable or responsive non-CNS disease. Trastuzumab-based therapy was associated with a 51% reduction in the risk of death (multiadjusted hazard ratio: 0.49; 95% CI, 0.29-0.83). In our experience, trastuzumab-based therapy for HER-overexpressing tumors was associated with improved survival in BM BC patients. This subgroup of patients may benefit from innovative approaches, in order to obtain better intra cerebral control

Significance of Lead Residues in Mallard Tissues

Science.gov (United States)

Longcore, J.R.; Locke, L.N.; Bagley, George E.; Andrews, R.

1974-01-01

Tissues of adult, lead-dosed mallards that either died or were sacrificed were analyzed for lead. Lead levels in brains, tibiae, and breast muscle of ducks that died and in tibiae of ducks that were sacrificed increased significantly from dosage until death. Lead in the heart, lung, and blood from sacrificed ducks decreased significantly from dosage until death. Lead concentrations in tissues from ducks in the two groups were not significantly different except for the liver, kidney, and lung. Average lead levels in the livers and kidneys of ducks that died were significantly higher than those in ducks that were sacrificed. The mean concentration of lead in the lungs of the ducks sacrificed was significantly higher than the mean level in the lungs of ducks that died. Measurements of the lead concentrations in this study, when compared with lead levels reported in the literature for avian and non-avian species, showed that arbitrary diagnostic levels indicating lead poisoning could be set. In mallard ducks, lead levels exceeding 3 ppm in the brain, 6 to 20 ppm in the kidney or liver, or 10 ppm in clotted blood from the heart indicated acute exposure to lead.

Significance of bacterial flora in abdominal irradiation-induced inhibition of lung metastases

International Nuclear Information System (INIS)

Matsumoto, T.; Ando, K.; Koike, S.

1988-01-01

We have previously reported that abdominal irradiation prior to i.v. injection of syngeneic tumor cells reduced metastases in lung. Our report described an investigation of the significance of intestinal organisms in the radiation effect. We found that eliminating intestinal organisms with antibiotics totally abolished the radiation effect. Monoassociation of germ-free mice revealed that the radiation effect was observable only for Enterobacter cloacae, never for Streptococcus faecium, Bifidobacterium adlesentis, or Escherichia coli. After abdominal irradiation of regular mice, E. cloacae multiplied in cecal contents, adhered to mucous membranes, invaded the cecal wall, and translocated to mesenteric lymph nodes. Intravenous administration of E. cloacae in place of abdominal irradiation inhibited metastases. E. cloacae-monoassociated mice developed fewer metastases than germ-free mice, and the reduction was further enhanced by abdominal irradiation. We concluded that abdominal irradiation caused the invasion of E. cloacae from the mucous membrane of the intestine and inhibited formation of lung metastases

Mining Significant Semantic Locations from GPS Data

DEFF Research Database (Denmark)

Cao, Xin; Cong, Gao; Jensen, Christian Søndergaard

2010-01-01

With the increasing deployment and use of GPS-enabled devices, massive amounts of GPS data are becoming available. We propose a general framework for the mining of semantically meaningful, significant locations, e.g., shopping malls and restaurants, from such data. We present techniques capable...... of extracting semantic locations from GPS data. We capture the relationships between locations and between locations and users with a graph. Significance is then assigned to locations using random walks over the graph that propagates significance among the locations. In doing so, mutual reinforcement between...

Discovering the Significance of Scientific Design Practice

DEFF Research Database (Denmark)

Pries-Heje, Jan; Baskerville, Richard

2016-01-01

This paper discusses and defines the achievement of significance in design science research. We review the values and processes of old-science and how this mode of science attacks the complexity of scientific knowledge production through analysis. We then explain how new-science attacks...... the complexity of scientific knowledge production through synthesis. The work argues that significance of the new-science contribution in design science can be obfuscated when wrapped in old-science. This understanding helps reveal how new-science, such as design science research, constitutes its significance...

Mining significant semantic locations from GPS data

DEFF Research Database (Denmark)

Cao, Xin; Cong, Gao; Jensen, Christian S.

2010-01-01

With the increasing deployment and use of GPS-enabled devices, massive amounts of GPS data are becoming available. We propose a general framework for the mining of semantically meaningful, significant locations, e.g., shopping malls and restaurants, from such data. We present techniques capable...... of extracting semantic locations from GPS data. We capture the relationships between locations and between locations and users with a graph. Significance is then assigned to locations using random walks over the graph that propagates significance among the locations. In doing so, mutual reinforcement between...

No significant effect of cannabis use on the count and percentage of circulating CD4 T-cells in HIV-HCV co-infected patients (ANRS CO13-HEPAVIH French cohort).

Science.gov (United States)

Marcellin, Fabienne; Lions, Caroline; Rosenthal, Eric; Roux, Perrine; Sogni, Philippe; Wittkop, Linda; Protopopescu, Camelia; Spire, Bruno; Salmon-Ceron, Dominique; Dabis, François; Carrieri, Maria Patrizia

2017-03-01

Despite cannabis use being very common in patients co-infected with HIV and hepatitis C virus (HCV), its effect on these patients' immune systems remains undocumented. Documenting the potential effect of cannabis use on HIV immunological markers would help caregivers make more targeted health recommendations to co-infected patients. We performed a longitudinal analysis of the relationship between cannabis use and peripheral blood CD4 T-cell measures in co-infected patients receiving antiretroviral therapy. Cannabis use was assessed using annual self-administered questionnaires in 955 patients (2386 visits) enrolled in the ANRS CO13-HEPAVIH cohort. The effect of cannabis use on circulating CD4 T-cell count and percentage was estimated using multivariate linear regression models with generalised estimating equations. Sensitivity analyses were conducted after excluding visits where (i) tobacco use and (ii) smoking >=10 tobacco cigarettes/day were reported. At the first visit, 48% of patients reported cannabis use during the previous four weeks, and 58% of these patients also smoked ≥10 tobacco cigarettes/day. After multiple adjustment, cannabis use was not significantly associated with either circulating CD4 T-cell count [model coefficient (95% confidence interval): 0.27 (-0.07; 0.62), P = 0.12] or percentage [-0.04 (-0.45; 0.36), P = 0.83]. Sensitivity analyses confirmed these results. Findings show no evidence for a negative effect of cannabis use on circulating CD4 T-cell counts/percentages in HIV-HCV co-infected patients. In-depth immunological studies are needed to document whether cannabis has a harmful effect on CD4 levels in lungs and on cells' functional properties. [Marcellin F, Lions C, Rosenthal E, Roux P, Sogni P, Wittkop L, Protopopescu C, Spire B, Salmon-Ceron D, Dabis F, Carrieri MP, HEPAVIH ANRS CO13 Study Group. No significant effect of cannabis use on the count and percentage of circulating CD4 T-cells in HIV-HCV co-infected patients

Gender and race are significant determinants of students' food choices on a college campus.

Science.gov (United States)

Boek, Stacey; Bianco-Simeral, Stephanie; Chan, Kenny; Goto, Keiko

2012-01-01

To examine the roles of gender and race in students' determinants of food choices on a college campus. A total of 405 college students participated in a survey entitled "Campus Food: You Tell Us!" Chi-square and logistic regression were used to examine associations between demographics and food choice determinants. Gender and race appeared to play a significant role in determinants of students' food dislikes. Males were significantly more likely to choose cost, taste, and poor quality over poor nutrition as determinants. White students were significantly less likely to choose cost, inconvenience, and taste over poor nutrition than students of other races. Gender was also a significant factor associated with student preferences for campus dining location and determinants of unhealthful food. Future marketing may be more effective if tailored to gender and race. Nutrition educators should consider addressing taste and convenience when attempting to influence students' food choices. Copyright © 2012 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Indexed effective orifice area is a significant predictor of higher mid- and long-term mortality rates following aortic valve replacement in patients with prosthesis-patient mismatch.

Science.gov (United States)

Chen, Jian; Lin, Yiyun; Kang, Bo; Wang, Zhinong

2014-02-01

Prosthesis-patient mismatch (PPM) is defined as a too-small effective orifice area (EOA) of an inserted prosthetic relative to body size, resulting in an abnormally high postoperative gradient. It is unclear, however, whether residual stenosis after aortic valve replacement (AVR) has a negative impact on mid- and long-term survivals. We searched electronic databases, including PubMed, Embase, Medline and the Cochrane controlled trials register, through October 2012, to identify published full-text English studies on the association between PPM and mortality rates. A significant PPM was defined as an indexed EOA (iEOA)<0.85 cm2/m2, and severe PPM as an iEOA<0.65 cm2/m2. Two reviewers independently assessed the studies for inclusion and extracted data. Fourteen observational studies, involving 14 874 patients, met our final inclusion criteria. Meta-analysis demonstrated that PPM significantly increased mid-term (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.19-1.69) and long-term (OR 1.52, 95% CI 1.26-1.84) all-cause mortalities. Subgroup analysis showed that PPM was associated with higher mid- and long-term mortality rates only in younger and predominantly female populations. Risk-adjusted sensitivity analysis showed that severe PPM was associated with reduced survival (adjusted hazard ratio [HR] 1.50, 95% CI 1.24-1.80), whereas moderate PPM was not (adjusted HR 0.96, 95% CI 0.86-1.07). Regardless of severity, however, PPM had a negative effect on survival in patients with impaired ejection fraction (adjusted HR 1.26, 95% CI 1.09-1.47). PPM (iEOA<0.85 cm2/m2) after AVR tended to be associated with increased long-term all-cause mortality in younger patients, females and patients with preoperative left ventricular dysfunction. Severe PPM (iEOA<0.65 cm2/m2) was a significant predictor of reduced long-term survival in all populations undergoing AVR.

Abrupt opium discontinuation has no significant triggering effect on acute myocardial infarction.

Science.gov (United States)

Masoomi, Mohammad; Zare, Jahangir; Nasri, Hamidreza; Mirzazadeh, Ali; Sheikhvatan, Mehrdad

2011-04-01

A deleterious effect of withdrawal symptoms due to abrupt discontinuation of opium on the cardiovascular system is one of the recent interesting topics in the cardiovascular field. The current study hypothesized that the withdrawal syndrome due to discontinuing opium might be an important trigger for the appearance of acute myocardial infarction. Eighty-one opium-addicted individuals who were candidates for cardiovascular clinical evaluation and consecutively hospitalized in the coronary care unit (CCU) ward of Shafa Hospital in Kerman between January and July 2009 were included in the study and categorized in the case group, including patients experiencing withdrawal symptoms within 6-12 h after the reduced or discontinued use of opium according to the Diagnostic and Statistical Manual of Mental Disorders-revised IV version (DSM-IV-R) criteria for opium dependence and withdrawal, and the control group, without opium withdrawal symptoms. The appearance of acute myocardial infarction was compared between the two groups using multivariable regression models. Acute myocardial infarction occurred in 50.0% of those with withdrawal symptoms and in 45.1% of patients without evidence of opium withdrawal (P = 0.669). Multivariable analysis showed that opium withdrawal symptoms were not a trigger for acute myocardial infarction adjusting for demographic characteristics, marital status, education level and common coronary artery disease risk profiles [odds ratio (OR) = 0.920, 95% confidence interval (CI) = 0.350-2.419, P = 0.866]. Also, daily dose of opium before reducing or discontinuing use did not predict the appearance of myocardial infarction in the presence of confounder variables (OR = 0.975, 95% CI = 0.832-1.143, P = 0.755). Withdrawal syndrome due to abrupt discontinuation of opium does not have a triggering role for appearance of acute myocardial infarction.

Activation of immune functions via induction of glutathione of lymphocytes by low-dose, whole-body irradiation with gamma-rays

International Nuclear Information System (INIS)

Shuji Kojima; Hisatake Hayase; Mareyuki Takahashi

2007-01-01

Complete text of publication follows. We have recently found that low doses of radiation, unlike higher doses, do not always cause a decrease of cellular glutathione, but they can increase it, leading to an elevation of Con A-induced proliferation of splenocytes. In this study, we first examined whether the increase of glutathione level induced by low-dose gamma-ray irradiation is involved in the appearance of enhanced natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC), leading to delayed tumor growth in Ehrlich solid tumor (EST)-bearing mice. NK activity in ICR mouse splenocytes was significantly increased from 4 h to 6 h after a single whole-body gamma-ray irradiation at 0.5 Gy, and thereafter decreased almost to the zero-time level by 24 h post-irradiation. ADCC was also increased significantly in a similar way. Reduced glutathione exogenously added to splenocytes obtained from normal mice enhanced both NK activity and ADCC in a dose-dependent manner. The inhibitory effect of the radiation on tumor growth was then examined in EST-bearing mice. Repeated low-dose irradiation (0.5 Gy, four times, before and within an early time after the inoculation) significantly delayed the tumor growth. Finally, the effect of single low-dose (0.5 Gy), whole-body gamma-ray irradiation on immune balance (Th1/Th2) was examined in order to elucidate the mechanism underlying the anti-tumor immunity. Recent studies indicate that Th1/Th2 balance plays an important role in the immune responses involved in anti-tumor immunity. The activity of NK is hallmarks of cell-mediated immunity, and play key roles in anti-tumor immunity. The percentage of B cells in blood lymphocytes was selectively decreased after the radiation, concomitantly with an increase in that of helper T cell population, favoring Th1 polarization. The IFN-gamma level in splenocyte culture prepared from EST-bearing mice was significantly increased 48 h after the radiation, though the level of

alpha-Lactalbumin species variation, HAMLET formation, and tumor cell death.

Science.gov (United States)

Pettersson, Jenny; Mossberg, Ann-Kristin; Svanborg, Catharina

2006-06-23

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a tumoricidal complex of apo alpha-lactalbumin and oleic acid, formed in casein after low pH treatment of human milk. This study examined if HAMLET-like complexes are present in casein from different species and if isolated alpha-lactalbumin from those species can form such complexes with oleic acid. Casein from human, bovine, equine, and porcine milk was separated by ion exchange chromatography and active complexes were only found in human casein. This was not explained by alpha-lactalbumin sequence variation, as purified bovine, equine, porcine, and caprine alpha-lactalbumins formed complexes with oleic acid with biological activity similar to HAMLET. We conclude that structural variation of alpha-lactalbumins does not preclude the formation of HAMLET-like complexes and that natural HAMLET formation in casein was unique to human milk, which also showed the highest oleic acid content.

IKKα Promotes Intestinal Tumorigenesis by Limiting Recruitment of M1-like Polarized Myeloid Cells

Directory of Open Access Journals (Sweden)

Serkan I. Göktuna

2014-06-01

Full Text Available The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC therapy.

