Registration of 'TAM 113' wheat

USDA-ARS?s Scientific Manuscript database

‘TAM 113’ (Reg. No. CV-1081, PI 666125), a hard red winter wheat (Triticum aestivum L.) cultivar with experimental designation TX02A0252, was developed and released by Texas AgriLife Research in 2010. TAM 113 is an F5–derived line from the cross TX90V6313/TX94V3724 made at Vernon, TX in 1995. Both T...

TAM receptors in apoptotic cell clearance, autoimmunity, and cancer.

PubMed

Nguyen, Khanh-Quynh; Tsou, Wen-I; Kotenko, Sergei; Birge, Raymond B

2013-08-01

Receptor tyrosine kinases, Tyro-3, Axl and Mer, collectively designated as TAM, are involved in the clearance of apoptotic cells. TAM ligands, Gas6 and Protein S, bind to the surfaces of apoptotic cells, and at the same time, interact directly with TAM expressed on phagocytes, impacting the engulfment and clearance of apoptotic cells and debris. The well-tuned and balanced actions of TAM may affect a variety of human pathologies including autoimmunity, retinal degeneration, and cancer. This article emphasizes some of the emerging findings and mechanistic insights into TAM functions that are clinically relevant and possibly therapeutically targeted.

Can National Healthcare-Associated Infections (HAIs) Data Differentiate Hospitals in the United States?

PubMed

Masnick, Max; Morgan, Daniel J; Sorkin, John D; Macek, Mark D; Brown, Jessica P; Rheingans, Penny; Harris, Anthony D

2017-10-01

OBJECTIVE To determine whether patients using the Centers for Medicare and Medicaid Services (CMS) Hospital Compare website (http://medicare.gov/hospitalcompare) can use nationally reported healthcare-associated infection (HAI) data to differentiate hospitals. DESIGN Secondary analysis of publicly available HAI data for calendar year 2013. METHODS We assessed the availability of HAI data for geographically proximate hospitals (ie, hospitals within the same referral region) and then analyzed these data to determine whether they are useful to differentiate hospitals. We assessed data for the 6 HAIs reported by hospitals to the Centers for Disease Control and Prevention (CDC). RESULTS Data were analyzed for 4,561 hospitals representing 88% of registered community and federal government hospitals in the United States. Healthcare-associated infection data are only useful for comparing hospitals if they are available for multiple hospitals within a geographic region. We found that data availability differed by HAI. Clostridium difficile infections (CDI) data were most available, with 82% of geographic regions (ie, hospital referral regions) having >50% of hospitals reporting them. In contrast, 4% of geographic regions had >50% of member hospitals reporting surgical site infections (SSI) for hysterectomies, which had the lowest availability. The ability of HAI data to differentiate hospitals differed by HAI: 72% of hospital referral regions had at least 1 pair of hospitals with statistically different risk-adjusted CDI rates (SIRs), compared to 9% for SSI (hysterectomy). CONCLUSIONS HAI data generally are reported by enough hospitals to meet minimal criteria for useful comparisons in many geographic locations, though this varies by type of HAI. CDI and catheter-associated urinary tract infection (CAUTI) are more likely to differentiate hospitals than the other publicly reported HAIs. Infect Control Hosp Epidemiol 2017;38:1167-1171.

TAM 2.0: tool for MicroRNA set analysis.

PubMed

Li, Jianwei; Han, Xiaofen; Wan, Yanping; Zhang, Shan; Zhao, Yingshu; Fan, Rui; Cui, Qinghua; Zhou, Yuan

2018-06-06

With the rapid accumulation of high-throughput microRNA (miRNA) expression profile, the up-to-date resource for analyzing the functional and disease associations of miRNAs is increasingly demanded. We here describe the updated server TAM 2.0 for miRNA set enrichment analysis. Through manual curation of over 9000 papers, a more than two-fold growth of reference miRNA sets has been achieved in comparison with previous TAM, which covers 9945 and 1584 newly collected miRNA-disease and miRNA-function associations, respectively. Moreover, TAM 2.0 allows users not only to test the functional and disease annotations of miRNAs by overrepresentation analysis, but also to compare the input de-regulated miRNAs with those de-regulated in other disease conditions via correlation analysis. Finally, the functions for miRNA set query and result visualization are also enabled in the TAM 2.0 server to facilitate the community. The TAM 2.0 web server is freely accessible at http://www.scse.hebut.edu.cn/tam/ or http://www.lirmed.com/tam2/.

Searching for management approaches to reduce HAI transmission (SMART): a study protocol.

PubMed

McAlearney, Ann Scheck; Hefner, Jennifer L; Sieck, Cynthia J; Walker, Daniel M; Aldrich, Alison M; Sova, Lindsey N; Gaughan, Alice A; Slevin, Caitlin M; Hebert, Courtney; Hade, Erinn; Buck, Jacalyn; Grove, Michele; Huerta, Timothy R

2017-06-28

Healthcare-associated infections (HAIs) impact patients' lives through prolonged hospitalization, morbidity, and death, resulting in significant costs to both health systems and society. Central line-associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) are two of the most preventable HAIs. As a result, these HAIs have been the focus of significant efforts to identify evidence-based clinical strategies to reduce infection rates. The Comprehensive Unit-based Safety Program (CUSP) provides a formal model for translating CLABSI-reduction evidence into practice. Yet, a national demonstration project found organizations experienced variable levels of success using CUSP to reduce CLABSIs. In addition, in Fiscal year 2019, Medicare will expand use of CLABSI and CAUTI metrics beyond ICUs to the entire hospital for reimbursement purposes. As a result, hospitals need guidance about how to successfully translate HAI-reduction efforts such as CUSP to non-ICU settings (clinical practice), and how to shape context (management practice)-including culture and management strategies-to proactively support clinical teams. Using a mixed-methods approach to evaluate the contribution of management factors to successful HAI-reduction efforts, our study aims to: (1) Develop valid and reliable measures of structural management practices associated with the recommended CLABSI Management Strategies for use as a survey (HAI Management Practice Guideline Survey) to support HAI-reduction efforts in both medical/surgical units and ICUs; (2) Develop, validate, and then deploy the HAI Management Practice Guideline Survey, first across Ohio hospitals, then nationwide, to determine the positive predictive value of the measurement instrument as it relates to CLABSI- and CAUTI-prevention; and (3) Integrate findings into a Management Practices Toolkit for HAI reduction that includes an organization-specific data dashboard for monitoring progress and an

TAM receptors regulate multiple features of microglial physiology.

PubMed

Fourgeaud, Lawrence; Través, Paqui G; Tufail, Yusuf; Leal-Bailey, Humberto; Lew, Erin D; Burrola, Patrick G; Callaway, Perri; Zagórska, Anna; Rothlin, Carla V; Nimmerjahn, Axel; Lemke, Greg

2016-04-14

Microglia are damage sensors for the central nervous system (CNS), and the phagocytes responsible for routine non-inflammatory clearance of dead brain cells. Here we show that the TAM receptor tyrosine kinases Mer and Axl regulate these microglial functions. We find that adult mice deficient in microglial Mer and Axl exhibit a marked accumulation of apoptotic cells specifically in neurogenic regions of the CNS, and that microglial phagocytosis of the apoptotic cells generated during adult neurogenesis is normally driven by both TAM receptor ligands Gas6 and protein S. Using live two-photon imaging, we demonstrate that the microglial response to brain damage is also TAM-regulated, as TAM-deficient microglia display reduced process motility and delayed convergence to sites of injury. Finally, we show that microglial expression of Axl is prominently upregulated in the inflammatory environment that develops in a mouse model of Parkinson's disease. Together, these results establish TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease.

Prognostic significance of hepatocyte growth factor activator inhibitor type 1 (HAI-1) immunoreactivity in pancreatic ductal adenocarcinoma.

PubMed

Sakugawa, Chihiro; Haruyama, Yukihiro; Tanaka, Hiroyuki; Fukushima, Tsuyoshi; Kawaguchi, Makiko; Kataoka, Hiroaki

2017-12-04

Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a membrane-bound serine protease inhibitor that is expressed on the surface of epithelial cells. Evidence has suggested that decreased cell surface HAI-1 in carcinoma cells results in enhanced invasiveness. However, little is known regarding the expression of HAI-1 in pancreatic ductal adenocarcinoma (PDAC). This study aimed to analyze HAI-1 expression in PDAC and its impact on patient prognosis. HAI-1 immunohistochemistry was performed on samples from 67 PDAC cases. HAI-1 expression was increased in intraepithelial neoplasia compared to the adjacent non-neoplastic ductal epithelium. Of the 67 samples tested, 58% (39/67) of PDAC cases showed diffuse (> 75%) immunoreactivity in PDAC cells. The remaining cases showed reduced HAI-1 immunoreactivity in a substantial number of cancer cells. Although there was no correlation between HAI-1 status and tumor size, histologic grade or lymph node metastasis, diffuse HAI-1 positive cases showed longer disease-free survival (DFS; p = 0.006, log-rank test). In conclusion, HAI-1 is upregulated in pancreatic intraepithelial neoplasia and broadly expressed in PDAC cells. However, PDAC cases having areas of reduced HAI-1 immunoreactivity may show shorter DFS.

Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice.

PubMed

Chen, Yongmei; Wang, Huizhen; Qi, Nan; Wu, Hui; Xiong, Weipeng; Ma, Jing; Lu, Qingxian; Han, Daishu

2009-10-01

Mice lacking TYRO3, AXL and MER (TAM) receptor tyrosine kinases (RTKs) are male sterile. The mechanism of TAM RTKs in regulating male fertility remains unknown. In this study, we analyzed in more detail the testicular phenotype of TAM triple mutant (TAM(-/-)) mice with an effort to understand the mechanism. We demonstrate that the three TAM RTKs cooperatively regulate male fertility, and MER appears to be more important than AXL and TYRO3. TAM(-/-) testes showed a progressive loss of germ cells from elongated spermatids to spermatogonia. Young adult TAM(-/-) mice exhibited oligo-astheno-teratozoospermia and various morphological malformations of sperm cells. As the mice aged, the germ cells were eventually depleted from the seminiferous tubules. Furthermore, we found that TAM(-/-) Sertoli cells have an impaired phagocytic activity and a large number of differentially expressed genes compared to wild-type controls. By contrast, the function of Leydig cells was not apparently affected by the mutation of TAM RTKs. Therefore, we conclude that the suboptimal function of Sertoli cells leads to the impaired spermatogenesis in TAM(-/-) mice. The results provide novel insight into the mechanism of TAM RTKs in regulating male fertility.

Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

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

Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.

Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant tomore » the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza.« less

Handbook: Collecting Groundwater Samples from Monitoring Wells in Frenchman Flat, CAU 98

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

Chapman, Jenny; Lyles, Brad; Cooper, Clay

Frenchman Flat basin on the Nevada National Security Site (NNSS) contains Corrective Action Unit (CAU) 98, which is comprised of ten underground nuclear test locations. Environmental management of these test locations is part of the Underground Test Area (UGTA) Activity conducted by the U.S. Department of Energy (DOE) under the Federal Facility Agreement and Consent Order (FFACO) (1996, as amended) with the U.S. Department of Defense (DOD) and the State of Nevada. A Corrective Action Decision Document (CADD)/Corrective Action Plan (CAP) has been approved for CAU 98 (DOE, 2011). The CADD/CAP reports on the Corrective Action Investigation that was conductedmore » for the CAU, which included characterization and modeling. It also presents the recommended corrective actions to address the objective of protecting human health and the environment. The recommended corrective action alternative is “Closure in Place with Modeling, Monitoring, and Institutional Controls.” The role of monitoring is to verify that Contaminants of Concern (COCs) have not exceeded the Safe Drinking Water Act (SDWA) limits (Code of Federal Regulations, 2014) at the regulatory boundary, to ensure that institutional controls are adequate, and to monitor for changed conditions that could affect the closure conditions. The long-term closure monitoring program will be planned and implemented as part of the Closure Report stage after activities specified in the CADD/CAP are complete. Groundwater at the NNSS has been monitored for decades through a variety of programs. Current activities were recently consolidated in an NNSS Integrated Sampling Plan (DOE, 2014). Although monitoring directed by the plan is not intended to meet the FFACO long-term monitoring requirements for a CAU (which will be defined in the Closure Report), the objective to ensure public health protection is similar. It is expected that data collected in accordance with the plan will support the transition to long-term monitoring

Healthcare-Associated Infections (HAIs) Data and Statistics

MedlinePlus

... Personnel PPE Training Infection Control Assessment Tools Water Management Programs Map: HAI Prevention Activities Research CDC Supported Projects Prevention Epicenters (PE) Healthcare Safety Research (SHEPheRD) Environmental ...

TAM Receptors in Leukemia: Expression, Signaling, and Therapeutic Implications

PubMed Central

Brandão, Luis; Migdall-Wilson, Justine; Eisenman, Kristen; Graham, Douglas K.

2016-01-01

In the past 30 years there has been remarkable progress in the treatment of leukemia and lymphoma. However, current treatments are largely ineffective against relapsed leukemia and, in the case of pediatric patients, are often associated with severe long-term toxicities. Thus, there continues to be a critical need for the development of effective biologically targeted therapies. The TAM family of receptor tyrosine kinases—Tyro3, Axl, and Mer—plays an important role in normal hematopoiesis, including natural killer cell maturation, macrophage function, and platelet activation and signaling. Furthermore, TAM receptor activation leads to upregulation of pro-survival and proliferation signaling pathways, and aberrant TAM receptor expression contributes to cancer development, including myeloid and lymphoid leukemia. This review summarizes the role of TAM receptors in leukemia. We outline TAM receptor expression patterns in different forms of leukemia, describe potential mechanisms leading to their overexpression, and delineate the signaling pathways downstream of receptor activation that have been implicated in leukemogenesis. Finally, we discuss the current research focused on inhibitors against these receptors in an effort to develop new therapeutic strategies for leukemia. PMID:22150307

Full-scale results for TAM limestone injection

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

Baer, S.

1996-12-31

Information is outlined on the use of thermally active marble (TAM) sorbents in boilers. Data are presented on: the comparison of TAM to limestone; NOVACON process development history; CFB test history; CFB pilot scale test; full-scale CFB trial; August, 1996 CFB demonstration; Foster Wheeler Mount Carmel sorbent feed rate comparison and Ca:S comparison; unburned carbon is ash; and advantages and savings in CFB boilers.

HAI-2 stabilizes, inhibits and regulates SEA-cleavage-dependent secretory transport of matriptase.

PubMed

Nonboe, Annika W; Krigslund, Oliver; Soendergaard, Christoffer; Skovbjerg, Signe; Friis, Stine; Andersen, Martin N; Ellis, Vincent; Kawaguchi, Makiko; Kataoka, Hiroaki; Bugge, Thomas H; Vogel, Lotte K

2017-06-01

It has recently been shown that hepatocyte growth factor activator inhibitor-2 (HAI-2) is able to suppress carcinogenesis induced by overexpression of matriptase, as well as cause regression of individual established tumors in a mouse model system. However, the role of HAI-2 is poorly understood. In this study, we describe 3 mutations in the binding loop of the HAI-2 Kunitz domain 1 (K42N, C47F and R48L) that cause a delay in the SEA domain cleavage of matriptase, leading to accumulation of non-SEA domain cleaved matriptase in the endoplasmic reticulum (ER). We suggest that, like other known SEA domains, the matriptase SEA domain auto-cleaves and reflects that correct oligomerization, maturation, and/or folding has been obtained. Our results suggest that the HAI-2 Kunitz domain 1 mutants influence the flux of matriptase to the plasma membrane by affecting the oligomerization, maturation and/or folding of matriptase, and as a result the SEA domain cleavage of matriptase. Two of the HAI-2 Kunitz domain 1 mutants investigated (C47F, R48L and C47F/R48L) also displayed a reduced ability to proteolytically silence matriptase. Hence, HAI-2 separately stabilizes matriptase, regulates the secretory transport, possibly via maturation/oligomerization and inhibits the proteolytic activity of matriptase in the ER, and possible throughout the secretory pathway. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry.

PubMed

Meertens, Laurent; Carnec, Xavier; Lecoin, Manuel Perera; Ramdasi, Rasika; Guivel-Benhassine, Florence; Lew, Erin; Lemke, Greg; Schwartz, Olivier; Amara, Ali

2012-10-18

Dengue viruses (DVs) are responsible for the most medically relevant arboviral diseases. However, the molecular interactions mediating DV entry are poorly understood. We determined that TIM and TAM proteins, two receptor families that mediate the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, serve as DV entry factors. Cells poorly susceptible to DV are robustly infected after ectopic expression of TIM or TAM receptors. Conversely, DV infection of susceptible cells is inhibited by anti-TIM or anti-TAM antibodies or knockdown of TIM and TAM expression. TIM receptors facilitate DV entry by directly interacting with virion-associated PtdSer. TAM-mediated infection relies on indirect DV recognition, in which the TAM ligand Gas6 acts as a bridging molecule by binding to PtdSer within the virion. This dual mode of virus recognition by TIM and TAM receptors reveals how DVs usurp the apoptotic cell clearance pathway for infectious entry. Copyright © 2012 Elsevier Inc. All rights reserved.

Biology and management of transient abnormal myelopoiesis (TAM) in children with Down syndrome.

PubMed

Roy, Anindita; Roberts, Irene; Vyas, Paresh

2012-08-01

Children with Down syndrome (DS) have an increased risk of Acute Myeloid Leukaemia (ML-DS), particularly megakaryoblastic leukaemia, which is clonally -related to the neonatal myeloproliferative syndrome, Transient Abnormal Myelopoiesis (TAM) unique to infants with DS. Molecular, biological, and clinical data indicate that TAM is initiated before birth when fetal liver haematopoietic cells trisomic for chromosome 21 acquire mutations in GATA1. TAM usually resolves spontaneously by 6 months; however 20-30% subsequently develop ML-DS harbouring the same GATA1 mutation(s). This review focuses on recent studies describing haematological, clinical and biological features of TAM and discusses approaches to diagnose, treat and monitor minimal residual disease in TAM. An important unanswered question is whether ML-DS is always preceded by TAM as it may be clinically and possibly haematologically 'silent'. We have briefly discussed the role of population-based screening for TAM and development of treatment strategies to eliminate the preleukaemic TAM clone, thereby preventing ML-DS. Copyright © 2012 Elsevier Ltd. All rights reserved.

GAS6/TAM Pathway Signaling in Hemostasis and Thrombosis.

PubMed

Law, Luke A; Graham, Douglas K; Di Paola, Jorge; Branchford, Brian R

2018-01-01

The GAS6/TYRO3-AXL-MERTK (TAM) signaling pathway is essential for full and sustained platelet activation, as well as thrombus stabilization. Inhibition of this pathway decreases platelet aggregation, shape change, clot retraction, aggregate formation under flow conditions, and surface expression of activation markers. Transgenic mice deficient in GAS6, or any of the TAM family of receptors that engage this ligand, exhibit in vivo protection against arterial and venous thrombosis but do not demonstrate either spontaneous or prolonged bleeding compared to their wild-type counterparts. Comparable results are observed in wild-type mice treated with pharmacological inhibitors of the GAS6-TAM pathway. Thus, GAS6/TAM inhibition offers an attractive novel therapeutic option that may allow for a moderate reduction in platelet activation and decreased thrombosis while still permitting the primary hemostatic function of platelet plug formation.

The Structure of a Conserved Domain of TamB Reveals a Hydrophobic β Taco Fold.

PubMed

Josts, Inokentijs; Stubenrauch, Christopher James; Vadlamani, Grishma; Mosbahi, Khedidja; Walker, Daniel; Lithgow, Trevor; Grinter, Rhys

2017-12-05

The translocation and assembly module (TAM) plays a role in the transport and insertion of proteins into the bacterial outer membrane. TamB, a component of this system spans the periplasmic space to engage with its partner protein TamA. Despite efforts to characterize the TAM, the structure and mechanism of action of TamB remained enigmatic. Here we present the crystal structure of TamB amino acids 963-1,138. This region represents half of the conserved DUF490 domain, the defining feature of TamB. TamB 963-1138 consists of a concave, taco-shaped β sheet with a hydrophobic interior. This β taco structure is of dimensions capable of accommodating and shielding the hydrophobic side of an amphipathic β strand, potentially allowing TamB to chaperone nascent membrane proteins from the aqueous environment. In addition, sequence analysis suggests that the structure of TamB 963-1138 is shared by a large portion of TamB. This architecture could allow TamB to act as a conduit for membrane proteins. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

On-site ocean horizontal aerosol extinction coefficient inversion under different weather conditions on the Bo-hai and Huang-hai Seas

NASA Astrophysics Data System (ADS)

Zeng, Xianjiang; Xia, Min; Ge, Yinghui; Guo, Wenping; Yang, Kecheng

2018-03-01

In this paper, we explore the horizontal extinction characteristics under different weather conditions on the ocean surface with on-site experiments on the Bo-hai and Huang-hai Seas in the summer of 2016. An experimental lidar system is designed to collect the on-site experimental data. By aiming at the inhomogeneity and uncertainty of the horizontal aerosol in practice, a joint retrieval method is proposed to retrieve the aerosol extinction coefficients (AEC) from the raw data along the optical path. The retrieval results of both the simulated and the real signals demonstrate that the joint retrieval method is practical. Finally, the sequence observation results of the on-site experiments under different weather conditions are reported and analyzed. These results can provide the attenuation information to analyze the atmospheric aerosol characteristics on the ocean surface.

The Gas6/TAM System and Multiple Sclerosis.

PubMed

Bellan, Mattia; Pirisi, Mario; Sainaghi, Pier Paolo

2016-10-28

Growth arrest specific 6 (Gas6) is a multimodular circulating protein, the biological actions of which are mediated by the interaction with three transmembrane tyrosine kinase receptors: Tyro3, Axl, and MerTK, collectively named TAM. Over the last few decades, many progresses have been done in the understanding of the biological activities of this highly pleiotropic system, which plays a role in the regulation of immune response, inflammation, coagulation, cell growth, and clearance of apoptotic bodies. Recent findings have further related Gas6 and TAM receptors to neuroinflammation in general and, specifically, to multiple sclerosis (MS). In this paper, we review the biology of the Gas6/TAM system and the current evidence supporting its potential role in the pathogenesis of MS.

Fluoropyrimidine-HAI (hepatic arterial infusion) versus systemic chemotherapy (SCT) for unresectable liver metastases from colorectal cancer.

PubMed

Mocellin, Simone; Pasquali, Sandro; Nitti, Donato

2009-07-08

Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the metastatic organ as compared to systemic chemotherapy (SCT), the benefit in terms of overall survival (OS) is unclear. We quantitatively summarized the results of randomised controlled trials (RCT) comparing HAI to SCT for the treatment of unresectable liver metastatic disease from colorectal cancer (CRC). The aim of this work is to quantitatively summarize the results of RCT comparing HAI to SCT for the treatment of unresectable hepatic metastases from CRC. A systematic review of reports published until September 2008 on the findings of RCT that compared HAI to SCT for the treatment of unresectable CRC liver metastases was performed by searching the MEDLINE, Embase, Cancerlit, Cochrane and GoogleScholar electronic databases as well as other databanks collecting information on clinical trials. Inclusion criteria were patients with unresectable CRC liver metastases enrolled in RCT comparing HAI to SCT. The outcome measures were tumor response rate and overall survival. Two authors independently carried out study selection and assessment of methodological quality. A third author performed a concordance analysis in order to unravel potential systematic biases. Ten RCT were identified that met the eligibility criteria. HAI regimens were based on floxuridine (FUDR), 5-fluorouracil or either one of these two fluoropyrimidines in eight and one RCT, respectively. SCT consisted of FUDR or 5-fluorouracil in three and seven RCT, respectively. By pooling the summary data, tumor response rate resulted 42.9% and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P < 0.0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT, respectively: the meta-risk of death was not statistically different between the two treatment groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = 0.24). Currently

The simulation of cropping pattern to improve the performance of irrigation network in Cau irrigation area

NASA Astrophysics Data System (ADS)

Wahyuningsih, Retno; Rintis Hadiani, RR; Sobriyah

2017-01-01

Cau irrigation area located in Madiun district, East Java Province, irrigates 1.232 Ha of land which covers Cau primary channel irrigation network, Wungu Secondary channel irrigation network, and Grape secondary channel irrigation network. The problems in Cau irrigation area are limited availability of water especially during the dry season (planting season II and III) and non-compliance to cropping patterns. The evaluation of irrigation system performance of Cau irrigation area needs to be done in order to know how far the irrigation system performance is, especially based on planting productivity aspect. The improvement of irrigation network performance through cropping pattern optimization is based on the increase of water necessity fulfillment (k factor), the realization of planting area and rice productivity. The research method of irrigation system performance is by analyzing the secondary data based on the Regulation of Ministry of Public Work and State Minister for Public Housing Number: 12/PRT/M/2015. The analysis of water necessity fulfillment (k factor) uses Public Work Plan Criteria Method. The performance level of planting productivity aspect in existing condition is 87.10%, alternative 1 is 93.90% dan alternative 2 is 96.90%. It means that the performance of the irrigation network from productivity aspect increases 6.80% for alternative 1 and 9.80% for alternative 2.

Hepatocyte growth factor activator inhibitor type-2 (HAI-2)/SPINT2 contributes to invasive growth of oral squamous cell carcinoma cells.

PubMed

Yamamoto, Koji; Kawaguchi, Makiko; Shimomura, Takeshi; Izumi, Aya; Konari, Kazuomi; Honda, Arata; Lin, Chen-Yong; Johnson, Michael D; Yamashita, Yoshihiro; Fukushima, Tsuyoshi; Kataoka, Hiroaki

2018-02-20

Hepatocyte growth factor activator inhibitor (HAI)-1/ SPINT1 and HAI-2/ SPINT2 are membrane-anchored protease inhibitors having homologous Kunitz-type inhibitor domains. They regulate membrane-anchored serine proteases, such as matriptase and prostasin. Whereas HAI-1 suppresses the neoplastic progression of keratinocytes to invasive squamous cell carcinoma (SCC) through matriptase inhibition, the role of HAI-2 in keratinocytes is poorly understood. In vitro homozygous knockout of the SPINT2 gene suppressed the proliferation of two oral SCC (OSCC) lines (SAS and HSC3) but not the growth of a non-tumorigenic keratinocyte line (HaCaT). Reversion of HAI-2 abrogated the growth suppression. Matrigel invasion of both OSCC lines was also suppressed by the loss of HAI-2. The levels of prostasin protein were markedly increased in HAI-2-deficient cells, and knockdown of prostasin alleviated the HAI-2 loss-induced suppression of OSCC cell invasion. Therefore, HAI-2 has a pro-invasive role in OSCC cells through suppression of prostasin. In surgically resected OSCC tissues, HAI-2 immunoreactivity increased along with neoplastic progression, showing intense immunoreactivities in invasive OSCC cells. In summary, HAI-2 is required for invasive growth of OSCC cells and may contribute to OSCC progression.

Small molecule inhibitors block Gas6-inducible TAM activation and tumorigenicity.

PubMed

Kimani, Stanley G; Kumar, Sushil; Bansal, Nitu; Singh, Kamalendra; Kholodovych, Vladyslav; Comollo, Thomas; Peng, Youyi; Kotenko, Sergei V; Sarafianos, Stefan G; Bertino, Joseph R; Welsh, William J; Birge, Raymond B

2017-03-08

TAM receptors (Tyro-3, Axl, and Mertk) are a family of three homologous type I receptor tyrosine kinases that are implicated in several human malignancies. Overexpression of TAMs and their major ligand Growth arrest-specific factor 6 (Gas6) is associated with more aggressive staging of cancers, poorer predicted patient survival, acquired drug resistance and metastasis. Here we describe small molecule inhibitors (RU-301 and RU-302) that target the extracellular domain of Axl at the interface of the Ig-1 ectodomain of Axl and the Lg-1 of Gas6. These inhibitors effectively block Gas6-inducible Axl receptor activation with low micromolar IC 50s in cell-based reporter assays, inhibit Gas6-inducible motility in Axl-expressing cell lines, and suppress H1299 lung cancer tumor growth in a mouse xenograft NOD-SCIDγ model. Furthermore, using homology models and biochemical verifications, we show that RU301 and 302 also inhibit Gas6 inducible activation of Mertk and Tyro3 suggesting they can act as pan-TAM inhibitors that block the interface between the TAM Ig1 ectodomain and the Gas6 Lg domain. Together, these observations establish that small molecules that bind to the interface between TAM Ig1 domain and Gas6 Lg1 domain can inhibit TAM activation, and support the further development of small molecule Gas6-TAM interaction inhibitors as a novel class of cancer therapeutics.

HAI-178 antibody-conjugated fluorescent magnetic nanoparticles for targeted imaging and simultaneous therapy of gastric cancer

NASA Astrophysics Data System (ADS)

Wang, Can; Bao, Chenchen; Liang, Shujing; Zhang, Lingxia; Fu, Hualin; Wang, Yutian; Wang, Kan; Li, Chao; Deng, Min; Liao, Qiande; Ni, Jian; Cui, Daxiang

2014-05-01

The successful development of safe and highly effective nanoprobes for targeted imaging and simultaneous therapy of in vivo gastric cancer is a great challenge. Herein we reported for the first time that anti-α-subunit of ATP synthase antibody, HAI-178 monoclonal antibody-conjugated fluorescent magnetic nanoparticles, was successfully used for targeted imaging and simultaneous therapy of in vivo gastric cancer. A total of 172 specimens of gastric cancer tissues were collected, and the expression of α-subunit of ATP synthase in gastric cancer tissues was investigated by immunohistochemistry method. Fluorescent magnetic nanoparticles were prepared and conjugated with HAI-178 monoclonal antibody, and the resultant HAI-178 antibody-conjugated fluorescent magnetic nanoparticles (HAI-178-FMNPs) were co-incubated with gastric cancer MGC803 cells and gastric mucous GES-1 cells. Gastric cancer-bearing nude mice models were established, were injected with prepared HAI-178-FMNPs via tail vein, and were imaged by magnetic resonance imaging and small animal fluorescent imaging system. The results showed that the α-subunit of ATP synthase exhibited high expression in 94.7% of the gastric cancer tissues. The prepared HAI-178-FMNPs could target actively MGC803 cells, realized fluorescent imaging and magnetic resonance imaging of in vivo gastric cancer, and actively inhibited growth of gastric cancer cells. In conclusion, HAI-178 antibody-conjugated fluorescent magnetic nanoparticles have a great potential in applications such as targeted imaging and simultaneous therapy of in vivo early gastric cancer cells in the near future.

TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis.

PubMed

van der Meer, Jonathan H M; van der Poll, Tom; van 't Veer, Cornelis

2014-04-17

TAM receptors (Tyro3, Axl, and Mer) belong to a family of receptor tyrosine kinases that have important effects on hemostasis and inflammation. Also, they affect cell proliferation, survival, adhesion, and migration. TAM receptors can be activated by the vitamin K-dependent proteins Gas6 and protein S. Protein S is more commonly known as an important cofactor for protein C as well as a direct inhibitor of multiple coagulation factors. To our knowledge, the functions of Gas6 are limited to TAM receptor activation. When activated, the TAM receptors have effects on primary hemostasis and coagulation and display an anti-inflammatory or a proinflammatory effect, depending on cell type. To comprehend the effects that the TAM receptors and their ligands have on hemostasis and inflammation, we compare studies that report the different phenotypes displayed by mice with deficiencies in the genes of this receptor family and its ligands (protein S(+/-), Gas6(-/-), TAM(-/-), and variations of these). In this manner, we aim to display which features are attributable to the different ligands. Because of the effects TAM receptors have on hemostasis, inflammation, and cancer growth, their modulation could make interesting therapeutic targets in thromboembolic disease, atherosclerosis, sepsis, autoimmune disease, and cancer.

Ligand Activation of TAM Family Receptors-Implications for Tumor Biology and Therapeutic Response.

PubMed

Davra, Viralkumar; Kimani, Stanley G; Calianese, David; Birge, Raymond B

2016-11-29

The TAM family of receptors (i.e., Tyro3, Axl, and Mertk), and their ligands Growth arrest specific factor 6 (Gas6) and Protein S (Pros1) contribute to several oncogenic processes, such as cell survival, invasion, migration, chemo-resistance, and metastasis, whereby expression often correlates with poor clinical outcomes. In recent years, there has been great interest in the study of TAM receptors in cancer, stemming both from their roles as oncogenic signaling receptors, as well as their roles in tumor immunology. As a result, several classes of TAM inhibitors that include small molecule tyrosine kinase inhibitors, monoclonal antibodies, decoy receptors, as well as novel strategies to target TAM ligands are being developed. This paper will review the biology of TAM receptors and their ligands with a focus on cancer, as well as evidence-based data for the continued pursuit of TAM/Gas6 inhibitors in clinical practice.

Corrective action investigation plan for CAU Number 453: Area 9 Landfill, Tonopah Test Range

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

NONE

This Corrective Action Investigation Plan (CAIP) contains the environmental sample collection objectives and criteria for conducting site investigation activities at the Area 9 Landfill, Corrective Action Unit (CAU) 453/Corrective Action (CAS) 09-55-001-0952, which is located at the Tonopah Test Range (TTR). The TTR, included in the Nellis Air Force Range, is approximately 255 kilometers (140 miles) northwest of Las Vegas, Nevada. The Area 9 Landfill is located northwest of Area 9 on the TTR. The landfill cells associated with CAU 453 were excavated to receive waste generated from the daily operations conducted at Area 9 and from range cleanup whichmore » occurred after test activities.« less

TAM receptor knockout mice are susceptible to retinal autoimmune induction.

PubMed

Ye, Fei; Li, Qiutang; Ke, Yan; Lu, Qingjun; Han, Lixia; Kaplan, Henry J; Shao, Hui; Lu, Qingxian

2011-06-16

TAM receptors are expressed mainly by dendritic cells and macrophages in the immune system, and mice lacking TAM receptors develop systemic autoimmune diseases because of inefficient negative control of the cytokine signaling in those cells. This study aims to test the susceptibility of the TAM triple knockout (tko) mice to the retina-specific autoantigen to develop experimental autoimmune uveoretinitis (EAU). TAM tko mice that were or were not immunized with interphotoreceptor retinoid-binding protein (IRBP) peptides were evaluated for retinal infiltration of the macrophages and CD3(+) T cells by immunohistochemistry, spontaneous activation of CD4(+) T cells, and memory T cells by flow cytometry and proliferation of IRBP-specific CD4(+) T cells by [(3)H]thymidine incorporation assay. Ocular inflammation induced by IRBP peptide immunization and specific T cell transfer were observed clinically by funduscopy and confirmed by histology. Tko mice were found to have less naive, but more activated, memory T cells, among which were exhibited high sensitivity to ocular IRBP autoantigens. Immunization with a low dose of IRBP and adoptive transfer of small numbers of IRBP-specific T cells from immunized tko mice caused the infiltration of lymphocytes, including CD3(+) T cells, into the tko retina. Mice without TAM receptor spontaneously develop IRBP-specific CD4(+) T cells and are more susceptible to retinal autoantigen immunization. This TAM knockout mouse line provides an animal model with which to study the role of antigen-presenting cells in the development of T cell-mediated uveitis.

The roles of TAM receptor tyrosine kinases in the mammalian testis and immunoprivileged sites.

PubMed

Deng, Tingting; Chen, Qiaoyuan; Han, Daishu

2016-01-01

Three members of a receptor tyrosine kinase family, including Tyro3, Axl, and Mer, are collectively called as TAM receptors. TAM receptors have two common ligands, namely, growth arrest specific gene 6 (Gas6) and protein S (ProS). The TAM-Gas6/ProS system is essential for phagocytic removal of apoptotic cells, and plays critical roles in regulating immune response. Genetic studies have shown that TAM receptors are essential regulators of the tissue homeostasis in immunoprivileged sites, including the testis, retina and brain. The mechanisms by which the TAM-Gas6/ProS system regulates the tissue homeostasis in immunoprivileged sites are emerging. The roles of the TAM-Gas6/ProS system in regulating the immune privilege were intensively investigated in the mouse testis, and several studies were performed in the eye and brain. This review summarizes our current understanding of TAM signaling in the testis and other immunoprivileged tissues, as well as highlights topics that are worthy of further investigation.

TAM Receptors Are Not Required for Zika Virus Infection in Mice.

PubMed

Hastings, Andrew K; Yockey, Laura J; Jagger, Brett W; Hwang, Jesse; Uraki, Ryuta; Gaitsch, Hallie F; Parnell, Lindsay A; Cao, Bin; Mysorekar, Indira U; Rothlin, Carla V; Fikrig, Erol; Diamond, Michael S; Iwasaki, Akiko

2017-04-18

Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection with the Zika virus (ZIKV), an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl -/- , Mertk -/- , Axl -/- Mertk -/- , and Axl -/- Tyro3 -/- mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR)-blocking (MAR1-5A3) antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection. In the absence of IFNAR-blocking antibody, adult female mice challenged intravaginally with ZIKV showed no difference in mucosal viral titers. Similarly, in young mice that were infected with ZIKV intracranially or intraperitoneally, ZIKV replication occurred in the absence of TAM receptors, and no differences in cell tropism were observed. These findings indicate that, in mice, TAM receptors are not required for ZIKV entry and infection. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Esterified dendritic TAM radicals with very high stability and enhanced oxygen sensitivity.

PubMed

Song, Yuguang; Liu, Yangping; Hemann, Craig; Villamena, Frederick A; Zweier, Jay L

2013-02-15

In this work, we have developed a new class of dendritic TAM radicals (TG, TdG, and dTdG) through a convergent method based on the TAM core CT-03 or its deuterated analogue dCT-03 and trifurcated Newkome-type monomer. Among these radicals, dTdG exhibits the best EPR properties with sharpest EPR singlet and highest O(2) sensitivity due to deuteration of both the ester linker groups and the TAM core CT-03. Like the previous dendritic TAM radicals, these new compounds also show extremely high stability toward various reactive species owing to the dendritic encapsulation. The highly charged nature of these molecules resulting from nine carboxylate groups prevents concentration-dependent EPR line broadening at physiological pH. Furthermore, we demonstrate that these TAM radicals can be easily derivatized (e.g., PEGylation) at the nine carboxylate groups and the resulting PEGylated analogue dTdG-PEG completely inhibits the albumin binding, thereby enhancing suitability for in vivo applications. These new dendritic TAM radicals show great potential for in vivo EPR oximetric applications and provide insights on approaches to develop improved and targeted EPR oximetric probes for biomedical applications.

Functional analysis of TamA, a coactivator of nitrogen-regulated gene expression in Aspergillus nidulans.