The Effect of Land Use on Availability of Japanese Freshwater Resources and Its Significance for Water Footprinting

Directory of Open Access Journals (Sweden)

Masaharu Motoshita

2016-01-01

Full Text Available All relevant effects on water must be assessed in water footprinting for identifying hotspots and managing the impacts of products, processes, and services throughout the life cycle. Although several studies have focused on physical water scarcity and degradation of water quality, the relevance of land use in water footprinting has not been widely addressed. Here, we aimed to verify the extent of land-use effect in the context of water footprinting. Intensity factors of land use regarding the loss of freshwater availability are modeled by calculating water balance at grid scale in Japan. A water footprint inventory and impacts related to land use are assessed by applying the developed intensity factors and comparing them with those related to water consumption and degradation. Artificial land use such as urban area results in the loss of many parts of available freshwater input by precipitation. When considering water footprint inventory, the dominance of land use is less than that of water consumption. However, the effect of land use is relevant to the assessment of water footprint impact by differentiating stress on water resources. The exclusion of land use effect underestimates the water footprint of goods produced in Japan by an average of around 37%.

Practical Significance of Basin Water Market Construction on Agricultural Production

Institute of Scientific and Technical Information of China (English)

2011-01-01

On the basis of introducing the concept of water market and the water market research in cluding both domestic market and foreign market,the system design features of water market are analyzed.The features include the prior distribution of agricultural water right,the close construction of market structure,reasonable price of water obtaining right and water pollution-discharge right and scientific stipulation of total volume of water use and total volume of pollution drainage.The practical significances of basin water market construction on Chinese agricultural production are revealed,which clover safeguarding the safety of agricultural water;effectively alleviating agricultural drought;saving the agricultural production water and improving the quality of agricultural products.

Significant Factors Influencing Rural Residents’ Well-Being with Regard to Electricity Consumption: An Empirical Analysis in China

Directory of Open Access Journals (Sweden)

Sen Guo

2016-11-01

Full Text Available The electric universal service policy, which has been implemented for many years in China, aims to meet the basic electricity demands of rural residents. Electricity consumption can facilitate the daily life of rural residents, such as lighting and cooking, which are necessary to their well-being. In practice, the well-being of rural residents due to electricity consumption is influenced by many factors. Therefore, to improve the well-being of rural residents, it is quite necessary to identify and optimize the significant factors that make the electric universal service policy play its prescribed role as well as possible. In this paper, the significant factors influencing rural residents’ well-being obtained from electricity consumption were identified and discussed by employing the Ordered Probit model. The results indicate that: (1 there are six significant factors, of which ‘educational level’, ‘health condition’, ‘each person income of a family per month’, and ‘service time of household appliances’ play positive roles in rural residents’ well-being, while ‘average power interruption times’ and ‘monthly electric charges’ have negative impacts; (2 for significant factors with positive roles, ‘educational level’ and ‘health condition’ show larger marginal effects on rural residents’ well-being; and (3 for significant factors with negative impacts, ‘average power interruption times’ has the greatest marginal effect. Finally, policy implications are proposed for improving rural residents’ well-being, which can also contribute to the effective implementation of the electric universal service policy in China.

Systemically administered AAV9-sTRAIL combats invasive glioblastoma in a patient-derived orthotopic xenograft model

Directory of Open Access Journals (Sweden)

Matheus HW Crommentuijn

2016-01-01

Full Text Available Adeno-associated virus (AAV vectors expressing tumoricidal genes injected directly into brain tumors have shown some promise, however, invasive tumor cells are relatively unaffected. Systemic injection of AAV9 vectors provides widespread delivery to the brain and potentially the tumor/microenvironment. Here we assessed AAV9 for potential glioblastoma therapy using two different promoters driving the expression of the secreted anti-cancer agent sTRAIL as a transgene model; the ubiquitously active chicken β-actin (CBA promoter and the neuron-specific enolase (NSE promoter to restrict expression in brain. Intravenous injection of AAV9 vectors encoding a bioluminescent reporter showed similar distribution patterns, although the NSE promoter yielded 100-fold lower expression in the abdomen (liver, with the brain-to-liver expression ratio remaining the same. The main cell types targeted by the CBA promoter were astrocytes, neurons and endothelial cells, while expression by NSE promoter mostly occurred in neurons. Intravenous administration of either AAV9-CBA-sTRAIL or AAV9-NSE-sTRAIL vectors to mice bearing intracranial patient-derived glioblastoma xenografts led to a slower tumor growth and significantly increased survival, with the CBA promoter having higher efficacy. To our knowledge, this is the first report showing the potential of systemic injection of AAV9 vector encoding a therapeutic gene for the treatment of brain tumors.

The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally?

Science.gov (United States)

Yoshimura, Teizo

2018-01-29

Macrophages are one of the most abundant leukocyte populations infiltrating tumor tissues and can exhibit both tumoricidal and tumor-promoting activities. In 1989, we reported the purification of monocyte chemoattractant protein-1 (MCP-1) from culture supernatants of mitogen-activated peripheral blood mononuclear cells and tumor cells. MCP-1 is a potent monocyte-attracting chemokine, identical to the previously described lymphocyte-derived chemotactic factor or tumor-derived chemotactic factor, and greatly contributes to the recruitment of blood monocytes into sites of inflammatory responses and tumors. Because in vitro-cultured tumor cells often produce significant amounts of MCP-1, tumor cells are considered to be the main source of MCP-1. However, various non-tumor cells in the tumor stroma also produce MCP-1 in response to stimuli. Studies performed in vitro and in vivo have provided evidence that MCP-1 production in tumors is a consequence of complex interactions between tumor cells and non-tumor cells and that both tumor cells and non-tumor cells contribute to the production of MCP-1. Although MCP-1 production was once considered to be a part of host defense against tumors, it is now believed to regulate the vicious cycle between tumor cells and macrophages that promotes the progression of tumors.Cellular and Molecular Immunology advance online publication, 29 January 2018; doi:10.1038/cmi.2017.135.

Significant prolongation of hamster liver transplant survival in Lewis rats by total-lymphoid irradiation, cyclosporine, and splenectomy

International Nuclear Information System (INIS)

Yamaguchi, Y.; Halperin, E.C.; Harland, R.C.; Wyble, C.; Bollinger, R.R.

1990-01-01

The effects of total lymphoid irradiation, cyclosporine and splenectomy alone and in combination have been studied in liver transplants from the LVG hamster to the LEW rat. Neither CsA alone, splenectomy alone, nor TLI alone prolonged graft survival. CsA/splenectomy and TLI/CsA produced significant prolongation of graft survival. TLI/CsA/splenectomy prolonged graft survival by over sixfold compared with controls. While CsA alone was ineffective in reducing lymphocytotoxic antidonor antibody, splenectomy alone or CsA/splenectomy did significantly suppress production of antibody. Only very low levels of antibody could be detected in animals treated with TLI/CsA/splenectomy. TLI/CsA/splenectomy has an immunosuppressive effect sufficient to significantly prolong liver graft survival in the LVG hamster to LEW rat combination and may represent a promising treatment protocol in experimental cross-species transplantation

NCK2 Is Significantly Associated with Opiates Addiction in African-Origin Men

Directory of Open Access Journals (Sweden)

Zhifa Liu

2013-01-01

Full Text Available Substance dependence is a complex environmental and genetic disorder with significant social and medical concerns. Understanding the etiology of substance dependence is imperative to the development of effective treatment and prevention strategies. To this end, substantial effort has been made to identify genes underlying substance dependence, and in recent years, genome-wide association studies (GWASs have led to discoveries of numerous genetic variants for complex diseases including substance dependence. Most of the GWAS discoveries were only based on single nucleotide polymorphisms (SNPs and a single dichotomized outcome. By employing both SNP- and gene-based methods of analysis, we identified a strong (odds ratio = 13.87 and significant (P value = 1.33E−11 association of an SNP in the NCK2 gene on chromosome 2 with opiates addiction in African-origin men. Codependence analysis also identified a genome-wide significant association between NCK2 and comorbidity of substance dependence (P value = 3.65E−08 in African-origin men. Furthermore, we observed that the association between the NCK2 gene (P value = 3.12E−10 and opiates addiction reached the gene-based genome-wide significant level. In summary, our findings provided the first evidence for the involvement of NCK2 in the susceptibility to opiates addiction and further revealed the racial and gender specificities of its impact.

Significance of non-classical damping in seismic qualification of equipment and piping

Energy Technology Data Exchange (ETDEWEB)

Gupta, Abhinav, E-mail: agupta1@ncsu.edu; Bose, Mrinal K.

2017-06-15

Highlights: • Damping in coupled building-piping or building-equipment systems is nonlclassical. • Significance of nonclassical damping is illustrated. • Classical damping assumption can over predict or under predict response. • Significance of nonclassical damping increases for very light secondary systems. • Composite modal damping is another form of classical damping. - Abstract: This paper presents a discussion on the significance of non-classical damping in coupled primary-secondary systems such as building-equipment or building-piping. Closed-form expressions are used to illustrate that the effect of non-classical damping is significant in systems with tuned or nearly tuned uncoupled modes when the mass-interaction is sufficiently small. Further, simple primary-secondary systems are used to illustrate that composite modal damping is another form of classical damping for which the transformed damping matrix, obtained after pre- and post-multiplication of the damping matrix with the modal matrix, contains only diagonal terms. Both the composite and the classical damping give almost identical results that can be much different from the corresponding results for non-classical damping. Finally, it is shown that consideration of classical damping (ignoring the off-diagonal terms) can give excessively conservative results in nearly tuned primary-secondary systems. For perfectly tuned primary-secondary systems, however, classical damping can give responses that are much lower than what they should be.

Performance evaluation recommendations of nuclear power plants outdoor significant civil structures earthquake resistance. Technical documentation

International Nuclear Information System (INIS)

2005-06-01

The Japan Society of Civil Engineers has updated performance evaluation recommendations of nuclear power plants outdoor significant civil structures earthquake resistance in June 2005. Experimental and analytical considerations on the seismic effects evaluation criteria, such as analytical seismic models of soils for underground structures, effects of vertical motions on time-history dynamic analysis and shear fracture of reinforced concretes by cyclic loadings, were shown in this document and incorporated in new recommendations. (T. Tanaka)

Development of Quantitative Framework for Event Significance Evaluation

International Nuclear Information System (INIS)

Lee, Durk Hun; Kim, Min Chull; Kim, Inn Seock

2010-01-01

There is an increasing trend in quantitative evaluation of the safety significance of operational events using Probabilistic Safety Assessment (PSA) technique. An integrated framework for evaluation of event significance has been developed by Korea Institute of Nuclear Safety (KINS), which consists of an assessment hierarchy and a number of matrices. The safety significance of various events, e.g., internal or external initiating events that occurred during at-power or shutdown conditions, can be quantitatively analyzed using this framework, and then, the events rated according to their significance. This paper briefly describes the basic concept of the integrated quantitative framework for evaluation of event significance, focusing on the assessment hierarchy

Identification of significant process variables for a flow-through supercritical water oxidation reactor

International Nuclear Information System (INIS)

Rossi, R.E.

1992-05-01

The effects of four process variables on the destruction efficiency of a flow-through supercritical water oxidation reactor were investigated. These process variables included: (1) reactor throughput (GPH), (2) concentration of the surrogate waste (% acetone), (3) maximum reactor tube-wall temperature (OC), and (4) applied stoichiometric oxygen. The analysis was conducted utilizing two-level factorial experiments, steepest ascent methods, and central composite designs. This experimental protocol assures efficient experimentation and allows for an empirical response surface model of the system to be developed. This experimentation identified a significant positive effect for stoichiometric oxygen applied and temperature variations between 400 to 500 degrees C. The increase in destruction efficiency due to stoichiometric 0 2 provides strong evidence that supercritical water oxidations are catalyzed by excess oxygen, and the strong temperature effect is a result of large increases in the kinetic rates for this temperature range. However, increasing temperature between 550 to 650 degrees C does not provide substantial increases in destruction efficiency. In addition, destruction efficiency is significantly unproved by increasing the Reynolds number and residence time. The destruction efficiency of the reactor is also dependent upon the initial concentration of surrogate waste. This concentration dependence may indicate first-order supercritical CO kinetics is inadequate for describing all waste types and reactor configurations. Alternatively, it may indicate reactant mixing, caused by local turbulence at the oxidation fronts of these higher concentration waste streams, results in higher destruction efficiencies

Effect of follow-up period on minimal-significant dose in the atomic-bomb survivor studies

Energy Technology Data Exchange (ETDEWEB)

Cologne, John; Grant, Eric J.; Cullings, Harry M.; Ozasa, Kotaro [Radiation Effects Research Foundation, Hiroshima (Japan); Preston, Dale L. [Hirosoft International, Eureka, CA (United States)

2018-03-15

It was recently suggested that earlier reports on solid-cancer mortality and incidence in the Life Span Study of atomic-bomb survivors contain still-useful information about low-dose risk that should not be ignored, because longer follow-up may lead to attenuated estimates of low-dose risk due to longer time since exposure. Here it is demonstrated, through the use of all follow-up data and risk models stratified on period of follow-up (as opposed to sub-setting the data by follow-up period), that the appearance of risk attenuation over time may be the result of less-precise risk estimation - in particular, imprecise estimation of effect-modification parameters - in the earlier periods. Longer follow-up, in addition to allowing more-precise estimation of risk due to larger numbers of radiation-related cases, provides more-precise adjustment for background mortality or incidence and more-accurate assessment of risk modification by age at exposure and attained age. It is concluded that the latest follow-up data are most appropriate for inferring low-dose risk. Furthermore, if researchers are interested in effects of time since exposure, the most-recent follow-up data should be considered rather than the results of earlier reports. (orig.)

The significant role of plasmonic effects in femtosecond laser-induced grating fabrication on the nanoscale

Energy Technology Data Exchange (ETDEWEB)

Huang, Min; Zhao, Fuli [State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-sen University, Guangzhou, 510275 (China); Cheng, Ya; Xu, Zhizhan [State Key Laboratory of High Field Laser Physics, Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, P.O. Box 800-211, Shanghai, 201800 (China)

2013-02-15

Nowadays, plasmonics aiming at manipulating light beyond the diffraction limit has aroused great interest on account of the promise of nanoscale optical devices. Generally, the ability to break diffraction barrier is achieved via controlling surface plasmons (SPs) on artificial structures as products of human ingenuity. Here, nevertheless, it is demonstrated that in short-pulse laser ablation ultrafast active plasmonic structures spontaneously generate by virtue of plasmonic effects rather than human will. First, with the experimental results on ZnO, Si, and GaAs, explicit evidence is provided for the grating-splitting phenomenon that acts as a direct route for the formation of laser-induced deep-subwavelength gratings. The splitting mechanism can break through the diffraction limit and push laser-induced structures towards the nanoscale. Then, through comprehensive numerical studies based on the viewpoint of plasmonics, it can be confirmed that the grating-splitting phenomenon originates in the conversion of SP modes from the resonant to the nonresonant mode and further to the inphase or antiphase asymmetric mode. In short, plasmonic effects play an important role in ultrafast laser-induced grating splitting towards the nanoscale, which will provide new insights into the mechanisms of ultrafast laser-induced nanostructures. (copyright 2012 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

The significant role of plasmonic effects in femtosecond laser-induced grating fabrication on the nanoscale

International Nuclear Information System (INIS)

Huang, Min; Zhao, Fuli; Cheng, Ya; Xu, Zhizhan

2013-01-01

Nowadays, plasmonics aiming at manipulating light beyond the diffraction limit has aroused great interest on account of the promise of nanoscale optical devices. Generally, the ability to break diffraction barrier is achieved via controlling surface plasmons (SPs) on artificial structures as products of human ingenuity. Here, nevertheless, it is demonstrated that in short-pulse laser ablation ultrafast active plasmonic structures spontaneously generate by virtue of plasmonic effects rather than human will. First, with the experimental results on ZnO, Si, and GaAs, explicit evidence is provided for the grating-splitting phenomenon that acts as a direct route for the formation of laser-induced deep-subwavelength gratings. The splitting mechanism can break through the diffraction limit and push laser-induced structures towards the nanoscale. Then, through comprehensive numerical studies based on the viewpoint of plasmonics, it can be confirmed that the grating-splitting phenomenon originates in the conversion of SP modes from the resonant to the nonresonant mode and further to the inphase or antiphase asymmetric mode. In short, plasmonic effects play an important role in ultrafast laser-induced grating splitting towards the nanoscale, which will provide new insights into the mechanisms of ultrafast laser-induced nanostructures. (copyright 2012 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Significance of 18F-FDG PET/CT imaging in the evaluation of the efficacy of lymphoma

Institute of Scientific and Technical Information of China (English)

CHEN Chengcheng; WANG Zhengguang; CHENG Nan

2014-01-01

To evaluate the 18F-labeled deoxyglucose (18F-FDG) PET/CT imaging in the evaluation of the efficacy of ly-mphoma significance.Methods:42 cases of our hospital patients with malignant lymphoma for 2-5 times 18F-FDG PET/CT imaging results in the treatment process, and the treatment process simple CT results were compared and analyzed, the final results were confirmed by pathology and clinical. Results:The lesions were found in153,including 141 malignant, benign 12, sensitivity, specificity, and accuracy evaluating of lymphoma treatment effect of 18F-FDG PET/CT were, 99.30%, 91.67%, 98.70%, were significantly better than CT examination (Peffective means of monitoring the efficacy of lymphoma, it can provide the basis for effective treatment programs in clinical work.

Mobile phone use for 5 minutes can cause significant memory impairment in humans.

Science.gov (United States)

Kalafatakis, F; Bekiaridis-Moschou, D; Gkioka, Eirini; Tsolaki, Magda

2017-01-01

control group the second measurement was better than the first and the third even better than both previous ones. All differences were statistically significant. The reduction of the performance in the task after using the MP was even higher for the age group of 60-80 years old in comparison with younger age groups, as well as for the individuals with MCI in comparison to healthy participants. Age was significantly negative correlated with performance in the task, while gender showed no significant correlation. MP use has a significant negative impact on working memory performance of human participants. The effect is apparent even for a 5 minute use of the MP. Working memory deficits are greater not only for the 60 years old and above participants but also for individuals with Mild Cognitive Impairment. These results are in agreement with previous studies on animals as well as humans on the effects of MP use on the brain. It is argued that low sensitivity of some of the cognitive tasks used until now and the lack of a validated tool in the form of a cognitive task may account for some of the variability in the literature so far. It is suggested that the experimental paradigm that was used in this study for an increased sensitivity measurement of cognitive function and working memory processes in particular may be used for the display of the effects of MP use on cognitive function and for the development of other tasks sensitive to it. Overall, it is concluded that the development of certain restrictions on MP use is necessary for the protection of the brain health of the users.

Significance of the carboxyhemoglobin level for out-of-hospital cardiopulmonary arrest

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Youichi Yanagawa

2012-01-01

Full Text Available Background: At low concentrations, carbon monoxide (CO can confer cyto and tissue-protective effects, such as endogenous Heme oxygenase 1 expression, which has antioxidative, anti-inflammatory, antiproliferative, and antiapoptotic effects. The level of carboxyhemoglobin in the blood is an indicator of the endogenous production of CO and inhaled CO. Aim of study: To investigate the significance of the value of carboxyhemoglobin for out-of-hospital (OH cardiopulmonary arrest (CPA. Materials and Methods: This study involved a medical chart review of cases treated from January to December 2005. The inclusion criteria included a patient who was transported to this department due to an OH CPA. The exclusion criteria included a patient who did not undergo blood gas analysis on arrival and who experienced CPA due to acute carbon monoxide intoxication. The subjects were divided into two groups based on their final outcome of either survival or non-survival. Results: There was no significant difference associated with the sex, age, frequency of witness collapse, bystander cardiopulmonary arrest, electrocardiogram at scene, cause of CPA, value of PCO 2 , HCO3 - , and methemoglobin. The frequency of OH return of spontaneous circulation and the value of pH, PO 2 , base excess, and carboxyhemoglobin in the survival group were greater than those values in the non-survival group. There were no subjects whose carboxyhemoglobin level was 0% on arrival in the survival groups. Conclusion: There appeared to be an association between higher carboxyhemoglobin levels and survival in comparison with non-survival patients.

An Acute Lateral Ankle Sprain Significantly Decreases Physical Activity across the Lifespan

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Tricia Hubbard-Turner, Erik A. Wikstrom, Sophie Guderian, Michael J. Turner

2015-09-01

Full Text Available We do not know the impact an ankle sprain has on physical activity levels across the lifespan. With the negative consequences of physical inactivity well established, understanding the effect of an ankle sprain on this outcome is critical. The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model. Thirty male mice (CBA/J were randomly placed into one of three groups: the transected calcaneofibular ligament (CFL group, the transected anterior talofibular ligament (ATFL/CFL group, and a SHAM group. Three days after surgery, all of the mice were individually housed in a cage containing a solid surface running wheel. Physical activity levels were recorded and averaged every week across the mouse’s lifespan. The SHAM mice ran significantly more distance each day compared to the remaining two running groups (post hoc p = 0.011. Daily duration was different between the three running groups (p = 0.048. The SHAM mice ran significantly more minutes each day compared to the remaining two running groups (post hoc p=0.046 while the ATFL/CFL mice ran significantly less minutes each day (post hoc p = 0.028 compared to both the SHAM and CFL only group. The SHAM mice ran at a faster daily speed versus the remaining two groups of mice (post hoc p = 0.019 and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group (post hoc p = 0.005. The results of this study indicate that a single ankle sprain significantly decreases physical activity across the lifespan in mice. This decrease in physical activity can potentially lead to the development of numerous chronic diseases. An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately.

Clinical significance of pretreatment FDG PET/CT IN MOBG-avid pediatric neuroblastoma

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Kang, Seo Young; Kim, Yong Il; Cheon, Gi Jeong; Kang, Keon Wook; Chung, June Key; Lee, Dong Soo; Kang, Hyoung Jin; Shin, Hee Young [Seoul National University Hospital, Seoul (Korea, Republic of); Kim, E. Edmund [Seoul National University, Seoul (Korea, Republic of); Rahim, Muhammad Kashif [Nishtar Medical College and Hospital, Multan (Pakistan)

2017-06-15

{sup 18}F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is well known to have clinical significance in the initial staging and response evaluation of the many kinds of neoplasms. However, its role in the pediatric neuroblastoma is not clearly defined. In the present study, the clinical significance of FDG-PET/computed tomography (CT) in 123I- or 131I-metaiodobenzylguanidine (MIBG)-avid pediatric neuroblastoma was investigated. Twenty patients with neuroblastoma who undertook pretreatment FDG PET/CT at our institute between 2008 and 2015 and showed MIBG avidity were retrospectively enrolled in the present study. Clinical information—including histopathology, and serum markers—and several PET parameters—including SUVmax of the primary lesion (Psuv), target-to-background ratio (TBR), metabolic tumor volume (MTV), and coefficient of variation (CV)—were analyzed. The prognostic effect of PET parameters was evaluated in terms of progression-free survival (PFS). Total 20 patients (4.5 ± 3.5 years) were divided as two groups by disease progression. Six patients (30.0 %) experienced disease progression and one patient (5.0 %) died during follow-up period. There were not statistically significant in age, stage, MYCN status, primary tumor size, serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE), and ferritin level between two groups with progression or no progression. However, Psuv (p = 0.017), TBR (p = 0.09), MTV (p = 0.02), and CV (p = 0.036) showed significant differences between two groups. In univariate analysis, PFS was significantly associated with Psuv (p = 0.021) and TBR (p = 0.023). FDG-PET parameters were significantly related with progression of neuroblastoma. FDG-PET/CT may have the potential as a valuable modality for evaluating prognosis in the patients with MIBG-avid pediatric neuroblastoma.

Clinical significance of percutaneous endoscopic gastrostomy for patients with severe craniocerebral injury

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Du Hanggen

2014-12-01

Full Text Available Objective: To investigate the application of percutaneous endoscopic gastrostomy (PEG to patients with severe craniocerebral injury for the purpose of nutritional support therapy and pulmonary infection prevention. Methods: A total of 43 patients with severe craniocerebral injury admitted to our department from January 2008 to December 2012 received PEG followed by nutritional therapy. There were other 82 patients who were prescribed nasal-feeding nutrition. Nutrition status was evaluated by comparing serum albumin levels, and the incidence of pulmonary infection 1 week before and 2 weeks after operation was identifi ed and compared. Results: Both PEG and nasal-feeding nutrition therapies have significantly levated serum albumin levels (P<0.05. Serum albumin levels before and after nutritional therapies showed no significant difference between the two groups (P>0.05. The incidence of pulmonary infection in PEG group was significantly decreased compared with that in nasal-feeding nutrition group (P<0.05. Conclusion: PEG is an effective method for severe craniocerebral injury patients. It can not only provide enteral nutrition but also prevent pulmonary infection induced by esophageal refl ux. Key words: Gastrostomy; Craniocerebral trauma; Enteral nutrition

Impact significance determination-Designing an approach

International Nuclear Information System (INIS)

Lawrence, David P.

2007-01-01

The question of how best to go about determining the significance of impacts has, to date, only been addressed in a partial and preliminary way. The assumption tends to be made that it is either only necessary to provide explicit, justified reasons for a judgment about significance and/or to explicitly apply a prescribed procedure-a procedure usually involving the staged application of thresholds and/or criteria. The detailed attributes, strengths and limitations of such approaches and possible alternative approaches have yet to be explored systematically. This article addresses these deficiencies by analyzing the characteristics, specific methods and positive and negative tendencies of three general impact significance determination approaches-the technical approach, the collaborative approach and the reasoned argumentation approach. A range of potential composite approaches are also described. With an enhanced understanding of these approaches, together with potential combinations, EIA practitioners and other EIA participants can be in a better position to select an approach appropriate to their needs, to reinforce the positive tendencies and offset the negative tendencies of the selected approach and to combine the best qualities of more than one approach

THE SIGNIFICANCE OF INTERCULTURAL COMPETENCE IN CROSS-CULTURAL COMMUNICATION

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Jadranka Zlomislić

2016-12-01

Full Text Available The aim of this study is to explore the influence of education and additional factors influencing students’ awareness of intercultural differences. For the purposes of this research assessment was carried out with regard to their role in promoting cultural awareness and facing cross-cultural challenges posed by unfamiliar cross-cultural contexts. Cultural education is presumed to be a key factor for achieving a significant increase of cultural sensitivity and cultural awareness in order to ensure successful cross-cultural communication and increase mobility of students/working professionals. For this study, it was assumed that the cultural awareness of students increases due to the courses they take and their overall study experience. A special questionnaire was developed for the purposes of this research, and the obtained results were statistically analyzed with the help of descriptive statistics, the non-parametric chi-square test, and the Mann-Whitney test. The research has shown that intercultural competence has a statistically significant positive effect on the readiness of students to participate in study and work programs abroad. Thus, it is mandatory that foreign language competence as well as intercultural competence be a priority of the curriculum if we are to increase the number of highly educated experts who will be capable to compete successfully as students or professionals in all fields and all cultural areas. If we recognize that globalization has made the world a global village, we all need the intercultural competence to successfully live in it.

Sensitization of Staphylococcus aureus to methicillin and other antibiotics in vitro and in vivo in the presence of HAMLET.

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Laura R Marks

Full Text Available HAMLET (human alpha-lactalbumin made lethal to tumor cells is a protein-lipid complex from human milk with both tumoricidal and bactericidal activities. HAMLET exerts a rather specific bactericidal activity against some respiratory pathogens, with highest activity against Streptococcus pneumoniae, but lacks activity against most other bacterial pathogens, including Staphylococci. Still, ion transport associated with death in S. pneumoniae is also detected to a lower degree in insensitive organisms. In this study we demonstrate that HAMLET acts as an antimicrobial adjuvant that can increase the activity of a broad spectrum of antibiotics (methicillin, vancomycin, gentamicin and erythromycin against multi-drug resistant Staphylococcus aureus, to a degree where they become sensitive to those same antibiotics, both in antimicrobial assays against planktonic and biofilm bacteria and in an in vivo model of nasopharyngeal colonization. We show that HAMLET exerts these effects specifically by dissipating the proton gradient and inducing a sodium-dependent calcium influx that partially depolarizes the plasma membrane, the same mechanism induced during pneumococcal death. These effects results in an increased cell associated binding and/or uptake of penicillin, gentamicin and vancomycin, especially in resistant stains. Finally, HAMLET inhibits the increased resistance of methicillin seen under antibiotic pressure and the bacteria do not become resistant to the adjuvant, which is a major advantageous feature of the molecule. These results highlight HAMLET as a novel antimicrobial adjuvant with the potential to increase the clinical usefulness of antibiotics against drug resistant strains of S. aureus.

Sensitization of Staphylococcus aureus to methicillin and other antibiotics in vitro and in vivo in the presence of HAMLET.