PubMed

Small, A J; Todd, R B; Zanker, M C; Delimitrou, S; Hynes, M J; Davis, M A

2001-06-01

The tam A gene of Aspergillus nidulans encodes a 739-amino acid protein with similarity to Uga35p/Dal81p/DurLp of Saccharomyces cerevisiae. It has been proposed that TamA functions as a co-activator of AreA, the major nitrogen regulatory protein in A. nidulans. Because AreA functions as a transcriptional activator under nitrogen-limiting conditions, we investigated whether TamA was also present in the nucleus. We found that a GFP-TamA fusion protein was predominantly localised to the nucleus in the presence and absence of ammonium, and that AreA was not required for this distribution. As the predicted DNA-binding domain of TamA is not essential for function, we have used a number of approaches to further define functionally important regions. We have cloned the tamA gene of A. oryzae and compared its functional and sequence characteristics with those of A. nidulans tamA and S. cerevisiae UGA35/DAL81/DURL. The Aspergillus homologues are highly conserved and functionally interchangeable, whereas the S. cerevisiae gene does not complement a tamA mutant when expressed in A. nidulans. Uga35p/Dal81p/DurLp was also found to be unable to recruit AreA. The sequence changes in a number of tamA mutant alleles were determined, and altered versions of TamA were tested for tamA complementation and interaction with AreA. Changes in most regions of TamA appeared to destroy its function, suggesting that the overall conformation of the protein may be critical for its activity.

Cytoplasmic PELP1 and ERRgamma Protect Human Mammary Epithelial Cells from Tam-Induced Cell Death

PubMed Central

Girard, Brian J.; Regan Anderson, Tarah M.; Welch, Siya Lem; Nicely, Julie; Seewaldt, Victoria L.; Ostrander, Julie H.

2015-01-01

Tamoxifen (Tam) is the only FDA-approved chemoprevention agent for pre-menopausal women at high risk for developing breast cancer. While Tam reduces a woman's risk of developing estrogen receptor positive (ER+) breast cancer, the molecular mechanisms associated with risk reduction are poorly understood. Prior studies have shown that cytoplasmic proline, glutamic acid and leucine rich protein 1 (PELP1) promotes Tam resistance in breast cancer cell lines. Herein, we tested for PELP1 localization in breast epithelial cells from women at high risk for developing breast cancer and found that PELP1 was localized to the cytoplasm in 36% of samples. In vitro, immortalized HMECs expressing a nuclear localization signal (NLS) mutant of PELP1 (PELP1-cyto) were resistant to Tam-induced death. Furthermore, PELP1-cyto signaling through estrogen-related receptor gamma (ERRγ) promoted cell survival in the presence of Tam. Overexpression of ERRγ in immortalized HMECs protected cells from Tam-induced death, while knockdown of ERRγ sensitized PELP1-cyto expressing HMECs to Tam. Moreover, Tam-induced HMEC cell death was independent of apoptosis and involved accumulation of the autophagy marker LC3-II. Expression of PELP1-cyto and ERRγ reduced Tam-induced LC3-II accumulation, and knockdown of ERRγ increased LC3-II levels in response to Tam. Additionally, PELP1-cyto expression led to the upregulation of MMP-3 and MAOB, known PELP1 and ERRγ target genes, respectively. Our data indicate that cytoplasmic PELP1 induces signaling pathways that converge on ERRγ to promote cell survival in the presence of Tam. These data suggest that PELP1 localization and/or ERRγ activation could be developed as tissue biomarkers for Tam responsiveness. PMID:25789479

Cytoplasmic PELP1 and ERRgamma protect human mammary epithelial cells from Tam-induced cell death.

PubMed

Girard, Brian J; Regan Anderson, Tarah M; Welch, Siya Lem; Nicely, Julie; Seewaldt, Victoria L; Ostrander, Julie H

2015-01-01

Tamoxifen (Tam) is the only FDA-approved chemoprevention agent for pre-menopausal women at high risk for developing breast cancer. While Tam reduces a woman's risk of developing estrogen receptor positive (ER+) breast cancer, the molecular mechanisms associated with risk reduction are poorly understood. Prior studies have shown that cytoplasmic proline, glutamic acid and leucine rich protein 1 (PELP1) promotes Tam resistance in breast cancer cell lines. Herein, we tested for PELP1 localization in breast epithelial cells from women at high risk for developing breast cancer and found that PELP1 was localized to the cytoplasm in 36% of samples. In vitro, immortalized HMECs expressing a nuclear localization signal (NLS) mutant of PELP1 (PELP1-cyto) were resistant to Tam-induced death. Furthermore, PELP1-cyto signaling through estrogen-related receptor gamma (ERRγ) promoted cell survival in the presence of Tam. Overexpression of ERRγ in immortalized HMECs protected cells from Tam-induced death, while knockdown of ERRγ sensitized PELP1-cyto expressing HMECs to Tam. Moreover, Tam-induced HMEC cell death was independent of apoptosis and involved accumulation of the autophagy marker LC3-II. Expression of PELP1-cyto and ERRγ reduced Tam-induced LC3-II accumulation, and knockdown of ERRγ increased LC3-II levels in response to Tam. Additionally, PELP1-cyto expression led to the upregulation of MMP-3 and MAOB, known PELP1 and ERRγ target genes, respectively. Our data indicate that cytoplasmic PELP1 induces signaling pathways that converge on ERRγ to promote cell survival in the presence of Tam. These data suggest that PELP1 localization and/or ERRγ activation could be developed as tissue biomarkers for Tam responsiveness.

Normalization of TAM post-receptor signaling reveals a cell invasive signature for Axl tyrosine kinase.

PubMed

Kimani, Stanley G; Kumar, Sushil; Davra, Viralkumar; Chang, Yun-Juan; Kasikara, Canan; Geng, Ke; Tsou, Wen-I; Wang, Shenyan; Hoque, Mainul; Boháč, Andrej; Lewis-Antes, Anita; De Lorenzo, Mariana S; Kotenko, Sergei V; Birge, Raymond B

2016-09-06

Tyro3, Axl, and Mertk (TAMs) are a family of three conserved receptor tyrosine kinases that have pleiotropic roles in innate immunity and homeostasis and when overexpressed in cancer cells can drive tumorigenesis. In the present study, we engineered EGFR/TAM chimeric receptors (EGFR/Tyro3, EGFR/Axl, and EGF/Mertk) with the goals to interrogate post-receptor functions of TAMs, and query whether TAMs have unique or overlapping post-receptor activation profiles. Stable expression of EGFR/TAMs in EGFR-deficient CHO cells afforded robust EGF inducible TAM receptor phosphorylation and activation of downstream signaling. Using a series of unbiased screening approaches, that include kinome-view analysis, phosphor-arrays, RNAseq/GSEA analysis, as well as cell biological and in vivo readouts, we provide evidence that each TAM has unique post-receptor signaling platforms and identify an intrinsic role for Axl that impinges on cell motility and invasion compared to Tyro3 and Mertk. These studies demonstrate that TAM show unique post-receptor signatures that impinge on distinct gene expression profiles and tumorigenic outcomes.

Measuring medicine prices in Peru: validation of key aspects of WHO/HAI survey methodology.

PubMed

Madden, Jeanne M; Meza, Edson; Ewen, Margaret; Laing, Richard O; Stephens, Peter; Ross-Degnan, Dennis

2010-04-01

To assess the possibility of bias due to the limited target list and geographic sampling of the World Health Organization (WHO)/Health Action International (HAI) Medicine Prices and Availability survey used in more than 70 rapid sample surveys since 2001. A survey was conducted in Peru in 2005 using an expanded sample of medicine outlets, including remote areas. Comprehensive data were gathered on medicines in three therapeutic classes to assess the adequacy of WHO/HAI's target medicines list and the focus on only two product versions. WHO/HAI median retail prices were compared with average wholesale prices from global pharmaceutical sales data supplier IMS Health. No significant differences were found in overall availability or prices of target list medicines by retail location. The comprehensive survey of angiotensin-converting enzyme inhibitor, anti-diabetic, and anti-ulcer products revealed that some treatments not on the target list were costlier for patients and more likely to be unavailable, particularly in remote areas. WHO/HAI retail prices and IMS wholesale prices were strongly correlated for higher priced products, and weakly correlated for lower priced products (which had higher estimated retailer markups). The WHO/HAI survey approach strikes an appropriate balance between modest research costs and optimal information for policy. Focusing on commonly used medicines yields sufficient and valid results. Surveyors elsewhere should consider the limits of the survey data as well as any local circumstances, such as scarcity, that may call for extra field efforts.

Targeting Gas6/TAM in cancer cells and tumor microenvironment.

PubMed

Wu, Guiling; Ma, Zhiqiang; Cheng, Yicheng; Hu, Wei; Deng, Chao; Jiang, Shuai; Li, Tian; Chen, Fulin; Yang, Yang

2018-01-31

Growth arrest-specific 6, also known as Gas6, is a human gene encoding the Gas6 protein, which was originally found to be upregulated in growth-arrested fibroblasts. Gas6 is a member of the vitamin K-dependent family of proteins expressed in many human tissues and regulates several biological processes in cells, including proliferation, survival and migration, by binding to its receptors Tyro3, Axl and Mer (TAM). In recent years, the roles of Gas6/TAM signalling in cancer cells and the tumour microenvironment have been studied, and some progress has made in targeted therapy, providing new potential directions for future investigations of cancer treatment. In this review, we introduce the Gas6 and TAM receptors and describe their involvement in different cancers and discuss the roles of Gas6 in cancer cells, the tumour microenvironment and metastasis. Finally, we introduce recent studies on Gas6/TAM targeting in cancer therapy, which will assist in the experimental design of future analyses and increase the potential use of Gas6 as a therapeutic target for cancer.

Clinical application and prognostic assessment of serum Tumor Associated Material (TAM) from esophageal cancer patients.

PubMed

Zhou, K; Yan, Y; Zhao, S; Li, B

2014-01-01

To explore the correlation between serum levels of Tumor Associated Materials (TAM) and clinicopathological parameters and prognosis in patients with esophageal cancer (EC). The levels of TAM were determined by chemical colorimetry in 100 EC patients and 100 healthy controls. Serum TAM levels were significantly higher in patients with esophageal carcinoma than in the control group (p < 0.001). High levels of TAM were associated with tumor size (p = 0.004), tumor depth (p < 0.001), stage (p < 0.001), lymph node metastases (p < 0.001), tumor differentiation (p = 0.001), tumor respectability (p = 0.002) and disease progression (p < 0.001). The poor prognostic outcomes were correlated with an elevated level of TAM (p = 0.001). Kaplan-Meier analysis showed patients with increased levels of TAM after operation had an lower overall survival (p < 0.001) and disease-free survival (p < 0.001). In addition, multivariate Cox proportional hazard analyses revealed that TAM may be an independent factor affecting the overall survival and disease-free survival (p < 0.001). The detection of TAM could be used to screen for tumor and assess unfavorable prognosis in patients with EC.

Regulation of phagocytosis by TAM receptors and their ligands

PubMed Central

Lu, Qingxian; Li, Qiutang; Lu, Qingjun

2010-01-01

The TAM family of receptors is preferentially expressed by professional and non-professional phagocytes, including macrophages, dendritic cells and natural killer cells in the immune system, osteoclasts in bone, Sertoli cells in testis, and retinal pigmental epithelium cells in the retina. Mutations in the Mertk single gene or in different combinations of the double or triple gene mutations in the same cell cause complete or partial impairment in phagocytosis of their preys; and as a result, either the normal apoptotic cells cannot be efficiently removed or the tissue neighbor cells die by apoptosis. This scenario of TAM regulation represents a widely adapted model system used by phagocytes in all different tissues. The present review will summarize current known functional roles of TAM receptors and their ligands, Gas 6 and protein S, in the regulation of phagocytosis. PMID:21057587

TAM receptors support neural stem cell survival, proliferation and neuronal differentiation.

PubMed

Ji, Rui; Meng, Lingbin; Jiang, Xin; Cvm, Naresh Kumar; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

2014-01-01

Tyro3, Axl and Mertk (TAM) receptor tyrosine kinases play multiple functional roles by either providing intrinsic trophic support for cell growth or regulating the expression of target genes that are important in the homeostatic regulation of immune responses. TAM receptors have been shown to regulate adult hippocampal neurogenesis by negatively regulation of glial cell activation in central nervous system (CNS). In the present study, we further demonstrated that all three TAM receptors were expressed by cultured primary neural stem cells (NSCs) and played a direct growth trophic role in NSCs proliferation, neuronal differentiation and survival. The cultured primary NSCs lacking TAM receptors exhibited slower growth, reduced proliferation and increased apoptosis as shown by decreased BrdU incorporation and increased TUNEL labeling, than those from the WT NSCs. In addition, the neuronal differentiation and maturation of the mutant NSCs were impeded, as characterized by less neuronal differentiation (β-tubulin III+) and neurite outgrowth than their WT counterparts. To elucidate the underlying mechanism that the TAM receptors play on the differentiating NSCs, we examined the expression profile of neurotrophins and their receptors by real-time qPCR on the total RNAs from hippocampus and primary NSCs; and found that the TKO NSC showed a significant reduction in the expression of both nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), but accompanied by compensational increases in the expression of the TrkA, TrkB, TrkC and p75 receptors. These results suggest that TAM receptors support NSCs survival, proliferation and differentiation by regulating expression of neurotrophins, especially the NGF.

NNSS Soils Monitoring: Plutonium Valley (CAU366) FY2012

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

Miller, Julianne J.; Mizell, Steve A.; Nikolich, George

2013-01-01

The U.S. Department of Energy (DOE) National Nuclear Security Administration (NNSA), Nevada Site Office (NSO), Environmental Restoration Soils Activity has authorized the Desert Research Institute (DRI) to conduct field assessments of potential sediment transport of contaminated soil from Corrective Action Unit (CAU) 366, Area 11 Plutonium Valley Dispersion Sites Contamination Area (CA) during precipitation runoff events. Field measurements at the T-4 Atmospheric Test Site (CAU 370) suggest that radionuclide-contaminated soils may have migrated along a shallow ephemeral drainage that traverses the site (NNSA/NSO, 2009). (It is not entirely clear how contaminated soils got into their present location at the T-4more » Site, but flow to the channel has been redirected and the contamination does not appear to be migrating at present.) Aerial surveys in selected portions of the Nevada National Security Site (NNSS) also suggest that radionuclide-contaminated soils may be migrating along ephemeral channels in Areas 3, 8, 11, 18, and 25 (Colton, 1999). In Area 11, several low-level airborne surveys of the Plutonium Valley Dispersion Sites (CAU 366) show plumes of Americium 241 (Am-241) extending along ephemeral channels (Figure 1, marker numbers 5 and 6) below Corrective Action Site (CAS) 11-23-03 (marker number 3) and CAS 11 23-04 (marker number 4) (Colton, 1999). Plutonium Valley in Area 11 of the NNSS was selected for the study because of the aerial survey evidence suggesting downstream transport of radionuclide-contaminated soil. The aerial survey (Figure 1) shows a well defined finger of elevated radioactivity (marker number 5) extending to the southwest from the southernmost detonation site (marker number 4). This finger of contamination overlies a drainage channel mapped on the topographic base map used for presentation of the survey data suggesting surface runoff as a likely cause of the contaminated area. Additionally, instrumenting sites strongly suspected of

Increased Circulating and Urinary Levels of Soluble TAM Receptors in Diabetic Nephropathy.

PubMed

Ochodnicky, Peter; Lattenist, Lionel; Ahdi, Mohamed; Kers, Jesper; Uil, Melissa; Claessen, Nike; Leemans, Jaklien C; Florquin, Sandrine; Meijers, Joost C M; Gerdes, Victor E A; Roelofs, Joris J T H

2017-09-01

TAM receptors (Tyro3, Axl, and Mer) have been implicated in innate immunity. Circulating TAM receptor soluble forms (sTyro3, sAxl, sMer) are related to autoimmune disorders. We investigated TAM and their ligand protein S in patients with diabetes. Urinary and plasma levels of protein S, sTyro3, sAxl, and sMer were determined in 126 patients with diabetes assigned to a normoalbuminuric or macroalbuminuric (urinary albumin excretion <30 mg/24 hours and >300 mg/24 hours, respectively) study group and 18 healthy volunteers. TAM and protein S immunostaining was performed on kidney biopsy specimens from patients with diabetic nephropathy (n = 9) and controls (n = 6). TAM expression and shedding by tubular epithelial cells were investigated by PCR and enzyme-linked immunosorbent assay in an in vitro diabetes model. Patients with macroalbuminuria diabetes had higher circulating levels of sMer and more urinary sTyro3 and sMer than normoalbuminuric diabetics. Increased clearance of sTyro3 and sMer was associated with loss of tubular Tyro3 and Mer expression in diabetic nephropathy tissue and glomerular depositions of protein S. During in vitro diabetes, human kidney cells had down-regulation of Tyro3 and Mer mRNA and increased shedding of sTyro3 and sMer. Renal injury in diabetes is associated with elevated systemic and urine levels of sMer and sTyro3. This is the first study reporting excretion of sTAM receptors in urine, identifying the kidney as a source of sTAM. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Healthcare acquired infection (HAIs): a deadly problem that is preventable: UV can help, what's holding it back?

NASA Astrophysics Data System (ADS)

Cowan, Troy E.

2018-02-01

Healthcare Acquired Infections (HAIs) pose a significant health risk to our nation, especially to those most in need of healthcare. One in every 25 people admitted to a hospital will be infected by one or more HAIs. Significant reductions in HAI risks can be advanced through innovative technologies, such as UV antimicrobial disinfecting devices. Development of such technologies, along with the associated Behavioral, Chemical and Technological protocols to combat infectious HAIs is a worthwhile pursuit for the public good. A significant good will be accomplished by engaging optical scientists and engineers as well as healthcare professionals in opportunities to advance light-driven antimicrobial devices to halt infections. Fundamental change can be effected through a path of advancing standards and methods including optical measurements, and testing the efficacy of UV light antimicrobial devices and related technologies.

Enveloped viruses disable innate immune responses in dendritic cells by direct activation of TAM receptors.

PubMed

Bhattacharyya, Suchita; Zagórska, Anna; Lew, Erin D; Shrestha, Bimmi; Rothlin, Carla V; Naughton, John; Diamond, Michael S; Lemke, Greg; Young, John A T

2013-08-14

Upon activation by the ligands Gas6 and Protein S, Tyro3/Axl/Mer (TAM) receptor tyrosine kinases promote phagocytic clearance of apoptotic cells and downregulate immune responses initiated by Toll-like receptors and type I interferons (IFNs). Many enveloped viruses display the phospholipid phosphatidylserine on their membranes, through which they bind Gas6 and Protein S and engage TAM receptors. We find that ligand-coated viruses activate TAM receptors on dendritic cells (DCs), dampen type I IFN signaling, and thereby evade host immunity and promote infection. Upon virus challenge, TAM-deficient DCs display type I IFN responses that are elevated in comparison to wild-type cells. As a consequence, TAM-deficient DCs are relatively resistant to infection by flaviviruses and pseudotyped retroviruses, but infection can be restored with neutralizing type I IFN antibodies. Correspondingly, a TAM kinase inhibitor antagonizes the infection of wild-type DCs. Thus, TAM receptors are engaged by viruses in order to attenuate type I IFN signaling and represent potential therapeutic targets. Copyright © 2013 Elsevier Inc. All rights reserved.

Phosphatidylserine Sensing by TAM Receptors Regulates AKT-Dependent Chemoresistance and PD-L1 Expression.

PubMed

Kasikara, Canan; Kumar, Sushil; Kimani, Stanley; Tsou, Wen-I; Geng, Ke; Davra, Viralkumar; Sriram, Ganapathy; Devoe, Connor; Nguyen, Khanh-Quynh N; Antes, Anita; Krantz, Allen; Rymarczyk, Grzegorz; Wilczynski, Andrzej; Empig, Cyril; Freimark, Bruce; Gray, Michael; Schlunegger, Kyle; Hutchins, Jeff; Kotenko, Sergei V; Birge, Raymond B

2017-06-01

Tyro3, Axl, and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases that bind vitamin K-dependent endogenous ligands, Protein S (ProS), and growth arrest-specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radioresistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment that can suppress host antitumor immunity. In the present study, we utilized TAM-IFNγR1 reporter lines and expressed TAM receptors in a variety of epithelial cell model systems to show that each TAM receptor has a unique pattern of activation by Gas6 or ProS, as well as unique dependency for PS on apoptotic cells and PS liposomes for activity. In addition, we leveraged this system to engineer epithelial cells that express wild-type TAM receptors and show that although each receptor can promote PS-mediated efferocytosis, AKT-mediated chemoresistance, as well as upregulate the immune checkpoint molecule PD-L1 on tumor cells, Mertk is most dominant in the aforementioned pathways. Functionally, TAM receptor-mediated efferocytosis could be partially blocked by PS-targeting antibody 11.31 and Annexin V, demonstrating the existence of a PS/PS receptor (i.e., TAM receptor)/PD-L1 axis that operates in epithelial cells to foster immune escape. These data provide a rationale that PS-targeting, anti-TAM receptor, and anti-PD-L1-based therapeutics will have merit as combinatorial checkpoint inhibitors. Implications: Many tumor cells are known to upregulate the immune checkpoint inhibitor PD-L1. This study demonstrates a role for PS and TAM receptors in the regulation of PD-L1 on cancer cells. Mol Cancer Res; 15(6); 753-64. ©2017 AACR

The role of TAM family receptors and ligands in the nervous system: From development to pathobiology.

PubMed

Shafit-Zagardo, Bridget; Gruber, Ross C; DuBois, Juwen C

2018-03-04

Tyro3, Axl, and Mertk, referred to as the TAM family of receptor tyrosine kinases, are instrumental in maintaining cell survival and homeostasis in mammals. TAM receptors interact with multiple signaling molecules to regulate cell migration, survival, phagocytosis and clearance of metabolic products and cell debris called efferocytosis. The TAMs also function as rheostats to reduce the expression of proinflammatory molecules and prevent autoimmunity. All three TAM receptors are activated in a concentration-dependent manner by the vitamin K-dependent growth arrest-specific protein 6 (Gas6). Gas6 and the TAMs are abundantly expressed in the nervous system. Gas6, secreted by neurons and endothelial cells, is the sole ligand for Axl. ProteinS1 (ProS1), another vitamin K-dependent protein functions mainly as an anti-coagulant, and independent of this function can activate Tyro3 and Mertk, but not Axl. This review will focus on the role of the TAM receptors and their ligands in the nervous system. We highlight studies that explore the function of TAM signaling in myelination, the visual cortex, neural cancers, and multiple sclerosis (MS) using Gas6 -/- and TAM mutant mice models. Copyright © 2018. Published by Elsevier Inc.

Subcellular compartmentalization of Cd and Zn in two bivalves. II. Significance of trophically available metal (TAM)

USGS Publications Warehouse

Wallace, W.G.; Luoma, S.N.

2003-01-01

This paper examines how the subcellular partitioning of Cd and Zn in the bivalves Macoma balthica and Potamocorbula amurensis may affect the trophic transfer of metal to predators. Results show that the partitioning of metals to organelles, 'enzymes' and metallothioneins (MT) comprise a subcellular compartment containing trophically available metal (TAM; i.e. metal trophically available to predators), and that because this partitioning varies with species, animal size and metal, TAM is similarly influenced. Clams from San Francisco Bay, California, were exposed for 14 d to 3.5 ??g 1-1 Cd and 20.5 ??g 1-1 Zn, including 109Cd and 65Zn as radiotracers, and were used in feeding experiments with grass shrimp Palaemon macrodatylus, or used to investigate the subcellular partitioning of metal. Grass shrimp fed Cd-contaminated P. amurensis absorbed ???60% of ingested Cd, which was in accordance with the partitioning of Cd to the bivalve's TAM compartment (i.e. Cd associated with organelles, 'enzymes' and MT); a similar relationship was found in previous studies with grass shrimp fed Cd-contaminated oligochaetes. Thus, TAM may be used as a tool to predict the trophic transfer of at least Cd. Subcellular fractionation revealed that ???34% of both the Cd and Zn accumulated by M. balthica was associated with TAM, while partitioning to TAM in P. amurensis was metal-dependent (???60% for TAM-Cd%, ???73% for TAM-Zn%). The greater TAM-Cd% of P. amurensis than M. balthica is due to preferential binding of Cd to MT and 'enzymes', while enhanced TAM-Zn% of P. amurensis results from a greater binding of Zn to organelles. TAM for most species-metal combinations was size-dependent, decreasing with increased clam size. Based on field data, it is estimated that of the 2 bivalves, P. amurensis poses the greater threat of Cd exposure to predators because of higher tissue concentrations and greater partitioning as TAM; exposure of Zn to predators would be similar between these species.

The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy.

PubMed

Paolino, Magdalena; Penninger, Josef M

2016-10-21

The TAM receptor protein tyrosine kinases-Tyro3, Axl, and Mer-are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases. Importantly, TAM receptors have also been associated with cancer development and progression. In a cancer setting, TAM receptors have a dual regulatory role, controlling the initiation and progression of tumor development and, at the same time, the associated anti-tumor responses of diverse immune cells. Thus, modulation of TAM receptors has emerged as a potential novel strategy for cancer treatment. In this review, we discuss our current understanding of how TAM receptors control immunity, with a particular focus on the regulation of anti-tumor responses and its implications for cancer immunotherapy.

The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy

PubMed Central

Paolino, Magdalena; Penninger, Josef M.

2016-01-01

The TAM receptor protein tyrosine kinases—Tyro3, Axl, and Mer—are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases. Importantly, TAM receptors have also been associated with cancer development and progression. In a cancer setting, TAM receptors have a dual regulatory role, controlling the initiation and progression of tumor development and, at the same time, the associated anti-tumor responses of diverse immune cells. Thus, modulation of TAM receptors has emerged as a potential novel strategy for cancer treatment. In this review, we discuss our current understanding of how TAM receptors control immunity, with a particular focus on the regulation of anti-tumor responses and its implications for cancer immunotherapy. PMID:27775650

IL6 induces TAM resistance via kinase-specific phosphorylation of ERα in OVCA cells.

PubMed

Wang, Yue; Niu, Xiu Long; Guo, Xiao Qin; Yang, Jing; Li, Ling; Qu, Ye; Xiu Hu, Cun; Mao, Li Qun; Wang, Dan

2015-06-01

About 40-60% of ovarian cancer (OVCA) cases express ERα, but only a small proportion of patients respond clinically to anti-estrogen treatment with estrogen receptor (ER) antagonist tamoxifen (TAM). The mechanism of TAM resistance in the course of OVCA progression remains unclear. However, IL6 plays a critical role in the development and progression of OVCA. Our recent results indicated that IL6 secreted by OVCA cells may promote the resistance of these cells to TAM via ER isoforms and steroid hormone receptor coactivator-1. Here we demonstrate that both exogenous (a relatively short period of treatment with recombinant IL6) and endogenous IL6 (generated as a result of transfection with a plasmid encoding sense IL6) increases expression of pERα-Ser118 and pERα-Ser167 in non-IL6-expressing A2780 cells, while deleting endogenous IL6 expression in IL6-overexpressing CAOV-3 cells (by transfection with a plasmid encoding antisense IL6) reduces expression of pERα-Ser118 and pERα-Ser167, indicating that IL6-induced TAM resistance may also be associated with increased expression of pERα-Ser118 and pERα-Ser167 in OVCA cells. Results of further investigation indicate that IL6 phosphorylates ERα at Ser118 and Ser167 by triggering activation of MEK/ERK and phosphotidylinositol 3 kinase/Akt signaling, respectively, to activate the ER pathway and thereby induce OVCA cells resistance to TAM. These results indicate that IL6 secreted by OVCA cells may also contribute to the refractoriness of these cells to TAM via the crosstalk between ER and IL6-mediated intracellular signal transduction cascades. Overexpression of IL6 not only plays an important role in OVCA progression but also promotes TAM resistance. Our results indicate that TAM-IL6-targeted adjunctive therapy may lead to a more effective intervention than TAM alone. © 2015 Society for Endocrinology.

Molecular insights of Gas6/TAM in cancer development and therapy.

PubMed

Wu, Guiling; Ma, Zhiqiang; Hu, Wei; Wang, Dongjin; Gong, Bing; Fan, Chongxi; Jiang, Shuai; Li, Tian; Gao, Jianyuan; Yang, Yang

2017-03-23

Since growth arrest-specific gene 6 (Gas6) was discovered in 1988, numerous studies have highlighted the role of the Gas6 protein and its receptors Tyro3, Axl and Mer (collectively referred to as TAM), in proliferation, apoptosis, efferocytosis, leukocyte migration, sequestration and platelet aggregation. Gas6 has a critical role in the development of multiple types of cancers, including pancreatic, prostate, oral, ovarian and renal cancers. Acute myelocytic leukaemia (AML) is a Gas6-dependent cancer, and Gas6 expression predicts poor prognosis in AML. Interestingly, Gas6 also has a role in establishing tumour dormancy in the bone marrow microenvironment and in suppressing intestinal tumorigenesis. Numerous studies regarding cancer therapy have targeted Gas6 and TAM receptors with good results. However, some findings have suggested that Gas6 is associated with the development of resistance to cancer therapies. Concerning these significant effects of Gas6 in numerous cancers, we discuss the roles of Gas6 in cancer development in this review. First, we introduce basic knowledge on Gas6 and TAM receptors. Next, we describe and discuss the involvement of Gas6 and TAM receptors in cancers from different organ systems. Finally, we highlight the progress in therapies targeting Gas6 and TAM receptors. This review presents the significant roles of Gas6 in cancers from different systems and may contribute to the continued promotion of Gas6 as a therapeutic target.

Arabidopsis Histone Methylase CAU1/PRMT5/SKB1 Acts as an Epigenetic Suppressor of the Calcium Signaling Gene CAS to Mediate Stomatal Closure in Response to Extracellular Calcium[W

PubMed Central

Fu, Yan-Lei; Zhang, Guo-Bin; Lv, Xin-Fang; Guan, Yuan; Yi, Hong-Ying; Gong, Ji-Ming

2013-01-01

Elevations in extracellular calcium ([Ca2+]o) are known to stimulate cytosolic calcium ([Ca2+]cyt) oscillations to close stomata. However, the underlying mechanisms regulating this process remain largely to be determined. Here, through the functional characterization of the calcium underaccumulation mutant cau1, we report that the epigenetic regulation of CAS, a putative Ca2+ binding protein proposed to be an external Ca2+ sensor, is involved in this process. cau1 mutant plants display increased drought tolerance and stomatal closure. A mutation in CAU1 significantly increased the expression level of the calcium signaling gene CAS, and functional disruption of CAS abolished the enhanced drought tolerance and stomatal [Ca2+]o signaling in cau1. Map-based cloning revealed that CAU1 encodes the H4R3sme2 (for histone H4 Arg 3 with symmetric dimethylation)-type histone methylase protein arginine methytransferase5/Shk1 binding protein1. Chromatin immunoprecipitation assays showed that CAU1 binds to the CAS promoter and modulates the H4R3sme2-type histone methylation of the CAS chromatin. When exposed to elevated [Ca2+]o, the protein levels of CAU1 decreased and less CAU1 bound to the CAS promoter. In addition, the methylation level of H4R3sme2 decreased in the CAS chromatin. Together, these data suggest that in response to increases in [Ca2+]o, fewer CAU1 protein molecules bind to the CAS promoter, leading to decreased H4R3sme2 methylation and consequent derepression of the expression of CAS to mediate stomatal closure and drought tolerance. PMID:23943859

A new sediment core from the early Aptian OAE1a: the Cau section (Prebetic Zone, Spain)

NASA Astrophysics Data System (ADS)

Alejandro Ruiz-Ortiz, Pedro; Castro, José Manuel; de Gea, Ginés A.; Jarvis, Ian; Loeser, Hannes; Molina, José Miguel; Nieto, Luis Miguel; Pancost, Richard; Quijano, María Luisa; Reolid, Matías; Skelton, Peter; Weissert, Helmut

2016-04-01

The occurrence of time intervals of enhanced deposition of organic matter (OM) during the Cretaceous, defined as Oceanic Anoxic Events (OAE), reflect abrupt changes in global carbon cycling. The exemplary Aptian OAE1a (120 Ma), is recorded in all the main ocean basins and associated with massive burial of OM in marine sediments [1]. OAE1a is concomitant with the 'nannoconid crisis', which represents a major biotic turnover [2], and also with widespread demise of carbonate platforms [1]. Much research has been done on the OAE1a from different sections in the world over the last decades, since the definition of the C-isotope stratigraphy of the event [3]. Notwithstanding, high-resolution studies across the entire event will be crucial to elucidate the precise timing and rates of the different environmental and biotic changes involved. In order to perform high-resolution studies, drill-cores can represent the best option. Previous cores with successful scientific results has been performed in two reference sections, the Cismon Apti-core [4], and more recently in La Bédoule [5]. Here we present a new drill-core from southern Spain, the Cau section core, drilled in the last quarter of 2015. The Cau section is located in the easternmost part of the Prebetic Zone (Betic Cordillera), which represents the platform deposits of the Southern Iberian Palaeomargin. The lower Aptian of the Cau section is represented by an hemipelagic unit (Almadich Formation, ca. 200 m thick), deposited in a highly subsiding sector of a tilted block, located in the distal parts of the Prebetic Platform. Previous studies of the early Aptian of the Cau section have focused on the stratigraphy, bioevents, C-isotope stratigraphy, and organic and elemental geochemistry [6], [7], among others. A recent study on the Cau section based on biomarkers has presented a detailed record of the PCO2, [8]. All these studies reveal that the Cau section represents an excellent site to investigate the OAE1a, based

Modeling the acceptance of clinical information systems among hospital medical staff: an extended TAM model.

PubMed

Melas, Christos D; Zampetakis, Leonidas A; Dimopoulou, Anastasia; Moustakis, Vassilis

2011-08-01

Recent empirical research has utilized the Technology Acceptance Model (TAM) to advance the understanding of doctors' and nurses' technology acceptance in the workplace. However, the majority of the reported studies are either qualitative in nature or use small convenience samples of medical staff. Additionally, in very few studies moderators are either used or assessed despite their importance in TAM based research. The present study focuses on the application of TAM in order to explain the intention to use clinical information systems, in a random sample of 604 medical staff (534 physicians) working in 14 hospitals in Greece. We introduce physicians' specialty as a moderator in TAM and test medical staff's information and communication technology (ICT) knowledge and ICT feature demands, as external variables. The results show that TAM predicts a substantial proportion of the intention to use clinical information systems. Findings make a contribution to the literature by replicating, explaining and advancing the TAM, whereas theory is benefited by the addition of external variables and medical specialty as a moderator. Recommendations for further research are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

TAM Receptor Tyrosine Kinases: Biologic Functions, Signaling, and Potential Therapeutic Targeting in Human Cancer

PubMed Central

Linger, Rachel M. A.; Keating, Amy K.; Earp, H. Shelton; Graham, Douglas K.

2011-01-01

Tyro-3, Axl, and Mer constitute the TAM family of receptor tyrosine kinases (RTKs) characterized by a conserved sequence within the kinase domain and adhesion molecule-like extracellular domains. This small family of RTKs regulates an intriguing mix of processes, including cell proliferation/survival, cell adhesion and migration, blood clot stabilization, and regulation of inflammatory cytokine release. Genetic or experimental alteration of TAM receptor function can contribute to a number of disease states, including coagulopathy, autoimmune disease, retinitis pigmentosa, and cancer. In this chapter, we first provide a comprehensive review of the structure, regulation, biologic functions, and down-stream signaling pathways of these receptors. In addition, we discuss recent evidence which suggests a role for TAM receptors in oncogenic mechanisms as family members are over-expressed in a spectrum of human cancers and have prognostic significance in some. Possible strategies for targeted inhibition of the TAM family in the treatment of human cancer are described. Further research will be necessary to evaluate the full clinical implications of TAM family expression and activation in cancer. PMID:18620092

Development of Test-Analysis Models (TAM) for correlation of dynamic test and analysis results

NASA Technical Reports Server (NTRS)

Angelucci, Filippo; Javeed, Mehzad; Mcgowan, Paul

1992-01-01

The primary objective of structural analysis of aerospace applications is to obtain a verified finite element model (FEM). The verified FEM can be used for loads analysis, evaluate structural modifications, or design control systems. Verification of the FEM is generally obtained as the result of correlating test and FEM models. A test analysis model (TAM) is very useful in the correlation process. A TAM is essentially a FEM reduced to the size of the test model, which attempts to preserve the dynamic characteristics of the original FEM in the analysis range of interest. Numerous methods for generating TAMs have been developed in the literature. The major emphasis of this paper is a description of the procedures necessary for creation of the TAM and the correlation of the reduced models with the FEM or the test results. Herein, three methods are discussed, namely Guyan, Improved Reduced System (IRS), and Hybrid. Also included are the procedures for performing these analyses using MSC/NASTRAN. Finally, application of the TAM process is demonstrated with an experimental test configuration of a ten bay cantilevered truss structure.

Regulation of matriptase and HAI-1 system, a novel therapeutic target in human endometrial cancer cells.

PubMed

Sun, Pengming; Xue, Lifang; Song, Yiyi; Mao, Xiaodan; Chen, Lili; Dong, Binhua; Braicu, Elena Loana; Sehouli, Jalid

2018-02-27

The effects of specific and non-specific regulation of matriptase on endometrial cancer cells in vitro were investigated. Messenger ribonucleic acid (mRNA) and protein expression of matriptase and hepatocyte growth factor activator inhibitor-1 (HAI-1) in RL-952, HEC-1A, and HEC-1B endometrial cancer cells were detected by real-time quantitative PCR (RT-qPCR) and western blot. The cells were infected with lentivirus-mediated small-interfering RNA (siRNA) targeted on matriptase (MA-siRNA) or treated with different cisplatin (DDP) concentrations. After treatment, invasion, migration, and cellular apoptosis were analyzed. Matriptase mRNA and protein expression significantly decreased to 80% after infection with MA-siRNA ( P < 0.01), and scratch and trans-well chamber assays showed significant inhibition of invasiveness and metastasis. Upon incubation with cisplatin at concentrations higher than the therapeutic dose for 24 h, the expressions of matriptase and HAI-1 significantly decreased ( P < 0.001). Moreover, the invasiveness, metastasis, and survival rate of HEC-1A and RL-952 endometrial cancer cells were significantly decreased ( P < 0.001) due to the down-regulation of matriptase and HAI-1 upon increasing cisplatin concentration. However, a slight increase in matriptase and HAI-1 expression was observed in cells treated with low cisplatin concentration ( P = 0.01). Moreover, matriptase expression was associated with metastasis and invasiveness. Down-regulation of matriptase by specific Ma-SiRNA or non-specific cisplatin in matriptase/HAI-1-positive endometrial cancer cells showed promising therapeutic features.