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Marks, Laura R; Clementi, Emily A; Hakansson, Anders P

2013-01-01

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex from human milk with both tumoricidal and bactericidal activities. HAMLET exerts a rather specific bactericidal activity against some respiratory pathogens, with highest activity against Streptococcus pneumoniae, but lacks activity against most other bacterial pathogens, including Staphylococci. Still, ion transport associated with death in S. pneumoniae is also detected to a lower degree in insensitive organisms. In this study we demonstrate that HAMLET acts as an antimicrobial adjuvant that can increase the activity of a broad spectrum of antibiotics (methicillin, vancomycin, gentamicin and erythromycin) against multi-drug resistant Staphylococcus aureus, to a degree where they become sensitive to those same antibiotics, both in antimicrobial assays against planktonic and biofilm bacteria and in an in vivo model of nasopharyngeal colonization. We show that HAMLET exerts these effects specifically by dissipating the proton gradient and inducing a sodium-dependent calcium influx that partially depolarizes the plasma membrane, the same mechanism induced during pneumococcal death. These effects results in an increased cell associated binding and/or uptake of penicillin, gentamicin and vancomycin, especially in resistant stains. Finally, HAMLET inhibits the increased resistance of methicillin seen under antibiotic pressure and the bacteria do not become resistant to the adjuvant, which is a major advantageous feature of the molecule. These results highlight HAMLET as a novel antimicrobial adjuvant with the potential to increase the clinical usefulness of antibiotics against drug resistant strains of S. aureus.

Cytokines in immunogenic cell death: Applications for cancer immunotherapy.

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Showalter, Anne; Limaye, Arati; Oyer, Jeremiah L; Igarashi, Robert; Kittipatarin, Christina; Copik, Alicja J; Khaled, Annette R

2017-09-01

Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions. Natural Killer (NK) cells are a front-line defense against drug-resistant tumors and can provide tumoricidal activity to enhance tumor immune surveillance. Cytokines like IFN-γ or TNF play a crucial role in creating an immunogenic microenvironment and therefore are key players in the fight against metastatic cancer. To this end, a group of anthracyclines or treatments like photodynamic therapy (PDT) exert their effects on cancer cells in a manner that activates the immune system. This process, known as immunogenic cell death (ICD), is characterized by the release of membrane-bound and soluble factors that boost the function of immune cells. This review will explore different types of ICD inducers, some in clinical trials, to demonstrate that optimizing the cytokine response brought about by treatments with ICD-inducing agents is central to promoting anti-cancer immunity that provides long-lasting protection against disease recurrence and metastasis. Copyright © 2017. Published by Elsevier Ltd.

Significantly enhanced thermal conductivity of indium arsenide nanowires via sulfur passivation.

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Xiong, Yucheng; Tang, Hao; Wang, Xiaomeng; Zhao, Yang; Fu, Qiang; Yang, Juekuan; Xu, Dongyan

2017-10-16

In this work, we experimentally investigated the effect of sulfur passivation on thermal transport in indium arsenide (InAs) nanowires. Our measurement results show that thermal conductivity can be enhanced by a ratio up to 159% by sulfur passivation. Current-voltage (I-V) measurements were performed on both unpassivated and S-passivated InAs nanowires to understand the mechanism of thermal conductivity enhancement. We observed a remarkable improvement in electrical conductivity upon sulfur passivation and a significant contribution of electrons to thermal conductivity, which account for the enhanced thermal conductivity of the S-passivated InAs nanowires.

Clinical significance of myoglobinuria and serum myoglobin in heroin-addicted patients

International Nuclear Information System (INIS)

Chen Xuehong; Zhong Ganping; Zhang Lan; Liu Jiangyan

2001-01-01

The authors study the relationship between myoglobinuria and acute rhabdomyolysis in heroin-addicted patients. The levels of myoglobin in serum and urine were determined by RIA in 106 heroin-addicted patients and 30 healthy volunteers who were selected as the controls. The levels of myoglobin in serum and urine increased significantly in heroin-addicted patients in 3 days after giving up heroin, and gradually decreased in 2 weeks but still higher than the levels of the controls (P 0.05). Urine myoglobin detection is a simple and effective method to find out acute rhabdomyolysis derived from heroin addiction early

Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in ApcMin/+ Mice

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Xin Qiao

2017-09-01

Full Text Available Colorectal cancer (CRC is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO on the progression of colon carcinogenesis in ApcMin/+ mice. In addition, these effects were also investigated in HCT116 and SW480 cells. After PEO oral administration (0.2% diet for 12 weeks, PEO significantly improved body weight changes and reduced the tumor burden and tumor multiplicity compared with the untreated mice. Meanwhile, western blot and immunohistochemistry results showed PEO significantly reduced the expression of β-catenin and cyclinD1 in both small intestine and the colon tissues compared with the untreated mice. In addition, PEO treatment significant decreased the cell viability in both HCT116 and SW480 cell lines. It also decreased the levels of β-catenin, cyclinD1, c-myc and p-GSK-3β in HCT116 and SW480 cells at 25 μM. These results indicate that PEO may have potential value in prevention of colon cancer by down-regulating Wnt-related protein.

Corrections for the effects of significant wave height and attitude on Geosat radar altimeter measurements

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Hayne, G. S.; Hancock, D. W., III

1990-01-01

Range estimates from a radar altimeter have biases which are a function of the significant wave height (SWH) and the satellite attitude angle (AA). Based on results of prelaunch Geosat modeling and simulation, a correction for SWH and AA was already applied to the sea-surface height estimates from Geosat's production data processing. By fitting a detailed model radar return waveform to Geosat waveform sampler data, it is possible to provide independent estimates of the height bias, the SWH, and the AA. The waveform fitting has been carried out for 10-sec averages of Geosat waveform sampler data over a wide range of SWH and AA values. The results confirm that Geosat sea-surface-height correction is good to well within the original dm-level specification, but that an additional height correction can be made at the level of several cm.

The historical significance of anaesthesia events at Pearl Harbor.

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Crowhurst, Ja

2014-07-01

Up to the end of World War II, less than 10% of the general anaesthetics administered was with intravenous barbiturates. The remaining 90% of anaesthetics given in the USA were with diethyl ether. In the United Kingdom and elsewhere, chloroform was also popular. Diethyl ether administration was a relatively safe and simple procedure, often delegated to nurses or junior doctors with little or no specific training in anaesthesia. During the Japanese attack on the US bases at Pearl Harbor, with reduced stocks of diethyl ether available, intravenous Sodium Pentothal(®), a most 'sophisticated and complex' drug, was used with devastating effects in many of those hypovolaemic, anaemic and septic patients. The hazards of spinal anaesthesia too were realised very quickly. These effects were compounded by the dearth of trained anaesthetists. This paper presents the significance of the anaesthesia tragedies at Pearl Harbor, and the discovery in the next few years of many other superior drugs that caused medical and other health professionals to realise that anaesthesia needed to be a specialist medical discipline in its own right. Specialist recognition, aided by the foundation of the National Health Service in the UK, the establishment of Faculties of Anaesthesia and appropriate training in pharmacology, physiology and other sciences soon followed. Modern anaesthesiology, as we understand it today, was born and a century or more of ether anaesthesia finally ceased.

Factors significantly related to science achievement of Malaysian middle school students: An analysis of TIMSS 1999 data

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Mokshein, Siti Eshah

The importance of science and technology in the global economy has led to growing emphasis on math and science achievement all over the world. In this study, I seek to identify variables at the student-level and school-level that account for the variation in science achievement of the eighth graders in Malaysia. Using the Third International Math and Science Study (TIMSS) 1999 for Malaysia, a series of HLM analysis was performed. Results indicate that (1) variation in overall science achievement is greater between schools than within schools; (2) both the selected student-level and school-level factors are Important in explaining the variation in the eight graders' achievement In science; (3) the selected student-level variables explain about 13% of the variation in students' achievement within schools, but as an aggregate, they account for a much larger proportion of the between-school variance; (4) the selected school-level variables account for about 55% of the variation between schools; (5) within schools, the effects of self-concept In science, awareness of the social implications of science, gender, and home educational resources are significantly related to achievement; (6) the effects of self-concept in science and awareness of social implications of science are significant even after controlling for the effects of SES; (7) between schools, the effects of the mean of home educational resources, mean of parents' education, mean of awareness of the social implications of science, and emphasis on conducting experiments are significantly related to achievement; (8) the effects of SES variables explain about 50% of the variation in the school means achievement; and (9) the effects of emphasis on conducting experiments on achievement are significant even after controlling for the effects of SES. Since it is hard to change the society, it is recommended that efforts to Improve science achievement be focused more at the school-level, concentrating on variables that

Evaluation of significance of positive familial history in prevalence of hypertension in Isfahan

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Tavassoli A

1997-09-01

Full Text Available Hypertension is one of the most important modifiable risk factors of vascular heart disease. Control of hypertension in different age groups has a significant effect upon the control and prevention of vascular heart disease. A familial pattern is observed in the distribution of blood pressure in different societies. Family history of hypertension has a profound effect on the future risk of developing hypertension. The blood pressure of approximately 8150 inhabitants of Isfahan aged above 18 years was measured during 1993-94. Blood pressure measurements were performed according to the standards set by WHO i.e., on two separate occasions, in the sitting position, and from both arms. A questionnaire was completed consisting of 26 questions, including questions regarding history of hypertension in first and second-degree relatives. Cases with a blood pressure of 140/90 mmHg or more, were referred to the Cardiovascular Research Center of Isfahan for further evaluation. Mean systolic and diastolic blood pressure was higher in cases with a positive family history of hypertension. In this study, 37.4% of the men with hypertension and 45.4% of hypertensive women had positive history of hypertension in first-degree relatives. The association between positive family history and hypertension was not significant in men (P=0.62, but it was significant in women (P=0.000. This difference was less pronounced in the older age groups, which could be explained by the illiteracy of most of the older cases and their ignorance of the existence of hypertension in family members. After correcting for the effects of confounding factors, it appears that positive family history has a stronger association with the development of hypertension in women. Moreover, positive family history is a strong prognostic factor in the likelihood of hypertension in the children of affected cases. These findings emphasize the importance of routine blood pressure measurement in children and

Lipopolysaccharide significantly influences the hepatic triglyceride metabolism in growing pigs.

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Liu, Zhiqing; Liu, Weifeng; Huang, Yanping; Guo, Jun; Zhao, Ruqian; Yang, Xiaojing

2015-06-30

In the practical commercial pig farms, inflammation is a perennial problem, yet most of studies on inflammation are focused on immune response. Actually, inflammation can induce body metabolism disorder which will finally influence animals' growth. In this study, we investigated the effect of acute inflammation on the triglyceride (TG) metabolism in the liver of growing pigs and the possible underlying mechanisms. Twelve male growing pigs were randomly divided into two groups, a control group (received saline) and a LPS group (intramuscular injected with 15 μg/kg LPS). Six hours after LPS injection, the pigs were euthanized and sampled. Biochemical indexes, inflammation factors, lipid metabolism related parameters and mitochondrial function were evaluated. The relationship between glucocorticoid receptor (GR) and the key enzymes of de novo lipogenesis were also investigated by chromatin immunoprecipitation assay (ChIP). LPS induced a serious inflammation in the liver of growing pigs proved by liver morphologic changes, the up-regulated plasma cortisol, tumor necrosis factor-α (TNF-α) content and gene expression of inflammation related genes in liver. For de novo lipogenesis, LPS significantly decreased the gene expression of fatty acid synthase (FAS), Acetyl-CoA carboxylase-1 (ACC-1) and Stearoyl-CoA desaturase-1 (SCD-1), and the protein expression of ACC-1 and SCD-1. For lipolysis, only the gene expression of adipose triglyceride lipase (ATGL) was decreased. LPS did nothing to the gene expression of hormone-sensitive lipase (HSL) and the lipolytic enzymes activities. For β-oxidation, LPS significantly increased the protein expression of CPT-1α, but the gene expression of mitochondrial DNA-encoded genes and the activities of mitochondrial complex IV and V demonstrated no obviously changes. Furthermore, ChIP results showed that LPS significantly decreased the level of GR binding to ACC-1 promoter. LPS infection has a profound impact on hepatic TG metabolism

The historical significance of oak

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J. V. Thirgood

1971-01-01

A brief history of the importance of oak in Europe, contrasting the methods used in France and Britain to propagate the species and manage the forests for continued productivity. The significance of oak as a strategic resource during the sailing-ship era is stressed, and mention is made of the early development of oak management in North America. The international...

Computational Approach to Annotating Variants of Unknown Significance in Clinical Next Generation Sequencing.

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Schulz, Wade L; Tormey, Christopher A; Torres, Richard

2015-01-01

Next generation sequencing (NGS) has become a common technology in the clinical laboratory, particularly for the analysis of malignant neoplasms. However, most mutations identified by NGS are variants of unknown clinical significance (VOUS). Although the approach to define these variants differs by institution, software algorithms that predict variant effect on protein function may be used. However, these algorithms commonly generate conflicting results, potentially adding uncertainty to interpretation. In this review, we examine several computational tools used to predict whether a variant has clinical significance. In addition to describing the role of these tools in clinical diagnostics, we assess their efficacy in analyzing known pathogenic and benign variants in hematologic malignancies. Copyright© by the American Society for Clinical Pathology (ASCP).

A significant-loophole-free test of Bell's theorem with entangled photons

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Giustina, Marissa; Versteegh, Marijn A. M.; Wengerowsky, Sören; Handsteiner, Johannes; Hochrainer, Armin; Phelan, Kevin; Steinlechner, Fabian; Kofler, Johannes; Larsson, Jan-Åke; Abellán, Carlos; Amaya, Waldimar; Mitchell, Morgan W.; Beyer, Jörn; Gerrits, Thomas; Lita, Adriana E.; Shalm, Lynden K.; Nam, Sae Woo; Scheidl, Thomas; Ursin, Rupert; Wittmann, Bernhard; Zeilinger, Anton

2017-10-01

John Bell's theorem of 1964 states that local elements of physical reality, existing independent of measurement, are inconsistent with the predictions of quantum mechanics (Bell, J. S. (1964), Physics (College. Park. Md). Specifically, correlations between measurement results from distant entangled systems would be smaller than predicted by quantum physics. This is expressed in Bell's inequalities. Employing modifications of Bell's inequalities, many experiments have been performed that convincingly support the quantum predictions. Yet, all experiments rely on assumptions, which provide loopholes for a local realist explanation of the measurement. Here we report an experiment with polarization-entangled photons that simultaneously closes the most significant of these loopholes. We use a highly efficient source of entangled photons, distributed these over a distance of 58.5 meters, and implemented rapid random setting generation and high-efficiency detection to observe a violation of a Bell inequality with high statistical significance. The merely statistical probability of our results to occur under local realism is less than 3.74×10-31, corresponding to an 11.5 standard deviation effect.

Clinical significance of plasma atrial natriuretic factor and endothelin detection in hyperthyroidism and hypothyroidism

International Nuclear Information System (INIS)

Zhu Yalin; Huo Ying; Pan Yunlong

2005-01-01

Plasma at rial natriuretic factor (ANF) and endothelin (ET) were detected by RIA in 58 cases of hyperthyroidism and 47 cases of hypothyroidism. Before the ANF and ET concentration of untreatment hyperthyroid patients was much higher than that of treatment hyperthyroid patients, hypothyroid patients before and after treatment and the normal group (P 3 and FT 4 . Compared with the normal group, ANF concentration in treatment hyperthyroid patients, hypothyroid patients before and after treatment was no significantly different (P>0.05), but that in hypothyroid patients before treatment was significantly decreased compared with hypothyroid patients after treatment (P 0.05), but that in hypothyroid patients before treatment was significantly decreased compared with others (P<0.01 and P<0.05). Detection of ANF and ET level may be have a role in supplementary diagnosis and curative effect observation of hyperthyroidism and hypothyroidism. (authors)

Safety significance evaluation system

International Nuclear Information System (INIS)

Lew, B.S.; Yee, D.; Brewer, W.K.; Quattro, P.J.; Kirby, K.D.

1991-01-01

This paper reports that the Pacific Gas and Electric Company (PG and E), in cooperation with ABZ, Incorporated and Science Applications International Corporation (SAIC), investigated the use of artificial intelligence-based programming techniques to assist utility personnel in regulatory compliance problems. The result of this investigation is that artificial intelligence-based programming techniques can successfully be applied to this problem. To demonstrate this, a general methodology was developed and several prototype systems based on this methodology were developed. The prototypes address U.S. Nuclear Regulatory Commission (NRC) event reportability requirements, technical specification compliance based on plant equipment status, and quality assurance assistance. This collection of prototype modules is named the safety significance evaluation system

[Bendamustine-rituximab therapy is effective for transformed follicular lymphoma with significant expression of p53].

Science.gov (United States)

Kuroda, Hiroyuki; Jomen, Wataru; Miura, Shogo; Arihara, Yohei; Yamada, Michiko; Hirako, Tasuku; Abe, Tomoyuki; Sakurai, Tamaki; Fujii, Shigeyuki; Maeda, Masahiro; Fujita, Miri; Nagashima, Kazuo; Okagawa, Yutaka; Hoki, Toshifumi; Kato, Junji

2013-08-01

We describe a patient with transformed follicular lymphoma(FL), expressing p53 but remaining in complete remission(CR) due to bendamustine-rituximab(BR)therapy. She was a 64-year-old female diagnosed with stage IV FL(grade 3A)in July 2007 when she was admitted with right lower abdominal pain and body weight loss. Colonoscopy revealed Bauhin' valve lymphoma of the terminal ileum, and computed tomography(CT)scan showed lymphadenopathy, involving the cervical, mediastinal para-aortic lymph nodes and right tonsil. She received chemotherapy with eight courses of CHOP therapy with rituximab and achieved CR. Two and a half years later, mediastinal lymph node swelling relapsed, and ibritumomab tiuxetan therapy induced the second CR. After ten months, however, a third relapse occurred as a submucosal tumor(SMT)of the stomach. Gastric SMT biopsy showed diffuse large B cell lymphoma(DLBCL)transformation with immunohistochemical expression of p53. Although gastric SMT disappeared after radiotherapy, which achieved the third CR, lymph node swelling was detected again in the para-aortic and-iliac artery lymph nodes in September 2011. Subsequently, she was treated with five courses of BR therapy, because bendamustine had been reported to be effective for p53 gene-deficient B cell neoplasms. The therapy was successful and achieved the fourth CR, demonstrating that BR therapy was effective for p53-expressing DLBCL.

Insect-Specific Virus Discovery: Significance for the Arbovirus Community

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Bethany G. Bolling

2015-09-01

Full Text Available Arthropod-borne viruses (arboviruses, especially those transmitted by mosquitoes, are a significant cause of morbidity and mortality in humans and animals worldwide. Recent discoveries indicate that mosquitoes are naturally infected with a wide range of other viruses, many within taxa occupied by arboviruses that are considered insect-specific. Over the past ten years there has been a dramatic increase in the literature describing novel insect-specific virus detection in mosquitoes, which has provided new insights about viral diversity and evolution, including that of arboviruses. It has also raised questions about what effects the mosquito virome has on arbovirus transmission. Additionally, the discovery of these new viruses has generated interest in their potential use as biological control agents as well as novel vaccine platforms. The arbovirus community will benefit from the growing database of knowledge concerning these newly described viral endosymbionts, as their impacts will likely be far reaching.

Compensation of significant parametric uncertainties using sliding mode online learning

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Schnetter, Philipp; Kruger, Thomas

An augmented nonlinear inverse dynamics (NID) flight control strategy using sliding mode online learning for a small unmanned aircraft system (UAS) is presented. Because parameter identification for this class of aircraft often is not valid throughout the complete flight envelope, aerodynamic parameters used for model based control strategies may show significant deviations. For the concept of feedback linearization this leads to inversion errors that in combination with the distinctive susceptibility of small UAS towards atmospheric turbulence pose a demanding control task for these systems. In this work an adaptive flight control strategy using feedforward neural networks for counteracting such nonlinear effects is augmented with the concept of sliding mode control (SMC). SMC-learning is derived from variable structure theory. It considers a neural network and its training as a control problem. It is shown that by the dynamic calculation of the learning rates, stability can be guaranteed and thus increase the robustness against external disturbances and system failures. With the resulting higher speed of convergence a wide range of simultaneously occurring disturbances can be compensated. The SMC-based flight controller is tested and compared to the standard gradient descent (GD) backpropagation algorithm under the influence of significant model uncertainties and system failures.

Cellular immunotherapy using irradiated lung cancer cell vaccine co-expressing GM-CSF and IL-18 can induce significant antitumor effects

International Nuclear Information System (INIS)

Tian, Hongwei; Zhang, Xiaomei; Dai, Lei; Chen, Xiaolei; Zhang, Shuang; Yang, Yang; Yu, Dechao; Wei, Yuquan; Deng, Hongxin; Shi, Gang; Yang, Guoyou; Zhang, Junfeng; Li, Yiming; Du, Tao; Wang, Jianzhou; Xu, Fen; Cheng, Lin

2014-01-01

Although the whole tumor cell vaccine can provide the best source of immunizing antigens, there is still a limitation that most tumors are not naturally immunogenic. Tumor cells genetically modified to secrete immune activating cytokines have been proved to be more immunogenic. IL-18 could augment proliferation of T cells and cytotoxicity of NK cells. GM-CSF could stimulate dendritic cells, macrophages and enhance presentation of tumor antigens. In our study, we used mouse GM-CSF combined with IL-18 to modify Lewis lung cancer LL/2, then investigated whether vaccination could suppress tumor growth and promote survival. The Lewis lung cancer LL/2 was transfected with co-expressing mouse GM-CSF and IL-18 plasmid by cationic liposome, then irradiated with a sublethal dose X ray (100 Gy) to prepare vaccines. Mice were subcutaneously immunized with this inactivated vaccine and then inoculated with autologous LL/2 to estimate the antitumor efficacy. The studies reported here showed that LL/2 tumor cell vaccine modified by a co-expressing mouse GM-CSF and IL-18 plasmid could significantly inhibit tumor growth and increased survival of the mice bearing LL/2 tumor whether prophylactic or adoptive immunotherapy in vivo. A significant reduction of proliferation and increase of apoptosis were also observed in the tumor treated with vaccine of co-expressing GM-CSF and IL-18. The potent antitumor effect correlated with higher secretion levels of pro-inflammatory cytokines such as IL-18, GM-CSF, interferon-γ in serum, the proliferation of CD4 + IFN-γ + , CD8 + IFN-γ + T lymphocytes in spleen and the infiltration of CD4 + , CD8 + T in tumor. Furthermore, the mechanism of tumor-specific immune response was further proved by 51 Cr cytotoxicity assay in vitro and depletion of CD4, CD8, NK immune cell subsets in vivo. The results suggested that the antitumor mechanism was mainly depended on CD4 + , CD8 + T lymphocytes. These results provide a new insight into therapeutic mechanisms

Moral significance of phenomenal consciousness.

Science.gov (United States)

Levy, Neil; Savulescu, Julian

2009-01-01

Recent work in neuroimaging suggests that some patients diagnosed as being in the persistent vegetative state are actually conscious. In this paper, we critically examine this new evidence. We argue that though it remains open to alternative interpretations, it strongly suggests the presence of consciousness in some patients. However, we argue that its ethical significance is less than many people seem to think. There are several different kinds of consciousness, and though all kinds of consciousness have some ethical significance, different kinds underwrite different kinds of moral value. Demonstrating that patients have phenomenal consciousness--conscious states with some kind of qualitative feel to them--shows that they are moral patients, whose welfare must be taken into consideration. But only if they are subjects of a sophisticated kind of access consciousness--where access consciousness entails global availability of information to cognitive systems--are they persons, in the technical sense of the word employed by philosophers. In this sense, being a person is having the full moral status of ordinary human beings. We call for further research which might settle whether patients who manifest signs of consciousness possess the sophisticated kind of access consciousness required for personhood.

Clinical significance of the fabella

International Nuclear Information System (INIS)

Dodevski, A.; Lazarova-Tosovska, D.; Zhivadinovik, J.; Lazareska, M.

2012-01-01

Full text: Introduction: There is variable number of sesamoid bones in the human body; one of them is fabella, located in the tendon of the gastrocnemius muscle. Aim of this study was to investigate the frequency of occurrence of fabella in the Macedonian population and to discuss about clinical importance of this bone. Materials and methods: We retrospectively examined radiographs of 53 patients who had knee exams undertaken for a variety of clinical reasons, performed as a part of their medical treatment. Over a time span of six months, 53 patients (38 males and 15 females, age range 19-60 years, mean age of 36.7±12.3 years) were examined. Results: In seven (13.2%) patients of 53 analyzed reports, fabella was found in the lateral tendon of gastrocnemius muscle. We did not find a significant gender or side difference in the appearance of fabella. Conclusion: Although anatomic studies emphasized a lack of significance of the fabella, this bone has been associated with a spectrum of pathology affecting the knee as fabellar syndrome, perineal nerve injury and fracture. We should think of this sesamoid bone while performing diagnostic and surgical procedures

Significance and Biological Importance of Pyrimidine in the Microbial World

Directory of Open Access Journals (Sweden)

Vinita Sharma

2014-01-01

Full Text Available Microbes are unique creatures that adapt to varying lifestyles and environment resistance in extreme or adverse conditions. The genetic architecture of microbe may bear a significant signature not only in the sequences position, but also in the lifestyle to which it is adapted. It becomes a challenge for the society to find new chemical entities which can treat microbial infections. The present review aims to focus on account of important chemical moiety, that is, pyrimidine and its various derivatives as antimicrobial agents. In the current studies we represent more than 200 pyrimidines as antimicrobial agents with different mono-, di-, tri-, and tetrasubstituted classes along with in vitro antimicrobial activities of pyrimidines derivatives which can facilitate the development of more potent and effective antimicrobial agents.

Level of headaches after surgical aneurysm clipping decreases significantly faster compared to endovascular coiled patients

Directory of Open Access Journals (Sweden)

Athanasios K. Petridis

2017-04-01

Full Text Available In incidental aneurysms, endovascular treatment can lead to post-procedural headaches. We studied the difference of surgical clipping vs. endovascular coiling in concern to post-procedural headaches in patients with ruptured aneurysms. Sixtyseven patients with aneurysmal subarachnoidal haemorrhage were treated in our department from September 1st 2015 - September 1st 2016. 43 Patients were included in the study and the rest was excluded because of late recovery or highgrade subarachnoid bleedings. Twenty-two were surgical treated and twenty-one were interventionally treated. We compared the post-procedural headaches at the time points of 24 h, 21 days, and 3 months after treatment using the visual analog scale (VAS for pain. After surgical clipping the headache score decreased for 8.8 points in the VAS, whereas the endovascular treated population showed a decrease of headaches of 3.3 points. This difference was highly statistical significant and remained significant even after 3 weeks where the pain score for the surgically treated patients was 0.68 and for the endovascular treated 1.8. After 3 months the pain was less than 1 for both groups with surgically treated patients scoring 0.1 and endovascular treated patients 0.9 (not significant. Clipping is relieving the headaches of patients with aneurysm rupture faster and more effective than endovascular coiling. This effect stays significant for at least 3 weeks and plays a crucial role in stress relieve during the acute and subacute ICU care of such patients.

Prognostic significance of erythropoietin in pancreatic adenocarcinoma.

Directory of Open Access Journals (Sweden)

Thilo Welsch

Full Text Available BACKGROUND: Erythropoietin (Epo administration has been reported to have tumor-promoting effects in anemic cancer patients. We investigated the prognostic impact of endogenous Epo in patients with pancreatic ductal adenocarcinoma (PDAC. METHODOLOGY: The clinico-pathological relevance of hemoglobin (Hb, n = 150, serum Epo (sEpo, n = 87 and tissue expression of Epo/Epo receptor (EpoR, n = 104 was analyzed in patients with PDAC. Epo/EpoR expression, signaling, growth, invasion and chemoresistance were studied in Epo-exposed PDAC cell lines. RESULTS: Compared to donors, median preoperative Hb levels were reduced by 15% in both chronic pancreatitis (CP, p<0.05 and PDAC (p<0.001, reaching anemic grade in one third of patients. While inversely correlating to Hb (r = -0.46, 95% of sEPO values lay within the normal range. The individual levels of compensation were adequate in CP (observed to predicted ratio, O/P = 0.99 but not in PDAC (O/P = 0.85. Strikingly, lower sEPO values yielding inadequate Epo responses were prominent in non-metastatic M0-patients, whereas these parameters were restored in metastatic M1-group (8 vs. 13 mU/mL; O/P = 0.82 vs. 0.96; p<0.01--although Hb levels and the prevalence of anemia were comparable. Higher sEpo values (upper quartile ≥ 16 mU/ml were not significantly different in M0 (20% and M1 (30% groups, but were an independent prognostic factor for shorter survival (HR 2.20, 10 vs. 17 months, p<0.05. The pattern of Epo expression in pancreas and liver suggested ectopic release of Epo by capillaries/vasa vasorum and hepatocytes, regulated by but not emanating from tumor cells. Epo could initiate PI3K/Akt signaling via EpoR in PDAC cells but failed to alter their functions, probably due to co-expression of the soluble EpoR isoform, known to antagonize Epo. CONCLUSION/SIGNIFICANCE: Higher sEPO levels counteract anemia but worsen outcome in PDAC patients. Further trials are required to clarify how overcoming a sEPO threshold �

Multiple thrombophilic single nucleotide polymorphisms lack a significant effect on outcomes in fresh IVF cycles: an analysis of 1717 patients.