Regulation of matriptase and HAI-1 system, a novel therapeutic target in human endometrial cancer cells

PubMed Central

Sun, Pengming; Xue, Lifang; Song, Yiyi; Mao, Xiaodan; Chen, Lili; Dong, Binhua; Braicu, Elena Loana; Sehouli, Jalid

2018-01-01

The effects of specific and non-specific regulation of matriptase on endometrial cancer cells in vitro were investigated. Messenger ribonucleic acid (mRNA) and protein expression of matriptase and hepatocyte growth factor activator inhibitor-1 (HAI-1) in RL-952, HEC-1A, and HEC-1B endometrial cancer cells were detected by real-time quantitative PCR (RT-qPCR) and western blot. The cells were infected with lentivirus-mediated small-interfering RNA (siRNA) targeted on matriptase (MA-siRNA) or treated with different cisplatin (DDP) concentrations. After treatment, invasion, migration, and cellular apoptosis were analyzed. Matriptase mRNA and protein expression significantly decreased to 80% after infection with MA-siRNA (P < 0.01), and scratch and trans-well chamber assays showed significant inhibition of invasiveness and metastasis. Upon incubation with cisplatin at concentrations higher than the therapeutic dose for 24 h, the expressions of matriptase and HAI-1 significantly decreased (P < 0.001). Moreover, the invasiveness, metastasis, and survival rate of HEC-1A and RL-952 endometrial cancer cells were significantly decreased (P < 0.001) due to the down-regulation of matriptase and HAI-1 upon increasing cisplatin concentration. However, a slight increase in matriptase and HAI-1 expression was observed in cells treated with low cisplatin concentration (P = 0.01). Moreover, matriptase expression was associated with metastasis and invasiveness. Down-regulation of matriptase by specific Ma-SiRNA or non-specific cisplatin in matriptase/HAI-1–positive endometrial cancer cells showed promising therapeutic features. PMID:29560101

Explaining the Discrepancy in the Mediating Role of Attitude in the TAM

ERIC Educational Resources Information Center

López-Bonilla, Luis Miguel; López-Bonilla, Jesús Manuel

2017-01-01

The debate about the role of attitude in the technology acceptance model (TAM) seems to have re-emerged in two prestigious journals in the field of educational technology. Among the publications on this debate, there are authors in favour of excluding the attitude of TAM, whereas others are in favour of including it. These opinions are derived…

TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation.

PubMed

Ji, Rui; Tian, Shifu; Lu, Helen J; Lu, Qingjun; Zheng, Yan; Wang, Xiaomin; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

2013-12-15

TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl(-/-)Mertk(-/-) double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.

The TAM receptor Mertk protects against neuroinvasive viral infection by maintaining blood-brain barrier integrity.

PubMed

Miner, Jonathan J; Daniels, Brian P; Shrestha, Bimmi; Proenca-Modena, Jose L; Lew, Erin D; Lazear, Helen M; Gorman, Matthew J; Lemke, Greg; Klein, Robyn S; Diamond, Michael S

2015-12-01

The TAM receptors Tyro3, Axl and Mertk are receptor tyrosine kinases that dampen host innate immune responses following engagement with their ligands Gas6 and Protein S, which recognize phosphatidylserine on apoptotic cells. In a form of apoptotic mimicry, many enveloped viruses display phosphatidylserine on the outer leaflet of their membranes, enabling TAM receptor activation and downregulation of antiviral responses. Accordingly, we hypothesized that a deficiency of TAM receptors would enhance antiviral responses and protect against viral infection. Unexpectedly, mice lacking Mertk and/or Axl, but not Tyro3, exhibited greater vulnerability to infection with neuroinvasive West Nile and La Crosse encephalitis viruses. This phenotype was associated with increased blood-brain barrier permeability, which enhanced virus entry into and infection of the brain. Activation of Mertk synergized with interferon-β to tighten cell junctions and prevent virus transit across brain microvascular endothelial cells. Because TAM receptors restrict pathogenesis of neuroinvasive viruses, these findings have implications for TAM antagonists that are currently in clinical development.

Utilization of Multimedia Laboratory: An Acceptance Analysis using TAM

NASA Astrophysics Data System (ADS)

Modeong, M.; Palilingan, V. R.

2018-02-01

Multimedia is often utilized by teachers to present a learning materials. Learning that delivered by multimedia enables people to understand the information of up to 60% of the learning in general. To applying the creative learning to the classroom, multimedia presentation needs a laboratory as a space that provides multimedia needs. This study aims to reveal the level of student acceptance on the multimedia laboratories, by explaining the direct and indirect effect of internal support and technology infrastructure. Technology Acceptance Model (TAM) is used as the basis of measurement on this research, through the perception of usefulness, ease of use, and the intention, it’s recognized capable of predicting user acceptance about technology. This study used the quantitative method. The data analysis using path analysis that focuses on trimming models, it’s performed to improve the model of path analysis structure by removing exogenous variables that have insignificant path coefficients. The result stated that Internal Support and Technology Infrastructure are well mediated by TAM variables to measure the level of technology acceptance. The implications suggest that TAM can measure the success of multimedia laboratory utilization in Faculty of Engineering UNIMA.

Clonal selection in xenografted TAM recapitulates the evolutionary process of myeloid leukemia in Down syndrome.

PubMed

Saida, Satoshi; Watanabe, Ken-ichiro; Sato-Otsubo, Aiko; Terui, Kiminori; Yoshida, Kenichi; Okuno, Yusuke; Toki, Tsutomu; Wang, RuNan; Shiraishi, Yuichi; Miyano, Satoru; Kato, Itaru; Morishima, Tatsuya; Fujino, Hisanori; Umeda, Katsutsugu; Hiramatsu, Hidefumi; Adachi, Souichi; Ito, Etsuro; Ogawa, Seishi; Ito, Mamoru; Nakahata, Tatsutoshi; Heike, Toshio

2013-05-23

Transient abnormal myelopoiesis (TAM) is a clonal preleukemic disorder that progresses to myeloid leukemia of Down syndrome (ML-DS) through the accumulation of genetic alterations. To investigate the mechanism of leukemogenesis in this disorder, a xenograft model of TAM was established using NOD/Shi-scid, interleukin (IL)-2Rγ(null) mice. Serial engraftment after transplantation of cells from a TAM patient who developed ML-DS a year later demonstrated their self-renewal capacity. A GATA1 mutation and no copy number alterations (CNAs) were detected in the primary patient sample by conventional genomic sequencing and CNA profiling. However, in serial transplantations, engrafted TAM-derived cells showed the emergence of divergent subclones with another GATA1 mutation and various CNAs, including a 16q deletion and 1q gain, which are clinically associated with ML-DS. Detailed genomic analysis identified minor subclones with a 16q deletion or this distinct GATA1 mutation in the primary patient sample. These results suggest that genetically heterogeneous subclones with varying leukemia-initiating potential already exist in the neonatal TAM phase, and ML-DS may develop from a pool of such minor clones through clonal selection. Our xenograft model of TAM may provide unique insight into the evolutionary process of leukemia.

Targeting of TAM Receptors Ameliorates Fibrotic Mechanisms in Idiopathic Pulmonary Fibrosis.

PubMed

Espindola, Milena S; Habiel, David M; Narayanan, Rohan; Jones, Isabelle; Coelho, Ana L; Murray, Lynne A; Jiang, Dianhua; Noble, Paul W; Hogaboam, Cory M

2018-06-01

Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling, which progressively abolishes lung function in an RTK (receptor tyrosine kinase)-dependent manner. Gas6 (growth arrest-specific 6) ligand, Tyro3 (TYRO3 protein tyrosine kinase 3), and Axl (anexelekto) RTK expression and activity are increased in IPF. To determine if targeting these RTK pathways would inhibit fibroblast activation and the development of pulmonary fibrosis. Quantitative genomic, proteomic, and functional analyses were used to determine Gas6/TAM (Tyro3, Axl, and Mertk [MER proto-oncogene, tyrosine kinase]) RTK expression and activation in tissues and fibroblasts from normal and IPF lungs. The profibrotic impact of these RTK pathways were also examined in bleomycin-induced pulmonary fibrosis and in SCID/Bg mice that developed pulmonary fibrosis after the intravenous administration of primary IPF fibroblasts. Gas6, Axl, and Tyro3 were increased in both rapidly and slowly progressive IPF compared with normal lung samples and fibroblasts. Targeting these pathways with either specific antibodies directed at Gas6 or Axl, or with small-molecule TAM inhibitors indicated that the small molecule-mediated targeting approach was more efficacious in both in vitro and in vivo studies. Specifically, the TAM receptor inhibitor R428 (also known as BGB324) significantly inhibited the synthetic, migratory, and proliferative properties of IPF fibroblasts compared with the other Gas6/TAM receptor targeting agents. Finally, loss of Gas6 expression decreased lung fibrotic responses to bleomycin and treatment with R428 inhibited pulmonary fibrosis in humanized SCID/Bg mice. Gas6/TAM receptor activity contributes to the activation of pulmonary fibroblasts in IPF, suggesting that targeting this RTK pathway might be an effective antifibrotic strategy in this disease.

Defect of Hepatocyte Growth Factor Activator Inhibitor Type 1/Serine Protease Inhibitor, Kunitz Type 1 (Hai-1/Spint1) Leads to Ichthyosis-Like Condition and Abnormal Hair Development in Mice

PubMed Central

Nagaike, Koki; Kawaguchi, Makiko; Takeda, Naoki; Fukushima, Tsuyoshi; Sawaguchi, Akira; Kohama, Kazuyo; Setoyama, Mitsuru; Kataoka, Hiroaki

2008-01-01

Hepatocyte growth factor activator inhibitor type 1 (HAI-1)/serine protease inhibitor, Kunitz type 1 (SPINT1) is a membrane-bound, serine proteinase inhibitor initially identified as an inhibitor of hepatocyte growth factor activator. It also inhibits matriptase and prostasin, both of which are membrane-bound serine proteinases that have critical roles in epidermal differentiation and function. In this study, skin and hair phenotypes of mice lacking the Hai-1/Spint1 gene were characterized. Previously, we reported that the homozygous deletion of Hai-1/Spint1 in mice resulted in embryonic lethality attributable to impaired placental development. To test the role of Hai-1/Spint1 in mice, the placental function of Hai-1/Spint1-mutant mice was rescued. Injection of Hai-1/Spint1+/+ blastocysts with Hai-1/Spint1−/− embryonic stem cells successfully generated high-chimeric Hai-1/Spint1−/− embryos (B6Hai-1−/−High) with normal placentas. These embryos were delivered without apparent developmental abnormalities, confirming that embryonic lethality of Hai-1/Spint1−/− mice was caused by placental dysfunction. However, newborn B6Hai-1−/−High mice showed growth retardation and died by 16 days. These mice developed scaly skin because of hyperkeratinization, reminiscent of ichthyosis, and abnormal hair shafts that showed loss of regular cuticular septation. The interfollicular epidermis showed acanthosis with enhanced Akt phosphorylation. Immunoblot analysis revealed altered proteolytic processing of profilaggrin in Hai-1/Spint1-deleted skin with impaired generation of filaggrin monomers. These findings indicate that Hai-1/Spint1 has critical roles in the regulated keratinization of the epidermis and hair development. PMID:18832587

HAI: A new TDLAS hygrometer for the HALO research aircraft

NASA Astrophysics Data System (ADS)

Klostermann, Tim; Afchine, Armin; Barthel, Jochen; Höh, Matthias; Wagner, Steven; Witzel, Oliver; Saathoff, Harald; Schiller, Cornelius; Ebert, Volker

2010-05-01

Water vapor is the most important greenhouse gas in the Earth's atmosphere and a key component for several physical and chemical processes. Therefore it is a key parameter to be measured during most research campaigns. The Hygrometer for Atmospheric Investigations (HAI) is especially designed for operations on the research aircraft HALO (High Altitude and LOng range research aircraft). HAI permits both, the in-situ measurement of water vapor with an open-path cell and the measurement of total water with an extractive close-path absorption cell. We are using TDLAS (Tunable Diode Laser Absorption Spectroscopy) in two water absorption bands with different line strength to increase the dynamical range. With this concept it is possible to measure from the middle troposphere up to the stratosphere. The open-path cell outside of the fuselage consists of a robust, aerodynamically designed aluminum structure with a single integrated White-cell for both laser beams. Although the mirror separation is only 15cm the cell allows an open absorption path of 4.8m. The detection of higher H2O concentrations is realized with a fiber coupled 1.4µm DFB diode laser. Inside the UTLS layer were small concentrations in the low ppm range are common, we employ up to 20 times stronger fundamental ro-vibration lines of the water molecule near 2.6µm. To supply this, the fiber coupled 2.6µm laser setup was developed and is a part of the HAI. Both detection wavelengths are introduced in the same open path cell via glass fibers which provide water measurements with a minimum of parasitic absorption. We will present the spectrometer design for high-quality airborne water measurements. Furthermore, first laboratory measurements will be shown.

The bromodomain protein LEX-1 acts with TAM-1 to modulate gene expression in C. elegans.

PubMed

Tseng, Rong-Jeng; Armstrong, Kristin R; Wang, Xiaodong; Chamberlin, Helen M

2007-11-01

In many organisms, repetitive DNA serves as a trigger for gene silencing. However, some gene expression is observed from repetitive genomic regions such as heterochromatin, suggesting mechanisms exist to modulate the silencing effects. From a genetic screen in C. elegans, we have identified mutations in two genes important for expression of repetitive sequences: lex-1 and tam-1. Here we show that lex-1 encodes a protein containing an ATPase domain and a bromodomain. LEX-1 is similar to the yeast Yta7 protein, which maintains boundaries between silenced and active chromatin. tam-1 has previously been shown to encode a RING finger/B-box protein that modulates gene expression from repetitive DNA. We find that lex-1, like tam-1, acts as a class B synthetic multivulva (synMuv) gene. However, since lex-1 and tam-1 mutants have normal P granule localization, it suggests they act through a mechanism distinct from other class B synMuvs. We observe intragenic (interallelic) complementation with lex-1 and a genetic interaction between lex-1 and tam-1, data consistent with the idea that the gene products function in the same biological process, perhaps as part of a protein complex. We propose that LEX-1 and TAM-1 function together to influence chromatin structure and to promote expression from repetitive sequences.

The carbon chain-selective adenylation enzyme TamA: the missing link between fatty acid and pyrrole natural product biosynthesis.

PubMed

Marchetti, Piera M; Kelly, Van; Simpson, Joanna P; Ward, Mairi; Campopiano, Dominic J

2018-04-18

The marine bacterium Pseudoalteromonas tunicata produces the bipyrrole antibiotic tambjamine YP1. This natural product is built from common amino acid and fatty acid building blocks in a biosynthetic pathway that is encoded in the tam operon which contains 19 genes. The exact role that each of these Tam proteins plays in tambjamine biosynthesis is not known. Here, we provide evidence that TamA initiates the synthesis and controls the chain length of the essential tambjamine fatty amine tail. Sequence analysis suggests the unusual TamA is comprised of an N-terminal adenylation (ANL) domain fused to a C-terminal acyl carrier protein (ACP). Mass spectrometry analysis of recombinant TamA revealed the surprising presence of bound C11 and C12 acyl-adenylate intermediates. Acylation of the ACP domain was observed upon attachment of the phosphopantetheine (4'-PP) arm to the ACP. We also show that TamA can transfer fatty acids ranging in chain length from C6-C13 to an isolated ACP domain. Thus TamA bridges the gap between primary and secondary metabolism by linking fatty acid and pyrrole biosynthetic pathways.

Characteristics of Tacca leontopetaloides L. Kuntze collected from An Giang in Vietnam

NASA Astrophysics Data System (ADS)

Vu, Quan Thi Hong; Le, Phung Thi Kim; Vo, Huy Pham Hoang; Nguyen, Triet Thanh; Nguyen, Tam Kim Minh

2017-09-01

Tacca leontopetaloides L. Kuntze has been known as a remedy in folk medicine and also a staple food source in many tropical countries. Nonetheless, there are currently few literature and research on the potential pharmaceutical benefits of this herbal plant. In this study, the constituents of leaves, peels and peeled tubers as well as its antioxidant and antimicrobial activities of Tacca cultivated from mountainous regions in Tinh Bien, An Giang Province, Vietnam were investigated. The results indicated that the highest of total phenolic content (TPC) and total flavonoid content (TFC) were presented in leaves of Tacca which were 16.69 mg GAE (gallic acid equivalent)/g dried weight, 57.24 mg QE (quercetin equivalent)/g dried weight, respectively. Besides, the yield of flour recovery process from Tacca tuber estimated from 18%-20%. The chemical compositions of Tacca flour were 0.66 % total of nitrogen, 0.91% lipid, 0.05% ash and 85.7% starch content on dried weight. Furthermore, the extract of peels possessed potential antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis whilst the extract of others did not show any significant inhibition at the same concentration. As a results, with high starch content (nearly 20% in tuber) is a highly promising new starch for food and pharmaceutical excipient industry, while the usefullness of peel in treatment need further investigation.

TAM: a method for enrichment and depletion analysis of a microRNA category in a list of microRNAs.

PubMed

Lu, Ming; Shi, Bing; Wang, Juan; Cao, Qun; Cui, Qinghua

2010-08-09

MicroRNAs (miRNAs) are a class of important gene regulators. The number of identified miRNAs has been increasing dramatically in recent years. An emerging major challenge is the interpretation of the genome-scale miRNA datasets, including those derived from microarray and deep-sequencing. It is interesting and important to know the common rules or patterns behind a list of miRNAs, (i.e. the deregulated miRNAs resulted from an experiment of miRNA microarray or deep-sequencing). For the above purpose, this study presents a method and develops a tool (TAM) for annotations of meaningful human miRNAs categories. We first integrated miRNAs into various meaningful categories according to prior knowledge, such as miRNA family, miRNA cluster, miRNA function, miRNA associated diseases, and tissue specificity. Using TAM, given lists of miRNAs can be rapidly annotated and summarized according to the integrated miRNA categorical data. Moreover, given a list of miRNAs, TAM can be used to predict novel related miRNAs. Finally, we confirmed the usefulness and reliability of TAM by applying it to deregulated miRNAs in acute myocardial infarction (AMI) from two independent experiments. TAM can efficiently identify meaningful categories for given miRNAs. In addition, TAM can be used to identify novel miRNA biomarkers. TAM tool, source codes, and miRNA category data are freely available at http://cmbi.bjmu.edu.cn/tam.

Device-Associated Healthcare-Associated Infections (DA-HAI) and the caveat of multiresistance in a multidisciplinary intensive care unit.

PubMed

Khan, Inam Danish; Basu, Atoshi; Kiran, Sheshadri; Trivedi, Shaleen; Pandit, Priyanka; Chattoraj, Anupam

2017-07-01

Device-Associated Healthcare-Associated Infections (DA-HAI), including Ventilator-Associated Pneumonia (VAP), Central-Line-Associated Blood Stream Infection (CLABSI), and Catheter-Related Urinary Tract Infection (CAUTI), are considered as principal contributors to healthcare hazard and threat to patient safety as they can cause prolonged hospital stay, sepsis, and mortality in the ICU. The study intends to characterize DA-HAI in a tertiary care multidisciplinary ICU of a teaching hospital in eastern India. This prospective outcome-surveillance study was conducted among 2157 ICU patients of a 760-bedded teaching hospital in Eastern India. Clinical, laboratory and environmental surveillance, and screening of HCPs were conducted using the US Centers for Disease Control and Prevention (CDC)'s National Healthcare Safety Network (NHSN) definitions and methods. With 8824 patient/bed/ICU days and 14,676 device days, pooled average device utilization ratio was 1.66, total episodes of DA-HAI were 114, and mean monthly rates of DA-HAI, VAP, CLABSI, and CAUTI were 4.75, 2, 1.4, and 1.25/1000 device days. Most common pathogens isolated from DA-HAI patients were Klebsiella pneumoniae (24.6%), Escherichia coli (21.9%), and Pseudomonas aeruginosa (20.2%). All Acinetobacter baumanii , >80% K. pneumoniae and E. coli , and >70% P. aeruginosa were susceptible only to colistin and tigecycline. One P. aeruginosa isolate was panresistant. Mean rates of VAP, CLABSI, and CAUTI were 14.4, 8.1, and 4.5 per 1000 device days, which are comparable with Indian and global ICUs. Patients and HCPs form important reservoirs of infection. Resolute conviction and sustained momentum in Infection Control Initiatives are an essential step toward patient safety.

An interview with Patrick Tam by Kathryn Senior.

PubMed

Tam, Patrick

2010-12-01

Patrick Tam's research is focused on the cellular and molecular mechanisms of body patterning during mouse development. He agreed to be interviewed by Development to talk about his interest in mouse development, new concepts in gastrulation, X-linked diseases and his dream of an African safari.

Understanding Student Teachers' Behavioural Intention to Use Technology: Technology Acceptance Model (TAM) Validation and Testing

ERIC Educational Resources Information Center

Wong, Kung-Teck; Osman, Rosma bt; Goh, Pauline Swee Choo; Rahmat, Mohd Khairezan

2013-01-01

This study sets out to validate and test the Technology Acceptance Model (TAM) in the context of Malaysian student teachers' integration of their technology in teaching and learning. To establish factorial validity, data collected from 302 respondents were tested against the TAM using confirmatory factor analysis (CFA), and structural equation…

Evaluation of Brāhmī ghṛtam in children suffering from Attention Deficit Hyperactivity Disorder

PubMed Central

Bhalerao, Supriya; Munshi, Renuka; Nesari, Tanuja; Shah, Heenal

2013-01-01

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity. In view of the adverse effects associated with psycho-stimulants used for the treatment of this disorder, efficacy of Brāhmī ghṛtam was evaluated in this condition. Materials and Methods: After following due ethical considerations, children of either sex between the age group of 6 and 12 years diagnosed to be suffering from mixed variety of ADHD as per The Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria irrespective of other co-morbid psychiatric illnesses were recruited in the study. Initially a pilot study (n = 10) was carried out to confirm the efficacy of the identified dose of Brāhmī ghṛtam. Using this dose, further therapeutic confirmatory study (n = 27) was carried out, wherein Brāhmī ghṛtam was compared with methylphenidate. Effect on ADHD symptoms was assessed using the Dupaul ADHD rating scale and this was the main efficacy parameter. Results: In the pilot exploratory study, Brāhmī ghṛtam showed 66% decrease in total ADHD score. In the therapeutic confirmatory study, only 16% improvement was seen with Brāhmī ghṛtam, which was similar to methylphenidate, standard treatment for ADHD that was used as a comparator in the present study. No side-effects were reported in both studies. Conclusion: Our study thus has adequately demonstrated efficacy and safety of Brāhmī ghṛtam in ADHD. PMID:25284947

TAM 304 wheat – Adapted to the adequate rainfall or high-input irrigation production system in the Southern Great Plains

USDA-ARS?s Scientific Manuscript database

TAM 304 wheat is a medium-early hard red winter wheat. It is a great dryland or semi-irrigated wheat. TAM 304 performs best under adequate rainfall, limited irrigation, or irrigation, but does not perform as well under extended drought. TAM 304 performs exceptionally well under foliar disease pressu...

Growth Arrest-Specific 6 (Gas6) and TAM Receptors in Mouse Platelets.

PubMed

Uras, Fikriye; Küçük, Burhanettin; Bingöl Özakpınar, Özlem; Demir, Ahmet Muzaffer

2015-03-05

Growth arrest-specific 6 (Gas6) is a newly discovered vitamin K-dependent protein, which is a ligand for TAM receptors [Tyro3 (Sky), Axl, and Mer] from the tyrosine kinase family. Gas6 knockout mice were resistant to venous and arterial thrombosis. There are contradictory reports on the presence of Gas6 and its receptors in mouse platelets. The objective of this study was to investigate whether Gas6 and its receptors were present in mouse platelets or not. Specific pathogen-free BALB/c male and female mice of 8-10 weeks old and 25-30 g in weight were anesthetized under light ether anesthesia and blood samples were taken from their hearts. RNAs were isolated from isolated platelets, and then mRNAs encoding Gas6 and TAM receptors were detected by reverse transcription-polymerase chain reaction (RT-PCR). Protein concentrations of Gas6 and TAM receptors in platelets were measured by ELISA, but not those of Mer, because of the absence of any commercial ELISA kit for mouse specimens. RT-PCR results indicated the presence of mRNAs encoding Gas6 and Mer in mouse platelets. However, although RT-PCR reactions were performed at various temperatures and cycles, we could not detect the presence of mRNAs encoding Axl and Tyro3 (Sky). Receptor protein levels of Axl and Tyro3 were below the detection limits of the ELISA method. We found the presence of mRNAs encoding Gas6 and the receptor Mer in mouse platelets, but not Axl and Tyro3. Gas6, Axl, and Tyro3 protein levels were below the detection limits of the ELISA. The presence of mRNA is not obvious evidence of protein expression in platelets that have no nucleus or DNA. Further studies are required to clarify the presence of Gas6/TAM receptors in platelets using real-time PCR and more sensitive immunological methods, and future studies on mechanisms will indicate whether the Gas6/TAM pathway is a strategy for treatment of disorders.

TAM receptor tyrosine kinase function and the immunopathology of liver disease.

PubMed

Mukherjee, S K; Wilhelm, A; Antoniades, C G

2016-06-01

Tyro3, Axl, MERTK (TAM) receptor tyrosine kinases are implicated in the regulation of the innate immune response through clearance of apoptotic cellular debris and control of cytokine signaling cascades. As a result they are pivotal in regulating the inflammatory response to tissue injury. Within the liver, immune regulatory signaling is employed to prevent the overactivation of innate immunity in response to continual antigenic challenge from the gastrointestinal tract. In this review we appraise current understanding of the role of TAM receptor function in the regulation of both innate and adaptive immunity, with a focus on its impact upon hepatic inflammatory pathology. Copyright © 2016 the American Physiological Society.

The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells.

PubMed

Paolino, Magdalena; Choidas, Axel; Wallner, Stephanie; Pranjic, Blanka; Uribesalgo, Iris; Loeser, Stefanie; Jamieson, Amanda M; Langdon, Wallace Y; Ikeda, Fumiyo; Fededa, Juan Pablo; Cronin, Shane J; Nitsch, Roberto; Schultz-Fademrecht, Carsten; Eickhoff, Jan; Menninger, Sascha; Unger, Anke; Torka, Robert; Gruber, Thomas; Hinterleitner, Reinhard; Baier, Gottfried; Wolf, Dominik; Ullrich, Axel; Klebl, Bert M; Penninger, Josef M

2014-03-27

Tumour metastasis is the primary cause of mortality in cancer patients and remains the key challenge for cancer therapy. New therapeutic approaches to block inhibitory pathways of the immune system have renewed hopes for the utility of such therapies. Here we show that genetic deletion of the E3 ubiquitin ligase Cbl-b (casitas B-lineage lymphoma-b) or targeted inactivation of its E3 ligase activity licenses natural killer (NK) cells to spontaneously reject metastatic tumours. The TAM tyrosine kinase receptors Tyro3, Axl and Mer (also known as Mertk) were identified as ubiquitylation substrates for Cbl-b. Treatment of wild-type NK cells with a newly developed small molecule TAM kinase inhibitor conferred therapeutic potential, efficiently enhancing anti-metastatic NK cell activity in vivo. Oral or intraperitoneal administration using this TAM inhibitor markedly reduced murine mammary cancer and melanoma metastases dependent on NK cells. We further report that the anticoagulant warfarin exerts anti-metastatic activity in mice via Cbl-b/TAM receptors in NK cells, providing a molecular explanation for a 50-year-old puzzle in cancer biology. This novel TAM/Cbl-b inhibitory pathway shows that it might be possible to develop a 'pill' that awakens the innate immune system to kill cancer metastases.

MicroRNA‑663b mediates TAM resistance in breast cancer by modulating TP73 expression.

PubMed

Jiang, Hua; Cheng, Lin; Hu, Pan; Liu, Renbin

2018-05-23

Breast cancer is the second leading cause of cancer‑associated mortalities in women. Tamoxifen (TAM) is an endocrine therapy commonly used in the treatment of patients with breast cancer expressing estrogen receptor α. However, treatment often ends in failure due to the emergence of drug resistance. MicroRNAs (miRNAs), a family of small non‑coding RNAs, serve critical roles in the regulation of gene expression and cell events. To date, whether miRNA‑663b could mediate TAM resistance in breast cancer remains unknown. Therefore, the aim of the present study was to investigate the role of miRNA‑663b in TAM resistance in breast cancer. The results demonstrated that miRNA‑663b was upregulated in breast cancer with TAM resistance. Tumor protein 73 (TP73) was a direct target of miRNA‑663b, and was negatively regulated by miRNA‑663b in MCF‑7 cells. Furthermore, it was identified that downregulation of miRNA‑663b inhibited cell proliferation ability and promoted cell apoptosis, resulting in enhanced TAM sensitivity. In addition, these findings suggested that TP73 silencing may have eliminated the effects of miRNA‑663b inhibitor on breast cancer cells. In conclusion, the present study verified a novel molecular link between miRNA‑663b and TP73, and indicated that miRNA‑663b may be a critical therapeutic target in breast cancer.

Genetic diversity and phylogenetic analysis of Tams1 of Theileria annulata isolates from three continents between 2000 and 2012.

PubMed

Wang, Jiay; Yang, Xianyong; Wang, Yuge; Jing, Zhihong; Meng, Kai; Liu, Jianzhu; Guo, Huijun; Xu, Ruixue; Cheng, Ziqiang

2014-01-01

Theileria annulata, which is part of the Theileria sergenti/Theileria buffeli/Theileria orientalis group, preferentially infects cattle and results in high mortality and morbidity in the Mediterranean, Middle East, and Central Asia. The polypeptide Tams1 is an immunodominant major merozoite piroplasm surface antigen of T. annulata that could be used as a marker for epidemiological studies and phylogenetic analysis. In the present study, a total of 155 Tams1 sequences were investigated for genetic diversity and phylogenetic relationships through phylogenetic analysis. Results showed that the Tams1 sequences were divided into two major groups and that distribution for some isolates also exhibited geographic specificity. As targeting polymorphic genes for parasite detection may result in underestimation of infection, polymerase chain reaction (PCR) assay using two different probes targeting tams-1 genes of these two groups can be more credible. In addition, the direction of the spread of the disease was discovered to be from the Mediterranean or the tropical zone to the Eurasian peninsula, Middle East, Southern Asia, and Africa, particularly for Group 2. A similar occurrence was also found between the Ms1 gene of Theileria lestoquardi and the Tams1 gene of T. annulata, which explains cross-immunogenicity to a certain extent. However, no potential glycosylation site in the Tams1 of T. annulata was found in this study, which illustrated that instead of N-glycosylation, other modifications have more significant effects on the immunogenicity of the Tams1 protein.

CORRECTIVE ACTION DECISION DOCUMENT FOR AREA 9 UXO LANDFILL, TONOPAH TEST RNGE, CAU 453, REVISION 0, MARCH 1998

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

none

1998-03-01

This Corrective Action Decision Document (CADD) has been prepared for the Area 9 Unexploded Ordnance (UXO) Landfill (Corrective Action Unit [CAU] 453) in accordance with the Federal Facility Agreement and Consent Order (FFACO) of 1996. Corrective Action Unit 453 is located at the Tonopah Test Range (TTR), Nevada, and is comprised of three individual landfill cells located northwest of Area 9. The cells are listed as one Corrective Action Site (CAS) 09-55-001-0952. The landfill cells have been designated as: � Cell A9-1 � Cell A9-2 � Cell A9-3 The purpose of this CADD is to identify and provide a rationalemore » for the selection of a recommended corrective action alternative for CAU 453. The scope of this CADD consists of the following tasks: � Develop corrective action objectives. � Identify corrective action alternative screening criteria. � Develop corrective action alternatives. � Perform detailed and comparative evaluations of the corrective action alternatives in relation to the corrective action objectives and screening criteria. � Recommend and justify a preferred corrective action alternative for the CAU. In June and July 1997, a corrective action investigation was performed that consisted of activities set forth in the Corrective Action Investigation Plan (CAIP) (DOE/NV, 1997). Subsurface investigation of the soils surrounding the cells revealed no contaminants of concern (COCs) above preliminary action levels. The cell contents were not investigated due to the potential for live UXO. Details concerning the analytical and investigation results can be found in Appendix A of this CADD. Based on the potential exposure pathways, the following corrective action objectives have been identified for CAU 453: � Prevent or mitigate human exposure to subsurface soils containing COCs, solid waste, and/or UXO. � Prevent adverse impacts to groundwater quality. Based on the review of existing data, future land use, and current operations at the TTR

Et Tu, Counselor: may an in-house attorney file a qui tam action against the attorney's employer?

PubMed

Brown, L C; Anwar, H R

1999-01-01

Most corporations probably do not consider their in-house counsel to be potential qui tam threats. That may be a naive assumption. Case law provides an illustrative view of the legal ramifications involved when an attorney brings a qui tam suit. In general, there is no prohibition on attorneys who wish to bring these actions. Nevertheless, a corporation can take preventive steps to eliminate the likelihood of attorney qui tam actions. In addition, the corporation can take advantage of state professional ethics laws to mount a defensive action against the attorney who files any such action.

TAM Receptor Tyrosine Kinases in Cancer Drug Resistance.

PubMed

Vouri, Mikaella; Hafizi, Sassan

2017-06-01

Receptor tyrosine kinases (RTK) are major regulators of key biological processes, including cell growth, survival, and differentiation, and were established early on as proto-oncogenes, with aberrant expression linked to tumor progression in many cancers. Therefore, RTKs have emerged as major targets for selective therapy with small-molecule inhibitors. However, despite improvements in survival rates, it is now apparent that the targeting of RTKs with selective inhibitors is only transiently effective, as the majority of patients eventually become resistant to therapy. As chemoresistance is the leading cause of cancer spread, progression, and mortality, there is an increasing need for understanding the mechanisms by which cancer cells can evade therapy-induced cell death. The TAM (Tyro3, Axl, Mer) subfamily of RTKs in particular feature in a variety of cancer types that have developed resistance to a broad range of therapeutic agents, including both targeted as well as conventional chemotherapeutics. This article reviews the roles of TAMs as tumor drivers and as mediators of chemoresistance, and the potential effectiveness of targeting them as part of therapeutic strategies to delay or combat resistance. Cancer Res; 77(11); 2775-8. ©2017 AACR . ©2017 American Association for Cancer Research.

TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to proinflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages.

PubMed

Zheng, Shasha; Hedl, Matija; Abraham, Clara

2015-02-15

Microbial-induced cytokine regulation is critical to intestinal immune homeostasis. Acute stimulation of nucleotide-binding oligomerization domain 2 (NOD2), the Crohn's disease-associated sensor of bacterial peptidoglycan, induces cytokines. However, cytokines are attenuated after chronic NOD2 and pattern recognition receptor stimulation of macrophages; similar attenuation is observed in intestinal macrophages. The role of Tyro3, Axl, and Mer (TAM) receptors in regulating chronic pattern recognition receptor stimulation and NOD2-induced outcomes has not been examined. Moreover, TAM receptors have been relatively less investigated in human macrophages. Whereas TAM receptors did not downregulate acute NOD2-induced cytokines in primary human macrophages, they were essential for downregulating signaling and proinflammatory cytokine secretion after chronic NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal tissues. Consistently, TAM expression was increased in human intestinal myeloid-derived cells. Chronic NOD2 stimulation led to IL-10- and TGF-β-dependent TAM upregulation in human macrophages, which, in turn, upregulated suppressor of cytokine signaling 3 expression. Restoring suppressor of cytokine signaling 3 expression under TAM knockdown conditions restored chronic NOD2-mediated proinflammatory cytokine downregulation. In contrast to the upregulated proinflammatory cytokines, attenuated IL-10 secretion was maintained in TAM-deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to upregulate IL-10 secretion; however, full restoration of MAPK activation under these conditions restored c-Fos, c-Jun, musculoaponeurotic fibrosarcoma oncogene homolog K, and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore, TAM receptors are critical for

[Effect of Evn-50 on cell growth and apoptosis in tamoxifen-resistance human breast cancer cell line MCF-7/TAM-R].

PubMed

Hu, Hui-yong; Zhou, Jun; Wan, Fang; Dong, Li-feng; Zhang, Feng; Wang, Yi-ke; Chen, Fang-fang; Chen, Yi-ding

2012-09-01

To investigate the effect of Evn-50 extracted from Vitex negundo on human breast cancer cell line MCF-7 and MCF-7/TAM-R cells in vitro. MCF-7 and tamoxifen-resistant MCF-7/TAM-R cells were treated with Evn-50,tamoxifen or combination of Evn-50 and tamoxifen. Cell proliferation inhibition rates were determined by MTT assay. The apoptosis rate and the change of cell cycle were detected by PI staining flow cytometry. Protein expression of phospho-MAPK 44/42 (Thr202/Tyr204),MAPK P44/42, phospho-AKT (Ser473) and AKT were detected with Western blotting. The viability of MCF-7 cells was decreased in combination group [(28.65 ±11.43)%] and Evn-50 group [(53.02 ±15.14)%] compared with TAM group (P<0.01). The cell viability of MCF-7/TAM-R in combination group [(42.11 ±14.30)%] was significantly lower than that in TAM group [(92.18 ±13.16)%] (P<0.01). The cell apoptosis rate was dependent on the time of treatment in all groups,the effects on apoptosis and G2/M phase cells were most prominent at 72 h (P<0.01). Western blotting revealed that protein levels of phosphorylated AKT and p-MAPK44/42 decreased,while the expression of total AKT and MAPK44/42 was stable. In MCF-7/TAM-R cells,the expression of phosphorylation of AKT and MAPK44/42 protein was not changed in Evn-50 or TAM alone group,but significantly inhibited in the combination group at 72 h. Evn-50 can inhibit cell growth and induce apoptosis in MCF-7 and MCF-7/TAM-R cells,it can reverse tamoxifen-resistance of MCF-7/TAM-R cells.The mechanisms may be related to the down-regulation of phosphorylated ERK1/2 in MAPK signal pathway and phosphorylated AKT in AKT signal pathway.

Evaluating the Feasibility of RESCUE: An Adjunctive HAI-Based Intervention for Veterans with PTSD

DTIC Science & Technology

2016-05-01

HAI) i) Study presented at symposium: “Human-Animal Interactions in Treating Veterans with PTSD” American Psychological Association ( APA ) 123rd Annual...Interactions in Treating Veterans with PTSD” American Psychological Association ( APA ) 123rd Annual Convention on 09-AUG-2015, Toronto, Canada.  Journal

Monocyte and plasma expression of TAM ligand and receptor in renal failure: Links to unregulated immunity and chronic inflammation.