Science.gov (United States)

Patounakis, George; Bergh, Eric; Forman, Eric J; Tao, Xin; Lonczak, Agnieszka; Franasiak, Jason M; Treff, Nathan; Scott, Richard T

2016-01-01

The aim of the study is to determine if thrombophilic single nucleotide polymorphisms (SNPs) affect outcomes in fresh in vitro fertilization (IVF) cycles in a large general infertility population. A prospective cohort analysis was performed at a university-affiliated private IVF center of female patients undergoing fresh non-donor IVF cycles. The effect of the following thrombophilic SNPs on IVF outcomes were explored: factor V (Leiden and H1299R), prothrombin (G20210A), factor XIII (V34L), β-fibrinogen (-455G → A), plasminogen activator inhibitor-1 (4G/5G), human platelet antigen-1 (a/b9L33P), and methylenetetrahydrofolate reductase (C677T and A1298C). The main outcome measures included positive pregnancy test, clinical pregnancy, embryo implantation, live birth, and pregnancy loss. Patients (1717) were enrolled in the study, and a total of 4169 embryos were transferred. There were no statistically significant differences in positive pregnancy test, clinical pregnancy, embryo implantation, live birth, or pregnancy loss in the analysis of 1717 patients attempting their first cycle of IVF. Receiver operator characteristics and logistic regression analyses showed that outcomes cannot be predicted by the cumulative number of thrombophilic mutations present in the patient. Individual and cumulative thrombophilic SNPs do not affect IVF outcomes. Therefore, initial screening for these SNPs is not indicated.

Radiation damage and repair in cells and cell components. Part 2. Physical radiations and biological significance. Final report

International Nuclear Information System (INIS)

Fluke, D.J.

1984-08-01

The report comprises a teaching text, encompassing all physical radiations likely to be of biological interest, and the relevant biological effects and their significance. Topics include human radiobiology, delayed effects, radiation absorption in organisms, aqueous radiation chemistry, cell radiobiology, mutagenesis, and photobiology

Significant and Basic Innovations in Urban Planning

Science.gov (United States)

Kolyasnikov, V. A.

2017-11-01

The article considers the development features of the innovative urban planning in the USSR and Russia in XVIII - XX centuries. Innovative urban planning is defined as an activity on innovations creation and their implementation to obtain a socio-economic, political, environmental or other effect. In the course of urban development history this activity represents a cyclic wave process in which there are phases of rise and fall. The study of cyclic waves in the development of innovative urban planning uses the concept of basic and epochal innovations selection. This concept was developed by scientists for the study of cyclic wave processes in economics. Its adaptation to the conditions of innovative urban planning development allows one to introduce the concept of “basic innovation” and “significant innovation” in the theory and practice of settlement formation and their systems as well as to identify opportunities to highlight these innovations in the history of Russian urban planning. From these positions, six innovation waves committed to the urban development over the past 300 years are being investigated. The observed basic innovations in the domestic urban area show that urban development is a vital area for ensuring the country’s geopolitical security. Basic innovations are translated in time and modernized under new conditions of urban planning development. In this regard, we can predict the development of four basic innovations in post-Soviet Russia.

Significant regional heterogeneity of coronary flow reserve in paediatric hypertrophic cardiomyopathy

International Nuclear Information System (INIS)

Tadamura, E.; Kudoh, T.; Kubo, S.; Konishi, J.; Motooka, M.; Nohara, R.; Matsumori, A.; Sasayama, S.; Matsuda, T.; Tamaki, N.

2000-01-01

Previous studies have indicated that cardiac events in young patients with hypertrophic cardiomyopathy (HCM) are related to ischaemia rather than to arrhythmia. We measured coronary flow reserve in paediatric HCM and compared the values with those in adult HCM. We studied 12 patients with HCM including six paediatric ( 20 years old: mean 62 years), and six healthy young adults (mean 29 years) as controls. Every patient underwent magnetic resonance imaging (MRI) for anatomical assessment. Myocardial blood flow at rest and after dipyridamole infusion was measured with dynamic nitrogen-13 ammonia positron emission tomography (PET). Partial volume effect was corrected for using the anatomical data obtained with MRI. In adult patients with HCM, coronary flow reserve in the hypertrophied septal region was not significantly different from that in the non-hypertrophied lateral wall (1.38±0.29 vs 1.77±0.39, respectively). In the paediatric patients, coronary flow reserve in the hypertrophied septal region was significantly lower than in the non-hypertrophied lateral wall (0.84±0.33 vs 2.74±0.90, respectively, P<0.01). In addition, coronary flow reserve in adult patients was lower than in control subjects both in the septal wall (1.38±0.29 vs 2.94±0.35, respectively, P<0.0001) and in the lateral wall (1.77±0.39 vs 2.85±0.69, respectively, P<0.05). In contrast, coronary flow reserve in paediatric patients was not significantly different from that in control subjects in the lateral wall (2.74±0.90 vs 2.85±0.69, respectively), while absolute reduction of myocardial blood flow was noted after pharmacological vasodilatation in the hypertrophied septal region. In conclusion, significant regional differences of coronary flow reserve were present in the paediatric patients with HCM. These results suggest that paediatric patients with HCM intrinsically have the potential to experience significant regional ischaemia even in the absence of coronary stenosis. (orig.)

Change in expression of cyclin G2 in kidney cancer cell and its significance.

Science.gov (United States)

Cui, D W; Sun, G G; Cheng, Y J

2014-04-01

This study aims to analyze the expression and clinical significance of cyclin G2 (CCNG2) in kidney carcinoma, and the biological effect in its cell line by CCNG2 overexpression. Immunohistochemistry and western blot were used to analyze CCNG2 protein expression in 63 cases of kidney cancer and normal tissues to study the relationship between CCNG2 expression and clinical factors. CCNG2 lentiviral vector and empty vector were respectively transfected into kidney ACHN cell line. During immunohistochemistry, the level of CCNG2 protein expression was found to be significantly lower in kidney cancer tissue than normal tissues (P kidney cancer tissue was respectively found to be significantly lower than in normal tissues (P 0.05), but it was correlated with lymph node metastasis, clinic stage, and histological grade (P kidney cancer and correlated significantly with lymph node metastasis, clinical stage, histological grade, and poor overall survival, suggesting that CCNG2 may play important roles as a negative regulator to kidney cancer ACHN cell by promoting degradation of CDK2.

Central Region Regionally Ecological Significant Areas

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Minnesota Department of Natural Resources — This is an analysis of regionally significant Terrestrial and Wetland Ecological Areas in the seven county metropolitan area. Individual forest, grassland and...

Chemical ecology of insect-plant interactions: ecological significance of plant secondary metabolites.

Science.gov (United States)

Nishida, Ritsuo

2014-01-01

Plants produce a diverse array of secondary metabolites as chemical barriers against herbivores. Many phytophagous insects are highly adapted to these allelochemicals and use such unique substances as the specific host-finding cues, defensive substances of their own, and even as sex pheromones or their precursors by selectively sensing, incorporating, and/or processing these phytochemicals. Insects also serve as pollinators often effectively guided by specific floral fragrances. This review demonstrates the ecological significance of such plant secondary metabolites in the highly diverse interactions between insects and plants.

The Harm Done to Reproducibility by the Culture of Null Hypothesis Significance Testing.

Science.gov (United States)

Lash, Timothy L

2017-09-15

In the last few years, stakeholders in the scientific community have raised alarms about a perceived lack of reproducibility of scientific results. In reaction, guidelines for journals have been promulgated and grant applicants have been asked to address the rigor and reproducibility of their proposed projects. Neither solution addresses a primary culprit, which is the culture of null hypothesis significance testing that dominates statistical analysis and inference. In an innovative research enterprise, selection of results for further evaluation based on null hypothesis significance testing is doomed to yield a low proportion of reproducible results and a high proportion of effects that are initially overestimated. In addition, the culture of null hypothesis significance testing discourages quantitative adjustments to account for systematic errors and quantitative incorporation of prior information. These strategies would otherwise improve reproducibility and have not been previously proposed in the widely cited literature on this topic. Without discarding the culture of null hypothesis significance testing and implementing these alternative methods for statistical analysis and inference, all other strategies for improving reproducibility will yield marginal gains at best. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Phenomenological study on the significance of the scalar potential and Lamb shift

International Nuclear Information System (INIS)

Yuan Xuhao; Li Xueqian; Ke Hongwei

2011-01-01

We indicated in our previous work that for QED the contributions of the scalar potential, which appears at the loop level, is much smaller than that of the vector potential, and in fact negligible. But the situation may be different for QCD, the reason being that the loop effects are more significant because α s is much larger than α, and secondly the non-perturbative QCD effects may induce the scalar potential. In this work, we phenomenologically study the contribution of the scalar potential to the spectra of charmonium. Taking into account both vector and scalar potentials, by fitting the well measured charmonium spectra, we re-fix the relevant parameters and test them by calculating other states of the charmonium family. We also consider the role of the Lamb shift and present the numerical results with and without involving the Lamb shift. (authors)

Life-table studies revealed significant effects of deforestation on the development and survivorship of Anopheles minimus larvae.

Science.gov (United States)

Wang, Xiaoming; Zhou, Guofa; Zhong, Daibin; Wang, Xiaoling; Wang, Ying; Yang, Zhaoqing; Cui, Liwang; Yan, Guiyun

2016-06-06

Many developing countries are experiencing rapid ecological changes such as deforestation and shifting agricultural practices. These environmental changes may have an important consequence on malaria due to their impact on vector survival and reproduction. Despite intensive deforestation and malaria transmission in the China-Myanmar border area, the impact of deforestation on malaria vectors in the border area is unknown. We conducted life table studies on Anopheles minimus larvae to determine the pupation rate and development time in microcosms under deforested, banana plantation, and forested environments. The pupation rate of An. minimus was 3.8 % in the forested environment. It was significantly increased to 12.5 % in banana plantations and to 52.5 % in the deforested area. Deforestation reduced larval-to-pupal development time by 1.9-3.3 days. Food supplementation to aquatic habitats in forested environments and banana plantations significantly increased larval survival rate to a similar level as in the deforested environment. Deforestation enhanced the survival and development of An. minimus larvae, a major malaria vector in the China-Myanmar border area. Experimental determination of the life table parameters on mosquito larvae under a variety of environmental conditions is valuable to model malaria transmission dynamics and impact by climate and environmental changes.

The significance of determination of renal tubular markers before and after treatment in the primary nephrotic syndrome

International Nuclear Information System (INIS)

Xie Bing; Jiang Liping

2011-01-01

Objective: To evaluate the damage of renal tubule of patients with primary nephrotic syndrome (PNS) by detecting renal tubule markers and investigate the significance of different therapeutic effects. Methods: Serum levels of interleukin-6(IL-6), ET-1, α 1 -microglobulin(α 1 -m), β 2 -microglobulin(β 2 -m) and plasma level of ET-1 were determined with RIA, fibrinogen degradation product (FDP) with ELISA, automatic biochemistry analysis N-acetyl-β-D-glucosaminidase(NAG), CH 2 O was determined with physico-method respectively. Results: The concentrations of IL-6, ET-1, α 1 -m, β 2 -m, FDP, NAG were significantly decreased in cases of complete remission after therapy (P 2 O excepted (P>0.05), the decrease of IL-6, ET-1, α 1 -m, FDP were no significant in cases of invalid (P>0.05), the concentrations of renal tubule markers in cases of partial remission and invalid were higher than those in cases of complete and significant remission. Conclusion: The determination of several renal tubule markers can be used for diagnose, monitor and judge the therapeutic effects of PNS. (authors)

Gut-directed hypnotherapy significantly augments clinical remission in quiescent ulcerative colitis

Science.gov (United States)

Keefer, Laurie; Taft, Tiffany H; Kiebles, Jennifer L; Martinovich, Zoran; Barrett, Terrence A; Palsson, Olafur S

2013-01-01

Summary Background Psychotherapy is not routinely recommended for in ulcerative colitis (UC). Gut-directed hypnotherapy (HYP) has been linked to improved function in the gastrointestinal tract and may operate through immune-mediated pathways in chronic diseases. Aims To determine the feasibility and acceptability of hypnotherapy and estimate the impact of hypnotherapy on clinical remission status over a 1 year period in patients with an historical flare rate of 1.3 times per year. Methods 54 patients were randomized at a single site to 7 sessions of gut-directed hypnotherapy (N = 26) or attention control (CON; N = 29) and followed for 1 year. The primary outcome was the proportion of participants in each condition that had remained clinically asymptomatic (clinical remission) through 52 weeks post-treatment. Results One-way ANOVA comparing hypnotherapy and control subjects on number of days to clinical relapse favored the hypnotherapy condition [F = 4.8 (1, 48), p = .03] by 78 days. Chi square analysis comparing the groups on proportion maintaining remission at 1 year was also significant [X2(1) = 3.9, p = .04], with 68% of hypnotherapy and 40% of control patients maintaining remission for 1 year. There were no significant differences between groups over time in quality of life, medication adherence, perceived stress or psychological factors. Conclusions This is the first prospective study that has demonstrated a significant effect of a psychological intervention on prolonging clinical remission in patients with quiescent UC. Clinical Trial # NCT00798642 PMID:23957526

The Improvement of Screening the Significant Factors of Oil Blends as Bio lubricant Base Stock

International Nuclear Information System (INIS)

Noor Hajarul Ashikin Shamsuddin; Rozaini Abdullah; Zainab Hamzah; Siti Jamilah Hanim Mohd Yusof

2015-01-01

A new formulation bio lubricant base stock was developed by blending of waste cooking oil (WCO) with Jatropha curcas oil (JCO). The objective of this research is to evaluate significant factors contributing to the production of oil blends for bio lubricant application. The significant factors used in this study were oil ratio (WCO:JCO), agitation times (min) and agitation speed (rpm). The blended oil bio based lubricant was used to determine the saponification, acid, peroxide and iodine values. The experimental design used in this study was the 2 level-factorial design. In this experiment, it was found that the effect of oil ratio and interaction of oil ratio and agitation speed gave the most significant effect in oil blends as bio lubricant base stock. The highest ratio of oil blend 80 %:20 % WCO:JCO, with low agitation speed of 300 rpm and low agitation time of 30 minutes gave the optimum results. The acid, saponification, peroxide and iodine values obtained were 0.517±0.08 mg KOH/ g, 126.23±1.62 mg/ g, 7.5±2.0 m eq/ kg and 50.42±2.85 mg/ g respectively. A higher ratio of waste cooking oil blends was found to be favourable as bio lubricant base stock. (author)

Economically Significant Sites - OSPR [ds356

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California Natural Resource Agency — This point data set shows locations of Economically Significant Sites along the California coast from Del Norte to San Diego counties. Data for locating these points...