PubMed

Lee, Iris J; Hilliard, Brendan A; Ulas, Mehriban; Yu, Daohai; Vangala, Chandan; Rao, Swati; Lee, Jean; Gadegbeku, Crystal A; Cohen, Philip L

2015-06-01

Chronic inflammation is increased in patients with chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality. Specific immune mechanisms and pathways that drive and maintain chronic inflammation in CKD are not well described. The TAM ligands (Gas6 and protein S) and receptors (Axl and Mer) have been recently recognized as playing a prominent role in immune regulation. The receptors exist in both soluble and cell-bound forms; the soluble receptors (sAxl and sMer) are believed to compete with the bound receptors and thus inhibit their function. In this study, we determined the expression of cell-bound and soluble TAM proteins in patients with CKD. CKD patients had significantly lower expression of Mer in monocytes, yet increased expression of soluble TAM receptors sAxl and sMer in plasma compared to controls. The metalloproteinase ADAM 17, responsible for cleavage of Mer to its soluble form, was increased in patient monocytes. Elevated levels of soluble TAM receptors were more evident in patients with progressive renal failure. These observations suggest that functional deficiency of TAM receptor-mediated regulation of inflammation may contribute to chronic inflammation in patients with CKD. Copyright © 2015 Elsevier Inc. All rights reserved.

Tyura Tam Space Launch Facility, Kazakhstan, CIS

NASA Technical Reports Server (NTRS)

1992-01-01

Located in Kazakhstan on the Syr Darya River, the Tyura Tam Cosmodrome has been the launch site for 72 cosmonaut crews. The landing runway of the Buran space shuttle can be seen in the left center. Further to the right, near the center is the launch site for the Soyuz. The mission control center is located 1,300 miles away near Moscow. In the lower right, is the city of Leninsk, seen as a dark region next to the river.

Investigating Students' Acceptance and Self-Efficacy of E-Learning at Al-Aqsa University Based on TAM Model

ERIC Educational Resources Information Center

Mahdi, Hasan Rebhi

2014-01-01

The study aimed at investigating the influence of E-learning Self-Efficacy (ELSE) on the acceptance of e-learning by using the Technology Acceptance Model (TAM). According to the TAM which used as the theoretical basis, both of the Perceived Usefulness (PU) and the Perceived Ease of Use (PEOU) influence directly the end user's Behavioral Intention…

Characterization of mangrove species using ALOS-2 PALSAR in Hai Phong city, Vietnam

NASA Astrophysics Data System (ADS)

Dat Pham, Tien; Yoshino, Kunihiko

2016-06-01

Hai Phong city is located in the Northern coast of Vietnam where the mangroves are distributed between zone I and zone II among the four mangrove zones in Vietnam. This city is vulnerable to rising sea levels associated with climate change and tropical cyclones, which are forecasted to become more severe due to the impact of climate change. In the past, mangrove forests in this city have decreased markedly because of over expansion of shrimp farming. Thus, identification of mangrove forests is important to monitor and support mangrove conservation and management in the coastal zone. The objectives of this research were to identify the locations of mangrove and characterize mangrove species in Hai Phong using HH and HV backscatters of the Advanced Land Observing Satellite 2 (ALOS-2) with enhanced Phased Array L-band Synthetic Aperture Radar (PALSAR). Image segmentation was used to identify the locations of mangrove forests. Moreover, Geographic Information System (GIS) was applied to update current status of mangrove species in 2015. The results showed that the means of HH and HV backscatter coefficients of K. obovata are lower than S. caseolaris. K. obovata has HH value around -13.9 dB until -10.3 dB and HV value around -20.6 dB until -16.2 dB. Higher HH values between about -14.9 dB and -6.8 dB and HV values between roughly -20.6 dB and -14.3 dB have observed by S. caseolaris. The total area of mangrove forest in Hai Phong in the year 2015 was around 4084 hectares, of which S. caseolaris occupied over 68% and mixed mangrove species was approximately 25.6%. This research indicates the potential for the use of L-band ALOS-2 PALSAR in characterizing mangrove forest species in the coastal zone.

Banded Iron Formations of the Cauê Formation, Quadrilátero Ferrífero Minas Gerais, Brazil: A novel pre-GOE record of biospheric evolution

NASA Astrophysics Data System (ADS)

Lee, B. K.; Tsikos, H.; Oliveira, E. P.; Lyons, T.

2016-12-01

The rise of atmospheric oxygen (O2) is a milestone in the history of life on Earth. Banded Iron Formations (BIFs) record major episodes of chemical sedimentation, while providing multiple lines of evidence for the environmental conditions present at the time of their deposition during the Archean and Paleoproterozoic. They are direct products of seawater redox, specifically of the balance between iron, sulfide, and oxygen availability. At the same, they are recorders of the broader isotopic and elemental compositions of seawater, which reflect diverse processes in the ocean and on land. In addition to their relevance to the history of environmental oxygen levels, BIFs also have enormous economic importance. BIFs from the Cauê Formation of the Minas Supergroup in the Quadrilátero Ferrífero (QF) ("Iron Quadrangle") are located on the southern edge of the São Francisco Craton. The Cauê Formation, a superior-type iron formation, is likely coeval with iron formations of the Transvaal and Hamersley basins. The geochemical properties of BIFs from the QF are poorly known, although previous studies suggest mild oxygenation of seawater at the depositional onset of the Cauê formation around 200 million years before the Great Oxidation Event (GOE) based on negative anomalies of Ce and Th/U ratios. The ultimate goal of this study is to evaluate environmental conditions proximal to the Archean-Paleoproterozoic boundary, but particularly prior to the GOE, as recorded in the Cauê Formation. Our drill core samples are unweathered and among the least altered materials available from the Itabira Group. These 197 samples cover the entire sequence of the Cauê Formation (dated at 2.65 Ga) as well as the overlying Gandarela Formation (2.4 Ga). We will look at the redox cycling of iron (Fe) and manganese (Mn) from these samples by analyzing variations on Fe and Mn concentrations as well as Fe isotope signatures that will potentially fingerprint the pathways of precipitation of

Dynamic Simulation of 1D Cellular Automata in the Active aTAM.

PubMed

Jonoska, Nataša; Karpenko, Daria; Seki, Shinnosuke

2015-07-01

The Active aTAM is a tile based model for self-assembly where tiles are able to transfer signals and change identities according to the signals received. We extend Active aTAM to include deactivation signals and thereby allow detachment of tiles. We show that the model allows a dynamic simulation of cellular automata with assemblies that do not record the entire computational history but only the current updates of the states, and thus provide a way for (a) algorithmic dynamical structural changes in the assembly and (b) reusable space in self-assembly. The simulation is such that at a given location the sequence of tiles that attach and detach corresponds precisely to the sequence of states the synchronous cellular automaton generates at that location.

Dynamic Simulation of 1D Cellular Automata in the Active aTAM

PubMed Central

Jonoska, Nataša; Karpenko, Daria; Seki, Shinnosuke

2016-01-01

The Active aTAM is a tile based model for self-assembly where tiles are able to transfer signals and change identities according to the signals received. We extend Active aTAM to include deactivation signals and thereby allow detachment of tiles. We show that the model allows a dynamic simulation of cellular automata with assemblies that do not record the entire computational history but only the current updates of the states, and thus provide a way for (a) algorithmic dynamical structural changes in the assembly and (b) reusable space in self-assembly. The simulation is such that at a given location the sequence of tiles that attach and detach corresponds precisely to the sequence of states the synchronous cellular automaton generates at that location. PMID:27789918

The relationship between the expression of TAM, survivin and the degree of necrosis of the tumor after cisplatin treatment in osteosarcoma.

PubMed

Chen, G

2017-02-01

To explore the relationship between the expression of TAM, survivin and the degree of necrosis of the tumor after cisplatin treatment in osteosarcoma. The mice model of osteosarcoma S180 were injected with 6 mg/kg/day of cisplatin (observation group) or the same amount of normal saline (control group) for 4 weeks. Mice were sacrificed at days 1, 4, 9, 14, 18, 22 and 28, respectively, 24 h before administration of the drug or saline, and tumor tissues were collected. The size of the tumor samples was measured and the correlation of TAM, survivin expression in osteosarcoma and necrosis degree of tumor tissue after cisplatin treatment was studied using various methods including fluorescence quantitative PCR, enzyme linked immunosorbent assay (ELISA), Western blotting and immunohistochemistry. Fluorescence quantitative PCR showed that the expression of TAM, survivin mRNA in the control group was significantly higher than that in the observation group. Also, the ELISA monitoring showed that the expression of mice TAM, survivin protein in vivo was significantly lower than TAM, survivin protein expression of mice in vivo in the observation group (2.3 µg/l, 1.6 µg/l) relatively to the control group (9.7 mg/l, 10.3 µg/l). Consistent with the Western blot data, ELISA results showed that the expression of survivin and TAM protein decreased gradually with the prolongation of drug treatment along the time in the observation group. The volume and weight of the tumor in the observation group were significantly less than that of the control group. Additionally, the tumor necrosis of mice in the observation group was more significant, suggesting that the meant of the size of tumor tissue decreased significantly with the extension of the time of drug treatment. Immunohistochemical results showed that the rate of the positive cell of TAM and survivin in the observation group (82.3%) was significantly higher (p<0.05) than that in the control group (19.5%). However, the rate of the

The Axl kinase domain in complex with a macrocyclic inhibitor offers first structural insights into an active TAM receptor kinase.

PubMed

Gajiwala, Ketan S; Grodsky, Neil; Bolaños, Ben; Feng, Junli; Ferre, RoseAnn; Timofeevski, Sergei; Xu, Meirong; Murray, Brion W; Johnson, Ted W; Stewart, Al

2017-09-22

The receptor tyrosine kinase family consisting of Tyro3, Axl, and Mer (TAM) is one of the most recently identified receptor tyrosine kinase families. TAM receptors are up-regulated postnatally and maintained at high levels in adults. They all play an important role in immunity, but Axl has also been implicated in cancer and therefore is a target in the discovery and development of novel therapeutics. However, of the three members of the TAM family, the Axl kinase domain is the only one that has so far eluded structure determination. To this end, using differential scanning fluorimetry and hydrogen-deuterium exchange mass spectrometry, we show here that a lower stability and greater dynamic nature of the Axl kinase domain may account for its poor crystallizability. We present the first structural characterization of the Axl kinase domain in complex with a small-molecule macrocyclic inhibitor. The Axl crystal structure revealed two distinct conformational states of the enzyme, providing a first glimpse of what an active TAM receptor kinase may look like and suggesting a potential role for the juxtamembrane region in enzyme activity. We noted that the ATP/inhibitor-binding sites of the TAM members closely resemble each other, posing a challenge for the design of a selective inhibitor. We propose that the differences in the conformational dynamics among the TAM family members could potentially be exploited to achieve inhibitor selectivity for targeted receptors. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The RING finger/B-box factor TAM-1 and a retinoblastoma-like protein LIN-35 modulate context-dependent gene silencing in Caenorhabditis elegans.

PubMed

Hsieh, J; Liu, J; Kostas, S A; Chang, C; Sternberg, P W; Fire, A

1999-11-15

Context-dependent gene silencing is used by many organisms to stably modulate gene activity for large chromosomal regions. We have used tandem array transgenes as a model substrate in a screen for Caenorhabditis elegans mutants that affect context-dependent gene silencing in somatic tissues. This screen yielded multiple alleles of a previously uncharacterized gene, designated tam-1 (for tandem-array-modifier). Loss-of-function mutations in tam-1 led to a dramatic reduction in the activity of numerous highly repeated transgenes. These effects were apparently context dependent, as nonrepetitive transgenes retained activity in a tam-1 mutant background. In addition to the dramatic alterations in transgene activity, tam-1 mutants showed modest alterations in expression of a subset of endogenous cellular genes. These effects include genetic interactions that place tam-1 into a group called the class B synMuv genes (for a Synthetic Multivulva phenotype); this family plays a negative role in the regulation of RAS pathway activity in C. elegans. Loss-of-function mutants in other members of the class-B synMuv family, including lin-35, which encodes a protein similar to the tumor suppressor Rb, exhibit a hypersilencing in somatic transgenes similar to that of tam-1 mutants. Molecular analysis reveals that tam-1 encodes a broadly expressed nuclear protein with RING finger and B-box motifs.

Definition of criteria and indicators for the prevention of Healthcare-Associated Infections (HAIs) in hospitals for the purposes of Italian institutional accreditation and performance monitoring.

PubMed

Tardivo, S; Moretti, F; Nobile, M; Agodi, A; Appignanesi, R; Arrigoni, C; Baldovin, T; Brusaferro, S; Canino, R; Carli, A; Chiesa, R; D'Alessandro, D; D'Errico, M M; Giuliani, G; Montagna, M T; Moro, M; Mura, I I; Novati, R; Orsi, G B; Pasquarella, C; Privitera, G; Ripabelli, G; Rossini, A; Saia, M; Sodano, L; Torregrossa, M V; Torri, E; Zarrilli, R; Auxilia, F; SItI, Gisio

2017-01-01

Healthcare-associated infections (HAIs) are an important issue in terms of quality of care. HAIs impact patient safety by contributing to higher rates of preventable mortality and prolonged hospitalizations. In Italy, analysis of the currently available accreditation systems shows a substantial heterogeneity of approaches for the prevention and surveillance of HAIs in hospitals. The aim of the present study is to develop and propose the use of a synthetic assessment tool that could be implemented homogenously throughout the nation. An analysis of nine international and of the 21 Italian regional accreditation systems was conducted in order to identify requirements and indicators implemented for HAI prevention and control. Two relevant reviews on this topic were further analyzed to identify additional evidence-based criteria. The project team evaluated all the requirements and indicators with consensus meeting methodology, then those applicable to the Italian context were grouped into a set of "focus areas". The analysis of international systems and Italian regional accreditation manuals led to the identification respectively of 19 and 14 main requirements, with relevant heterogeneity in their application. Additional evidence-based criteria were included from the reviews analysis. From the consensus among the project team members all the standards were compared and 20 different thematic areas were identified, with a total of 96 requirements and indicators for preventing and monitoring HAIs. The study reveals a great heterogeneity in the definition of accreditation criteria between the Italian regions. The introduction of a uniform, synthetic assessment instrument, based on the review of national and international standards, may serve as a self-assessment tool to evaluate the achievement of a minimum standards set for HAIs prevention and control in healthcare facilities. This may be used as an assessment tool by the Italian institutional accreditation system, also

TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to pro-inflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages1

PubMed Central

Zheng, Shasha; Hedl, Matija; Abraham, Clara

2014-01-01

Microbial-induced cytokine regulation is critical to intestinal immune homeostasis. Acute stimulation of NOD2, the Crohn’s disease-associated sensor of bacterial peptidoglycan, induces cytokines. However, cytokines are attenuated after chronic NOD2 and pattern recognition receptor (PRR) stimulation of macrophages; similar attenuation is observed in intestinal macrophages. The role of Tyro3, Axl and Mer (TAM) receptors in regulating chronic PRR stimulation and NOD2-induced outcomes has not been examined. Moreover, TAM receptors have been relatively less investigated in human macrophages. Whereas TAM receptors did not downregulate acute NOD2-induced cytokines in primary human macrophages, they were essential for downregulating signaling and pro-inflammatory cytokine secretion after chronic NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal tissues. Consistently, TAM expression was increased in human intestinal myeloid-derived cells. Chronic NOD2 stimulation led to IL-10- and TGFβ-dependent TAM upregulation in human macrophages, which in turn, upregulated SOCS3 expression. Restoring SOCS3 expression under TAM knockdown conditions restored chronic NOD2-mediated pro-inflammatory cytokine downregulation. In contrast to the upregulated pro-inflammatory cytokines, attenuated IL-10 secretion was maintained in TAM-deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to upregulate IL-10 secretion; however, full restoration of MAPK activation under these conditions restored c-Fos, c-Jun, MAFK and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore, TAM receptors are critical for downregulating pro-inflammatory cytokines under the chronic NOD2 stimulation conditions observed in the intestinal environment. PMID:25567680

The Tyrosine Aminomutase TAM1 Is Required for β-Tyrosine Biosynthesis in Rice

PubMed Central

Yan, Jian; Aboshi, Takako; Teraishi, Masayoshi; Strickler, Susan R.; Spindel, Jennifer E.; Tung, Chih-Wei; Takata, Ryo; Matsumoto, Fuka; Maesaka, Yoshihiro; McCouch, Susan R.; Okumoto, Yutaka; Mori, Naoki; Jander, Georg

2015-01-01

Non-protein amino acids, often isomers of the standard 20 protein amino acids, have defense-related functions in many plant species. A targeted search for jasmonate-induced metabolites in cultivated rice (Oryza sativa) identified (R)-β-tyrosine, an isomer of the common amino acid (S)-α-tyrosine in the seeds, leaves, roots, and root exudates of the Nipponbare cultivar. Assays with 119 diverse cultivars showed a distinct presence/absence polymorphism, with β-tyrosine being most prevalent in temperate japonica cultivars. Genetic mapping identified a candidate gene on chromosome 12, which was confirmed to encode a tyrosine aminomutase (TAM1) by transient expression in Nicotiana benthamiana and in vitro enzyme assays. A point mutation in TAM1 eliminated β-tyrosine production in Nipponbare. Rice cultivars that do not produce β-tyrosine have a chromosome 12 deletion that encompasses TAM1. Although β-tyrosine accumulation was induced by the plant defense signaling molecule jasmonic acid, bioassays with hemipteran and lepidopteran herbivores showed no negative effects at physiologically relevant β-tyrosine concentrations. In contrast, root growth of Arabidopsis thaliana and other tested dicot plants was inhibited by concentrations as low as 1 μM. As β-tyrosine is exuded into hydroponic medium at higher concentrations, it may contribute to the allelopathic potential of rice. PMID:25901084

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

PubMed

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.

State-of-the-art of small molecule inhibitors of the TAM family: the point of view of the chemist.

PubMed

Baladi, Tom; Abet, Valentina; Piguel, Sandrine

2015-11-13

The TAM family of tyrosine kinases receptors (Tyro3, Axl and Mer) is implicated in cancer development, autoimmune reactions and viral infection and is therefore emerging as an effective and attractive therapeutic target. To date, only a few small molecules have been intentionally designed to block the TAM kinases, while most of the inhibitors were developed for blocking different protein kinases and then identified through selectivity profile studies. This minireview will examine in terms of chemical structure the different compounds able to act on either one, two or three TAM kinases with details about structure-activity relationships, drug-metabolism and pharmacokinetics properties where they exist. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Dissolved inorganic carbon dynamics in the waters surrounding forested mangroves of the Ca Mau Province (Vietnam)

NASA Astrophysics Data System (ADS)

Koné, Y. J.-M.; Borges, A. V.

2008-04-01

Dissolved inorganic carbon (DIC) and ancillary data were obtained during the dry and rainy seasons in the waters surrounding two 10-year-old forested mangrove sites (Tam Giang and Kiên Vàng) located in the Ca Mau Province (South-West Vietnam). During both seasons, the spatial variations of partial pressure of CO 2 (pCO 2) were marked, with values ranging from 704 ppm to 11481 ppm during the dry season, and from 1209 ppm to 8136 ppm during the rainy season. During both seasons, DIC, pCO 2, total alkalinity (TAlk) and oxygen saturation levels (%O 2) were correlated with salinity in the mangrove creeks suggesting that a combination of lower water volume and longer residence time (leading to an increase in salinity due to evaporation) enhanced the enrichment in DIC, pCO 2 and TAlk, and an impoverishment in O 2. The low O 2 and high DIC and pCO 2 values suggest that heterotrophic processes in the water column and sediments controlled these variables. The latter processes were meaningful since the high DIC and TAlk values in the creek waters were related to some extent to the influx of pore waters, consistent with previous observations. This was confirmed by the stochiometric relationship between TAlk and DIC that shows that anaerobic processes control these variables, although this approach did not allow identifying unambiguously the dominant diagenetic carbon degradation pathway. During the rainy season, dilution led to significant decreases of salinity, TAlk and DIC in both mangrove creeks and adjacent main channels. In the Kiên Vàng mangrove creeks a distinct increase of pCO 2 and decrease of %O 2 were observed. The increase of TSM suggested enhanced inputs of organic matter probably from land surrounding the mangrove creeks, that could have led to higher benthic and water column heterotrophy. However, the flushing of water enriched in dissolved CO 2 originating from soil respiration and impoverished in O 2 could also have explained to some extent the patterns

Age-related changes in expression and signaling of TAM receptor inflammatory regulators in monocytes.

PubMed

Wang, Xiaomei; Malawista, Anna; Qian, Feng; Ramsey, Christine; Allore, Heather G; Montgomery, Ruth R

2018-02-09

The multifactorial immune deterioration in aging--termed "inflamm-aging"--is comprised of a state of low-grade, chronic inflammation and complex dysregulation of responses to immune stimulation. The TAM family (Tyro 3, Axl, and Mer) of receptor tyrosine kinases are negative regulators of Toll like receptor-mediated immune responses that broadly inhibit cytokine receptor cascades to inhibit inflammation. Here we demonstrate elevated expression of TAM receptors in monocytes of older adults, and an age-dependent difference in signaling mediator AKT resulting in dysregulated responses to signaling though Mer. Our results may be especially significant in tissue, where levels of Mer are highest, and may present avenues for modulation of chronic tissue inflammation noted in aging.

Nanoparticle formulation enhanced protective immunity provoked by PYGPI8p-transamidase related protein (PyTAM) DNA vaccine in Plasmodium yoelii malaria model.

PubMed

Cherif, Mahamoud Sama; Shuaibu, Mohammed Nasir; Kodama, Yukinobu; Kurosaki, Tomoaki; Helegbe, Gideon Kofi; Kikuchi, Mihoko; Ichinose, Akitoyo; Yanagi, Tetsuo; Sasaki, Hitoshi; Yui, Katsuyuki; Tien, Nguyen Huy; Karbwang, Juntra; Hirayama, Kenji

2014-04-07

We have previously reported the new formulation of polyethylimine (PEI) with gamma polyglutamic acid (γ-PGA) nanoparticle (NP) to have provided Plasmodium yoelii merozoite surface protein-1 (PyMSP-1) plasmid DNA vaccine with enhanced protective cellular and humoral immunity in the lethal mouse malaria model. PyGPI8p-transamidase-related protein (PyTAM) was selected as a possible candidate vaccine antigen by using DNA vaccination screening from 29 GPI anchor and signal sequence motif positive genes picked up using web-based bioinformatics tools; though the observed protection was not complete. Here, we observed augmented protective effect of PyTAM DNA vaccine by using PEI and γ-PGA complex as delivery system. NP-coated PyTAM plasmid DNA immunized mice showed a significant survival rate from lethal P. yoelii challenge infection compared with naked PyTAM plasmid or with NP-coated empty plasmid DNA group. Antigen-specific IgG1 and IgG2b subclass antibody levels, proportion of CD4 and CD8T cells producing IFN-γ in the splenocytes and IL-4, IFN-γ, IL-12 and TNF-α levels in the sera and in the supernatants from ex vivo splenocytes culture were all enhanced by the NP-coated PyTAM DNA vaccine. These data indicates that NP augments PyTAM protective immune response, and this enhancement was associated with increased DC activation and concomitant IL-12 production. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impaired CXCL4 expression in tumor-associated macrophages (TAMs) of ovarian cancers arising in endometriosis.

PubMed

Furuya, Mitsuko; Tanaka, Reiko; Miyagi, Etsuko; Kami, Daisuke; Nagahama, Kiyotaka; Miyagi, Yohei; Nagashima, Yoji; Hirahara, Fumiki; Inayama, Yoshiaki; Aoki, Ichiro

2012-06-01

Inflammatory cells play important roles in progression of solid neoplasms including ovarian cancers. Tumor-associated macrophages (TAMs) contribute to angiogenesis and immune suppression by modulating microenvironment. Ovarian cancer develops occasionally on the bases of endometriosis, a chronic inflammatory disease. We have recently demonstrated differential expressions of CXCR3 variants in endometriosis and ovarian cancers. In this study, we showed impaired CXCL4 expression in TAMs of ovarian cancers arising in endometriosis. The expressions of CXCL4 and its variant CXCL4L1 were investigated among normal ovaries (n = 26), endometriosis (n = 18) and endometriosis-associated ovarian cancers (EAOCs) composed of clear cell (n = 13) and endometrioid (n = 11) types. In addition, four cases of EAOCs that contained both benign and cancer lesions contiguously in single cysts were investigated in the study. Western blot and quantitative RT-PCR analyses revealed significant downregulation of CXCL4 and CXCL4L1 in EAOCs compared with those in endometriosis. In all EAOCs coexisting with endometriosis in the single cyst, the expression levels of CXCL4 and CXCL4L1 were significantly lower in cancer lesions than in corresponding endometriosis. Histopathological study revealed that CXCL4 was strongly expressed in CD68 (+) infiltrating macrophages of endometriosis. In microscopically transitional zone between endometriosis and EAOC, CD68 (+) macrophages often demonstrated CXCL4 (-) pattern. The majority of CD68 (+) TAMs in overt cancer lesions were negative for CXCL4. Collective data indicate that that CXCL4 insufficiency may be involved in specific inflammatory microenvironment of ovarian cancers arising in endometriosis. Suppression of CXCL4 in cancer lesions is likely to be attributable to TAMs in part.

Impaired CXCL4 expression in tumor-associated macrophages (TAMs) of ovarian cancers arising in endometriosis

PubMed Central

Furuya, Mitsuko; Tanaka, Reiko; Miyagi, Etsuko; Kami, Daisuke; Nagahama, Kiyotaka; Miyagi, Yohei; Nagashima, Yoji; Hirahara, Fumiki; Inayama, Yoshiaki; Aoki, Ichiro

2012-01-01

Inflammatory cells play important roles in progression of solid neoplasms including ovarian cancers. Tumor-associated macrophages (TAMs) contribute to angiogenesis and immune suppression by modulating microenvironment. Ovarian cancer develops occasionally on the bases of endometriosis, a chronic inflammatory disease. We have recently demonstrated differential expressions of CXCR3 variants in endometriosis and ovarian cancers. In this study, we showed impaired CXCL4 expression in TAMs of ovarian cancers arising in endometriosis. The expressions of CXCL4 and its variant CXCL4L1 were investigated among normal ovaries (n = 26), endometriosis (n = 18) and endometriosis-associated ovarian cancers (EAOCs) composed of clear cell (n = 13) and endometrioid (n = 11) types. In addition, four cases of EAOCs that contained both benign and cancer lesions contiguously in single cysts were investigated in the study. Western blot and quantitative RT-PCR analyses revealed significant downregulation of CXCL4 and CXCL4L1 in EAOCs compared with those in endometriosis. In all EAOCs coexisting with endometriosis in the single cyst, the expression levels of CXCL4 and CXCL4L1 were significantly lower in cancer lesions than in corresponding endometriosis. Histopathological study revealed that CXCL4 was strongly expressed in CD68+ infiltrating macrophages of endometriosis. In microscopically transitional zone between endometriosis and EAOC, CD68+ macrophages often demonstrated CXCL4− pattern. The majority of CD68+ TAMs in overt cancer lesions were negative for CXCL4. Collective data indicate that that CXCL4 insufficiency may be involved in specific inflammatory microenvironment of ovarian cancers arising in endometriosis. Suppression of CXCL4 in cancer lesions is likely to be attributable to TAMs in part. PMID:22555803

Porphyromonas gingivalis Promotes Unrestrained Type I Interferon Production by Dysregulating TAM Signaling via MYD88 Degradation.

PubMed

Mizraji, Gabriel; Nassar, Maria; Segev, Hadas; Sharawi, Hafiz; Eli-Berchoer, Luba; Capucha, Tal; Nir, Tsipora; Tabib, Yaara; Maimon, Avraham; Dishon, Shira; Shapira, Lior; Nussbaum, Gabriel; Wilensky, Asaf; Hovav, Avi-Hai

2017-01-10

Whereas type I interferons (IFNs-I) were proposed to be elevated in human periodontitis, their role in the disease remains elusive. Using a bacterial-induced model of murine periodontitis, we revealed a prolonged elevation in IFN-I expression. This was due to the downregulation of TAM signaling, a major negative regulator of IFN-I. Further examination revealed that the expression of certain TAM components was reduced as a result of prolonged degradation of MYD88 by the infection. As a result of such prolonged IFN-I production, innate immunological functions of the gingiva were disrupted, and CD4 + T cells were constitutively primed by dendritic cells, leading to elevated RANKL expression and, subsequently, alveolar bone loss (ABL). Blocking IFN-I signaling restored proper immunological function and prevented ABL. Importantly, a loss of negative regulation on IFN-I expression by TAM signaling was also evident in periodontitis patients. These findings thus suggest a role for IFN-I in the pathogenesis of periodontitis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Fast, multi-phase H2O measurements on board of HALO: Results from the novel HAI instrument during the first field campaigns.

NASA Astrophysics Data System (ADS)

Buchholz, Bernhard; Afchine, Armin; Krämer, Martina; Ebert, Volker

2014-05-01

Water vapor is a key species for many questions in atmospheric research [1] [2] but is also a gas species which is complex to handle. A particular challenge is the simultaneous quantification of gas and condensed phase water. This is especially true for measurements on airborne platforms but also for laboratory experiments [3]. On research aircraft, total water measurement (i.e. the sum of gas-phase and ice-phase) is realized by sampling air with an inlet faced into flight direction ('forward' sampling) and subsequent evaporation of the ice crystals in the heated sampling lines. Gas-phase detection is typically realized using inlets facing against flight direction ('backward' sampling) or 'Rosemount' inlets where an air stream is sampled perpendicular to the high speed airflow through the inlet. For both methods it is believed that no ice crystals reach the downstream hygrometer, but the question remains - especially for Rosemount inlets - if some small ice particles or water droplets may have entered the sampling lines. In addition to the question of proper sampling of the water phases, currently no hygrometer exists that measures all phases with the same measurement principle in one instrument. In the rare occasions that multi-phase measurements are realized, gas-and condensed-phase observations rely on different methods and calibration strategies so that precision and accuracy levels are difficult to compare. The novel HAI (Hygrometer for Atmospheric Investigation) realizes a simultaneous multi-phase hygrometer in a unique concept [4]. Water detection with HAI is based on Tunable Diode Laser Absorption Spectroscopy (TDLAS) with a special evaluation method allowing absolute water vapor measurements without any sensor calibration [5]. The HAI instrument contains two independent dual-channel spectrometers, one at 1.4 μm and one at 2.6 μm which allows to cover a very wide water concentration range from 1 to 30 000 ppmv. Both HAI spectrometers couple one light path

Structural elucidation of the DFG-Asp in and DFG-Asp out states of TAM kinases and insight into the selectivity of their inhibitors.

PubMed

Messoussi, Abdellah; Peyronnet, Lucile; Feneyrolles, Clémence; Chevé, Gwénaël; Bougrin, Khalid; Yasri, Aziz

2014-10-10

Structural elucidation of the active (DFG-Asp in) and inactive (DFG-Asp out) states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members Tyro-3, Axl and Mer. DFG-Asp in and DFG-Asp out homology models of each one were built based on the X-ray structure of c-Met kinase, an enzyme with a closely related sequence. Structural validation and in silico screening enabled identification of critical amino acids for ligand binding within the active site of each DFG-Asp in and DFG-Asp out model. The position and nature of amino acids that differ among Tyro-3, Axl and Mer, and the potential role of these residues in the design of selective TAM ligands, are discussed.

Extended TAM Model: Impacts of Convenience on Acceptance and Use of Moodle

ERIC Educational Resources Information Center

Hsu, Hsiao-hui; Chang, Yu-ying

2013-01-01

The increasing online access to courses, programs, and information has shifted the control and responsibility of learning process from instructors to learners. Learners' perceptions of and attitudes toward e-learning constitute a critical factor to the success of such system. The purpose of this study is to take TAM (technology acceptance model)…

Sulfonyl chlorides as an efficient tool for the postsynthetic modification of Cr-MIL-101-SO3H and CAU-1-NH2.

PubMed

Klinkebiel, Arne; Reimer, Nele; Lammert, Martin; Stock, Norbert; Lüning, Ulrich

2014-08-25

Postsynthetic modification can be used to introduce sulfonamide functionalities into MOF frameworks. Using sulfonyl chlorides as reactive intermediates, Cr-MIL-SO3H and CAU-1-NH2 have been further modified to give hitherto unknown functionalized MOFs in which a sulfonamide group is bound to the framework either by its N or its S atom.

A novel RNA binding surface of the TAM domain of TIP5/BAZ2A mediates epigenetic regulation of rRNA genes.

PubMed

Anosova, Irina; Melnik, Svitlana; Tripsianes, Konstantinos; Kateb, Fatiha; Grummt, Ingrid; Sattler, Michael

2015-05-26

The chromatin remodeling complex NoRC, comprising the subunits SNF2h and TIP5/BAZ2A, mediates heterochromatin formation at major clusters of repetitive elements, including rRNA genes, centromeres and telomeres. Association with chromatin requires the interaction of the TAM (TIP5/ARBP/MBD) domain of TIP5 with noncoding RNA, which targets NoRC to specific genomic loci. Here, we show that the NMR structure of the TAM domain of TIP5 resembles the fold of the MBD domain, found in methyl-CpG binding proteins. However, the TAM domain exhibits an extended MBD fold with unique C-terminal extensions that constitute a novel surface for RNA binding. Mutation of critical amino acids within this surface abolishes RNA binding in vitro and in vivo. Our results explain the distinct binding specificities of TAM and MBD domains to RNA and methylated DNA, respectively, and reveal structural features for the interaction of NoRC with non-coding RNA. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

DOE Project 353: TAMS Prototype and production coupling alignment units

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

Field, K.V.

1996-02-01

TAMS is an electronic measurement system used to determine the alignment of turbine-generator shafts at the coupling interface. The displacement transducer is a strain gage based sensor mounted in a portable probe. The measurement system was experiencing zero input drift and temperature induced drift. This project endeavored to determine the source of these problems and to revise a unit to be returned to a customer, Baltimore Gas and Electric (BGE), within a period of five weeks.

OSD1 promotes meiotic progression via APC/C inhibition and forms a regulatory network with TDM and CYCA1;2/TAM.

PubMed

Cromer, Laurence; Heyman, Jefri; Touati, Sandra; Harashima, Hirofumi; Araou, Emilie; Girard, Chloe; Horlow, Christine; Wassmann, Katja; Schnittger, Arp; De Veylder, Lieven; Mercier, Raphael

2012-01-01

Cell cycle control is modified at meiosis compared to mitosis, because two divisions follow a single DNA replication event. Cyclin-dependent kinases (CDKs) promote progression through both meiosis and mitosis, and a central regulator of their activity is the APC/C (Anaphase Promoting Complex/Cyclosome) that is especially required for exit from mitosis. We have shown previously that OSD1 is involved in entry into both meiosis I and meiosis II in Arabidopsis thaliana; however, the molecular mechanism by which OSD1 controls these transitions has remained unclear. Here we show that OSD1 promotes meiotic progression through APC/C inhibition. Next, we explored the functional relationships between OSD1 and the genes known to control meiotic cell cycle transitions in Arabidopsis. Like osd1, cyca1;2/tam mutation leads to a premature exit from meiosis after the first division, while tdm mutants perform an aberrant third meiotic division after normal meiosis I and II. Remarkably, while tdm is epistatic to tam, osd1 is epistatic to tdm. We further show that the expression of a non-destructible CYCA1;2/TAM provokes, like tdm, the entry into a third meiotic division. Finally, we show that CYCA1;2/TAM forms an active complex with CDKA;1 that can phosphorylate OSD1 in vitro. We thus propose that a functional network composed of OSD1, CYCA1;2/TAM, and TDM controls three key steps of meiotic progression, in which OSD1 is a meiotic APC/C inhibitor.

Purification and Bicelle Crystallization for Structure Determination of the E. coli Outer Membrane Protein TamA.

PubMed

Gruss, Fabian; Hiller, Sebastian; Maier, Timm

2015-01-01

TamA is an Omp85 protein involved in autotransporter assembly in the outer membrane of Escherichia coli. It comprises a C-terminal 16-stranded transmembrane β-barrel as well as three periplasmic POTRA domains, and is a challenging target for structure determination. Here, we present a method for crystal structure determination of TamA, including recombinant expression in E. coli, detergent extraction, chromatographic purification, and bicelle crystallization in combination with seeding. As a result, crystals in space group P21212 are obtained, which diffract to 2.3 Å resolution. This protocol also serves as a template for structure determination of other outer membrane proteins, in particular of the Omp85 family.

Organizing the Library to Suit the Undergraduates' Information Gathering Behavior at the Tel-Hai Academic College in Israel

ERIC Educational Resources Information Center

Chai, Iris

2007-01-01

The study examined the factors influencing information gathering behavior of undergraduates at Tel-Hai Academic College, so that library services can cope effectively with this behavior. Related to the findings, we changed our circulation desk to become a "one stop shop" for directions to all library information.

Development of CANDLES low background HPGe detector and half-life measurement of 180Tam

NASA Astrophysics Data System (ADS)

Chan, W. M.; Kishimoto, T.; Umehara, S.; Matsuoka, K.; Suzuki, K.; Yoshida, S.; Nakajima, K.; Iida, T.; Fushimi, K.; Nomachi, M.; Ogawa, I.; Tamagawa, Y.; Hazama, R.; Takemoto, Y.; Nakatani, N.; Takihira, Y.; Tozawa, M.; Kakubata, H.; Trang, V. T. T.; Ohata, T.; Tetsuno, K.; Maeda, T.; Khai, B. T.; Li, X. L.; Batpurev, T.

2018-01-01

A low background HPGe detector system was developed at CANDLES Experimental Hall for multipurpose use. Various low background techniques were employed, including hermatic shield design, radon gas suppression, and background reduction analysis. A new pulse shape discrimination (PSD) method was specially created for coaxial Ge detector. Using this PSD method, microphonics noise and background event at low energy region less than 200 keV can be rejected effectively. Monte Carlo simulation by GEANT4 was performed to acquire the detection efficiency and study the interaction of gamma-rays with detector system. For rare decay measurement, the detector was utilized to detect the nature's most stable isomer tantalum-180m (180Tam) decay. Two phases of tantalum physics run were completed with total livetime of 358.2 days, which Phase II has upgraded shield configuration. The world most stringent half-life limit of 180Tam has been successfully achieved.

Field evaluation of spatial repellency of metofluthrin-impregnated latticework plastic strips against Aedes aegypti (L.) and analysis of environmental factors affecting its efficacy in My Tho City, Tien Giang, Vietnam.

PubMed

Kawada, Hitoshi; Iwasaki, Tomonori; LE Loan, Luu; Tien, Tran Khanh; Mai, Nguyen Thi Nhu; Shono, Yoshinori; Katayama, Yasuyuki; Takagi, Masahiro

2006-12-01

Spatial repellency of metofluthrin-impregnated polyethylene latticework plastic strips against Aedes aegypti mosquitoes was evaluated. Analysis of environmental factors affecting the efficacy of these strips, such as room temperature, humidity, and house structure, was performed in a residential area in My Tho City, Tien Giang Province, Vietnam. Treatment with the strips at the rate of 1 strip per 2.6-5.52 m(2) (approximately 600 mg per 2.6-5.52 m(2)) reduced the collection of Ae. aegypti resting inside the houses for at least eight weeks. Multiple regression analysis indicated that both increase in the average room temperature and decrease in the area of openings in the rooms that were treated with the strips positively affected the spatial repellency of metofluthrin.

Somatostatin Derivate (smsDX) Attenuates the TAM-Stimulated Proliferation, Migration and Invasion of Prostate Cancer via NF-κB Regulation.

PubMed

Guo, Zhaoxin; Xing, Zhaoquan; Cheng, Xiangyu; Fang, Zhiqing; Jiang, Chao; Su, Jing; Zhou, Zunlin; Xu, Zhonghua; Holmberg, Anders; Nilsson, Sten; Liu, Zhaoxu

2015-01-01

Tumor development and progression are influenced by macrophages of the surrounding microenvironment. To investigate the influences of an inflammatory tumor microenvironment on the growth and metastasis of prostate cancer, the present study used a co-culture model of prostate cancer (PCa) cells with tumor-associated macrophage (TAM)-conditioned medium (MCM). MCM promoted PCa cell (LNCaP, DU145 and PC-3) growth, and a xenograft model in nude mice consistently demonstrated that MCM could promote tumor growth. MCM also stimulated migration and invasion in vitro. Somatostatin derivate (smsDX) significantly attenuated the TAM-stimulated proliferation, migration and invasion of prostate cancer. Immunohistochemistry revealed that NF-κB was over-expressed in PCa and BPH with chronic inflammatory tissue specimens and was positively correlated with macrophage infiltration. Further investigation into the underlying mechanism revealed that NF-κB played an important role in macrophage infiltration. SmsDX inhibited the paracrine loop between TAM and PCa cells and may represent a potential therapeutic agent for PCa.

Assessing the utility of TAM, TPB, and UTAUT for advanced driver assistance systems.

PubMed

Rahman, Md Mahmudur; Lesch, Mary F; Horrey, William J; Strawderman, Lesley

2017-11-01

Advanced Driver Assistance Systems (ADAS) are intended to enhance driver performance and improve transportation safety. The potential benefits of these technologies, such as reduction in number of crashes, enhancing driver comfort or convenience, decreasing environmental impact, etc., have been acknowledged by transportation safety researchers and federal transportation agencies. Although these systems afford safety advantages, they may also challenge the traditional role of drivers in operating vehicles. Driver acceptance, therefore, is essential for the implementation of these systems into the transportation system. Recognizing the need for research into the factors affecting driver acceptance, this study assessed the utility of the Technology Acceptance Model (TAM), the Theory of Planned Behavior (TPB), and the Unified Theory of Acceptance and Use of Technology (UTAUT) for modelling driver acceptance in terms of Behavioral Intention to use an ADAS. Each of these models propose a set of factors that influence acceptance of a technology. Data collection was done using two approaches: a driving simulator approach and an online survey approach. In both approaches, participants interacted with either a fatigue monitoring system or an adaptive cruise control system combined with a lane-keeping system. Based on their experience, participants responded to several survey questions to indicate their attitude toward using the ADAS and their perception of its usefulness, usability, etc. A sample of 430 surveys were collected for this study. Results found that all the models (TAM, TPB, and UTAUT) can explain driver acceptance with their proposed sets of factors, each explaining 71% or more of the variability in Behavioral Intention. Among the models, TAM was found to perform the best in modelling driver acceptance followed by TPB. The findings of this study confirm that these models can be applied to ADAS technologies and that they provide a basis for understanding driver

The TAM-family receptor Mer mediates production of HGF through the RhoA-dependent pathway in response to apoptotic cells.

PubMed

Park, Hyun-Jung; Baen, Ji-Yeon; Lee, Ye-Ji; Choi, Youn-Hee; Kang, Jihee Lee

2012-08-01

The TAM receptor protein tyrosine kinases Tyro3, Axl, and Mer play important roles in macrophage function. We investigated the roles of the TAM receptors in mediating the induction of hepatocyte growth factor (HGF) during the interaction of macrophages with apoptotic cells. Mer-specific neutralizing antibody, small interfering RNA (siRNA), and a recombinant Mer protein (Mer/Fc) inhibited HGF mRNA and protein expression, as well as activation of RhoA, Akt, and specific mitogen-activated protein (MAP) kinases in response to apoptotic cells. Inhibition of Axl or Tyro3 with specific antibodies, siRNA, or Fc-fusion proteins did not prevent apoptotic cell-induced HGF mRNA and protein expression and did not inhibit activation of the postreceptor signaling molecules RhoA and certain MAP kinases, including extracellular signal-regulated protein kinase and c-Jun NH(2)-terminal kinase. However, Axl- and Tyro3-specific blockers did inhibit the activation of Akt and p38 MAP kinase in response to apoptotic cells. In addition, none of the TAM receptors mediated the effects of apoptotic cells on transforming growth factor-β or epidermal growth factor mRNA expression. However, they were involved in the induction of vascular endothelial growth factor mRNA expression. Our data provide evidence that when macrophages interact with apoptotic cells, only Mer of the TAM-family receptors is responsible for mediating transcriptional HGF production through a RhoA-dependent pathway.

High-resolution C and O stable isotope geochemistry of the early Aptian OAE1a at Cau (Prebetic Zone, Spain): Preliminary results from sediment core.

NASA Astrophysics Data System (ADS)

Alejandro Ruiz-Ortiz, Pedro; Aguado, Roque; Castro, José Manuel; Gallego, David; de Gea, Ginés Alfonso; Jarvis, Ian; Molina, José Miguel; Nieto, Luis Miguel; Pancost, Richard; Quijano, María Luisa; Reolid, Matías; Rodriguez, Rafael; Skelton, Peter; Weisser, Helmut

2017-04-01

The occurrence of time intervals of enhanced deposition of organic matter (OM) during the Cretaceous, defined as Oceanic Anoxic Events (OAE), reflect abrupt changes in global carbon cycling. The Aptian OAE1a (120 Ma), represents an excellent example, recorded in all the main ocean basins, associated to massive burial of organic matter in marine sediments [1]. Much research has been done on the OAE1a from different sections in the world over the last decades, including the definition of the C-isotope stratigraphy of the event [2]. Notwithstanding, higher-resolution studies across the entire event will be crucial to shed light into the precise timing and rates of the different environmental and biotic changes that occurred. The Cau section is located in the easternmost part of the Prebetic Zone (Betic Cordillera), which represents the platform deposits of the Southern Iberian palaeomargin. The Lower Aptian of the Cau section is represented by a hemipelagic unit (Almadich Formation, ca. 200 m thick), deposited in a highly subsiding sector of a tilted block, located in the distal parts of the Prebetic Platform. Previous studies of the Lower Aptian of the Cau section have focused on the stratigraphy, bioevents, C-isotope stratigraphy, and organic and elemental geochemistry [3], [4], and in the reconstruction of pCO2 from organic geochemistry proxies [5]. All these studies reveal that the Cau section represents an excellent site to investigate the OAE 1a, based on its unusual high thickness and stratigraphic continuity, the quality and preservation of fossils and the geochemical signatures. Here we present the first results of a high-resolution carbonate C-isotope study based on the the analysis of three new research cores drilled at Cau in autumn 2015 [6]. These new data represent an important advance in the knowledge of the C-isotope record of the OAE 1a, presenting a more continuous record at a higher resolution than previous studies. This leads to the refining of the

Exploring the relationship between irrigation water requirements and potential yield in the Huang-Huai-Hai plain

NASA Astrophysics Data System (ADS)

Tang, Huaxiu; Zhan, Jinyan; Deng, Xiangzheng; Ma, Jinsong

2007-11-01

By using the GIS technologies, we interpolate the site-based meteorological data into climatic surface data, which are the main input parameters for the CropWat model, used to estimate the reference evapotranspiration (ET 0). And then by combining the ET 0 with the information on share of cultivated land decoded from the Landsat TM/ETM digital imagines covering the entire case study area, the Huang-Huai-Hai plain, we estimate the amount of irrigation water requirements (IWRs) in the years of 1991 and 2000. We then introduce the potential yield (PY) of cultivated land estimated from the Estimation Model for the Agricultural Productivity Potential (EMAPP) to explore the relationship between the IWRs and the PY . By conducting GIS-based spatial overlay analyses, we explore the positive correlation relationship between the IWRs and the PY of cultivated land. Finally, we conclude that the IWRs is now a constrain factor on the PY of cultivated land in the Huang-Huai-Hai plain in those areas with the irrigation water constrains. The result has offered a scientific basis for the decision makings in the exploitation and utilization of resources and energy as well as the land use planning, protection of the potential yields and the managements of irrigation water at the regional level.

Understanding Intention to Use Electronic Information Resources: A Theoretical Extension of the Technology Acceptance Model (TAM)

PubMed Central

Tao, Donghua

2008-01-01

This study extended the Technology Acceptance Model (TAM) by examining the roles of two aspects of e-resource characteristics, namely, information quality and system quality, in predicting public health students’ intention to use e-resources for completing research paper assignments. Both focus groups and a questionnaire were used to collect data. Descriptive analysis, data screening, and Structural Equation Modeling (SEM) techniques were used for data analysis. The study found that perceived usefulness played a major role in determining students’ intention to use e-resources. Perceived usefulness and perceived ease of use fully mediated the impact that information quality and system quality had on behavior intention. The research model enriches the existing technology acceptance literature by extending TAM. Representing two aspects of e-resource characteristics provides greater explanatory information for diagnosing problems of system design, development, and implementation. PMID:18999300

Understanding intention to use electronic information resources: A theoretical extension of the technology acceptance model (TAM).

PubMed

Tao, Donghua

2008-11-06

This study extended the Technology Acceptance Model (TAM) by examining the roles of two aspects of e-resource characteristics, namely, information quality and system quality, in predicting public health students' intention to use e-resources for completing research paper assignments. Both focus groups and a questionnaire were used to collect data. Descriptive analysis, data screening, and Structural Equation Modeling (SEM) techniques were used for data analysis. The study found that perceived usefulness played a major role in determining students' intention to use e-resources. Perceived usefulness and perceived ease of use fully mediated the impact that information quality and system quality had on behavior intention. The research model enriches the existing technology acceptance literature by extending TAM. Representing two aspects of e-resource characteristics provides greater explanatory information for diagnosing problems of system design, development, and implementation.

‘TAM 112’ Wheat, resistant to greenbug and wheat curl mite and adapted to the dryland production system in the Southern High Plains

USDA-ARS?s Scientific Manuscript database

‘TAM 112’ (PI 643143), a hard red winter wheat (Triticum aestivum L.) is an F4 derived line from the cross U1254-7-9-2-1/TXGH10440. U1254-7-9-2 is a USDA-ARS germplasm line from the Plant Science and Entomology Research unit, Manhattan, Kansas. It was developed from the cross TAM 200/TA2460. TA24...

Drug injecting and HIV risk among injecting drug users in Hai Phong, Vietnam: a qualitative analysis.

PubMed

Ahmed, Tanvir; Long, Thanh Nguyen; Huong, Phan Thi; Stewart, Donald Edwin

2015-01-29

Hai Phong, located in northern Vietnam, has become a high HIV prevalence province among Injecting Drug Users (IDUs) since the infection shifted from the southern to the northern region of the country. Previous research indicates high levels of drug and sex related risk behaviour especially among younger IDUs. Our recent qualitative research provides a deeper understanding of HIV risk behaviour and highlights views and experiences of IDUs relating to drug injecting and sharing practices. Fifteen IDUs participated in semi-structured interviews conducted in September-October, 2012. Eligible participants were selected from those recruited in a larger scale behavioural research project and identified through screening questions. Interviews were conducted by two local interviewers in Vietnamese and were audiotaped. Ethical procedures, including informed consent and participants' understanding of their right to skip and withdraw, were applied. Transcripts were translated and double checked. The data were categorised and coded according to themes. Thematic analysis was conducted and a qualitative data analysis thematic framework was used. Qualitative analysis highlighted situational circumstances associated with HIV risks among IDUs in Hai Phong and revealed three primary themes: (i) places for injecting, (ii) injecting drugs in small groups, and (iii) sharing practices. Our results showed that shared use of jointly purchased drugs and group injecting were widespread among IDUs without adequate recognition of these as HIV risk behaviours. Frequent police raids generated a constant fear of arrest. As a consequence, the majority preferred either rail lines or isolated public places for injection, while some injected in their own or a friend's home. Price, a heroin crisis, and strong group norms encouraged collective preparation and group injecting. Risk practices were enhanced by a number of factors: the difficulty in getting new syringes, quick withdrawal management

Examining the Antecedents of ICT Adoption in Education Using an Extended Technology Acceptance Model (TAM)

ERIC Educational Resources Information Center

Teeroovengadum, Viraiyan; Heeraman, Nabeel; Jugurnath, Bhavish

2017-01-01

This study assesses the determinants of ICT adoption by educators in the teaching and learning process in the context of a developing country, Mauritius. A hierarchical regression analysis is used, to firstly determine the incremental effects of factors from the technology acceptance model (TAM) while controlling for demographic variables such as…

Rapid Ascent From Zero Quality to International Organization for Standardization Accreditation: A Case Study of Hai Duong Preventive Medicine Center in Vietnam, 2012-2013.

PubMed

Duong, Cuong Ngoc; Bond, Kyle B; Carvalho, Humberto; Thi Thu, Hien Bui; Nguyen, Thuong; Rush, Thomas

2017-04-01

In 2012, the Vietnam Ministry of Health sought to improve the quality of health laboratories by introducing international quality standards. Strengthening Laboratory Management Toward Accreditation (SLMTA), a year-long, structured, quality improvement curriculum (including projects and mentorship) was piloted in 12 laboratories. Progress was measured using a standardized audit tool (Stepwise Laboratory Quality Improvement Process Towards Accreditation). All 12 pilot laboratories (a mix of hospital and public health) demonstrated improvement; median scores rose from 44% to 78% compliance. The public health laboratory in Hai Duong Province entered the program with the lowest score of the group (28%) yet concluded with the highest score (86%). Five months after the completion of the program, without any additional external support, they were accredited. Laboratory management/staff describe factors key to their success: support from the facility senior management, how-to guidance provided by SLMTA, support from the site mentor, and strong commitment of laboratory staff. Hai Duong preventive medical center is one of only a handful of laboratories to reach accreditation after participation in SLMTA and the only laboratory to do so without additional support. Due to the success seen in Hai Duong and other pilot laboratories, Vietnam has expanded the use of SLMTA. American Society for Clinical Pathology, 2017. This work is written by US Government employees and is in the public domain in the US.

Possible presence of some human remains of the Wadjak type found at Cau Giat (Quynh Luu Bay, North Vietnam)Présence probable de formes de type Wadjak dans la baie fossile de Quyhn Luu au Nord Viêt-nam sur le site de Cau Giat

NASA Astrophysics Data System (ADS)

Demeter, Fabrice; Peyre, Evelyne; Coppens, Yves

2000-03-01

French archaeologists have known the Cau Giat site, excavated by Mrs Colani and Mr Pajot, since 1930. Many artefacts and human remains have been found, but human fossil material has long been lost and forgotten. However, the study of rediscovered fossil material highlights some morphological aspects that allow consideration of a human presence resembling the Wadjak in North Vietnam. Recognition of particular characters of the Wadjak type, outside Indonesia, leads to the hypothesis of the existence of migratory ways or diffusion between the Indonesian islands and the Eurasiatic continent.

Recombinant expression, purification, crystallization and preliminary X-ray diffraction analysis of the C-terminal DUF490(963-1138) domain of TamB from Escherichia coli.

PubMed

Josts, Inokentijs; Grinter, Rhys; Kelly, Sharon M; Mosbahi, Khedidja; Roszak, Aleksander; Cogdell, Richard; Smith, Brian O; Byron, Olwyn; Walker, Daniel

2014-09-01

TamB is a recently described inner membrane protein that, together with its partner protein TamA, is required for the efficient secretion of a subset of autotransporter proteins in Gram-negative bacteria. In this study, the C-terminal DUF490963-1138 domain of TamB was overexpressed in Escherichia coli K-12, purified and crystallized using the sitting-drop vapour-diffusion method. The crystals belonged to the primitive trigonal space group P3121, with unit-cell parameters a = b = 57.34, c = 220.74 Å, and diffracted to 2.1 Å resolution. Preliminary secondary-structure and X-ray diffraction analyses are reported. Two molecules are predicted to be present in the asymmetric unit. Experimental phasing using selenomethionine-labelled protein will be undertaken in the future.

Soluble TAM receptor tyrosine kinases in rheumatoid arthritis: correlation with disease activity and bone destruction.

PubMed

Xu, L; Hu, F; Zhu, H; Liu, X; Shi, L; Li, Y; Zhong, H; Su, Y

2018-04-01

The TAM receptor tyrosine kinases (TAM RTK) are a subfamily of receptor tyrosine kinases, the role of which in autoimmune diseases such as systemic lupus erythematosus has been well explored, while their functions in rheumatoid arthritis (RA) remain largely unknown. In this study, we investigated the role of soluble TAM receptor tyrosine kinases (sAxl/sMer/sTyro3) in patients with RA. A total of 306 RA patients, 100 osteoarthritis (OA) patients and 120 healthy controls (HCs) were enrolled into this study. The serum concentrations of sAxl/sMer/sTyro3 were measured by enzyme-linked immunosorbent assay (ELISA), then the associations between sAxl/sMer/sTyro3 levels and clinical features of RA patients were analysed. We also investigated whether sTyro3 could promote osteoclast differentiation in vitro in RA patients. The results showed that compared with healthy controls (HCs), sTyro3 levels in the serum of RA patients were elevated remarkably and sMer levels were decreased significantly, whereas there was no difference between HCs and RA patients on sAxl levels. The sTyro3 levels were correlated weakly but positively with white blood cells (WBC), immunoglobulin (Ig)M, rheumatoid factor (RF), swollen joint counts, tender joint counts, total sharp scores and joint erosion scores. Conversely, there were no significant correlations between sMer levels and the above indices. Moreover, RA patients with high disease activity also showed higher sTyro3 levels. In-vitro osteoclast differentiation assay showed further that tartrate-resistant acid phosphatase (TRAP) + osteoclasts were increased significantly in the presence of sTyro3. Collectively, our study indicated that serum sTyro3 levels were elevated in RA patients and correlated positively with disease activity and bone destruction, which may serve as an important participant in RA pathogenesis. © 2017 British Society for Immunology.

Activation of TrkB with TAM-163 Results in Opposite Effects on Body Weight in Rodents and Non-Human Primates

PubMed Central

Perreault, Mylène; Feng, Guo; Will, Sarah; Gareski, Tiffany; Kubasiak, David; Marquette, Kimberly; Vugmeyster, Yulia; Unger, Thaddeus J.; Jones, Juli; Qadri, Ariful; Hahm, Seung; Sun, Ying; Rohde, Cynthia M.; Zwijnenberg, Raphael; Paulsen, Janet; Gimeno, Ruth E.

2013-01-01

Strong genetic data link the Tyrosine kinase receptor B (TrkB) and its major endogenous ligand brain-derived neurotrophic factor (BDNF) to the regulation of energy homeostasis, with loss-of-function mutations in either gene causing severe obesity in both mice and humans. It has previously been reported that peripheral administration of the endogenous TrkB agonist ligand neurotrophin-4 (NT-4) profoundly decreases food intake and body weight in rodents, while paradoxically increasing these same parameters in monkeys. We generated a humanized TrkB agonist antibody, TAM-163, and characterized its therapeutic potential in several models of type 2 diabetes and obesity. In vitro, TAM-163 bound to human and rodent TrkB with high affinity, activated all aspects of the TrkB signaling cascade and induced TrkB internalization and degradation in a manner similar to BDNF. In vivo, peripheral administration of TAM-163 decreased food intake and/or body weight in mice, rats, hamsters, and dogs, but increased food intake and body weight in monkeys. The magnitude of weight change was similar in rodents and non-human primates, occurred at doses where there was no appreciable penetration into deep structures of the brain, and could not be explained by differences in exposures between species. Rather, peripherally administered TAM-163 localized to areas in the hypothalamus and the brain stem located outside the blood-brain barrier in a similar manner between rodents and non-human primates, suggesting differences in neuroanatomy across species. Our data demonstrate that a TrkB agonist antibody, administered peripherally, causes species-dependent effects on body weight similar to the endogenous TrkB ligand NT-4. The possible clinical utility of TrkB agonism in treating weight regulatory disorder, such as obesity or cachexia, will require evaluation in man. PMID:23700410

HAI: A novel airborne multi-channel hygrometer for fast multi-phase H2O quantification: Performance of the HAI instrument during the first flights on the German HALO aircraft

NASA Astrophysics Data System (ADS)

Buchholz, B.; Ebert, V.; Kraemer, M.; Afchine, A.

2014-12-01

Common gas phase H2O measurements on fast airborne platforms e.g. using backward facing or "Rosemount"-inlets can lead to a high risk of ice and droplets contamination. In addition, currently no single hygrometer exists that allows a simultaneous, high-speed measurement of all phases (gas, liquid, ice) with the same detection principle. In the rare occasions multi-phase measurements are realized, gas-and condensed-phase observations rely on different methods, instruments and calibration strategies so that precision and accuracy levels are quite difficult to quantify. This is effectively avoided by the novel TDLAS instrument, HAI, Hygrometer for Atmospheric Investigation, which allows a simultaneous, high speed, multi-phase detection without any sensor calibration in a unique "2+2" channel concept. Hai combines two independent wavelength channels, at 1.4 µm and at 2.6 µm, for a wide dynamic range from 1 to 30 000 ppmv, with a simultaneous closed path (extractive) and open path detection. Thus, "Total", i.e. gas-phase plus condensed-phase water is measured by sampling via a forward facing inlet into "closed-path" extractive cells. A selective, sampling-free, high speed gas phase detection is realized via a dual-wavelength "open-path" cell placed outside of the aircraft fuselage. All channels can be sampled with 120 Hz (measurement cycle time Dt=1.6 ms) allowing an unprecedented spatial resolution of 30 cm at 900 km/h. The evaluation of the individual multi-channel raw-data is done post flight, without any channel interdependencies, in calibration-free mode, thus allowing fast, accurate and precise multi-phase water detection in flight. The performance could be shown in more than 200 net flights hours in three scientific flight campaigns (TACTS, ESMVal, ML-CIRRUS) on the new German HALO aircraft. In addition the level of the accuracy of the calibration free evaluation was evaluated at the German national primary water vapor standard.

Temperature Control and Numerical Analysis for Mass Concrete Pile Cap of Hai-huang Bridge

NASA Astrophysics Data System (ADS)

Shi, Han; Hao, Yang; Yong-liang, Wang

2018-05-01

In order to study the heat of hydration in massive concrete, this paper takes Hai-huang bridge for engineering background and uses the finite element analysis software of FEA to analyze the heat of hydration effect of the cushion cap. Comparing the measured data with the theory data, the results showed that the concrete crack was controlled effectively and ensure the construction quality by adopted reasonable temperature control measures. The results of the research prove that the measured data was consistent with calculation data, and it proves the accuracy of the finite element analysis. Finally, the study provides certain reference and guiding significance for similar project.

HAI, a new airborne, absolute, twin dual-channel, multi-phase TDLAS-hygrometer: background, design, setup, and first flight data

NASA Astrophysics Data System (ADS)

Buchholz, Bernhard; Afchine, Armin; Klein, Alexander; Schiller, Cornelius; Krämer, Martina; Ebert, Volker

2017-01-01

The novel Hygrometer for Atmospheric Investigation (HAI) realizes a unique concept for simultaneous gas-phase and total (gas-phase + evaporated cloud particles) water measurements. It has been developed and successfully deployed for the first time on the German HALO research aircraft. This new instrument combines direct tunable diode laser absorption spectroscopy (dTDLAS) with a first-principle evaluation method to allow absolute water vapor measurements without any initial or repetitive sensor calibration using a reference gas or a reference humidity generator. HAI contains two completely independent dual-channel (closed-path, open-path) spectrometers, one at 1.4 and one at 2.6 µm, which together allow us to cover the entire atmospheric H2O range from 1 to 40 000 ppmv with a single instrument. Both spectrometers each comprise a separate, wavelength-individual extractive, closed-path cell for total water (ice and gas-phase) measurements. Additionally, both spectrometers couple light into a common open-path cell outside of the aircraft fuselage for a direct, sampling-free, and contactless determination of the gas-phase water content. This novel twin dual-channel setup allows for the first time multiple self-validation functions, in particular a reliable, direct, in-flight validation of the open-path channels. During the first field campaigns, the in-flight deviations between the independent and calibration-free channels (i.e., closed-path to closed-path and open-path to closed-path) were on average in the 2 % range. Further, the fully autonomous HAI hygrometer allows measurements up to 240 Hz with a minimal integration time of 1.4 ms. The best precision is achieved by the 1.4 µm closed-path cell at 3.8 Hz (0.18 ppmv) and by the 2.6 µm closed-path cell at 13 Hz (0.055 ppmv). The requirements, design, operation principle, and first in-flight performance of the hygrometer are described and discussed in this work.

TAM receptors Tyro3 and Mer as novel targets in colorectal cancer.

PubMed

Schmitz, Robin; Valls, Aida Freire; Yerbes, Rosario; von Richter, Sophie; Kahlert, Christoph; Loges, Sonja; Weitz, Jürgen; Schneider, Martin; Ruiz de Almodovar, Carmen; Ulrich, Alexis; Schmidt, Thomas

2016-08-30

CRC remains the third most common cancer worldwide with a high 5-year mortality rate in advanced cases. Combined with chemotherapy, targeted therapy is an additional treatment option. However as CRC still escapes targeted therapy the vigorous search for new targets is warranted to increase patients´ overall survival. In this study we describe a new role for Gas6/protein S-TAM receptor interaction in CRC. Gas6, expressed by tumor-infiltrating M2-like macrophages, enhances malignant properties of tumor cells including proliferation, invasion and colony formation. Upon chemotherapy macrophages increase Gas6 synthesis, which significantly attenuates the cytotoxic effect of 5-FU chemotherapy on tumor cells. The anti-coagulant protein S has similar effects as Gas6.In CRC patient samples Tyro3 was overexpressed within the tumor. In-vitro inhibition of Tyro3 and Mer reduces tumor cell proliferation and sensitizes tumor cells to chemotherapy. Moreover high expression of Tyro3 and Mer in tumor tissue significantly shortens CRC patients´ survival. Various in vitro models were used to investigate the role of Gas6 and its TAM receptors in human CRC cells, by stimulation (rhGas6) and knockdown (siRNA) of Axl, Tyro3 and Mer. In terms of a translational research, we additionally performed an expression analysis in human CRC tissue and analyzed the medical record of these patients. Tyro3 and Mer represent novel therapeutic targets in CRC and warrant further preclinical and clinical investigation in the future.

Qualitative and quantitative trait loci conditioning resistance to Puccinia coronata pathotypes NQMG and LGCG in the oat (Avena sativa L.) cultivars Ogle and TAM O-301.

PubMed

Jackson, E W; Obert, D E; Menz, M; Hu, G; Bonman, J M

2008-02-01

Mapping disease resistance loci relies on the type and precision of phenotypic measurements. For crown rust of oat, disease severity is commonly assessed based on visual ratings of infection types (IT) and/or diseased leaf area (DLA) of infected plants in the greenhouse or field. These data can be affected by several variables including; (i) non-uniform disease development in the field; (ii) atypical symptom development in the greenhouse; (iii) the presence of multiple pathogenic races or pathotypes in the field, and (iv) rating bias. To overcome these limitations, we mapped crown rust resistance to single isolates in the Ogle/TAM O-301 (OT) recombinant inbred line (RIL) population using detailed measurements of IT, uredinia length (UL) and relative fungal DNA (FDNA) estimates determined by q-PCR. Measurements were taken on OT parents and recombinant inbred lines (RIL) inoculated with Puccinia coronata pathotypes NQMG and LGCG in separate greenhouse and field tests. Qualitative mapping identified an allele conferred by TAM O-301 on linkage group (LG) OT-11, which produced a bleached fleck phenotype to both NQMG and LGCG. Quantitative mapping identified two major quantitative trait loci (QTL) originating from TAM O-301 on LGs OT-11 and OT-32 which reduced UL and FDNA of both isolates in all experiments. Additionally, minor QTLs that reduced UL and FDNA were detected on LGs OT-15 and OT-8, originating from TAM O-301, and on LG OT-27, originating from Ogle. Detailed assessments of the OT population using two pathotypes in both the greenhouse and field provided comprehensive information to effectively map the genes responsible for crown rust resistance in Ogle and TAM O-301 to NQMG and LGCG.

Validating the Satisfaction and Continuance Intention of E-Learning Systems: Combining TAM and IS Success Models

ERIC Educational Resources Information Center

Lin, Tung-Cheng; Chen, Ching-Jen

2012-01-01

Many e-learning studies have evaluated learning attitudes and behaviors, based on TAM. However, a successful e-learning system (ELS) should take both system and information quality into account by applying ISM developed by Delone and McLean. In addition, the acceptance for information system depends on the perceived usefulness and ease of use…

Anticancer effect of luteolin is mediated by downregulation of TAM receptor tyrosine kinases, but not interleukin-8, in non-small cell lung cancer cells.

PubMed

Lee, Youn Ju; Lim, Taeho; Han, Min Su; Lee, Sun-Hwa; Baek, Suk-Hwan; Nan, Hong-Yan; Lee, Chuhee

2017-02-01

TAM receptor tyrosine kinases (RTKs), Tyro3, Axl and MerTK, transduce diverse signals responsible for cell survival, growth, proliferation and anti-apoptosis. In the present study, we demonstrated the effect of luteolin, a flavonoid with antioxidant, anti-inflammatory and anticancer activities, on the expression and activation of TAM RTKs and the association with its cytotoxicity in non-small cell lung cancer (NSCLC) cells. We observed the cytotoxic effect of luteolin in parental A549 and H460 cells as well as in cisplatin-resistant A549/CisR and H460/CisR cells. Exposure of these cells to luteolin also resulted in a dose‑dependent decrease in clonogenic ability. Next, luteolin was found to decrease the protein levels of all three TAM RTKs in the A549 and A549/CisR cells in a dose‑dependent manner. In a similar manner, in H460 and H460/CisR cells, the protein levels of Axl and Tyro3 were decreased following luteolin treatment. In addition, Axl promoter activity was decreased by luteolin, indicating that luteolin suppresses Axl expression at the transcriptional level. We next found that luteolin abrogated Axl phosphorylation in response to growth arrest-specific 6 (Gas6), its ligand, implying the inhibitory effect of luteolin on Gas6-induced Axl activation. Ectopic expression of Axl was observed to attenuate the antiproliferative effect of luteolin, while knockdown of the Axl protein level using a gold nanoparticle-assisted gene delivery system increased its cytotoxicity. In contrast to the inhibitory effect of luteolin on the expression of TAM RTKs, interleukin-8 (IL-8) production was not decreased by luteolin in H460 and H460/CisR cells, while IL-8 production/cell was increased. Collectively, our data suggest that TAM RTKs, but not IL-8, are promising therapeutic targets of luteolin to abrogate cell proliferation and to overcome chemoresistance in NSCLC cells.

Vitamin K-dependent proteins GAS6 and Protein S and TAM receptors in patients of systemic lupus erythematosus: correlation with common genetic variants and disease activity.

PubMed

Recarte-Pelz, Pedro; Tàssies, Dolors; Espinosa, Gerard; Hurtado, Begoña; Sala, Núria; Cervera, Ricard; Reverter, Joan Carles; de Frutos, Pablo García

2013-03-12

Growth arrest-specific gene 6 protein (GAS6) and protein S (ProS) are vitamin K-dependent proteins present in plasma with important regulatory functions in systems of response and repair to damage. They interact with receptor tyrosine kinases of the Tyro3, Axl and MerTK receptor tyrosine kinase (TAM) family, involved in apoptotic cell clearance (efferocytosis) and regulation of the innate immunity. TAM-deficient mice show spontaneous lupus-like symptoms. Here we tested the genetic profile and plasma levels of components of the system in patients with systemic lupus erythematosus (SLE), and compare them with a control healthy population. Fifty SLE patients and 50 healthy controls with matched age, gender and from the same geographic area were compared. Genetic analysis was performed in GAS6 and the TAM receptor genes on SNPs previously identified. The concentrations of GAS6, total and free ProS, and the soluble forms of the three TAM receptors (sAxl, sMerTK and sTyro3) were measured in plasma from these samples. Plasma concentrations of GAS6 were higher and, total and free ProS were lower in the SLE patients compared to controls, even when patients on oral anticoagulant treatment were discarded. Those parameters correlated with SLE disease activity index (SLEDAI) score, GAS6 being higher in the most severe cases, while free and total ProS were lower. All 3 soluble receptors increased its concentration in plasma of lupus patients. The present study highlights that the GAS6/ProS-TAM system correlates in several ways with disease activity in SLE. We show here that this correlation is affected by common polymorphisms in the genes of the system. These findings underscore the importance of mechanism of regulatory control of innate immunity in the pathology of SLE.

Vitamin K-dependent proteins GAS6 and Protein S and TAM receptors in patients of systemic lupus erythematosus: correlation with common genetic variants and disease activity

PubMed Central

2013-01-01

Introduction Growth arrest-specific gene 6 protein (GAS6) and protein S (ProS) are vitamin K-dependent proteins present in plasma with important regulatory functions in systems of response and repair to damage. They interact with receptor tyrosine kinases of the Tyro3, Axl and MerTK receptor tyrosine kinase (TAM) family, involved in apoptotic cell clearance (efferocytosis) and regulation of the innate immunity. TAM-deficient mice show spontaneous lupus-like symptoms. Here we tested the genetic profile and plasma levels of components of the system in patients with systemic lupus erythematosus (SLE), and compare them with a control healthy population. Methods Fifty SLE patients and 50 healthy controls with matched age, gender and from the same geographic area were compared. Genetic analysis was performed in GAS6 and the TAM receptor genes on SNPs previously identified. The concentrations of GAS6, total and free ProS, and the soluble forms of the three TAM receptors (sAxl, sMerTK and sTyro3) were measured in plasma from these samples. Results Plasma concentrations of GAS6 were higher and, total and free ProS were lower in the SLE patients compared to controls, even when patients on oral anticoagulant treatment were discarded. Those parameters correlated with SLE disease activity index (SLEDAI) score, GAS6 being higher in the most severe cases, while free and total ProS were lower. All 3 soluble receptors increased its concentration in plasma of lupus patients. Conclusions The present study highlights that the GAS6/ProS-TAM system correlates in several ways with disease activity in SLE. We show here that this correlation is affected by common polymorphisms in the genes of the system. These findings underscore the importance of mechanism of regulatory control of innate immunity in the pathology of SLE. PMID:23497733

Social representation and practices related to dementia in Hai District of Tanzania.

PubMed

Mushi, Declare; Rongai, Amen; Paddick, Stella-Maria; Dotchin, Catherine; Mtuya, Chauka; Walker, Richard

2014-03-19

With the increasing number of people surviving into old age in Africa, dementia is becoming an important public health problem. Understanding the social dynamics of dementia in resource-poor settings is critical for developing effective interventions. We explored the socio-cultural beliefs surrounding dementia and the life experience of people with dementia (PWD) and their caregivers in the Hai District of Kilimanjaro, Tanzania. Cross-sectional qualitative design. Forty one PWD were purposively sampled from the Hai District of Kilimanjaro. Twenty five paired interviews with PWD and with caregivers, and 16 with caregivers alone, were conducted. Interviews were tape recorded, transcribed verbatim and analyzed using content analysis approach. Forty one PWD (26 females), aged 70 years and older, were recruited but due to speech difficulties only 25 participated in the interviews. Married were 13, widow in 22 and widower 6. The majority, 33/41 were illiterate. PWD and carers perceived memory problems as a normal part of ageing. Dementia was commonly referred as "ugonjwa wa uzeeni" (disease of old people) or memory loss disease. The majority of PWD 13/12 and carers 7/16 did not know what dementia is or what causes it. Dementia was felt to be associated with stroke, high blood pressure, diabetes, old age, curse/witchcraft and life stress. Half of the participants had used modern care and alternative care such as herbs, prayers or traditional healers. Caregivers complained about the burden of caring for PWD and suggested that community organizations should be involved in addressing the problem. Knowledge about dementia is low and the symptoms are accepted as a problem of old age. PWD and carers demonstrate pluralistic behaviour in seeking help from modern care, prayers and traditional healers. The disease adds significant burden to family members. Family and caregivers need more education on early recognition of symptoms and cost effective management of dementia at family

EPR Oximetry Sensor-Developing a TAM Derivative for In Vivo Studies.

PubMed

Boś-Liedke, Agnieszka; Walawender, Magdalena; Woźniak, Anna; Flak, Dorota; Gapiński, Jacek; Jurga, Stefan; Kucińska, Małgorzata; Plewiński, Adam; Murias, Marek; Elewa, Marwa; Lampp, Lisa; Imming, Peter; Tadyszak, Krzysztof

2018-06-01

Oxygenation is one of the most important physiological parameters of biological systems. Low oxygen concentration (hypoxia) is associated with various pathophysiological processes in different organs. Hypoxia is of special importance in tumor therapy, causing poor response to treatment. Triaryl methyl (TAM) derivative radicals are commonly used in electron paramagnetic resonance (EPR) as sensors for quantitative spatial tissue oxygen mapping. They are also known as magnetic resonance imaging (MRI) contrast agents and fluorescence imaging compounds. We report the properties of the TAM radical tris(2,3,5,6-tetrachloro-4-carboxy-phenyl)methyl, (PTMTC), a potential multimodal (EPR/fluorescence) marker. PTMTC was spectrally analyzed using EPR and characterized by estimation of its sensitivity to the oxygen in liquid environment suitable for intravenous injection (1 mM PBS, pH = 7.4). Further, fluorescent emission of the radical was measured using the same solvent and its quantum yield was estimated. An in vitro cytotoxicity examination was conducted in two cancer cell lines, HT-29 (colorectal adenocarcinoma) and FaDu (squamous cell carcinoma) and followed by uptake studies. The stability of the radical in different solutions (PBS pH = 7.4, cell media used for HT-29 and FaDu cells culturing and cytotoxicity procedure, full rat blood and blood plasma) was determined. Finally, a primary toxicity test of PTMTC was carried out in mice. Results of spectral studies confirmed the multimodal properties of PTMTC. PTMTC was demonstrated to be not absorbed by cancer cells and did not interfere with luciferin-luciferase based assays. Also in vitro and in vivo tests showed that it was non-toxic and can be freely administrated till doses of 250 mg/kg BW via both i.v. and i.p. injections. This work illustrated that PTMTC is a perfect candidate for multimodal (EPR/fluorescence) contrast agent in preclinical studies.