SIGWX Charts - High Level Significant Weather

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National Oceanic and Atmospheric Administration, Department of Commerce — High level significant weather (SIGWX) forecasts are provided for the en-route portion of international flights. NOAA's National Weather Service Aviation Center...

Role of tumor microenvironment in triple-negative breast cancer and its prognostic significance

Institute of Scientific and Technical Information of China (English)

Tianjian Yu; Genhong Di

2017-01-01

Breast cancer has been shown to live in the tumor microenvironment,which consists of not only breast cancer cells themselves but also a significant amount of pathophysiologically altered surrounding stroma and cells.Diverse components of the breast cancer microenvironment,such as suppressive immune cells,re-programmed fibroblast cells,altered extracellular matrix (ECM) and certain soluble factors,synergistically impede an effective anti-tumor response and promote breast cancer progression and metastasis.Among these components,stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways,whereas the ECM features biochemical and biomechanical changes.However,triple-negative breast cancer (TNBC),the most aggressive subtype of this disease that lacks effective therapies available for other subtypes,is considered to feature a unique microenvironment distinct from that of other subtypes,especially compared to Luminal A subtype.Because these changes are now considered to significantly impact breast cancer development and progression,these unique alterations may serve as promising prognostic factors of clinical outcome or potential therapeutic targets for the treatment of TNBC.In this review,we focus on the composition of the TNBC microenvironment,concomitant distinct biological alteration,specific interplay between various cell types and TNBC cells,and the prognostic implications of these findings.

Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial

Energy Technology Data Exchange (ETDEWEB)

Westover, Kenneth D. [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Loo, Billy W. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Gerber, David E. [Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Iyengar, Puneeth; Choy, Hak [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Diehn, Maximilian [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Hughes, Randy; Schiller, Joan; Dowell, Jonathan [Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wardak, Zabi [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Sher, David [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Christie, Alana; Xie, Xian-Jin [Department of Clinical Science, Southwestern Medical Center, Dallas, Texas (United States); Corona, Irma [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Sharma, Akanksha [School of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wadsworth, Margaret E. [Radiation Oncology of Mississippi, Jackson, Mississippi (United States); Timmerman, Robert, E-mail: Robert.Timmerman@utsouthwestern.edu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States)

2015-09-01

Purpose: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Methods and Materials: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. Results: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P=.24). The median overall survival was 6 months with no significant differences between dose levels (P=.59). Conclusions: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long

The Health Significance of Positive Emotions in Adulthood and Later Life.

Science.gov (United States)

Ong, Anthony D; Mroczek, Daniel K; Riffin, Catherine

2011-08-01

A growing body of literature supports a link between positive emotions and health in older adults. In this article, we review evidence of the effects of positive emotions on downstream biological processes and meaningful clinical endpoints, such as adult morbidity and mortality. We then present relevant predictions from lifespan theories that suggest changes in cognition and motivation may play an important role in explaining how positive emotions are well maintained in old age, despite pervasive declines in cognitive processes. We conclude by discussing how the application of psychological theory can inform greater understanding of the adaptive significance of positive emotions in adulthood and later life.

Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications.

Science.gov (United States)

Cao, Yi

2015-09-01

Environmental pollution is one of the main causes of human cancer. Exposures to environmental carcinogens result in genetic and epigenetic alterations which induce cell transformation. Epigenetic changes caused by environmental pollution play important roles in the development and progression of environmental pollution-related cancers. Studies on DNA methylation are among the earliest and most conducted epigenetic research linked to cancer. In this review, the roles of DNA methylation in carcinogenesis and their significance in clinical medicine were summarized, and the effects of environmental pollutants, particularly air pollutants, on DNA methylation were introduced. Furthermore, prospective applications of DNA methylation to environmental pollution detection and cancer prevention were discussed.

SRS Process Facility Significance Fire Frequency

Energy Technology Data Exchange (ETDEWEB)

Sarrack, A.G. [Westinghouse Savannah River Company, AIKEN, SC (United States)

1995-10-01

This report documents the method and assumptions of a study performed to determine a site generic process facility significant fire initiator frequency and explains the proper way this value should be used.

SRS Process Facility Significance Fire Frequency

International Nuclear Information System (INIS)

Sarrack, A.G.

1995-10-01

This report documents the method and assumptions of a study performed to determine a site generic process facility significant fire initiator frequency and explains the proper way this value should be used

Mid-Treatment Sleep Duration Predicts Clinically Significant Knee Osteoarthritis Pain reduction at 6 months: Effects From a Behavioral Sleep Medicine Clinical Trial.

Science.gov (United States)

Salwen, Jessica K; Smith, Michael T; Finan, Patrick H

2017-02-01

To determine the relative influence of sleep continuity (sleep efficiency, sleep onset latency, total sleep time [TST], and wake after sleep onset) on clinical pain outcomes within a trial of cognitive behavioral therapy for insomnia (CBT-I) for patients with comorbid knee osteoarthritis and insomnia. Secondary analyses were performed on data from 74 patients with comorbid insomnia and knee osteoarthritis who completed a randomized clinical trial of 8-session multicomponent CBT-I versus an active behavioral desensitization control condition (BD), including a 6-month follow-up assessment. Data used herein include daily diaries of sleep parameters, actigraphy data, and self-report questionnaires administered at specific time points. Patients who reported at least 30% improvement in self-reported pain from baseline to 6-month follow-up were considered responders (N = 31). Pain responders and nonresponders did not differ significantly at baseline across any sleep continuity measures. At mid-treatment, only TST predicted pain response via t tests and logistic regression, whereas other measures of sleep continuity were nonsignificant. Recursive partitioning analyses identified a minimum cut-point of 382 min of TST achieved at mid-treatment in order to best predict pain improvements 6-month posttreatment. Actigraphy results followed the same pattern as daily diary-based results. Clinically significant pain reductions in response to both CBT-I and BD were optimally predicted by achieving approximately 6.5 hr sleep duration by mid-treatment. Thus, tailoring interventions to increase TST early in treatment may be an effective strategy to promote long-term pain reductions. More comprehensive research on components of behavioral sleep medicine treatments that contribute to pain response is warranted. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Time to significant pain reduction following DETP application vs placebo for acute soft tissue injuries.

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Yanchick, J; Magelli, M; Bodie, J; Sjogren, J; Rovati, S

2010-08-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) provide fast and effective acute pain relief, but systemic administration has increased risk for some adverse reactions. The diclofenac epolamine 1.3% topical patch (DETP) is a topical NSAID with demonstrated safety and efficacy in treatment of acute pain from minor soft tissue injuries. Significant pain reduction has been observed in clinical trials within several hours following DETP application, suggesting rapid pain relief; however, this has not been extensively studied for topical NSAIDs in general. This retrospective post-hoc analysis examined time to onset of significant pain reduction after DETP application compared to a placebo patch for patients with mild-to-moderate acute ankle sprain, evaluating the primary efficacy endpoint from two nearly identical studies. Data from two double-blind, randomized, parallel-group, placebo-controlled studies (N = 274) of safety and efficacy of the DETP applied once daily for 7 days for acute ankle sprain were evaluated post-hoc using statistical modeling to estimate time to onset of significant pain reduction following DETP application. Pain on active movement on a 100 mm Visual Analog Scale (VAS) recorded in patient diaries; physician- and patient-assessed tolerability; and adverse events. DETP treatment resulted in significant pain reduction within approximately 3 hours compared to placebo. Within-treatment post-hoc analysis based on a statistical model suggested significant pain reduction occurred as early as 1.27 hours for the DETP group. The study may have been limited by the retrospective nature of the analyses. In both studies, the DETP was well tolerated with few adverse events, limited primarily to application site skin reactions. The DETP is an effective treatment for acute minor soft tissue injury, providing pain relief as rapidly as 1.27 hours post-treatment. Statistical modeling may be useful in estimating time to onset of pain relief for comparison of topical

Evaluation of the significance of inverse oxidation for HTGR graphites

International Nuclear Information System (INIS)

Lee, B.S.; Heiser, J. III; Sastre, C.

1983-01-01

The inverse oxidation refers to a higher mass loss inside the graphite than the outside. In 1980, Wichner et al reported this phenomenon (referred to as inside/out corrosion) observed in some H451 graphites, and offered an explanation that a catalyst (almost certainly Fe) is activated by the progressively increasing reducing conditions found in the graphite interior. Recently, Morgan and Thomas (1982) investigated this phenomenon is PGX graphites, and agreed on the existing mechanism to explain this pheomenon. They also called for attention to the possibility that this phenomenon may occur under HTGR (High Temperature Gas-Cooled Reactor) operating conditions. The purpose of this paper is to confirm the above mentioned explanation for this phenomenon and to evaluate the significance of this effect for HTGR graphites under realistic reactor conditions

Functionally significant, rare transcription factor variants in tetralogy of Fallot.

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Ana Töpf

Full Text Available Rare variants in certain transcription factors involved in cardiac development cause Mendelian forms of congenital heart disease. The purpose of this study was to systematically assess the frequency of rare transcription factor variants in sporadic patients with the cardiac outflow tract malformation tetralogy of Fallot (TOF.We sequenced the coding, 5'UTR, and 3'UTR regions of twelve transcription factor genes implicated in cardiac outflow tract development (NKX2.5, GATA4, ISL1, TBX20, MEF2C, BOP/SMYD1, HAND2, FOXC1, FOXC2, FOXH, FOXA2 and TBX1 in 93 non-syndromic, non-Mendelian TOF cases. We also analysed Illumina Human 660W-Quad SNP Array data for copy number variants in these genes; none were detected. Four of the rare variants detected have previously been shown to affect transactivation in in vitro reporter assays: FOXC1 p.P297S, FOXC2 p.Q444R, FOXH1 p.S113T and TBX1 p.P43_G61del PPPPRYDPCAAAAPGAPGP. Two further rare variants, HAND2 p.A25_A26insAA and FOXC1 p.G378_G380delGGG, A488_491delAAAA, affected transactivation in in vitro reporter assays. Each of these six functionally significant variants was present in a single patient in the heterozygous state; each of the four for which parental samples were available were maternally inherited. Thus in the 93 TOF cases we identified six functionally significant mutations in the secondary heart field transcriptional network.This study indicates that rare genetic variants in the secondary heart field transcriptional network with functional effects on protein function occur in 3-13% of patients with TOF. This is the first report of a functionally significant HAND2 mutation in a patient with congenital heart disease.

The impact of significant other expressed emotion on patient outcomes in chronic fatigue syndrome.

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Band, Rebecca; Barrowclough, Christine; Wearden, Alison

2014-09-01

Previous literature has identified the importance of interpersonal processes for patient outcomes in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), particularly in the context of significant other relationships. The current study investigated expressed emotion (EE), examining the independent effects of critical comments and emotional overinvolvement (EOI) in association with patient outcomes. Fifty-five patients with CFS/ME and their significant others were recruited from specialist CFS/ME services. Significant other EE status was coded from a modified Camberwell Family Interview. Patient outcomes (fatigue severity, disability, and depression) were derived from questionnaire measures. Forty-four patients (80%) completed follow-up questionnaires 6-months after recruitment. Significant other high-EE categorized by both high levels of critical comments and high EOI was predictive of worse fatigue severity at follow-up. High-critical EE was associated with higher levels of patient depressive symptoms longitudinally; depressive symptoms were observed to mediate the relationship between high critical comments and fatigue severity reported at follow-up. There were higher rates of high-EE in parents than in partners, and this was because of higher rates of EOI in parents. Patients with high-EE significant others demonstrated poorer outcomes at follow-up compared with patients in low-EE dyads. One mechanism for this appears to be as a result of increased patient depression. Future research should seek to further clarify whether the role of interpersonal processes in CFS/ME differs across different patient-significant other relationships. The development of significant other-focused treatment interventions may be particularly beneficial for both patients and significant others. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

The Strasbourg Large Refractor and Dome: Significant Improvements and Failed Attempts

Science.gov (United States)

Heck, Andre

2009-01-01

Founded by the German Empire in the late 19th century, Strasbourg Astronomical Observatory featured several novelties from the start. According to Mueller (1978), the separation of observing buildings from the study area and from the astronomers' residence was a revolution in observatory construction. The instruments were, as much as possible, isolated from the vibrations of the buildings themselves. "Gas flames" and water were used to reduce temperature effects. Thus the Large Dome (ca 11m diameter), housing the Large Refractor (ca 49cm, then the largest in Germany) and covered by zinc over wood, could be cooled down by water running from the top. Reports (including by the French who took over the observatory after World War I) are however somehow nonexistent on the effective usage and actual efficiency of such a system (which must have generated locally a significant amount of humidity). The paper will detail these technical attempts as well as the specificities of the instruments installed in that new observatory intended as a showcase of German astronomy.

Affective significance enhances covert attention: roles of anxiety and word familiarity.

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Calvo, Manuel G; Eysenck, Michael W

2008-11-01

To investigate the processing of emotional words by covert attention, threat-related, positive, and neutral word primes were presented parafoveally (2.2 degrees away from fixation) for 150 ms, under gaze-contingent foveal masking, to prevent eye fixations. The primes were followed by a probe word in a lexical-decision task. In Experiment 1, results showed a parafoveal threat-anxiety superiority: Parafoveal prime threat words facilitated responses to probe threat words for high-anxiety individuals, in comparison with neutral and positive words, and relative to low-anxiety individuals. This reveals an advantage in threat processing by covert attention, without differences in overt attention. However, anxiety was also associated with greater familiarity with threat words, and the parafoveal priming effects were significantly reduced when familiarity was covaried out. To further examine the role of word knowledge, in Experiment 2, vocabulary and word familiarity were equated for low- and high-anxiety groups. In these conditions, the parafoveal threat-anxiety advantage disappeared. This suggests that the enhanced covert-attention effect depends on familiarity with words.