S100A9+ MDSC and TAM-mediated EGFR-TKI resistance in lung adenocarcinoma: the role of RELB.

PubMed

Feng, Po-Hao; Yu, Chih-Teng; Chen, Kuan-Yuan; Luo, Ching-Shan; Wu, Shen Ming; Liu, Chien-Ying; Kuo, Lu Wei; Chan, Yao-Fei; Chen, Tzu-Tao; Chang, Chih-Cheng; Lee, Chun-Nin; Chuang, Hsiao-Chi; Lin, Chiou-Feng; Han, Chia-Li; Lee, Wei-Hwa; Lee, Kang-Yun

2018-01-26

Monocytic myeloid-derived suppressor cells (MDSCs), particularly the S100A9+ subset, has been shown initial clinical relevance. However, its role in EGFR-mutated lung adenocarcinoma, especially to EGFR-tyrosine kinase inhibitor (EGFR-TKI) is not clear. In a clinical setting of EGFR mutated lung adenocarcinoma, a role of the MDSC apart from T cell suppression was also investigated. Blood monocytic S100A9 + MDSC counts were higher in lung cancer patients than healthy donors, and were associated with poor treatment response and shorter progression-free survival (PFS). S100A9 + MDSCs in PBMC were well correlated to tumor infiltrating CD68 + and S100A9 + cells, suggesting an origin of TAMs. Patient's MDMs, mostly from S100A9 + MDSC, similar to primary alveolar macrophages from patients, both expressed S100A9 and CD206, attenuated EGFR-TKI cytotoxicity. Microarray analysis identified up-regulation of the RELB signaling genes, confirmed by Western blotting and functionally by RELB knockdown. In conclusion, blood S100A9 + MDSC is a predictor of poor treatment response to EGFR-TKI, possibly via its derived TAMs through activation of the non-canonical NF-κB RELB pathway. Patients with activating EGFR mutation lung adenocarcinoma receiving first line EGFR TKIs were prospectively enrolled. Peripheral blood mononuclear cells (PBMCs) were collected for MDSCs analysis and for monocyte-derived macrophages (MDMs) and stored tissue for TAM analysis by IHC. A transwell co-culture system of MDMs/macrophages and H827 cells was used to detect the effect of macrophages on H827 and microarray analysis to explore the underlying molecular mechanisms, functionally confirmed by RNA interference.

Phosphatidylserine Is the Signal for TAM Receptors and Their Ligands.

PubMed

Lemke, Greg

2017-09-01

Nature repeatedly repurposes, in that molecules that serve as metabolites, energy depots, or polymer subunits are at the same time used to deliver signals within and between cells. The preeminent example of this repurposing is ATP, which functions as a building block for nucleic acids, an energy source for enzymatic reactions, a phosphate donor to regulate intracellular signaling, and a neurotransmitter to control the activity of neurons. A series of recent studies now consolidates the view that phosphatidylserine (PtdSer), a common phospholipid constituent of membrane bilayers, is similarly repurposed for use as a signal between cells and that the ligands and receptors of the Tyro3/Axl/Mer (TAM) family of receptor tyrosine kinases (RTKs) are prominent transducers of this signal. Copyright © 2017 Elsevier Ltd. All rights reserved.

Consumer acceptance of a quick response (QR) code for the food traceability system: Application of an extended technology acceptance model (TAM).

PubMed

Kim, Yeong Gug; Woo, Eunju

2016-07-01

The objectives of this study are to apply the TAM using the addition of perceived information to individuals' behavioral intention to use the QR code for the food traceability system; and to determine the moderating effects of food involvement on the relationship between perceived information and perceived usefulness. Results from a survey of 420 respondents are analyzed using structural equation modeling. The study findings reveal that the extended TAM has a satisfactory fit to the data and that the underlying dimensions have a significant effect on consumers' intention to use the QR code for the food traceability system. In addition, food involvement plays a significant moderating function in the relationship between perceived information and perceived usefulness. The implications of this study for future research are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Review of the CDC Recommendations for Prevention of HAIs in Outpatient Settings.

PubMed

Garrett, J Hudson

2015-05-01

According to the Centers for Disease Control and Prevention (CDC), most health care-associated infections (HAIs) are caused by contamination from the hands of health care providers or patients, contamination from the environment, and contamination from the patient's own skin. To mitigate common sources of infection transmission, frontline health care providers must be compliant with basic infection-prevention interventions, including hand hygiene, environmental cleaning and disinfection, safe injection practices, and designation of a trained health care professional to be responsible for the infection prevention and control program. Integration of CDC recommendations should incorporate a bundled approach to these interventions and should be part of a comprehensive approach to infection prevention and control. Effective infection-prevention practices in outpatient settings are critical for reducing the risk of infection transmission, improving patient safety and patient outcomes, and reducing costs associated with health care delivery. Copyright © 2015 AORN, Inc. Published by Elsevier Inc. All rights reserved.

Investigating the Effect of Learning Styles in a Blended E-Learning System: An Extension of the Technology Acceptance Model (TAM)

ERIC Educational Resources Information Center

Al-Azawei, Ahmed; Parslow, Patrick; Lundqvist, Karsten

2017-01-01

This study assesses learner perceptions of a blended e-learning system (BELS) and the feasibility of accommodating educational hypermedia systems (EHSs) according to learning styles using a modified version of the technology acceptance model (TAM). Recently, Moodle has been adopted by an Iraqi university alongside face-to-face (F2F) classrooms to…

Knowledge, attitude and practices on family planning services among adolescents in secondary schools in Hai District, northern Tanzania.

PubMed

Dangat, Celina M; Njau, Bernard

2013-01-01

Almost 65% of the Tanzanian population is under the age of 24 and almost 20 % of the population is aged 15-24 years. Yet, this important group faces many significant health challenges, such as early sexual debut, early pregnancies, risky behaviours and sexually transmitted infections. The objective of this study was to assess knowledge, attitudes and practices on family planning services among adolescents in secondary schools in Hai District in northern Tanzania. A cross sectional study was conducted between April and June 2011 among 316 randomly selected students in 10 secondary schools using a self administered pre-tested questionnaire. Median age of participants was 17 years (15-19 years). Two-thirds (67.4%) of the respondents had adequate level of knowledge on family planning services (FPS) and the most popular source of information was the radio (65.8 %). Being in a lower class (χ2 =8.6; P<0.02) and attending co education schools (χ2 =12.9; P< 0.001) were predictors of inadequate level of knowledge on FPS. Most, 71.2% (225/316) respondents reported that FPS should not be used by adolescents and mentioned several reasons against its use. Less than 6 % (18/316) of all respondents had used FPS in their lifetime, with 44.4 % (8/18) in the past month, 33.3 %(6/18) in the past year, and 22.3 % (4/18) in the past 5 years. In conclusion, most secondary school students in Hai District do not utilize family planning services despite of adequate level of knowledge on FPS. Interventions to improve utilization of FPS among secondary school students should address barriers to low utilization of FPS mentioned in this study.

Investigation of Kelvin wave periods during Hai-Tang typhoon using Empirical Mode Decomposition

NASA Astrophysics Data System (ADS)

Kishore, P.; Jayalakshmi, J.; Lin, Pay-Liam; Velicogna, Isabella; Sutterley, Tyler C.; Ciracì, Enrico; Mohajerani, Yara; Kumar, S. Balaji

2017-11-01

Equatorial Kelvin waves (KWs) are fundamental components of the tropical climate system. In this study, we investigate Kelvin waves (KWs) during the Hai-Tang typhoon of 2005 using Empirical Mode Decomposition (EMD) of regional precipitation, zonal and meridional winds. For the analysis, we use daily precipitation datasets from the Global Precipitation Climatology Project (GPCP) and wind datasets from the European Centre for Medium-Range Weather Forecasts (ECMWF) Interim Re-analysis (ERA-Interim). As an additional measurement, we use in-situ precipitation datasets from rain-gauges over the Taiwan region. The maximum accumulated precipitation was approximately 2400 mm during the period July 17-21, 2005 over the southwestern region of Taiwan. The spectral analysis using the wind speed at 950 hPa found in the 2nd, 3rd, and 4th intrinsic mode functions (IMFs) reveals prevailing Kelvin wave periods of ∼3 days, ∼4-6 days, and ∼6-10 days, respectively. From our analysis of precipitation datasets, we found the Kelvin waves oscillated with periods between ∼8 and 20 days.

Heavy metals in estuarine surface sediments of the Hai River Basin, variation characteristics, chemical speciation and ecological risk.

PubMed

Lei, Pei; Zhang, Hong; Shan, Baoqing; Lv, Shucong; Tang, Wenzhong

2016-04-01

The Hai River Basin (HRB) is considered to be one of the most polluted areas in China due to the high regional population density and rapid economic development. The estuaries of the HRB, which receive pollutants from terrestrial rivers, may subsequently suffer potential pollution and result in ecological risk of heavy metals. Six heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn) were measured in estuarine surface sediments from 10 estuaries of the HRB to investigate their variation characteristics and ecological risks. The spatial difference of Cr, Ni, Pb, and Zn in sediments was higher than that of the rest two elements. The Yongdingxin Estuary (YDX) and Ziyaxin Estuary (ZYX) in the Northern Hai River System (NHRS) were the most severe in terms of heavy metal contamination. According to the Risk Assessment Code (RAC) classification, Cd associated with the exchangeable and carbonate fraction (the average of 21.3 %) indicated medium risk to high risk. More than 50 % of Cr, Cu, Ni, and Zn on average were associated with the residual fraction. Based on the sum of the first three fractions (exchangeable and carbonate + reducible + oxidizable), the mobility order of these heavy metals was Cd >Pb > Zn ≈ Cu > Ni > Cr. Compared to the background values of cinnamon soil, the potential ecological risk index (RI) values ranged from 25.6 to 168, with an average of 91.2, indicating a low ecological risk in estuarine sites of the HRB. Cd and Pb were the dominant contributors to the toxic-response factor (45.8 and 25.5 %, respectively). The results give insight into the different control measures pertaining to heavy metal pollution and risk for both relatively clean estuaries and urban seriously polluted areas, respectively, for the formation of protect strategies of aquatic environment in the HRB.

Exploring the Intrinsic Motivation of Hedonic Information Systems Acceptance: Integrating Hedonic Theory and Flow with TAM

NASA Astrophysics Data System (ADS)

Wang, Zhihuan

Research on Information Systems (IS) acceptance is substantially focused on extrinsic motivation in workplaces, little is known about the underlying intrinsic motivations of Hedonic IS (HIS) acceptance. This paper proposes a hybrid HIS acceptance model which takes the unique characteristics of HIS and multiple identities of a HIS user into consideration by interacting Hedonic theory, Flow theory with Technology Acceptance Model (TAM). The model was empirically tested by a field survey. The result indicates that emotional responses, imaginal responses, and flow experience are three main contributions of HIS acceptance.

Arsenic and other trace elements in groundwater and human urine in Ha Nam province, the Northern Vietnam: contamination characteristics and risk assessment.

PubMed

Pham, Long Hai; Nguyen, Hue Thi; Van Tran, Cuong; Nguyen, Ha Manh; Nguyen, Tung Hoang; Tu, Minh Binh

2017-06-01

The contamination characteristics of arsenic and other trace elements in groundwater and the potential risks of arsenic from the groundwater were investigated. Elevated contamination of arsenic, barium and manganese was observed in tube-well water of two villages (Chuyen Ngoai and Chau Giang) in Ha Nam province in the Northern Vietnam. Concentrations of As in the groundwater ranged from 12.8 to 884 µg/L with mean values in Chuyen Ngoai and Chau Giang were 614.7 and 160.1 µg/L, respectively. About 83 % of these samples contained As concentrations exceeding WHO drinking water guideline of 10 μg/L. The mean values of Mn and Ba in groundwater from Chuyen Ngoai and Chau Giang were 300 and 657 μg/L and 650 and 468 μg/L, respectively. The mean value of Ba concentration in groundwater in both Chuyen Ngoai and Chau Giang was about 22 % of the samples exceeded the WHO guideline (700 µg/L). Arsenic concentrations in human urine of residents from Chuyen Ngoai and Chau Giang were the range from 8.6 to 458 µg/L. The mean values of Mn and Ba in human urine of local people from Chuyen Ngoai were 46.9 and 62.8 μg/L, respectively, while those in people from Chau Giang were 25.9 and 45.9 μg/L, respectively. The average daily dose from ingesting arsenic for consuming both untreated and treated groundwater is from 0.02 to 11.5 and 0.003 to 1.6 μg/kg day, respectively. Approximately, 57 % of the families using treated groundwater and 64 % of the families using untreated groundwater could be affected by elevated arsenic exposure.

Etude du risque d'inondation en aval du delta du fleuve rouge en utilisant la teledetection et les sig: Le cas du district de Bac Hung Hai

NASA Astrophysics Data System (ADS)

Bui, Duc Viet

The Bac Hung Hai zone is the greatest basin in the Red River Delta in Vietnam and also one of the most densely populated regions of the planet. It is mainly a rural region and its economy is dominated by agriculture. In the context of frequent and larger floods in the Bac Hung Hai zone, causing deep socio-economical consequences, the focus of this study is to establish cartography of the high risk areas for flooding in the Bac Hung Hai region using remote sensing and GIS to assist land management. The preparation of a map describing land management in this region is more complicated because parcels for farming are very small and not homogeneous. A consistent and precise map of land use is essential for studies of flooding. The secondary objective is to improve the land use map. To this effect, a classification has been applied to the combination of the spectral bands and textures (TM and ETM+) of Landsat and a radar image (ERS). The addition of this information to the spectral bands increases the accuracy of classification by 1% to 4%, according to the dates selected. Additionally, in the study zone where there are few days without clouds, a problem related to the optical satellite image is the cloud cover. Then, the use of radar images will provide ground information for areas hidden by clouds where spectral images are not sufficient. To reach these goals, we have determined the main biophysical considerations that influence flooding. Then, these considerations have been combined in a multi-criteria analysis to evaluate the risks of flooding in the entire basin area. The results show that high to very high risks affect 47% of the area studied and that the south-east region, center, and north-east present the greatest risk. Keywords. Flood risks, remote sensing, GIS, land use, multicriteria analysis, Red river delta, Vietnam.

American Confederation of Urology (CAU) experience in minimally invasive partial nephrectomy.

PubMed

Secin, Fernando P; Castillo, Octavio A; Rozanec, José J; Featherston, Marcelo; Holst, Pablo; Milfont, José Cocisfran Alves; García Marchiñena, Patricio; Jurado Navarro, Alberto; Autrán, Anamaría; Rovegno, Agustín R; Faba, Oscar Rodríguez; Palou, Joan; Teixeira Dubeux, Victor; Nuñez Bragayrac, Luciano; Sotelo, Rene; Zequi, Stenio; Guimarães, Gustavo Cardoso; Álvarez-Maestro, Mario; Martínez-Piñeiro, Luis; Villoldo, Gustavo; Villaronga, Alberto; Abreu Clavijo, Diego; Decia, Ricardo; Frota, Rodrigo; Vidal-Mora, Ivar; Finkelstein, Diana; Monzó Gardiner, Juan I; Schatloff, Oscar; Hernández-Porrás, Andres; Santaella-Torres, Félix; Quesada, Emilio T; Sánchez-Salas, Rodolfo; Dávila, Hugo; Mavric, Humberto Villavicencio

2017-01-01

To describe the perioperative and oncology outcomes in a series of laparoscopic or robotic partial nephrectomies (PN) for renal tumors treated in diverse institutions of Hispanic America from the beginning of their minimally invasive (MI) PN experience through December 2014. Seventeen institutions participated in the CAU generated a MI PN database. We estimated proportions, medians, 95 % confidence intervals, Kaplan-Meier curves, multivariate logistic and Cox regression analyses. Clavien-Dindo classification was used. We evaluated 1501 laparoscopic (98 %) or robotic (2 %) PNs. Median age: 58 years. Median surgical time, warm ischemia and intraoperative bleeding were 150, 20 min and 200 cc. 81 % of the lesions were malignant, with clear cell histology being 65 % of the total. Median maximum tumor diameter is 2.7 cm, positive margin is 8.2 %, and median hospitalization is 3 days. One or more postoperative complication was recorded in 19.8 % of the patients: Clavien 1: 5.6 %; Clavien 2: 8.4 %; Clavien 3A: 1.5 %; Clavien 3B: 3.2 %; Clavien 4A: 1 %; Clavien 4B: 0.1 %; Clavien 5: 0 %. Bleeding was the main cause of a reoperation (5.5 %), conversion to radical nephrectomy (3 %) or open partial nephrectomy (6 %). Transfusion rate is 10 %. In multivariate analysis, RENAL nephrometry score was the only variable associated with complications (OR 1.1; 95 % CI 1.02-1.2; p = 0.02). Nineteen patients presented disease progression or died of disease in a median follow-up of 1.37 years. The 5-year progression or kidney cancer mortality-free rate was 94 % (95 % CI 90, 97). Positive margins (HR 4.98; 95 % CI 1.3-19; p = 0.02) and females (HR 5.6; 95 % CI 1.7-19; p = 0.005) were associated with disease progression or kidney cancer mortality after adjusting for maximum tumor diameter. Laparoscopic PN in these centers of Hispanic America seem to have acceptable perioperative complications and short-term oncologic outcomes.

Berberine enhances the anti‑tumor activity of tamoxifen in drug‑sensitive MCF‑7 and drug‑resistant MCF‑7/TAM cells.

PubMed

Wen, Chunjie; Wu, Lanxiang; Fu, Lijuan; Zhang, Xue; Zhou, Honghao

2016-09-01

Berberine, an isoquinoline alkaloid, has been previously demonstrated to possess anti‑breast cancer properties. Tamoxifen is widely used in the prevention and treatment of estrogen receptor-positive breast cancer. Thus, the aim of the present study was to assess whether berberine enhanced the anticancer effect of tamoxifen, and the underlying mechanism involved in this combined effect in tamoxifen-sensitive (MCF-7) and tamoxifen-resistant (MCF-7/TAM) cells using MTS, flow cytometry and western blot assays. The results indicated that berberine demonstrated dose‑ and time‑dependent anti‑proliferative activity in MCF‑7 and MCF‑7/TAM cells. Furthermore, the combination of berberine and tamoxifen induced cell growth inhibition more effectively than tamoxifen alone. The present study also demonstrated that combinational treatment is more effective in inducing G1 phase arrest and activating apoptosis compared tamoxifen alone, which may be due to upregulation of P21 expression and downregulation of the B‑cell CLL/lymphoma 2(Bcl‑2)/Bcl‑2 associated X protein ratio. The results of the present study suggested that berberine may potentially be useful as an adjuvant agent in cancer chemotherapy to enhance the effect of tamoxifen, which will be useful for anti‑tumor therapy and further research.

A Qualitative Case Study to Investigate the Technology Acceptance Experience Outlined in the TAM Using the Kubler-Ross Stages of Grieving and Acceptance

ERIC Educational Resources Information Center

Sotelo, Benjamin Eladio

2015-01-01

The Technology Acceptance Model (TAM) has been an important model for the understanding of end user acceptance regarding technology and a framework used in thousands of researched scenarios since publication in 1986. Similarly, the Kubler-Ross model of death and dying has also been used as a model for the study of acceptance within the medical…

Assessing the Intention to Use Technology among Pre-Service Teachers in Singapore and Malaysia: A Multigroup Invariance Analysis of the Technology Acceptance Model (TAM)

ERIC Educational Resources Information Center

Teo, Timothy; Lee, Chwee Beng; Chai, Ching Sing; Wong, Su Luan

2009-01-01

This study assesses the pre-service teachers' self-reported future intentions to use technology in Singapore and Malaysia. A survey was employed to validate items from past research. Using the Technology Acceptance Model (TAM) as a research framework, 495 pre-service teachers from Singapore and Malaysia responded to an 11-item questionnaires…

Low Carbon Rice Farming Practices in the Mekong Delta Yield Significantly Higher Profits and Lower Greenhouse Gas Emissions

NASA Astrophysics Data System (ADS)

Rudek, J.; Van Sanh, N.; Tinh, T. K.; Tin, H. Q.; Thu Ha, T.; Pha, D. N.; Cui, T. Q.; Tin, N. H.; Son, N. N.; Thanh, H. H.; Kien, H. T.; Kritee, K.; Ahuja, R.

2014-12-01

The Vietnam Low-Carbon Rice Project (VLCRP) seeks to significantly reduce GHG emissions from rice cultivation, an activity responsible for more than 30% of Vietnam's overall GHG emissions, while improving livelihoods for the rice farmer community by decreasing costs and enhancing yield as well as providing supplemental farmer income through the sale of carbon credits. The Mekong Delta makes up 12% of Vietnam's land area, but produces more than 50% of the country's rice, including more than 90% of the rice for export. Rice cultivation is the main source of income for 80% of farmers in the Mekong Delta. VLCRP was launched in late 2012 in the Mekong Delta in two major rice production provinces, Kien Giang and An Giang. To date, VLCRP has completed 11 crop seasons (in Kien Giang and An Giang combined), training over 400 farmer households in applying VLCRP's package of practices (known as 1 Must - 6 Reductions) and building technical capacity to its key stakeholders and rice farmer community leaders. By adopting the 1 Must- 6 Reductions practices (including reduced seeding density, reduced fertilizer and pesticide application, and alternative wetting and drying water management), rice farmers reduce their input costs while maintaining or improving yields, and decreasing greenhouse gas emissions. The VLCRP package of practices also deliver other environmental and social co-benefits, such as reduced water pollution, improved habitat for fishery resources and reduced health risks for farmers through the reduction of agri-chemicals. VLCRP farmers use significantly less inputs (50% reduction in seed, 30% reduction in fertilizer, 40-50% reduction in water) while improving yields 5-10%, leading to an increase in profit from 10% to as high as 60% per hectare. Preliminary results indicate that the 1 Must- 6 Reductions practices have led to approximately 40-65% reductions in greenhouse gas emissions, equivalent to 4 tons of CO2e/ha/yr in An Giang and 35 tons of CO2e/ha/yr in KienGiang

Closure Report (CR) for Corrective Action Unit (CAU) 91: Area 3 U-3fi Injection Well with Errata Sheet and Certification, Revision 0

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

Navarro Nevada Environmental Services

The closure report for CAU 91 has no Use Restriction Form or drawing/map included in the document to describe the use restricted area, however, Section 3.3.3 states that the site will be fenced and signage placed indicating the area as a Resource Conservation and Recovery Act (RCRA) Unit. The drawing that was placed in the FFACO indicating the use restricted area lists the coordinates for the RCRA Unit in Nevada State Plan Coordinates - North American Datum of 1983. In the ensuing years the reporting of coordinates has been standardized so that all coordinates are reported in the same manner,more » which is: NAD 27 UTM Zone 11 N, meters. This Errata Sheet updates the coordinate reporting to the currently accepted method and includes an aerial photo showing the RCRA Unit with the coordinates listed showing the use restricted area.« less

STUDY ON BIOLOGICAL CHARACTERISTICS OF HETEROTROPHIC MARINE MICROALGA-SCHIZOCHYTRIUM MANGROVEI PQ6 ISOLATED FROM PHU QUOC ISLAND, KIEN GIANG PROVINCE, VIETNAM(1).

PubMed

Hong, Dang Diem; Anh, Hoang Thi Lan; Thu, Ngo Thi Hoai

2011-08-01

Schizochytrium sp. PQ6, a heterotrophic microalga isolated from Phu Quoc (PQ) Island in the Kien Giang province of Vietnam, contains a high amount of docosahexaenoic acid (DHA, C22:6n-3). In this study, the culture conditions are developed to maximize biomass and DHA production. Nucleotide sequence analysis of partial 18S rRNA gene from genomic DNA showed that PQ6 has a phylogenetic relationship close to Schizochytrium mangrovei Raghu-Kumar. The highest growth rate and DHA accumulation of this strain were obtained in 6.0% glucose, 1.0% yeast extract, 50% artificial seawater (ASW), and pH 7 at 28°C. In addition, carbon and nitrogen sources could be replaced by glycerol, ammonium acetate, sodium nitrate, or fertilizer N-P-K. Total lipid content reached 38.67% of dry cell weight (DCW), in which DHA and eicosapentaenoic acid (EPA, C20:5n-3) contents accounted for 43.58% and 0.75% of the total fatty acid (TFA), respectively. In 5 and 10 L fermenters, the cell density, DCW, total lipid content, and maximum DHA yield were 46.50 × 10(6)  cells · mL(-1) , 23.7 g · L(-1) , 38.56% of DCW, and 8.71 g · L(-1) (in 5 L fermenter), respectively, and 49.71 × 10(6)  cells · mL(-1) , 25.34 g · L(-1) , 46.23% of DCW, and 11.55 g · L(-1) (in 10 L fermenter), respectively. Biomass of PQ6 strain possessed high contents of Na, I, and Fe (167.185, 278.3, and 43.69 mg · kg(-1) DCW, respectively). These results serve as a foundation for the efficient production of PQ6 biomass that can be used as a food supplement for humans and aquaculture in the future. © 2011 Phycological Society of America.

Experimental screening of porous materials for high pressure gas adsorption and evaluation in gas separations: application to MOFs (MIL-100 and CAU-10).

PubMed

Wiersum, Andrew D; Giovannangeli, Christophe; Vincent, Dominique; Bloch, Emily; Reinsch, Helge; Stock, Norbert; Lee, Ji Sun; Chang, Jong-San; Llewellyn, Philip L

2013-02-11

A high-throughput gas adsorption apparatus is presented for the evaluation of adsorbents of interest in gas storage and separation applications. This instrument is capable of measuring complete adsorption isotherms up to 40 bar on six samples in parallel using as little as 60 mg of material. Multiple adsorption cycles can be carried out and four gases can be used sequentially, giving as many as 24 adsorption isotherms in 24 h. The apparatus has been used to investigate the effect of metal center (MIL-100) and functional groups (CAU-10) on the adsorption of N(2), CO(2), and light hydrocarbons on MOFs. This demonstrates how it can serve to evaluate sample quality and adsorption reversibility, to determine optimum activation conditions and to estimate separation properties. As such it is a useful tool for the screening of novel adsorbents for different applications in gas separation, providing significant time savings in identifying potentially interesting materials.

Beetle and plant arrow poisons of the Ju|'hoan and Hai||om San peoples of Namibia (Insecta, Coleoptera, Chrysomelidae; Plantae, Anacardiaceae, Apocynaceae, Burseraceae).

PubMed

Chaboo, Caroline S; Biesele, Megan; Hitchcock, Robert K; Weeks, Andrea

2016-01-01

The use of archery to hunt appears relatively late in human history. It is poorly understood but the application of poisons to arrows to increase lethality must have occurred shortly after developing bow hunting methods; these early multi-stage transitions represent cognitive shifts in human evolution. This paper is a synthesis of widely-scattered literature in anthropology, entomology, and chemistry, dealing with San ("Bushmen") arrow poisons. The term San (or Khoisan) covers many indigenous groups using so-called 'click languages' in southern Africa. Beetles are used for arrow poison by at least eight San groups and one non-San group. Fieldwork and interviews with Ju|'hoan and Hai||om hunters in Namibia revealed major differences in the nature and preparation of arrow poisons, bow and arrow construction, and poison antidote. Ju|'hoan hunters use leaf-beetle larvae of Diamphidia Gerstaecker and Polyclada Chevrolat (Chrysomelidae: Galerucinae: Alticini) collected from soil around the host plants Commiphora africana (A. Rich.) Engl. and Commiphora angolensis Engl. (Burseracaeae). In the Nyae Nyae area of Namibia, Ju|'hoan hunters use larvae of Diamphidia nigroornata Ståhl. Larvae and adults live above-ground on the plants and eat leaves, but the San collect the underground cocoons to extract the mature larvae. Larval hemolymph is mixed with saliva and applied to arrows. Hai||om hunters boil the milky plant sap of Adenium bohemianum Schinz (Apocynaceae) to reduce it to a thick paste that is applied to their arrows. The socio-cultural, historical, and ecological contexts of the various San groups may determine differences in the sources and preparation of poisons, bow and arrow technology, hunting behaviors, poison potency, and perhaps antidotes.

Risk Behaviors for HIV and HCV Infection Among People Who Inject Drugs in Hai Phong, Viet Nam, 2014.

PubMed

Duong, Huong Thi; Jarlais, Don Des; Khuat, Oanh Hai Thi; Arasteh, Kamyar; Feelemyer, Jonathan; Khue, Pham Minh; Giang, Hoang Thi; Laureillard, Didier; Hai, Vinh Vu; Vallo, Roselyne; Michel, Laurent; Moles, Jean Pierre; Nagot, Nicolas

2017-06-13

We examined the potential for HIV and hepatitis C (HCV) transmission across persons who inject drugs (PWID), men-who-have-sex-with-men (MSM) and female commercial sex workers (CSW) PWID and the potential for sexual transmission of HIV from PWID to the general population in Hai Phong, Viet Nam. Using respondent driven and convenience sampling we recruited 603 participants in 2014. All participants used heroin; 24% used non-injected methamphetamine. HIV prevalence was 25%; HCV prevalence was 67%. HIV infection was associated with HCV prevalence and both infections were associated with length of injecting career. Reported injecting risk behaviors were low; unsafe sexual behavior was high among MSM-PWID and CSW-PWID. There is strong possibility of sexual transmission to primary partners facilitated by methamphetamine use. We would suggest future HIV prevention programs utilize multiple interventions including "treatment as prevention" to potential sexual transmission of HIV among MSM and CSW-PWID and from PWID to the general population.

The Technology Acceptance Model for Resource-Limited Settings (TAM-RLS): A Novel Framework for Mobile Health Interventions Targeted to Low-Literacy End-Users in Resource-Limited Settings.

PubMed

Campbell, Jeffrey I; Aturinda, Isaac; Mwesigwa, Evans; Burns, Bridget; Santorino, Data; Haberer, Jessica E; Bangsberg, David R; Holden, Richard J; Ware, Norma C; Siedner, Mark J

2017-11-01

Although mobile health (mHealth) technologies have shown promise in improving clinical care in resource-limited settings (RLS), they are infrequently brought to scale. One limitation to the success of many mHealth interventions is inattention to end-user acceptability, which is an important predictor of technology adoption. We conducted in-depth interviews with 43 people living with HIV in rural Uganda who had participated in a clinical trial of a short messaging system (SMS)-based intervention designed to prompt return to clinic after an abnormal laboratory test. Interviews focused on established features of technology acceptance models, including perceived ease of use and perceived usefulness, and included open-ended questions to gain insight into unexplored issues related to the intervention's acceptability. We used conventional (inductive) and direct content analysis to derive categories describing use behaviors and acceptability. Interviews guided development of a proposed conceptual framework, the technology acceptance model for resource-limited settings (TAM-RLS). This framework incorporates both classic technology acceptance model categories as well as novel factors affecting use in this setting. Participants described how SMS message language, phone characteristics, and experience with similar technologies contributed to the system's ease of use. Perceived usefulness was shaped by the perception that the system led to augmented HIV care services and improved access to social support from family and colleagues. Emergent themes specifically related to mHealth acceptance among PLWH in Uganda included (1) the importance of confidentiality, disclosure, and stigma, and (2) the barriers and facilitators downstream from the intervention that impacted achievement of the system's target outcome. The TAM-RLS is a proposed model of mHealth technology acceptance based upon end-user experiences in rural Uganda. Although the proposed model requires validation, the TAM

Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury.

PubMed

Brosius Lutz, Amanda; Chung, Won-Suk; Sloan, Steven A; Carson, Glenn A; Zhou, Lu; Lovelett, Emilie; Posada, Sean; Zuchero, J Bradley; Barres, Ben A

2017-09-19

Ineffective myelin debris clearance is a major factor contributing to the poor regenerative ability of the central nervous system. In stark contrast, rapid clearance of myelin debris from the injured peripheral nervous system (PNS) is one of the keys to this system's remarkable regenerative capacity, but the molecular mechanisms driving PNS myelin clearance are incompletely understood. We set out to discover new pathways of PNS myelin clearance to identify novel strategies for activating myelin clearance in the injured central nervous system, where myelin debris is not cleared efficiently. Here we show that Schwann cells, the myelinating glia of the PNS, collaborate with hematogenous macrophages to clear myelin debris using TAM (Tyro3, Axl, Mer) receptor-mediated phagocytosis as well as autophagy. In a mouse model of PNS nerve crush injury, Schwann cells up-regulate TAM phagocytic receptors Axl and Mertk following PNS injury, and Schwann cells lacking both of these phagocytic receptors exhibit significantly impaired myelin phagocytosis both in vitro and in vivo. Autophagy-deficient Schwann cells also display reductions in myelin clearance after mouse nerve crush injury, as has been recently shown following nerve transection. These findings add a mechanism, Axl/Mertk-mediated myelin clearance, to the repertoire of cellular machinery used to clear myelin in the injured PNS. Given recent evidence that astrocytes express Axl and Mertk and have previously unrecognized phagocytic potential, this pathway may be a promising avenue for activating myelin clearance after CNS injury.

Highly efficient and porous TiO2-coated Ag@Fe3O4@C-Au microspheres for degradation of organic pollutants

NASA Astrophysics Data System (ADS)

Shen, Mao; Chen, Suqing; Jia, Wenping; Fan, Guodong; Jin, Yanxian; Liang, Huading

2016-12-01

In this paper, we reported a novel hierarchical porous Ag@Fe3O4@C-Au@TiO2 core@shell microspheres with a highly photocatalytic activity and magnetically separable properties. The synthesis method is included of a Fe3O4 magnetic embedded Ag core (Ag@Fe3O4), an interlayer of carbon modified by PEI to form sufficient amounts of amine functional groups (Ag@Fe3O4@C-PEI), the grafting of Au nanoparticles on the surface of Ag@Fe3O4@C-PEI (Ag@Fe3O4@C-Au), and an ordered porous TiO2 structured shell. As an example of the applications, the photocatalytic activities of the samples were investigated by the reduction of Rhodamine B (RhB) under visible-light irradiation. The results show that the porous Ag@Fe3O4@C-Au@TiO2 core@shell microspheres display higher adsorption and photocatalytic activities compared to the pure porous TiO2 and Ag@Fe3O4@C@TiO2 microspheres, which are attributed to the local surface plasmon resonance (LSPR) by the Ag and Au nanoparticles and the high specific surface area.

[Applicability of established drought index in Huang-Huai-Hai region based on actual evapotranspiration.

PubMed

Wang, Ying; Wu, Rong Jun; Guo, Zhao Bing

2016-05-01

Based on the modeled products of actual evapotranspiration with NOAH land surface model, the temporal and spatial variations of actual evapotranspiration were analyzed for the Huang-Huai-Hai region in 2002-2010. In the meantime, the agricultural drought index, namely, drought severity index (DSI) was constructed, incorporated with products of MOD17 potential evapotranspiration and MOD13 NDVI. Furthermore, the applicability of established DSI in this region in the whole year of 2002 was investigated based on the Palmer drought severity index (PDSI), the yield reduction rate of winter wheat, and drought severity data. The results showed that the annual average actual evapotranspiration within the survey region increased from the northwest to the southeast, with the maximum of 800-900 mm in the southeast and the minimum less than 300 mm in the northwest. The DSI and PDSI had positive correlation (R 2 =0.61) and high concordance in change trend. They all got the low point (-0.61 and -1.33) in 2002 and reached the peak (0.81 and 0.92) in 2003. The correlation between DSI and yield reduction rate of winter wheat (R 2 =0.43) was more significant than that between PDSI and yield reduction rate of winter wheat (R 2 =0.06). So, the DSI reflected a high spatial resolution of drought pattern and could reflect the region agricultural drought severity and intensity more accurately.

The expression of inflammatory cytokines, TAM tyrosine kinase receptors and their ligands is upregulated in venous leg ulcer patients: a novel insight into chronic wound immunity.

PubMed

Filkor, Kata; Németh, Tibor; Nagy, István; Kondorosi, Éva; Urbán, Edit; Kemény, Lajos; Szolnoky, Győző

2016-08-01

The systemic host defence mechanisms, especially innate immunity, in venous leg ulcer patients are poorly investigated. The aim of the current study was to measure Candida albicans killing activity and gene expressions of pro- and anti-inflammatory cytokines and innate immune response regulators, TAM receptors and ligands of peripheral blood mononuclear cells separated from 69 venous leg ulcer patients and 42 control probands. Leg ulcer patients were stratified into responder and non-responder groups on the basis of wound healing properties. No statistical differences were found in Candida killing among controls, responders and non-responders. Circulating blood mononuclear cells of patients overexpress pro-inflammatory (IL-1α, TNFα, CXCL-8) and anti-inflammatory (IL-10) cytokines as well as TAM receptors (Tyro, Axl, MerTK) and their ligands Gas6 and Protein S compared with those of control individuals. IL-1α is notably overexpressed in venous leg ulcer treatment non-responders; in contrast, Axl gene expression is robustly stronger among responders. These markers may be considered as candidates for the prediction of treatment response among venous leg ulcer patients. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Safety incidents involving confused and forgetful older patients in a specialised care setting--analysis of the safety incidents reported to the HaiPro reporting system.

PubMed

Kinnunen-Luovi, Kaisa; Saarnio, Reetta; Isola, Arja

2014-09-01

To describe the safety incidents involving confused and forgetful older patients in a specialised care setting entered in the HaiPro reporting system. About 10% of patients experience a safety incident during hospitalisation, which causes or could cause them harm. The possibility of a safety incident during hospitalisation increases significantly with age. A mild or moderate memory disorder and acute confusion are often present in the safety incidents originating with an older patient. The design of the study was action research with this study using findings from one of the first-phase studies, which included qualitative and quantitative analysed data. Data were collected from the reporting system for safety incidents (HaiPro) in a university hospital in Finland. There were 672 reported safety incidents from four acute medical wards during the years 2009-2011, which were scrutinised. Seventy-five of them were linked to a confused patient and were analysed. The majority of the safety incidents analysed involved patient-related accidents. In addition to challenging behaviour, contributing factors included ward routines, shortage of nursing staff, environmental factors and staff knowledge and skills. Nurses tried to secure the patient safety in many different ways, but the modes of actions were insufficient. Nursing staff need evidence-based information on how to assess the cognitive status of a confused patient and how to encounter such patients. The number of nursing staff and ward routines should be examined critically and put in proportion to the care intensity demands caused by the patient's confused state. The findings can be used as a starting point in the prevention of safety incidents and in improving the care of older patients. © 2013 John Wiley & Sons Ltd.

Beetle and plant arrow poisons of the Ju|’hoan and Hai||om San peoples of Namibia (Insecta, Coleoptera, Chrysomelidae; Plantae, Anacardiaceae, Apocynaceae, Burseraceae)

PubMed Central

Chaboo, Caroline S.; Biesele, Megan; Hitchcock, Robert K.; Weeks, Andrea

2016-01-01

Abstract The use of archery to hunt appears relatively late in human history. It is poorly understood but the application of poisons to arrows to increase lethality must have occurred shortly after developing bow hunting methods; these early multi-stage transitions represent cognitive shifts in human evolution. This paper is a synthesis of widely-scattered literature in anthropology, entomology, and chemistry, dealing with San (“Bushmen”) arrow poisons. The term San (or Khoisan) covers many indigenous groups using so-called ‘click languages’ in southern Africa. Beetles are used for arrow poison by at least eight San groups and one non-San group. Fieldwork and interviews with Ju|’hoan and Hai||om hunters in Namibia revealed major differences in the nature and preparation of arrow poisons, bow and arrow construction, and poison antidote. Ju|’hoan hunters use leaf-beetle larvae of Diamphidia Gerstaecker and Polyclada Chevrolat (Chrysomelidae: Galerucinae: Alticini) collected from soil around the host plants Commiphora africana (A. Rich.) Engl. and Commiphora angolensis Engl. (Burseracaeae). In the Nyae Nyae area of Namibia, Ju|’hoan hunters use larvae of Diamphidia nigroornata Ståhl. Larvae and adults live above-ground on the plants and eat leaves, but the San collect the underground cocoons to extract the mature larvae. Larval hemolymph is mixed with saliva and applied to arrows. Hai||om hunters boil the milky plant sap of Adenium bohemianum Schinz (Apocynaceae) to reduce it to a thick paste that is applied to their arrows. The socio-cultural, historical, and ecological contexts of the various San groups may determine differences in the sources and preparation of poisons, bow and arrow technology, hunting behaviors, poison potency, and perhaps antidotes. PMID:27006594

Drought evolution characteristics and precipitation intensity changes during alternating dry-wet changes in the Huang-Huai-Hai River basin

NASA Astrophysics Data System (ADS)

Yan, D. H.; Wu, D.; Huang, R.; Wang, L. N.; Yang, G. Y.

2013-03-01

According to the Chinese climate divisions and the Huang-Huai-Hai River basin digital elevation map, the basin is divided into seven sub-regions by means of cluster analysis of the basin meteorological stations using the self-organizing map (SOM) neural network method. Based on the daily precipitation data of 171 stations for the years 1961-2011, the drought frequency changes with different magnitudes are analyzed and the number of consecutive days without precipitation is used to identify the drought magnitudes. The first precipitation intensity after a drought period is analyzed with the Pearson-III frequency curve, then the relationship between rainfall intensity and different drought magnitudes is observed, as are the drought frequency changes for different years. The results of the study indicated the following: (1) the occurrence frequency of different drought level shows an overall increasing trend; there is no clear interdecadal change shown, but the spatial difference is significant. The occurrence frequencies of severe and extraordinary drought are higher on the North China Plain, Hetao Plains in Ningxia-Inner Mongolia, as well as on the Inner Mongolia and the Loess Plateaus, and in the Fen-Wei Valley basin. (2) As the drought level increases, the probability of extraordinary rainstorm becomes lower, and the frequency of occurrence of spatial changes in different precipitation intensities vary. In the areas surrounding Bo Sea, the Shandong Peninsula and the Huai River downstream, as the drought level increases, the occurrence frequency of different precipitation intensities first shows a decreasing trend, which becomes an increasing trend when extraordinary drought occurs. In the middle and upper reaches of the Huai River basin, on the Hai River basin piedmont plain and Hetao Plains in Ningxia-Inner Mongolia, Inner Mongolia and Loess Plateaus, and in the Fen-Wei Valley basin, the probability of the different precipitation intensities shows an overall

Assessment of River Habitat Quality in the Hai River Basin, Northern China.

PubMed

Ding, Yuekui; Shan, Baoqing; Zhao, Yu

2015-09-17

We applied a river habitat quality (RHQ) assessment method to the Hai River Basin (HRB); an important economic centre in China; to obtain baseline information for water quality improvement; river rehabilitation; and watershed management. The results of the assessment showed that the river habitat in the HRB is seriously degraded. Specifically; 42.41% of the sites; accounting for a river length of 3.31 × 10⁴ km; were designated poor and bad. Habitat in the plain areas is seriously deteriorated; and nearly 50% of the sites; accounting for a river length of 1.65 × 10⁴ km; had either poor or bad habitats. River habitat degradation was attributable to the limited width of the riparian zone (≤5 m); lower coverage of riparian vegetation (≤40%); artificial land use patterns (public and industrial land); frequent occurrence of farming on the river banks and high volumes of solid waste (nearly 10 m³); single flow channels; and rare aquatic plants (≤1 category). At the regional scale; intensive artificial land use types caused by urbanization had a significant impact on the RHQ in the HRB. RHQ was significantly and negatively correlated with farmland (r = 1.000; p < 0.01) and urban land (r = 0.998; p < 0.05); and was significantly and positively correlated with grassland and woodland (r = 1.000; p < 0.01). Intensive artificial land use; created through urbanization processes; has led to a loss of the riparian zone and its native vegetation; and has disrupted the lateral connectivity of the rivers. The degradation of the already essentially black rivers is exacerbated by poor longitudinal connectivity (index of connectivity is 2.08-16.56); caused by reservoirs and sluices. For river habitat rehabilitation to be successful; land use patterns need to be changed and reservoirs and sluices will have to be regulated.

Assessment of River Habitat Quality in the Hai River Basin, Northern China

PubMed Central

Ding, Yuekui; Shan, Baoqing; Zhao, Yu

2015-01-01

We applied a river habitat quality (RHQ) assessment method to the Hai River Basin (HRB); an important economic centre in China; to obtain baseline information for water quality improvement; river rehabilitation; and watershed management. The results of the assessment showed that the river habitat in the HRB is seriously degraded. Specifically; 42.41% of the sites; accounting for a river length of 3.31 × 104 km; were designated poor and bad. Habitat in the plain areas is seriously deteriorated; and nearly 50% of the sites; accounting for a river length of 1.65 × 104 km; had either poor or bad habitats. River habitat degradation was attributable to the limited width of the riparian zone (≤5 m); lower coverage of riparian vegetation (≤40%); artificial land use patterns (public and industrial land); frequent occurrence of farming on the river banks and high volumes of solid waste (nearly 10 m3); single flow channels; and rare aquatic plants (≤1 category). At the regional scale; intensive artificial land use types caused by urbanization had a significant impact on the RHQ in the HRB. RHQ was significantly and negatively correlated with farmland (r = 1.000; p < 0.01) and urban land (r = 0.998; p < 0.05); and was significantly and positively correlated with grassland and woodland (r = 1.000; p < 0.01). Intensive artificial land use; created through urbanization processes; has led to a loss of the riparian zone and its native vegetation; and has disrupted the lateral connectivity of the rivers. The degradation of the already essentially black rivers is exacerbated by poor longitudinal connectivity (index of connectivity is 2.08–16.56); caused by reservoirs and sluices. For river habitat rehabilitation to be successful; land use patterns need to be changed and reservoirs and sluices will have to be regulated. PMID:26393628

[Diversity of soil fauna in corn fields in Huang-Huai-Hai Plain of China under effects of conservation tillage].

PubMed

Zhu, Qiang-Gen; Zhu, An-Ning; Zhang, Jia-Bao; Zhang, Huan-Chao; Huang, Ping; Zhang, Cong-Zhi

2009-10-01

An investigation was made on the abundance and diversity of soil fauna in the corn fields under conventional and conservation tillage in Huang-Huai-Hai Plain of China. The abundance and diversity of soil fauna were higher at corn maturing (September) than at its jointing stage (July), and higher at jointing stage under conservation tillage than under conventional tillage. Soil fauna mainly distributed in surface soil layer (0-10 cm), but still had a larger number in 10-20 cm layer under conservation tillage. The individuals of acari, diptera, diplura, and microdrile oligochaetes, especially those of acari, were higher under conservation tillage than under conventional tillage. At maturing stage, an obvious effect of straw-returning under conservation tillage was observed, i. e., the more the straw returned, the higher the abundance of soil fauna, among which, the individuals of collembola, acari, coleopteran, and psocoptera, especially those of collembolan, increased significantly. The abundance of collembola at both jointing and maturing stages was significantly positively correlated with the quantity of straw returned, suggesting that collembola played an important role in straw decomposition and nutrient cycling.

Comparative water-quality assessment of the Hai He River basin in the People's Republic of China and three similar basins in the United States

USGS Publications Warehouse

Domagalski, Joseph L.; Xinquan, Zhou; Chao, Lin; Deguo, Zhi; Chi, Fan Lan; Kaitai, Xu; Ying, Lu; Luo, Yang; Shide, Liu; Dewen, Liu; Yong, Guo; Qi, Tian; Jing, Liu; Weidong, Yu; Shedlock, Robert; Knifong, Donna

2001-01-01

Ground-water quality with respect to nitrate, major inorganic constituents, pesticides, stable isotopes, and tritium was assessed in the agricultural Tangshan region in the Hai He River basin of the People's Republic of China and compared with three similar regions in the United States: the Delmarva Peninsula of the States of Delaware, Maryland, and Virginia, and the San Joaquin and Sacramento Valleys of the State of California. These four regions are considered similar with respect to size, land use, or climate. Median nitrate concentrations were found to be similar in the four regions in most instances, and those median concentrations were below the American nitrate drinking water standard of 10 milligrams per liter, however, higher concentrations, and a greater range of concentration, were evident for the Tangshan region.

Post-Closure Report for Closed Resource Conservation and Recovery Act Corrective Action Units, Nevada National Security Site, Nevada for fiscal year 2013 (October 2012 - September 2013)

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

None, None

2014-01-31

This report serves as the combined annual report for post-closure activities for the following closed Corrective Action Units (CAUs): CAU 90, Area 2 Bitcutter Containment; CAU 91, Area 3 U-3fi Injection Well; CAU 92, Area 6 Decon Pond Facility; CAU 110, Area 3 WMD U-3ax/bl Crater; CAU 111, Area 5 WMD Retired Mixed Waste Pits; and, CAU 112, Area 23 Hazardous Waste Trenches.

Early Modern Humans and Morphological Variation in Southeast Asia: Fossil Evidence from Tam Pa Ling, Laos

PubMed Central

Demeter, Fabrice; Shackelford, Laura; Westaway, Kira; Duringer, Philippe; Bacon, Anne-Marie; Ponche, Jean-Luc; Wu, Xiujie; Sayavongkhamdy, Thongsa; Zhao, Jian-Xin; Barnes, Lani; Boyon, Marc; Sichanthongtip, Phonephanh; Sénégas, Frank; Karpoff, Anne-Marie; Patole-Edoumba, Elise; Coppens, Yves; Braga, José

2015-01-01

Little is known about the timing of modern human emergence and occupation in Eastern Eurasia. However a rapid migration out of Africa into Southeast Asia by at least 60 ka is supported by archaeological, paleogenetic and paleoanthropological data. Recent discoveries in Laos, a modern human cranium (TPL1) from Tam Pa Ling‘s cave, provided the first evidence for the presence of early modern humans in mainland Southeast Asia by 63-46 ka. In the current study, a complete human mandible representing a second individual, TPL 2, is described using discrete traits and geometric morphometrics with an emphasis on determining its population affinity. The TPL2 mandible has a chin and other discrete traits consistent with early modern humans, but it retains a robust lateral corpus and internal corporal morphology typical of archaic humans across the Old World. The mosaic morphology of TPL2 and the fully modern human morphology of TPL1 suggest that a large range of morphological variation was present in early modern human populations residing in the eastern Eurasia by MIS 3. PMID:25849125

Closure Report for CAU No. 430: Buried Depleted Uraniuim Artillery Round No. 1, Tonopah Test Range, Revision 0

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

None

1997-02-25

1.1 Purpose This Closure Report presents the information obtained from investigative actions performed to justify the decision for clean closure of CAU 430 through "No Further Action." The investigative actions were performed per the Streamlined Approach for Environmental Restoration Plan, CA UNO. 430: Buried Depleted Uranium Artille~ Round No. 1, Tonopah Test Range (DOE/NV, 1996a) (hereafter referred to as the SAFER Plan). The Buried DU Artillery Round No. 1 is located approximately 1.1 kilometers (km) (0.7 mile [mi]) south of Avenue 13 in the test area south of Area 9 (Figure 1-2). The site was thought to consist of amore » potentially unexploded W-79 Joint Test Assembly (JTA) test artillery projectile with high explosives (HE) and DU. The DU was substituted for Special Nuclear Material to prevent a nuclear explosion and yet retain the physical characteristics of uranium for ballistic and other mechanical tests. The projectile was reportedly buried in one pit, approximately 5 to 10 feet (ft) deep (Smith, 1993; Smith, 1996; Quas, 1996). The exact location of the burial pit is unknown; however, three disturbed areas (Sites A, B, and C) were identified through geophysical surveys, site visits, and employee interviews as possible locations of the test projectile (Figure 1-3). Results of the investigation are summarized within this Closure Report. Additional information about the site and investigation activities may be found in the SAFER Plan (DOE/NV, 1996a). 1.2 Scope The objectives of the SAFER Plan (DOE/NV, 1996a) activities were to prepare the site for closure through locating and identi~ing the projectile (Buried DU Artillery Round No. 1), destroying the projectile and any remaining components, collecting soil samples to detect residual contamination resulting from projectile destruction, and finally, remediating residual contamination.« less

Capacity of Commune Health Stations in Chi Linh District, Hai Duong Province, for Prevention and Control of Noncommunicable Diseases.

PubMed

Thi Thuy Nga, Nguyen; Thi My Anh, Bui; Nguyen Ngoc, Nguyen; Minh Diem, Dang; Duy Kien, Vu; Bich Phuong, Tran; Quynh Anh, Tran; Van Minh, Hoang

2017-07-01

The primary health care system in Vietnam has been playing an important role in prevention and control of diseases. This study aimed to describe the capacity of commune health stations in Chi Linh district, Hai Duong province for prevention and control of noncommunicable diseases (NCDs). A mixed-methods (quantitative and qualitative approaches) approach was applied to collect data in 20 commune health stations. The participants, including health workers, stakeholders, and patients with NCDs, were selected for the study. The findings reported that the main activities of prevention and control of NCDs at commune health stations (CHSs) still focused on information-education-community (IECs), unqualified for providing screening, diagnosis, and treatments of NCDs. The capacity for prevention and control of NCDs in CHSs was inadequate to provide health care services related to prevention and control of NCDs and unmet with the community's demands. In order to ensure the role and implementation of primary care level, there is an urgent need to improve the capacity of CHSs for prevention and control of NCDs, particularly a national budget for NCDs prevention and control, the essential equipment and medicines recommended by the World Health Organization should be provided and available at the CHSs.

Post-Closure Inspection Report for the Tonopah Test Range, Nevada, For Calendar Year 2011

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

NSTec Environmental Restoration

This report provides the results of the annual post-closure inspections conducted at the closed Corrective Action Units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2011 and includes inspection and repair activities completed at the following CAUs: (1) CAU 400: Bomblet Pit and Five Points Landfill (TTR); (2) CAU 407: Roller Coaster RadSafe Area (TTR); (3) CAU 424: Area 3 Landfill Complexes (TTR); (4) CAU 453: Area 9 UXO Landfill (TTR); and (5) CAU 487: Thunderwell Site (TTR) Inspections were conducted according to the post-closure plans in the approved Closure Reports. The post-closure inspectionmore » plan for each CAU is included in Appendix B. The inspection checklists are included in Appendix C, field notes are included in Appendix D, and photographs taken during inspections are included in Appendix E. The annual post-closure inspections were conducted May 3 and 4, 2011. Maintenance was performed at CAU 424, CAU 453, and CAU 487. At CAU 424, two surface grade monuments at Landfill Cell A3-3 could not be located during the inspection. The two monuments were located and marked with lava rock on July 13, 2011. At CAU 453, there was evidence of animal burrowing. Animal burrows were backfilled on July 13, 2011. At CAU 487, one use restriction warning sign was missing, and wording was faded on the remaining signs. A large animal burrow was also present. The signs were replaced, and the animal burrow was backfilled on July 12, 2011. As a best management practice, the use restriction warning signs at CAU 407 were replaced with standard Federal Facility Agreement and Consent Order signs on July 13, 2011. Vegetation monitoring was performed at the CAU 400 Five Points Landfill and CAU 407 in June 2011, and the vegetation monitoring report is included in Appendix F.« less

Prevalence of Self-Treatment Practice and Related Factors Among Workers Aged 15 to 60 Years in Chi Linh Town, Hai Duong Province, Vietnam.

PubMed

Quynh Nguyen, Thuy; Tran, Thi Thu Thuy; Le, Thi Vui; Quyen, Thi Tu Bui; Trinh, Van Hung; Tran, Huu Bich

2017-07-01

Self-treatment is particularly prevalent in Vietnam. However, the prevalence of this practice among the working population is unclear. This study aims to describe the prevalence of self-treatment and related factors among workers aged 15 to 60 years in the suburban area of Chi Linh, Hai Duong, Vietnam. Secondary data of 3128 respondents was retrieved from the CHILILAB HDSS 2016 survey for analysis using logistic regression with a significance level of .05. Results show that 47.5% of respondents treated themselves at least once during one previous year. While rural residence and the presence of acute health symptoms and chronic diseases significantly associate with the choice of self-treatment among all investigated workers, lower education level and health insurance status only significantly relate to this practice among the formally employed workers. The findings imply the need for specific measures to manage self-treatment practices among different groups of workers.

Post-Closure Inspection Report for the Tonopah Test Range, Nevada, for Calendar Year 2013

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

Silvas, A. J.

2014-03-03

This report provides the results of the annual post-closure inspections conducted at the closed Corrective Action Units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2013 and includes inspection and repair activities completed at the following CAUs: • CAU 400: Bomblet Pit and Five Points Landfill (TTR) • CAU 407: Roller Coaster RadSafe Area (TTR) • CAU 424: Area 3 Landfill Complexes (TTR) • CAU 453: Area 9 UXO Landfill (TTR) • CAU 487: Thunderwell Site (TTR) Inspections were conducted according to the post-closure plans in the approved Closure Reports and subsequent correspondence withmore » the Nevada Division of Environmental Protection. The post-closure inspection plans and subsequent correspondence modifying the requirements for each CAU are included in Appendix B. The inspection checklists are included in Appendix C. Field notes are included in Appendix D. Photographs taken during inspections are included in Appendix E. The annual post-closure inspections were conducted on May 14, 2013. Maintenance was performed at CAU 400, CAU 424, and CAU 453. At CAU 400, animal burrows were backfilled. At CAU 424, erosion repairs were completed at Landfill Cell A3-3, subsidence was repaired at Landfill Cell A3-4, and additional lava rock was placed in high-traffic areas to mark the locations of the surface grade monuments at Landfill Cell A3-3 and Landfill Cell A3-8. At CAU 453, two areas of subsidence were repaired and animal burrows were backfilled. Vegetation monitoring was performed at the CAU 400 Five Points Landfill and CAU 407 in June 2013. The vegetation monitoring report is included in Appendix F.« less

Evaluating availability and price of essential medicines in Boston area (Massachusetts, USA) using WHO/HAI methodology.

PubMed

Sharma, Abhishek; Rorden, Lindsey; Ewen, Margaret; Laing, Richard

2016-01-01

Many patients even those with health insurance pay out-of-pocket for medicines. We investigated the availability and prices of essential medicines in the Boston area. Using the WHO/HAI methodology, availability and undiscounted price data for both originator brand (OB) and lowest price generic (LPG) equivalent versions of 25 essential medicines (14 prescription; 11 over-the-counter (OTC)) were obtained from 17 private pharmacies. The inclusion and prices of 26 essential medicines in seven pharmacy discount programs were also studied. The medicine prices were compared with international reference prices (IRPs). In surveyed pharmacies, the OB medicines were less available as compared to the generics. The OB and LPG versions of OTC medicines were 21.33 and 11.53 times the IRP, respectively. The median prices of prescription medicines were higher, with OB and LPG versions at 158.14 and 38.03 times the IRP, respectively. In studied pharmacy discount programs, the price ratios of surveyed medicines varied from 4.4-13.9. While noting the WHO target that consumers should pay no more than four times the IRPs, medicine prices were considerably higher in the Boston area. The prices for medicines included in the pharmacy discount programs were closest to WHO's target. Consumers should shop around, as medicine inclusion and prices vary across discount programs. In order for consumers to identify meaningful potential savings through comparison shopping, price transparency is needed.

Heavy Metal Accumulation by Periphyton Is Related to Eutrophication in the Hai River Basin, Northern China

PubMed Central

Tang, Wenzhong; Cui, Jingguo; Shan, Baoqing; Wang, Chao; Zhang, Wenqiang

2014-01-01

The Hai River Basin (HRB) is one of the most polluted river basins in China. The basin suffers from various types of pollutants including heavy metals and nutrients due to a high population density and rapid economic development in this area. We assessed the relationship between heavy metal accumulation by periphyton playing an important role in fluvial food webs and eutrophication in the HRB. The concentrations of the unicellular diatoms (type A), filamentous algae with diatoms (type B), and filamentous algae (type C) varied along the river, with type A dominating upstream, and types B then C increasing in concentration further downstream, and this was consistent with changes in the trophic status of the river. The mean heavy metal concentrations in the type A, B and C organisms were Cr: 18, 18 and 24 mg/kg, respectively, Ni: 9.2, 10 and 12 mg/kg, respectively, Cu: 8.4, 19 and 29 mg/kg, respectively, and Pb: 11, 9.8 and 7.1 mg/kg respectively. The bioconcentration factors showed that the abilities of the organisms to accumulate Cr, Ni and Pb decreased in the order type A, type B, then type C, but their abilities to accumulate Cu increased in that order. The Ni concentration was a good predictor of Cr, Cu and Pb accumulation by all three periphyton types. Our study shows that heavy metal accumulation by periphyton is associated with eutrophication in the rivers in the HRB. PMID:24482681

Post-Closure Report for Closed Resource Conservation and Recovery Act Corrective Action Units, Nevada National Security Site, Nevada For Fiscal Year 2012 (October 2011–September 2012)

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

NSTec Environmental Restoration

2013-01-17

This report serves as the combined annual report for post-closure activities for the following closed Corrective Action Units (CAUs): · CAU 90, Area 2 Bitcutter Containment · CAU 91, Area 3 U-3fi Injection Well · CAU 92, Area 6 Decon Pond Facility · CAU 110, Area 3 WMD U-3ax/bl Crater · CAU 111, Area 5 WMD Retired Mixed Waste Pits · CAU 112, Area 23 Hazardous Waste Trenches This report covers fiscal year 2012 (October 2011–September 2012).

Agonistic TAM-163 antibody targeting tyrosine kinase receptor-B: applying mechanistic modeling to enable preclinical to clinical translation and guide clinical trial design.

PubMed

Vugmeyster, Yulia; Rohde, Cynthia; Perreault, Mylene; Gimeno, Ruth E; Singh, Pratap

2013-01-01

TAM-163, an agonist monoclonal antibody targeting tyrosine receptor kinase-B (TrkB), is currently being investigated as a potential body weight modulatory agent in humans. To support the selection of the dose range for the first-in-human (FIH) trial of TAM-163, we conducted a mechanistic analysis of the pharmacokinetic (PK) and pharmacodynamic (PD) data (e.g., body weight gain) obtained in lean cynomolgus and obese rhesus monkeys following single doses ranging from 0.3 to 60 mg/kg. A target-mediated drug disposition (TMDD) model was used to describe the observed nonlinear PK and Emax approach was used to describe the observed dose-dependent PD effect. The TMDD model development was supported by the experimental determination of the binding affinity constant (9.4 nM) and internalization rate of the drug-target complex (2.08 h(-1)). These mechanistic analyses enabled linking of exposure, target (TrkB) coverage, and pharmacological activity (e.g., PD) in monkeys, and indicated that ≥ 38% target coverage (time-average) was required to achieve significant body weight gain in monkeys. Based on the scaling of the TMDD model from monkeys to humans and assuming similar relationship between the target coverage and pharmacological activity between monkey and humans, subcutaneous (SC) doses of 1 and 15 mg/kg in humans were projected to be the minimally and the fully pharmacologically active doses, respectively. Based on the minimal anticipated biological effect level (MABEL) approach for starting dose selection, the dose of 0.05 mg/kg (3 mg for a 60 kg human) SC was recommended as the starting dose for FIH trials, because at this dose level<10% target coverage was projected at Cmax (and all other time points). This study illustrates a rational mechanistic approach for the selection of FIH dose range for a therapeutic protein with a complex model of action.

Promiscuity and selectivity of small-molecule inhibitors across TAM receptor tyrosine kinases in pediatric leukemia.

PubMed

Liu, Mao-Hua; Chen, Shi-Bing; Yu, Juan; Liu, Cheng-Jun; Zhang, Xiao-Jing

2017-08-01

The TAM receptor tyrosine kinase family member Mer has been recognized as an attractive therapeutic target for pediatric leukemia. Beside Mer the family contains other two kinases, namely, Tyro3 and Axl, which are highly homologues with Mer and thus most existing small-molecule inhibitors show moderate or high promiscuity across the three kinases. Here, the structural basis and energetic property of selective binding of small-molecule inhibitors to the three kinases were investigated at molecular level. It is found that the selectivity is primarily determined by the size, shape and configuration of kinase's ATP-binding site; the Mer and Axl possess a small, closed active pocket as compared to the bulky, open pocket of Tyro3. The location and conformation of active-site residues of Mer and Axl are highly consistent, suggesting that small-molecule inhibitors generally have a low Mer-over-Axl selectivity and a high Mer-over-Tyro3 selectivity. We demonstrated that the difference in ATP binding potency to the three kinases is also responsible for inhibitor selectivity. We also found that the long-range interactions and allosteric effect arising from rest of the kinase's active site can indirectly influence inhibitor binding and selectivity. Copyright © 2017 Elsevier Inc. All rights reserved.

Dangerous subtlety: relationship-related determinants of consistency of condom use among female sex workers and their regular, non-commercial partners in Hai Phong, Viet Nam.

PubMed

Hoffman, Leah; Nguyen, Ha Thi Thu; Kershaw, Trace S; Niccolai, Linda M

2011-10-01

Research indicates female sex workers use condoms more consistently with their clients than with regular, non-commercial partners (partners). The purpose of this study was to better understand the relationship between couple communication and HIV risk behavior by examining (1) sex worker-partner divergence on communication measures and (2) the association between intra-couple communication divergence and consistent condom use. In this cross-sectional study, 50 sex workers and their partners in Hai Phong, Viet Nam were separately asked about their relationships and condom use. When asked about HIV risk communication in their relationship, sex workers reported significantly higher HIV communication content than their partners (p < 0.001). Higher communication divergence between partners was associated with a decreased likelihood of consistent condom use (OR 0.54 95% CI 0.30, 0.97). Sex workers urgently need interventions that build their communication skills and address their risk behavior in non-commercial relationships.

Exacerbation of innate immune response in mouse primary cultured sertoli cells caused by nanoparticulate TiO2 involves the TAM/TLR3 signal pathway.

PubMed

Wu, Nan; Hong, Fashui; Zhou, Yingjun; Wang, Yajing

2017-01-01

Sertoli cells provide appropriate mitogens, differentiation factors and sources of energy for developing germ cells throughout the lifetime of males, and protect these germ cells from harmful agents and from the host's own immune system. Therefore, reductions in the rate and quality of spermatogenesis caused by nanoparticulate titanium dioxide (nano-TiO 2 ) may be closely involved in the immunoregulation of Sertoli cells. However, the underlying mechanism of this response is still unclear. To address this issue, we used mouse primary cultured Sertoli cells to examine the toxic effects of nano-TiO 2 via alterations in morphology, cell viability, and activation of the TAM/TLR3 signal pathway. The results demonstrated that nano-TiO 2 could cross the cytomembrane into the cytoplasm or nucleus, decrease Sertoli cell viability, damage morphology (such as elongated fusiform, cellular and nuclear shrinkage) and induce the expression of various immune mediators and inflammatory cytokines, including TLR3(+0.31-fold to +0.81-fold), IL-lβ(+0.33-fold to +5.0-fold), NF-κB(+0.22-fold to +3.65-fold), IL-6(+0.47-fold to +3.53-fold), TNF-α(+0.14-fold to +2.44-fold), IFN-α(+0.17-fold to +2.27-fold), and IFN-β(+0.09-fold to +2.29-fold), and suppress the expression of Tyro3(-9.33% to -61.93%), Axl(-19.03% to -60.67%), Mer(-8.04% to -59.16%), and IκB(-34.35% to -86.59%) in primary cultured Sertoli cells. These results suggest that testicular innate immune responses to pathogens caused by nano-TiO 2 may be involved in the regulatory mechanisms of TAM/TLR3 signaling in testicular Sertoli cells. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 198-208, 2017. © 2016 Wiley Periodicals, Inc.

Post-Closure Report for Closed Resource Conservation and Recovery Act Corrective Action Units, Nevada National Security Site, Nevada: For Fiscal Year 2015 (October 2014–September 2015), Revision 0

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

Matthews, Patrick

This report serves as the combined annual report for post-closure activities for the following closed corrective action units (CAUs); CAU 90, Area 2 Bitcutter Containment; CAU 91, Area 3 U-3fi Injection Well; CAU 92, Area 6 Decon Pond Facility; CAU 110, Area 3 WMD U-3ax/bl Crater; CAU 111, Area 5 WMD Retired Mixed Waste Pits; and CAU 112, Area 23 Hazardous Waste Trenches. This report covers fiscal year 2015 (October 2014 through September 2015). The post-closure requirements for these sites are described in Resource Conservation and Recovery Act Permit Number NEV HW0101 and are summarized in each CAU-specific section inmore » Section 1.0 of this report. The results of the inspections, a summary of maintenance activities, and an evaluation of monitoring data are presented in this report.« less

Post-Closure Inspection Report for the Tonopah Test Range, Nevada, for Calendar Year 2012

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

NSTec Environmental Restoration

2013-01-28

This report provides the results of the annual post-closure inspections conducted at the closed Corrective Action Units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2012 and includes inspection and repair activities completed at the following CAUs: · CAU 400: Bomblet Pit and Five Points Landfill (TTR) · CAU 407: Roller Coaster RadSafe Area (TTR) · CAU 424: Area 3 Landfill Complexes (TTR) · CAU 453: Area 9 UXO Landfill (TTR) · CAU 487: Thunderwell Site (TTR)

Healthcare-associated infections in Australia: time for national surveillance.

PubMed

Russo, Philip L; Cheng, Allen C; Richards, Michael; Graves, Nicholas; Hall, Lisa

2015-02-01

Healthcare-associated infection (HAI) surveillance programs are critical for infection prevention. Australia does not have a comprehensive national HAI surveillance program. The purpose of this paper is to provide an overview of established international and Australian statewide HAI surveillance programs and recommend a pathway for the development of a national HAI surveillance program in Australia. This study examined existing HAI surveillance programs through a literature review, a review of HAI surveillance program documentation, such as websites, surveillance manuals and data reports and direct contact with program representatives. Evidence from international programs demonstrates national HAI surveillance reduces the incidence of HAIs. However, the current status of HAI surveillance activity in Australian states is disparate, variation between programs is not well understood, and the quality of data currently used to compose national HAI rates is uncertain. There is a need to develop a well-structured, evidence-based national HAI program in Australia to meet the increasing demand for validated reliable national HAI data. Such a program could be leveraged off the work of existing Australian and international programs.

Comparing topical hydrocortisone cream with Hai's Perianal Support in managing symptomatic hemorrhoids in pregnancy: a preliminary trial.

PubMed

Lim, Soo Soo; Yu, Chye Wah; Aw, Lin Da

2015-02-01

The prevalence of hemorrhoids among pregnant women is high in late pregnancy. This study was to evaluate the efficacy between drug treatment with Procort (topical hydrocortisone cream 1%) and mechanical treatment with a Hai's Perianal Support (HPS) toilet seat device in managing symptomatic hemorrhoids during the third trimester of pregnancy. A prospective randomized controlled study was conducted on 23 pregnant women with gestation above the 28th week and presented with symptomatic hemorrhoids. Pre- and post-interventional assessment was carried out to obtain data on symptoms of pain, itching, swelling, discomfort and bleeding associated with hemorrhoids. The control group was treated with topical hydrocortisone cream 1% and the test group was provided and taught to use a HPS, a posterior perineal support toilet seat device (Colorec). The results showed improvement in symptoms of pain, swelling, bleeding, itching and discomfort in both the test and control groups. However, statistically significant differences were found on symptoms of pain, swelling and discomfort between the test and control groups. There was also a statistically significant difference in well-being and overall improvement between the test and control groups. HPS has to a certain extent significantly reduced the symptoms of hemorrhoids in pregnancy and improved the well-being of pregnant women in comparison with topical treatment with hydrocortisone cream. However, more clinical trials need to be carried out to recomfirm the role of HPS in hemorrhoids in pregnancy. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Post-Closure Inspection Report for the Tonopah Test Range, Nevada, for Calendar Year 2014

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

Silvas, A. J.; Lantow, Tiffany A.

This report provides the results of the annual post-closure inspections conducted at the closed Corrective Action Units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2014 and includes inspection and repair activities completed at the following CAUs; CAU 400: Bomblet Pit and Five Points Landfill (TTR); CAU 407: Roller Coaster RadSafe Area (TTR); CAU 424: Area 3 Landfill Complexes (TTR); CAU 453: Area 9 UXO Landfill (TTR); and CAU 487: Thunderwell Site (TTR) Inspections were conducted according to the post-closure plans in the approved Closure Reports and subsequent correspondence with the Nevada Division ofmore » Environmental Protection. The post-closure inspection plans and subsequent correspondence modifying the requirements for each CAU are included in Appendix B. The inspection checklists are included in Appendix C. Photographs taken during inspections are included in Appendix D. The annual post-closure inspections were conducted on May 28, 2014. Maintenance was required at CAU 407. Animal burrows were backfilled and erosion repairs were performed. Vegetation monitoring was performed at CAU 407 in June 2014. The vegetation monitoring report is included in Appendix E.« less

Post-Closure Inspection Report for the Tonopah Test Range, Nevada: For Calendar Year 2017, Revision 0

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

Alvarado, Juan; Matthews, Patrick

This report provides the results of the annual post-closure inspections conducted at the closed corrective action units (CAUs) located on the Tonopah Test Range (TTR) and the Nevada Test and Training Range (NTTR). This report covers calendar year 2017 and includes visual inspection and repair activities completed at the following CAUs: CAU 400: Bomblet Pit and Five Points Landfill (TTR) CAU 407: Roller Coaster RadSafe Area (TTR) CAU 424: Area 3 Landfill Complexes (TTR) CAU 453: Area 9 UXO Landfill (TTR) CAU 487: Thunderwell Site (TTR) Visual inspections were conducted according to the post-closure plans in the approved closure reportsmore » and subsequent correspondence with the Nevada Division of Environmental Protection. The annual post-closure inspections were conducted on May 23, 2017. No maintenance or repair issues were noted at CAU 400 and CAU 487. Maintenance items and subsequent repairs include the following: CAU 407: A large animal burrow was observed in the southeast corner of the cover during the inspection. Two additional animal burrows were discovered during repair actions. All cover defects were repaired on January 9, 2018. CAU 424: CAS 03-08-002-A304 (Landfill Cell A3-4): A new monument was installed and the subsidence area was repaired on January 9, 2018. CAU 424: CAS 03-08-002-A308 (Landfill Cell A3-8): Lava rock, used to mark the two eastern monument locations, was noted as missing during the inspection. The lava rock was replaced on January 9, 2018. CAU 453: Five large animal burrows, located near the east–central portion of cover, was noted during the inspection. Eight additional animal burrows were discovered during repair actions. All cover defects were repaired on January 9, 2018.« less

Post-Closure Report for Closed Resource Conservation and Recovery Act Corrective Action Units, Nevada National Security Site, Nevada: For Calendar Year 2017, Revision 0

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

Matthews, Patrick; Alvarado, Juan

This report serves as the combined annual report for post-closure activities for the following closed corrective action units (CAUs): CAU 90, Area 2 Bitcutter Containment CAU 91, Area 3 U-3fi Injection Well CAU 92, Area 6 Decon Pond Facility CAU 110, Area 3 WMD U-3ax/bl Crater CAU 111, Area 5 WMD Retired Mixed Waste Pits CAU 112, Area 23 Hazardous Waste Trenches The results of the inspections, a summary of maintenance activities, and an evaluation of monitoring data are presented in this report. Site inspections are conducted annually at CAUs 90, 91, and 112; semiannually at CAUs 92 and 110;more » and quarterly at CAU 111. Additional inspections are conducted at CAU 92 if precipitation occurs in excess of 1.0 inches in a 24-hour period and at CAU 111 if precipitation occurs in excess of 1.0 inch in a 24-hour period. Inspections include an evaluation of the condition of the units, including covers, fences, signs, gates, and locks. At CAU 110, soil moisture monitoring, vegetation evaluations, and subsidence surveys are conducted in addition to the visual inspections. At CAU 111, soil moisture monitoring, vegetation evaluations, subsidence surveys, direct radiation monitoring, air monitoring, radon flux monitoring, and groundwater monitoring are conducted. This report will address all monitoring items notes above except groundwater monitoring. Groundwater monitoring is documented in the Nevada National Security Site Data Report: Groundwater Monitoring Program Area 5 Radioactive Waste Management Site. All required inspections, maintenance, and monitoring were conducted in accordance with the post-closure requirements of the permit. Revision 4 of Permit NEV HW0101 was issued effective December 10, 2015, and remains in effect until December 10, 2020.« less

Post-Closure Inspection Report for the Tonopah Test Range, Nevada. For Calendar Year 2015, Revision 0

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

Matthews, Patrick; Petrello, Jaclyn

This report provides the results of the annual post-closure inspections conducted at the closed corrective action units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2015 and includes inspection and repair activities completed at the following CAUs; CAU 400: Bomblet Pit and Five Points Landfill (TTR); CAU 407: Roller Coaster RadSafe Area (TTR); CAU 424: Area 3 Landfill Complexes (TTR); CAU 453: Area 9 UXO Landfill (TTR); and CAU 487: Thunderwell Site (TTR) Inspections were conducted according to the post-closure plans in the approved closure reports and subsequent correspondence with the Nevada Division ofmore » Environmental Protection. The post-closure inspection plans and subsequent correspondence modifying the requirements for each CAU are included in Appendix B. The inspection checklists are included in Appendix C. Field notes are included in Appendix D. The annual post-closure inspections were conducted on May 12, 2015. Maintenance was required at CAU 453. Cracking along the north trench was repaired. One monument is missing at CAU 424; it will be replaced in 2016. Postings at CAUs 407, 424, 453, and 487 contain contact information for TTR Security. It was noted that protocols may not be in place to ensure that the U.S. Department of Energy, National Nuclear Security Administration Nevada Field Office (NNSA/NFO) is notified if access is needed at these sites. NNSA/NFO is working with the U.S. Air Force and Sandia to determine whether more appropriate contact information or new protocols are warranted for each CAU. Based on these inspections, there has not been a significant change in vegetation, and vegetation monitoring was not recommended at CAU 400 or CAU 407 in 2015.« less

[Complete responses in patients with unresectable liver metastases from colorectal cancer with weekly high-dose 5-FU plus one-shot CDDP HAI].