Hyoscine butylbromide significantly decreases motion artefacts and allows better delineation of anatomic structures in mp-MRI of the prostate

Energy Technology Data Exchange (ETDEWEB)

Ullrich, T.; Quentin, M.; Schmaltz, A.K.; Rubbert, C.; Blondin, D.; Antoch, G.; Schimmoeller, L. [University Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Dusseldorf (Germany); Arsov, C.; Rabenalt, R.; Albers, P. [University Dusseldorf, Medical Faculty, Department of Urology, Dusseldorf (Germany)

2018-01-15

To prospectively evaluate the effect of hyoscine butylbromide (HBB) on visualisation of anatomical details and motion-related artefacts in mp-MRI of the prostate at 3.0 Tesla. One hundred and three consecutive patients (65 ± 10 years) were included in this trial, powered to demonstrate an improvement of image quality after HBB administration, assessed on a 5-point scale by two blinded readers. All patients received high-spatial resolution axial T2-weighted TSE sequences at 3.0 T without spasmolytic agent, repeated after application of 40 mg HBB and followed by routine mp-MRI. Secondary endpoints were (1) susceptibility to side effects, (2) dependence of spasmolytic effect on patients and acute; weight, and (3) prostate volume. In 68% of patients, HBB significantly improved the anatomic score (mean 3.4 ± 0.9 before and 4.4 ± 0.7 after HBB for both readers, p = <0.001). In 67%, HBB significantly enhanced the artefact score (mean 3.2 ± 1 before and 4.2 ± 0.8 after HBB for reader 1, p = <0.001; 3.2 ± 1 and 4.1 ± 0.8 for reader 2, p = <0.001). Subgroup analysis revealed no statistically significant difference between patients with different bodyweight or prostate volume. Inter-reader agreement was excellent (k = 0.95-0.98). Hyoscine butylbromide significantly improves image quality and reduces motion-related artefacts in mp-MRI of the prostate independent of bodyweight or prostate volume. No side effects were reported. (orig.)

Hyoscine butylbromide significantly decreases motion artefacts and allows better delineation of anatomic structures in mp-MRI of the prostate

International Nuclear Information System (INIS)

Ullrich, T.; Quentin, M.; Schmaltz, A.K.; Rubbert, C.; Blondin, D.; Antoch, G.; Schimmoeller, L.; Arsov, C.; Rabenalt, R.; Albers, P.

2018-01-01

To prospectively evaluate the effect of hyoscine butylbromide (HBB) on visualisation of anatomical details and motion-related artefacts in mp-MRI of the prostate at 3.0 Tesla. One hundred and three consecutive patients (65 ± 10 years) were included in this trial, powered to demonstrate an improvement of image quality after HBB administration, assessed on a 5-point scale by two blinded readers. All patients received high-spatial resolution axial T2-weighted TSE sequences at 3.0 T without spasmolytic agent, repeated after application of 40 mg HBB and followed by routine mp-MRI. Secondary endpoints were (1) susceptibility to side effects, (2) dependence of spasmolytic effect on patients and acute; weight, and (3) prostate volume. In 68% of patients, HBB significantly improved the anatomic score (mean 3.4 ± 0.9 before and 4.4 ± 0.7 after HBB for both readers, p = <0.001). In 67%, HBB significantly enhanced the artefact score (mean 3.2 ± 1 before and 4.2 ± 0.8 after HBB for reader 1, p = <0.001; 3.2 ± 1 and 4.1 ± 0.8 for reader 2, p = <0.001). Subgroup analysis revealed no statistically significant difference between patients with different bodyweight or prostate volume. Inter-reader agreement was excellent (k = 0.95-0.98). Hyoscine butylbromide significantly improves image quality and reduces motion-related artefacts in mp-MRI of the prostate independent of bodyweight or prostate volume. No side effects were reported. (orig.)

Synthesis of hydroxyapatite in the presence of biologically significant molecules

International Nuclear Information System (INIS)

Alvarez, R.; Evans, L.A.

2000-01-01

In bone mineralization non-collagenous phosphoproteins containing polycarboxylate sequences are thought to control crystal nucleation and to subsequently modify crystal growth. Invertebrate calcified tissues may also contain significant amounts of phosphoserine and/or acidic amino acid residues together with chitin (a polysaccharide). The present study investigated the effect of synthetic phosphorylated compounds as well as monomeric/polymeric carboxylic acid compounds on the formation of hydroxyapatite (HAp) under conditions of physiological pH, temperature and ionic strength. Poly-L-sodium aspartate was found to have the greatest inhibitory effect; only octacalcium phosphate (a known precursor of hydroxyapatite) could be detected in the presence of this polymer. Resultant minerals showed a variety of aggregation states. The biomimetically formed calcium phosphate minerals were identified and characterised by a variety of analytical thechniques, including laser Raman, Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy and x-ray diffraction analysis. In addition, a series of experiments were performed to induce the formation of HAp on biogenic substrates, such as chitin and its derivatives, chitosan, reconstituted chitin and phosphorylated chitin. Granular aggregates of hydroxyapatite could be induced to form directly on phosphorylated chitin surfaces, but not on other biogenically-derived substrates. Copyright (2000) The Australian Ceramic Society

Identification of significant problems related to light water reactor piping systems

International Nuclear Information System (INIS)

1980-07-01

Work on the project was divided into three tasks. In Task 1, past surveys of LWR piping system problems and recent Licensee Event Report summaries are studied to identify the significant problems of LWR piping systems and the primary causes of these problems. Pipe cracking is identified as the most recurring problem and is mainly due to the vibration of pipes due to operating pump-pipe resonance, fluid-flow fluctuations, and vibration of pipe supports. Research relevant to the identified piping system problems is evaluated. Task 2 studies identify typical LWR piping systems and the current loads and load combinations used in the design of these systems. Definitions of loads are reviewed. In Task 3, a comparative study is carried out on the use of nonlinear analysis methods in the design of LWR piping systems. The study concludes that the current linear-elastic methods of analysis may not predict accurately the behavior of piping systems under seismic loads and may, under certain circumstances, result in nonconservative designs. Gaps at piping supports are found to have a significant effect on the response of the piping systems

Significance of Shear Wall in Multi-Storey Structure With Seismic Analysis

Science.gov (United States)

Bongilwar, Rajat; Harne, V. R.; Chopade, Aditya

2018-03-01

In past decades, shear walls are one of the most appropriate and important structural component in multi-storied building. Therefore, it would be very interesting to study the structural response and their systems in multi-storied structure. Shear walls contribute the stiffness and strength during earthquakes which are often neglected during design of structure and construction. This study shows the effect of shear walls which significantly affect the vulnerability of structures. In order to test this hypothesis, G+8 storey building was considered with and without shear walls and analyzed for various parameters like base shear, storey drift ratio, lateral displacement, bending moment and shear force. Significance of shear wall has been studied with the help of two models. First model is without shear wall i.e. bare frame and other another model is with shear wall considering opening also in it. For modeling and analysis of both the models, FEM based software ETABS 2016 were used. The analysis of all models was done using Equivalent static method. The comparison of results has been done based on same parameters like base shear, storey drift ratio, lateral displacement, bending moment and shear force.

Noninvasive scoring system for significant inflammation related to chronic hepatitis B

Science.gov (United States)

Hong, Mei-Zhu; Ye, Linglong; Jin, Li-Xin; Ren, Yan-Dan; Yu, Xiao-Fang; Liu, Xiao-Bin; Zhang, Ru-Mian; Fang, Kuangnan; Pan, Jin-Shui

2017-03-01

Although a liver stiffness measurement-based model can precisely predict significant intrahepatic inflammation, transient elastography is not commonly available in a primary care center. Additionally, high body mass index and bilirubinemia have notable effects on the accuracy of transient elastography. The present study aimed to create a noninvasive scoring system for the prediction of intrahepatic inflammatory activity related to chronic hepatitis B, without the aid of transient elastography. A total of 396 patients with chronic hepatitis B were enrolled in the present study. Liver biopsies were performed, liver histology was scored using the Scheuer scoring system, and serum markers and liver function were investigated. Inflammatory activity scoring models were constructed for both hepatitis B envelope antigen (+) and hepatitis B envelope antigen (-) patients. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve were 86.00%, 84.80%, 62.32%, 95.39%, and 0.9219, respectively, in the hepatitis B envelope antigen (+) group and 91.89%, 89.86%, 70.83%, 97.64%, and 0.9691, respectively, in the hepatitis B envelope antigen (-) group. Significant inflammation related to chronic hepatitis B can be predicted with satisfactory accuracy by using our logistic regression-based scoring system.

Geckos significantly alter foot orientation to facilitate adhesion during downhill locomotion.

Science.gov (United States)

Birn-Jeffery, Aleksandra V; Higham, Timothy E

2014-10-01

Geckos employ their adhesive system when moving up an incline, but the directionality of the system may limit function on downhill surfaces. Here, we use a generalist gecko to test whether limb modulation occurs on downhill slopes to allow geckos to take advantage of their adhesive system. We examined three-dimensional limb kinematics for geckos moving up and down a 45° slope. Remarkably, the hind limbs were rotated posteriorly on declines, resulting in digit III of the pes facing a more posterior direction (opposite to the direction of travel). No significant changes in limb orientation were found in any other condition. This pes rotation leads to a dramatic shift in foot function that facilitates the use of the adhesive system as a brake/stabilizer during downhill locomotion and, although this rotation is not unique to geckos, it is significant for the deployment of adhesion. Adhesion is not just advantageous for uphill locomotion but can be employed to help deal with the effects of gravity during downhill locomotion, highlighting the incredible multi-functionality of this key innovation. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

[Significance and necessity of developing quality of life questionnaire for cancer patients adapting to traditional Chinese medicine].

Science.gov (United States)

You, Jie

2006-09-01

The clinical evaluation system for therapeutic effects of tumor, which focuses on survival period and tumor response rate, has been proved not very proper for evaluating the therapeutic effects of traditional Chinese medicine (TCM). Quality of life (QOL) has been introduced into the effective evaluation system of TCM and integrative medicine because of its similarity in concept and extension with TCM at theory basis, syndrome differentiation-treatment, and evaluation of therapeutic effects. But there are no QOL questionnaires which can evaluate the therapeutic effects of TCM and integrative medicine precisely. This article discussed the necessity and significance of developing QOL questionnaire special for TCM.

Cytochrome c oxidase inhibition by calcium at physiological ionic composition of the medium: Implications for physiological significance of the effect.

Science.gov (United States)

Vygodina, Tatiana V; Mukhaleva, Elizaveta; Azarkina, Natalia V; Konstantinov, Alexander A

2017-12-01

Cytochrome c oxidase (CcO) from mammalian mitochondria binds Ca 2+ and Na + in a special cation binding site. Binding of Ca 2+ brings about partial inhibition of the enzyme while Na + competes with Ca 2+ for the binding site and protects the enzyme from the inhibition [Vygodina, T., Kirichenko, A. and Konstantinov, A.A. (2013). Direct Regulation of Cytochrome c oxidase by Calcium Ions. PLoS One 8(9): e74436]. In the original studies, the inhibition was found to depend significantly on the ionic composition of the buffer. Here we describe inhibition of CcO by Ca 2+ in media containing the main ionic components of cytoplasm (150mM KCl, 12mM NaCl and 1mM MgCl 2 ). Under these conditions, Ca 2+ inhibits CcO with effective K i of 20-26μM, that is an order of magnitude higher than determined earlier in the absence of Na + . At physiological value of ionic strength, the inhibition can be observed at any turnover number of CcO, rather than only at low TN (calcium matches closely the known value of "K m " for Ca 2+ -induced activation of the mitochondrial calcium uniporter. The inhibition of CcO by Ca 2+ is proposed to modulate mitochondrial Ca 2+ -uptake via the mitochondrial calcium uniporter, promote permeability transition pore opening and induce reduction of Mia40 in the mitochondrial intermembrane space. Copyright © 2017 Elsevier B.V. All rights reserved.

Gas revenue increasingly significant

International Nuclear Information System (INIS)

Megill, R.E.

1991-01-01

This paper briefly describes the wellhead prices of natural gas compared to crude oil over the past 70 years. Although natural gas prices have never reached price parity with crude oil, the relative value of a gas BTU has been increasing. It is one of the reasons that the total amount of money coming from natural gas wells is becoming more significant. From 1920 to 1955 the revenue at the wellhead for natural gas was only about 10% of the money received by producers. Most of the money needed for exploration, development, and production came from crude oil. At present, however, over 40% of the money from the upstream portion of the petroleum industry is from natural gas. As a result, in a few short years natural gas may become 50% of the money revenues generated from wellhead production facilities

Sleep disorders and their clinical significance in children with Down syndrome.

Science.gov (United States)

Stores, Gregory; Stores, Rebecca

2013-02-01

Our aim was to review basic aspects of sleep disorders in children with Down syndrome in the light of present-day findings of such disorders in children in general, including other groups of children with developmental disabilities. A literature search of adverse developmental effects of sleep disturbance, types of sleep disturbance in children with Down syndrome, their aetiology, including possible contributions of physical and psychiatric comorbidities and medication effects, principles of assessment and diagnosis, and treatment issues, was carried out. Sleep disturbance is particularly common in children with developmental disorders including Down syndrome. Although there are just three basic sleep problems (sleeplessness or insomnia, excessive daytime sleepiness, and parasomnias) there are many possible underlying causes (sleep disorders), the nature of which dictates the particular treatment required. In children with Down syndrome, in addition to the same influences in other children, various comorbid physical and psychiatric conditions are capable of disturbing sleep. Possible adverse medication effects also need to be considered. Screening for sleep disorders and their causes should be routine; positive findings call for detailed diagnosis. Management should acknowledge the likely multifactorial aetiology of the sleep disorders in Down syndrome. Successful treatment can be expected to alleviate significantly the difficulties of both child and family. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

75 FR 64107 - Continuation of the National Emergency With Respect to Significant Narcotics Traffickers Centered...

Science.gov (United States)

2010-10-18

..., corruption, and harm such actions cause in the United States and abroad. Because the actions of significant... economy of the United States and cause an extreme level of violence, corruption, and harm in the United... thereto to deal with that emergency, must continue in effect beyond October 21, 2010. Therefore, in...

Clinical significance of radiation therapy in breast recurrence and prognosis in breast-conserving surgery

International Nuclear Information System (INIS)

Nishimura, Reiki; Nagao, Kazuharu; Miyayama, Haruhiko

1999-01-01

Significant risk factors for recurrence of breast cancer after breast-conserving therapy, which has become a standard treatment for breast cancer, are positive surgical margins and the failure to perform radiation therapy. In this study, we evaluated the clinical significance of radiation therapy after primary surgery or breast recurrence. In 344 cases of breast-conserving surgery, disease recurred in 43 cases (12.5%), which were classified as follows: 17 cases of breast recurrence, 13 cases of breast and distant metastasis, and 13 cases of distant metastasis. Sixty-two patients (16.7%) received radiation therapy. A positive surgical margin and younger age were significant risk factors for breast recurrence in patients not receiving postoperative radiation therapy but not in patients receiving radiation therapy. Radiation therapy may be beneficial for younger patients with positive surgical margins. Furthermore, radiation therapy after recurrence was effective in the cases not treated with postoperative radiation but not in cases with inflammatory recurrence. Patients with breast recurrence alone had significantly higher survival rates than did patients with distant metastases regardless of breast recurrence. These findings suggest that the adaptation criteria of radiation therapy for local control must be clarified. (author)