PubMed

Udagawa, M; Okabe, S; Kuwabara, H; Ootsukasa, S; Arai, T; Maruyama, S; Murase, N; Yamashita, H; Iwai, T

1999-10-01

Thirty-two patients with unresectable liver metastases from colorectal cancer, treated by intermittent hepatic arterial infusion of high-dose 5-FU combined with CDDP, were assessed. As a result of this treatment, the overall response rate was 65.6%, and eight patients (25%) which contained three autopsy cases revealed a complete response. The mean doses of 5-FU and CDDP which was administered in the eight patients were 24.3 g and 65 mg, respectively. One of the eight patients showed complete disappearance of liver metastasis on the CT scan after arterial infusion of 4.5 g of 5-FU, and necrosis or disappearance of the tumor was present in more than 2/3 of the whole lesion. Autopsy showed focal or zonal necrosis, distorted reconstruction of architecture, and cholangiolitis of the liver which were administered more than 15 g of 5-FU. Intermittent hepatic arterial infusion of high-dose 5-FU combined with CDDP is proved to be a useful locoregional chemotherapy for liver metastasis from colorectal cancer. We should evolve new treatment modalities for extrahepatic metastases, as HAI combined with the systemic chemotherapeutic regimen.

Passively Q-switched Tm-doped fiber laser based on concave gold bipyramids assembled quasi-2D saturable absorber

NASA Astrophysics Data System (ADS)

Song, Jiaxin; Wu, Hanshuo; Wu, Jian; Xu, Jiangming; Xiao, Hu; Leng, Jinyong; Zhou, Pu; Liu, Zejin

2018-07-01

We demonstrated a concave gold bipyramids (CAuBPs) quasi-2D saturable absorbers (SAs) based ~2 μm band fiber laser for the first time. CAuBPs were synthesized by using modified aqueous wet-chemical synthesis method. Through controlling the size and morphology of CAuBPs, the longitudinal surface plasmon resonance peak of CAuBPs based quasi-2D SA is tuned to be ~2 μm. Passively Q-switched lasing of thulium-doped fiber laser is achieved successfully with a maximum average output power of 9.72 mW and ~9% slope efficiency. The minimum pulse width is 4.56 µs at the repetition rate of 20 kHz. Experimental results reveals that CAuBPs could be used as SAs in the 2 µm region, which verifies the saturable absorption properties of CAuBPs.

Exploring the role of ethnic media and the community readiness to combat stigma attached to mental illness among Vietnamese immigrants: the pilot project Tam An (Inner Peace in Vietnamese).

PubMed

Han, Meekyung; Cao, Lien; Anton, Karen

2015-01-01

Vietnamese Americans are at high risk for developing mental health disorders due to multiple risk factors such as trauma and acculturative stress. However, the utilization of mental health services has been low. The pilot project Tam An was implemented to raise mental health awareness by engaging community resources in the Vietnamese population. Informed by the Community Readiness Model and through local ethnic media sources, messages to destigmatize mental health and promote the willingness to initiate mental health treatment were presented. Using an exploratory perspective, findings from focus group data suggest that the project improved the community's stage of readiness.

Surveillance of healthcare associated infections in pediatric cancer patients between 2004 and 2009 in a public pediatric hospital in Mexico city, Mexico.

PubMed

Hernández Orozco, Hilda; Lucas Resendiz, Esperanza; Castañeda, Jose Luis; De Colsa, Agustin; Ramirez Mayans, Jaime; Johnson, Kyle M; Gonzalez, Napoleon; Caniza, Miguela A

2014-03-01

Pediatric oncology and hematology patients are at increased risk of developing healthcare associated infections (HAIs). We conducted a prospective surveillance study on children with cancer admitted to the pediatric hematology and oncology units at a public pediatric hospital in Mexico from January 2004 to December 2009. The incidence of HAIs and groups at greatest risk for HAIs were analyzed. The annual HAI incidence rate and incidence density were calculated. Risk factors such as site of infection, HAI types, and cancer diagnosis were studied. A total of 9420 patients participated, and 409 had HAIs (479 episodes). Annual HAI rates were 3.7 to 5.5 per 100 admissions and the incidence density was 5.75 to 6 HAIs per 1000 inpatient days annually. There were 272 (56.8%) bloodstream infections, 45 (9.4%) pneumonia cases, and 44 (9.2%) skin and soft tissue infections. Children with acute lymphoblastic leukemia had 37.2% and those with acute myeloid leukemia had 16.4% of the HAIs. A total of 11.5% of the HAIs were in children with osteosarcoma. The most common pathogens were Gram-negative bacteria. The HAI-associated mortality rate was 3.7%. Although the overall HAI rate is in line with published reports, the mortality rate was higher, suggesting the incorporation of more aggressive methods to treat infections at our hospital.

Correlates of Heterosexual Anal Intercourse among Women in the 2006-2010 National Survey of Family Growth.

PubMed

Benson, Lyndsey S; Martins, Summer L; Whitaker, Amy K

2015-08-01

Heterosexual anal intercourse (HAI) is common among U.S. women. Receptive anal intercourse is a known risk factor for HIV, yet there is a paucity of data on HAI frequency and distribution in the United States. Condom use is lower with HAI vs. vaginal intercourse, but little is known regarding of correlates of HAI with and without condoms. The aims of this study were to describe recent (past 12 months) and lifetime HAI among sexually active reproductive-aged U.S. women, and to characterize women who engage in HAI with and without condoms. We analyzed a sample of 10,463 heterosexually active women aged 15-44 years for whom anal intercourse data were available in the 2006-2010 National Survey of Family Growth. Weighted bivariate and multivariable analyses were used to determine HAI prevalence and correlates. Primary outcomes were lifetime HAI, recent (last 12 months) HAI, and condom use at last HAI. In our sample, 13.2% of women had engaged in recent HAI and 36.3% in lifetime HAI. Women of all racial and ethnic backgrounds and religions reported recent anal intercourse. Condom use was more common at last vaginal intercourse than at last anal intercourse (28% vs. 16.4%, P < 0.001). In multivariable analysis, correlates of recent HAI included: less frequent church attendance, younger age at first intercourse, multiple sexual partners, history of oral intercourse, history of unintended pregnancy, and treatment for sexually transmitted infections (all P < 0.05). Correlates of lifetime HAI were similar, with the addition of older age, higher education, higher income, and history of drug use (all P < 0.05). Women of all ages and ethnicities engage in HAI, at rates higher than providers might realize. Condom use is significantly lower for HAI vs. vaginal intercourse, putting these women at risk for acquisition of sexually transmitted infections. © 2015 International Society for Sexual Medicine.

Development of a trans-admittance mammography (TAM) using 60×60 electrode array

NASA Astrophysics Data System (ADS)

Zhao, Mingkang; Liu, Qin; In Oh, Tong; Woo, Eung Je; Seo, Jin Keun

2010-04-01

We have developed a trans-admittance mammography (TAM) system as a supplementary or alternative method of the X-ray mammography to diagnose the breast cancer. Mechanical structure of the system is similar to the X-ray mammography with the breast placed between two plates. The pair of plates is movable to accommodate breasts with different sizes and rotatable to provide multiple images with different projection angles. Without using ionizing radiation, it acquires a projection image of tissue admittivity values. One plate is a flat solid electrode where we apply a constant sinusoidal voltage with a variable frequency. The other is equipped with 60×60 array of current-sensing electrodes, of which potentials are kept at the signal reference level. The electrode array is connected to six switching modules and each module routes current signals from 600 electrodes to two ammeter modules. Each ammeter module includes six channels of ammeters and each one of them comprises an independent current-to-voltage converter, voltage amplifier, ADC and digital phase-sensitive demodulator. Each ammeter sequentially measures exit currents from 50 electrodes chosen by the corresponding switching module. An FPGA controls six ammeters to collect real- and imaginary-parts of trans-admittance data from 300 electrodes. A separate FPGA arbitrates data and command exchanges between a DSP-based main controller and ammeter modules. It also generates a sinusoidal voltage signal to be applied to the breast. All the 3600 complex current data from 12 ammeter modules are transferred to the main controller, which is interfaced to a PC through an isolated USB. The system is provided with a program to display real- and imaginary-parts of measured trans-admittance maps. The measured maps at multiple frequencies are incorporated into a frequency-difference anomaly detection algorithm. In this paper, we describe the design and construction of the system.

Consumers' acceptance of medicinal herbs: An application of the technology acceptance model (TAM).

PubMed

Jokar, Nargesh Khatun; Noorhosseini, Seyyed Ali; Allahyari, Mohammad Sadegh; Damalas, Christos A

2017-07-31

The shift in consumers' preferences from synthetic to 'natural' products has led to a resurgence of interest in medicinal plants, particularly in developing countries. However, research data about consumers' preferences for particular products is hard to find. The main objective of this study was to contribute to the general understanding of consumers' intention for selecting medicinal herbs for consumption. Factors underpinning consumers' acceptance of medicinal herbs were studied with the technology acceptance model (TAM) in Rasht City of Iran using a structured questionnaire. Most respondents had low to moderate familiarity with consumption of medicinal herbs. However, about half of the respondents (47.5%) showed a high level of acceptance of medicinal herbs. Herbs like spearmint (Mentha spicata L.), spinach (Spinacia oleracea L.), basil (Ocimum basilicum L.), Damask rose (Rosa × damascena Herrm.), saffron (Crocus sativus L.), cinnamon (Cinnamomum verum J.Presl), flixweed [Descurainia sophia (L.) Webb ex Prantl], red feathers (Echium amoenum Fisch. & C.A.Mey.), and green tea [Camellia sinensis (L.) Kuntze] had the highest consumption rate among the majority (over 75%) of citizens of Rasht. The highest rate of perceived usefulness of medicinal herbs was related to their perceived role in healing diseases. The variable of importance of use of medicinal herbs had the strongest direct effect and the variables of perceived usefulness and attitude towards use had the second and third strongest direct effect on the acceptance of medicinal herbs' use at p < 0.01. Findings provide a useful evaluation of the acceptance of medicinal herbs and may serve as a benchmark for future research and evaluation concerning the use of medicinal herbs over time. For plant producers, more effective and targeted crop development should be encouraged, whereas for retailers better marketing and delivery strategies should be sought. Copyright © 2017 Elsevier Ireland Ltd. All rights

Hospital-acquired infection in public hospital buildings in the Philippines: Is the type of ventilation increasing the risk?

PubMed

Vergeire-Dalmacion, Godofreda Ruiz; Itable, Jill Rafols; Baja, Emmanuel Saporna

2016-11-24

Hospital-acquired infections (HAIs) are associated with increased morbidity and mortality, especially in developing countries. However, limited information is available about the risk of HAIs in naturally ventilated wards (NVWs) and mechanically ventilated intensive care units (MVICUs) of public hospitals in the Philippines. We aimed to assess the association between HAIs and type of ventilation in an urban tertiary care hospital in the Philippines. A cross-sectional point-prevalence survey of infections was done in NVWs and MVICUs of a tertiary care hospital in December 2013. Multivariate analyses were done to examine the associations between HAIs and type of ventilation and other risk factors. Of the 224 patients surveyed, 63 (28%) patients had 69 HAIs. Pneumonia was the most common HAI (35%). Wards near areas with high vehicular activity had more respiratory HAI cases. Being immunocompromised is a risk factor for HAI for pediatric and adult patients. Among pediatric patients, staying in MVICUs had a lower risk for HAIs (adjusted odds ratio [AOR]: 0.33; 95% confidence interval [CI]: 0.10-1.08) compared to staying in NVWs. For adult patients, a higher risk for HAIs (AOR: 2.41; 95% CI: 0.29-18.20) was observed in MVICUs compared to NVWs. Type of ventilation is not a risk factor for HAIs. Patients who are immunocompromised may be at a higher risk for HAI. Indoor air pollution, proximity to congested main thoroughfare, and increased human foot traffic may contribute to the susceptibility of patients to HAIs. Hospital layout should be considered in infection control.

The Reactive-Causal Architecture: Introducing an Emotion Model along with Theories of Needs

NASA Astrophysics Data System (ADS)

Aydin, Ali Orhan; Orgun, Mehmet Ali

In the entertainment application area, one of the major aims is to develop believable agents. To achieve this aim, agents should be highly autonomous, situated, flexible, and display affect. The Reactive-Causal Architecture (ReCau) is proposed to simulate these core attributes. In its current form, ReCau cannot explain the effects of emotions on intelligent behaviour. This study aims is to further improve the emotion model of ReCau to explain the effects of emotions on intelligent behaviour. This improvement allows ReCau to be emotional to support the development of believable agents.

75 FR 4396 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-27

.... Proposed Project Prevalence Survey of Healthcare Associated Infections (HAIs) and Antimicrobial Use in U.S... Infections (HAIs) prevalence and antimicrobial use in the United States. Preventing HAIs is a CDC priority... antimicrobial-resistant pathogens. The scope and magnitude of HAIs in the U.S. were last directly estimated in...

Quantitative Analysis of Microbial Burden on Hospital Room Environmental Surfaces Contributing to Healthcare-Associated Infections

PubMed Central

Rutala, William A; Kanamori, Hajime; Gergen, Maria; Sickbert-Bennett, Emily; Knelson, Lauren P; Chen, Luke F; Anderson, Deverick; Sexton, Daniel; Weber, David J

2017-01-01

Abstract Background Contaminated environmental surfaces are involved in the transmission of epidemiologically important pathogens. It remains unknown which level of microbial load can contribute to healthcare-associated infections (HAI). We used microbiological data obtained from the Benefits of Enhanced Terminal Room (BETR) Disinfection Study to investigate the quantitative relationship between microbial burden and risk of HAI. Methods Microbiological samples were collected from high-frequency-touch hospital room surfaces using Rodac plates (25 cm2/plate) in rooms after terminal room disinfection. All rooms were randomly assigned to standard disinfection (Quaternary ammonium [Quat]) or an enhanced disinfection (Quat/ultraviolet light [UV-C], Bleach, Bleach/UV-C). The Quat/UV-C arm was excluded from further analysis since HAI were not observed in this arm. All new patients in study rooms were monitored for HAI following terminal disinfection through the BETR study standard protocols. We analyzed the relationship between the total colony forming units (CFU) of bacterial loads from 2,395 environmental samples in 60 rooms and HAI among new patients in the room (6 patients with HAI and 54 patients without HAI). Each arm had 2 patients with HAI. Statistical significance was determined by the Wilcoxon test, and P < 0.05 was considered significant. Results Overall, samples in rooms of patients with HAI had a mean 39.3 CFU, while samples from rooms of patients without HAI had a mean 35.6 CFU (Table 1). In the standard disinfection, the sampled rooms from the HAI patients had a significantly higher number of total CFU (mean 65.1 CFU) than non-HAI group (mean 35.5 CFU) (P = 0.019). In the enhanced disinfection rooms, there was no statistical significance between HAI and non-HAI groups. Conclusion Although our sample size may have been too small to detect contaminated microbial load in a room though a large clinical trial was conducted, our data based on the Quat arm as

Spread of hospital-acquired infections: A comparison of healthcare networks

PubMed Central

Astagneau, Pascal; Crépey, Pascal

2017-01-01

Hospital-acquired infections (HAIs), including emerging multi-drug resistant organisms, threaten healthcare systems worldwide. Efficient containment measures of HAIs must mobilize the entire healthcare network. Thus, to best understand how to reduce the potential scale of HAI epidemic spread, we explore patient transfer patterns in the French healthcare system. Using an exhaustive database of all hospital discharge summaries in France in 2014, we construct and analyze three patient networks based on the following: transfers of patients with HAI (HAI-specific network); patients with suspected HAI (suspected-HAI network); and all patients (general network). All three networks have heterogeneous patient flow and demonstrate small-world and scale-free characteristics. Patient populations that comprise these networks are also heterogeneous in their movement patterns. Ranking of hospitals by centrality measures and comparing community clustering using community detection algorithms shows that despite the differences in patient population, the HAI-specific and suspected-HAI networks rely on the same underlying structure as that of the general network. As a result, the general network may be more reliable in studying potential spread of HAIs. Finally, we identify transfer patterns at both the French regional and departmental (county) levels that are important in the identification of key hospital centers, patient flow trajectories, and regional clusters that may serve as a basis for novel wide-scale infection control strategies. PMID:28837555

Sensitivity and specificity of the method used for ascertainment of healthcare-associated infections in the second Slovenian national prevalence survey.

PubMed

Serdt, Mojca; Lejko Zupanc, Tatjana; Korošec, Aleš; Klavs, Irena

2016-12-01

The second Slovenian national healthcare-associated infections (HAIs) prevalence survey (SNHPS) was conducted in acute-care hospitals in 2011. The objective was to assess the sensitivity and specificity of the method used for the ascertainment of six types of HAIs (bloodstream infections, catheter-associated infections, lower respiratory tract infections, pneumoniae, surgical site infections, and urinary tract infections) in the University Medical Centre Ljubljana (UMCL). A cross-sectional study was conducted in patients surveyed in the SNHPS in the UMCL using a retrospective medical chart review (RMCR) and European HAIs surveillance definitions. Sensitivity and specificity of the method used in the SNHPS using RMCR as a reference was computed for ascertainment of patients with any of the six selected types of HAIs and for individual types of HAIs. Agreement between the SNHPS and RMCR results was analyzed using Cohen's kappa coefficient. 1474 of 1742 (84.6%) patients surveyed in the SNHPS were included in RMCR. The sensitivity of the SNHPS method for detecting any of six HAIs was 90% (95% confidence interval (CI): 81%-95%) and specificity 99% (95% CI: 98%-99%). The sensitivity by type of HAI ranged from 63% (lower respiratory tract infections) to 92% (bloodstream infections). Specificity was at least 99% for all types of HAIs. Agreement between the two data collection approaches for HAIs overall was very good (κ=0.83). The overall sensitivity of SNHPS collection method for ascertaining HAIs overall was high and the specificity was very high. This suggests that the estimated prevalence of HAIs in the SNHPS was credible.

Bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels for targeted X-ray computed tomography imaging and chemotherapy of breast tumors.

PubMed

Zhu, Yaqin; Wang, Xiuxiu; Chen, Jing; Zhang, Jian; Meng, Fenghua; Deng, Chao; Cheng, Ru; Feijen, Jan; Zhong, Zhiyuan

2016-12-28

Nanotheranostics is a rapidly growing field combining disease diagnosis and therapy, which ultimately may add in the development of 'personalized medicine'. Here, we designed and developed bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels (HAI-NGs) for targeted X-ray computed tomography (CT) imaging and chemotherapy of MCF-7 human breast tumors. HAI-NGs were obtained with a small size of ca. 90nm, bright green fluoresence and high serum stability from hyaluronic acid-cystamine-tetrazole and reductively degradable polyiodixanol-methacrylate via nanoprecipitation and a photo-click crosslinking reaction. Notably, paclitaxel (PTX)-loaded HAI-NGs showed a fast glutathione-responsive drug release. Confocal microscopy displayed efficient uptake of HAI-NGs by CD44 overexpressing MCF-7 cells via a receptor-mediated mechanism. MTT assays revealed that HAI-NGs were nontoxic to MCF-7 cells even at a high concentration of 1mg/mL whereas PTX-loaded HAI-NGs exhibited strong inhibition of MCF-7 cells. The in vivo pharmcokinetics, near-infrared imaging and biodistribution studies revealed that HAI-NGs significantly prolonged the blood circulation time and enhanced tumor accumulation of PTX. Interestingly, significantly enhanced CT imaging was observed for MCF-7 breast tumors in nude mice via either intratumoral or intravenous injection of HAI-NGs as compared to iodixanol. HAI-NGs fluoresence was distributed thoughout the whole tumor indicating deep tumor penetration. PTX-loaded HAI-NGs showed effective suppression of tumor growth with little systemic toxicity. HAI-NGs appear as a "smart" theranostic nanoplatform for the treatment of CD44 positive tumors. Copyright © 2016 Elsevier B.V. All rights reserved.

Associated with Health Care-Associated Infections in Cardiac Surgery

PubMed Central

Greco, Giampaolo; Shi, Wei; Michler, Robert E.; Meltzer, David O.; Ailawadi, Gorav; Hohmann, Samuel F.; Thourani, Vinod; Argenziano, Michael; Alexander, John; Sankovic, Kathy; Gupta, Lopa; Blackstone, Eugene H.; Acker, Michael A.; Russo, Mark J.; Lee, Albert; Burks, Sandra G.; Gelijns, Annetine C.; Bagiella, Emilia; Moskowitz, Alan J.; Gardner, Timothy J.

2014-01-01

BACKGROUND Health care-associated infections (HAIs) are the most common noncardiac complications after cardiac surgery and are associated with increased morbidity and mortality. Current information about their economic burden is limited. OBJECTIVES To determine the cost associated with major types of HAIs during the first 2 months after cardiac surgery. METHODS Prospectively collected data from a multicenter observational study of the Cardiothoracic Surgery Clinical Trials Network, in which patients were monitored for infections for 65 days after surgery, were merged with related financial data, routinely collected by the University HealthSystem Consortium. Incremental length of stay (LOS) and cost associated with HAIs were estimated using generalized linear models, adjusting for patient demographics, clinical history, baseline laboratory values, and surgery type. RESULTS Among 4,320 cardiac surgery patients, mean age of 64 ± 13 years, 119 (2.8%) experienced a major HAI during the index hospitalization. The most common HAIs were pneumonia (48%), sepsis (20%) and C. Difficile colitis (18%). On average, the estimated incremental cost associated with a major HAI was nearly $38,000, of which 47% was related to intensive care unit services. The incremental LOS was 14 days. Overall, there were 849 readmissions, among these, 8.7% were attributed to major HAIs. The cost of readmissions due to major HAI was on average nearly three times as much as readmissions not related to HAI. CONCLUSIONS Hospital cost, length of stay, and readmissions are strongly associated with HAIs. These associations suggest the potential for large reductions in costs if HAIs following cardiac surgery can be reduced. PMID:25572505

Closure Report for Corrective Action Unit 118: Area 27 Super Kukla Facility, Nevada Test Site, Nevada with ROTC 1, Revision 0

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

Mark Burmeister

2007-09-01

This CR provides documentation and justification for the closure of CAU 118 without further corrective action. This justification is based on process knowledge and the results of the investigative and closure activities conducted in accordance with the CAU 118 SAFER Plan: Streamlined Approach for Environmental Restoration (SAFER) Plan for CAU 118: Area 27 Super Kukla Facility, Nevada Test Site, Nevada (NNSA/NSO, 2006). The SAFER Plan provides information relating to site history as well as the scope and planning of the investigation. This CR also provides the analytical and radiological survey data to confirm that the remediation goals were met asmore » specified in the CAU 118 SAFER Plan (NNSA/NSO, 2006). The Nevada Division of Environmental Protection (NDEP) approved the CAU 118 SAFER Plan (Murphy, 2006), which recommends closure in place with use restrictions (URs).« less

Computer Surveillance of Hospital-Acquired Infections: A 25 year Update

PubMed Central

Evans, R. Scott; Abouzelof, Rouett H.; Taylor, Caroline W.; Anderson, Vickie; Sumner, Sharon; Soutter, Sharon; Kleckner, Ruth; Lloyd, James F.

2009-01-01

Hospital-acquired infections (HAIs) are a significant cause of patient harm and increased healthcare cost. Many states have instituted mandatory hospital-wide reporting of HAIs which will increase the workload of infection preventionists and the Center for Medicare and Medicaid Services is no longer paying hospitals to treat certain HAIs. These competing priorities for increased reporting and prevention have many hospitals worried. Manual surveillance of HAIs cannot provide the speed, accuracy and consistency of computerized surveillance. Computer tools can also improve the speed and accuracy of HAI analysis and reporting. Computerized surveillance for HAIs was implemented at LDS Hospital in 1984, but that system required manual entry of data for analysis and reporting. This paper reports on the current functionality and status of the updated computer system for HAI surveillance, analysis and reporting used at LDS Hospital and the 21 other Intermountain Healthcare hospitals. PMID:20351845

Prospective surveillance of device-associated health care-associated infection in an intensive care unit of a tertiary care hospital in New Delhi, India.

PubMed

Kumar, Shilpee; Sen, Poornima; Gaind, Rajni; Verma, Pardeep Kumar; Gupta, Poonam; Suri, Prem Rose; Nagpal, Sunita; Rai, Anil Kumar

2018-02-01

Surveillance of health care-associated infections (HAIs) plays a key role in the hospital infection control program and reduction of HAIs. In India, most of the surveillance of HAIs is reported from private sector hospitals that do not depict the situation of government sector hospitals. Other studies do not confirm with the Centers for Disease Control and Prevention's (CDC) National Healthcare Safety Network (NHSN) surveillance criterion, or deal with ventilator-associated pneumonia (VAP) instead of ventilator-associated event (VAE). The aim of this study was to identify the incidences of 3 device-associated HAIs (DA-HAIs) (VAE, central line-associated bloodstream infection [CLABSI], and catheter-associated urinary tract infection [CAUTI]) by active surveillance using CDC's NHSN surveillance criteria and to identify the pathogens associated with these DA-HAIs. This was a prospective surveillance study (January 2015-December 2016) conducted in an intensive care unit (ICU) of a large, tertiary care, government hospital situated in Delhi, India. Targeted surveillance was done as per the CDC's NHSN 2016 surveillance criteria. There were 343 patients admitted to the ICU that were included in the study. The surveillance data was reported over 3,755 patient days. A DA-HAIs attack rate of 20.1 per 100 admissions and incidence of 18.3 per 1,000 patient days was observed. The duration of use for each device for patients with DA-HAIs was significantly longer than for patients without DA-HAIs. The device utilization ratios of central line, ventilator, and urinary catheters were 0.57, 0.85, and 0.72, respectively. The crude excess length of stay for patients with DA-HAI was 13 days, and crude excess mortality rate was 11.8%. VAE, CLABSI, and CAUTI rates were 11.8, 7.4, and 9.7 per 1,000 device days, respectively. Among 69 DA-HAIs reported, pathogens could be identified for 49 DA-HAI cases. Klebsiella spp was the most common organism isolated, accounting 28.5% for all DA-HAI

Functional analysis of a missense mutation in the serine protease inhibitor SPINT2 associated with congenital sodium diarrhea.

PubMed

Faller, Nicolas; Gautschi, Ivan; Schild, Laurent

2014-01-01

Membrane-bound serine proteases play important roles in different biological processes. Their regulation by endogenous inhibitors is poorly understood. A Y163C mutation in the SPINT2 gene encoding the serine protease inhibitor Hepatocyte Growth Factor Inhibitor HAI-2 is associated with a congenital sodium diarrhea. The functional consequences of this mutation on HAI-2 activity and its physiological targets are unknown. We established a cellular assay in Xenopus laevis oocytes to study functional interactions between HAI-2 and candidate membrane-bound serine proteases expressed in the gastro-intestinal tract. We found that the wild-type form of HAI-2 is a potent inhibitor of nine gastro-intestinal serine proteases. The Y163C mutation in the second Kunitz domain of HAI-2 resulted in a complete loss of inhibitory activity on two intestinal proteases, prostasin and tmprss13. The effect of the mutation of the homologous Y68C in the first Kunitz domain of HAI-2 is consistent with a differential contribution of the two Kunitz domains of HAI-2 in the inhibition of serine proteases. By contrast to the Tyr to Cys, the Tyr to Ser substitution did not change the inhibitory potency of HAI-2, indicating that the thiol-group of the cysteine rather than the Tyr deletion is responsible for the HAI-2 loss of function. Our functional assay allowed us to identify membrane-bound serine proteases as cellular target for inhibition by HAI-2 wild type and mutants, and to better define the role of the Tyr in the second Kunitz domain in the inhibitory activity of HAI-2.

Role of cyclooxygenase in the vascular response to locally delivered acetylcholine in Caucasian and African descent individuals.

PubMed

Maley, Matthew J; House, James R; Tipton, Michael J; Eglin, Clare M

2017-05-01

Individuals of African descent (AFD) are more susceptible to non-freezing cold injury (NFCI) compared with Caucasian individuals (CAU). Vasodilatation to acetylcholine (ACh) is lower in AFD compared with CAU in the non-glabrous foot and finger skin sites; the reason for this is unknown. Prostanoids are responsible, in part, for the vasodilator response to ACh, however it is not known whether the contribution differs between ethnicities. 12 CAU and 12 AFD males received iontophoresis of ACh (1 w/v%) on non-glabrous foot and finger skin sites following placebo and then aspirin (600mg, single blinded). Aspirin was utilised to inhibit prostanoid production by inhibiting the cyclooxygenase (COX) enzyme. Laser Doppler flowmetry was utilised to measure changes in skin blood flow. Not all participants could receive iontophoresis charge due to high skin resistance; these participants were therefore excluded from the analyses. Foot: ACh elicited greater maximal vasodilatation in CAU than AFD following placebo (P=0.003) and COX inhibition (COXib) (P<0.001). COXib did not affect blood flow responses in AFD, but caused a reduction in the area under the curve for CAU (P=0.031). Finger: ACh elicited a greater maximal vasodilatation in CAU than AFD following placebo (P=0.013) and COXib (P=0.001). COXib tended to reduce the area under the curve in AFD (P=0.053), but did not affect CAU. CAU have a greater endothelial reactivity than AFD in both foot and finger skin sites irrespective of COXib. It is concluded that the lower ACh-induced vasodilatation in AFD is not due to a compromised COX pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

A Human Factors Evaluation of the Space Shuttle Cockpit Avionics Upgrade

DTIC Science & Technology

2012-09-01

cockpit design . This study assesses the CAU design employing human factors principles, evaluates baseline and CAU simulation data, and traces MW and SA...differences back to CAU design modifications. Significant improvements were found in all measures and across all conditions. These improvements were...found to be greater for ascent scenarios than for entry. From the findings, recommendations for the design and evaluation of future spacecraft

[Healthcare-associated infections in a paediatric haematology/oncology unit in Morocco].

PubMed

Cherkaoui, Siham; Lamchahab, Mouna; Samira, Hassoun; Zerouali, Khalid; Madani, Abdallah; Benchekroun, Said; Quessar, Asmaa

2014-01-01

HAI cause considerable morbidity and mortality and are associated with prolonged hospital stay and increased health care costs. To describe the incidence of HAI in paediatric cancer patients as the first step towards improving infection control policies. A prospective surveillance study was performed in the Casablanca university hospital paediatric haematology/oncology unit over an 8-month period from January to August 2011. Data including extrinsic risk factors associated with HAI were recorded. The incidence of HAI was 28 per 1000 patient-days. The median age was 9.6 years and the most frequent diagnosis was acute myeloid leukaemia (32%). Neutropenia at diagnosis was significantly correlated with the risk of HAI. 55.7% of HAls were nosocomial fever of unknown origin. Gram-negative bacteria were the main pathogens (60%), gram-positive cocci were responsible for 26% of HAI and Candida for 14% of HAI. The length of hospital stay for patients with and without infection were 16.5 and 5 days, respectively (P < 0.001). Six of the 11 deaths were related to HAI. These findings suggest the need to evaluate infection control measures in order to reduce morbidity and mortality in paediatric haematology/oncology units.

Targeted Assessment for Prevention of Healthcare-Associated Infections: A New Prioritization Metric.

PubMed

Soe, Minn M; Gould, Carolyn V; Pollock, Daniel; Edwards, Jonathan

2015-12-01

To develop a method for calculating the number of healthcare-associated infections (HAIs) that must be prevented to reach a HAI reduction goal and identifying and prioritizing healthcare facilities where the largest reductions can be achieved. Acute care hospitals that report HAI data to the Centers for Disease Control and Prevention's National Healthcare Safety Network. METHODS :The cumulative attributable difference (CAD) is calculated by subtracting a numerical prevention target from an observed number of HAIs. The prevention target is the product of the predicted number of HAIs and a standardized infection ratio goal, which represents a HAI reduction goal. The CAD is a numeric value that if positive is the number of infections to prevent to reach the HAI reduction goal. We calculated the CAD for catheter-associated urinary tract infections for each of the 3,639 hospitals that reported such data to National Healthcare Safety Network in 2013 and ranked the hospitals by their CAD values in descending order. Of 1,578 hospitals with positive CAD values, preventing 10,040 catheter-associated urinary tract infections at 293 hospitals (19%) with the highest CAD would enable achievement of the national 25% catheter-associated urinary tract infection reduction goal. The CAD is a new metric that facilitates ranking of facilities, and locations within facilities, to prioritize HAI prevention efforts where the greatest impact can be achieved toward a HAI reduction goal.

Understanding the patient experience of health care-associated infection: A qualitative systematic review.

PubMed

Currie, Kay; Melone, Lynn; Stewart, Sally; King, Caroline; Holopainen, Arja; Clark, Alex M; Reilly, Jacqui

2018-01-30

The global burden of health care-associated infection (HAI) is well recognized; what is less well known is the impact HAI has on patients. To develop acceptable, effective interventions, greater understanding of patients' experience of HAI is needed. This qualitative systematic review sought to explore adult patients' experiences of common HAIs. Five databases were searched. Search terms were combined for qualitative research, HAI terms, and patient experience. Study selection was conducted by 2 researchers using prespecified criteria. Critical Appraisal Skills Programme quality appraisal tools were used. Internationally recognized Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied. The Noblit and Hare (1988) approach to meta-synthesis was adopted. Seventeen studies (2001-2017) from 5 countries addressing 5 common types of HAI met the inclusion criteria. Four interrelated themes emerged: the continuum of physical and emotional responses, experiencing the response of health care professionals, adapting to life with an HAI, and the complex cultural context of HAI. The impact of different HAIs may vary; however, there are many similarities in the experience recounted by patients. The biosociocultural context of contagion was graphically expressed, with potential impact on social relationships and professional interactions highlighted. Further research to investigate contemporary patient experience in an era of antimicrobial resistance is warranted. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Multi-centre point prevalence survey of hospital-acquired infections in Ghana.

PubMed

Labi, Appiah-Korang; Obeng-Nkrumah, Noah; Owusu, Enid; Bjerrum, Stephanie; Bediako-Bowan, Antoinette; Sunkwa-Mills, Gifty; Akuffo, Christiana; Fenny, Ama Pokua; Opintan, Japheth Awuletey; Enweronu-Laryea, Christabel; Debrah, Samuel; Damale, Nelson; Bannerman, Cynthia; Newman, Mercy Jemima

2018-05-03

There is a paucity of data describing hospital acquired infections (HAIs) in Africa. To describe the prevalence and distribution of HAIs in acute care hospitals in Ghana. Between September and December 2016, point prevalence surveys were conducted in participating hospitals using protocols of the European Centre for Disease Prevention and Control. We reviewed medical records of eligible inpatients at or before 8am on the day of survey to identify HAIs present at the time of survey. Ten hospitals were surveyed, representing 32.9% of all acute care beds in government hospitals. Of 2107 inpatients surveyed, 184 HAIs were identified among 172 patients, corresponding to an overall prevalence of 8.2%. The prevalence values in hospitals ranged from 3.5 to 14.4% with higher proportion of infections in secondary and tertiary care facilities. The most frequent HAIs were surgical site infections (32.6%), bloodstream infections (19.5%), urinary tract infections (18.5%), and respiratory tract infections (16.3%). Device-associated infections accounted for 7.1% of HAIs. For 12.5% of HAIs, a microorganism was reported; the most isolated microorganism was Escherichia coli. Approximately 61% of all patients surveyed were on antibiotics; 89.5% of patients with an HAI received at least one antimicrobial agent on the day of survey. The strongest independent predictors for HAI were the presence of invasive device before onset of infection and duration of hospital stay. We recorded a low HAI burden compared to findings from other low and middle income countries. Copyright © 2018. Published by Elsevier Ltd.

Reducing Time-dependent Bias in Estimates of the Attributable Cost of Health Care-associated Methicillin-resistant Staphylococcus aureus Infections: A Comparison of Three Estimation Strategies.

PubMed

Nelson, Richard E; Samore, Matthew H; Jones, Makoto; Greene, Tom; Stevens, Vanessa W; Liu, Chuan-Fen; Graves, Nicholas; Evans, Martin F; Rubin, Michael A

2015-09-01

Previous estimates of the excess costs due to health care-associated infection (HAI) have scarcely addressed the issue of time-dependent bias. We examined time-dependent bias by estimating the health care costs attributable to an HAI due to methicillin-resistant Staphylococcus aureus (MRSA) using a unique dataset in the Department of Veterans Affairs (VA) that makes it possible to distinguish between costs that occurred before and after an HAI. In addition, we compare our results to those from 2 other estimation strategies. Using a historical cohort study design to estimate the excess predischarge costs attributable to MRSA HAIs, we conducted 3 analyses: (1) conventional, in which costs for the entire inpatient stay were compared between patients with and without MRSA HAIs; (2) post-HAI, which included only costs that occurred after an infection; and (3) matched, in which costs for the entire inpatient stay were compared between patients with an MRSA HAI and subset of patients without an MRSA HAI who were matched based on the time to infection. In our post-HAI analysis, estimates of the increase in inpatient costs due to MRSA HAI were $12,559 (P<0.0001) and $24,015 (P<0.0001) for variable and total costs, respectively. The excess variable and total cost estimates were 33.7% and 31.5% higher, respectively, when using the conventional methods and 14.6% and 11.8% higher, respectively, when using matched methods. This is the first study to account for time-dependent bias in the estimation of incremental per-patient health care costs attributable to HAI using a unique dataset in the VA. We found that failure to account for this bias can lead to overestimation of these costs. Matching on the timing of infection can reduce this bias substantially.

Healthcare Associated Infections in a Resource Limited Setting.

PubMed

Bammigatti, Chanaveerappa; Doradla, Saikumar; Belgode, Harish Narasimha; Kumar, Harichandra; Swaminathan, Rathinam Palamalai

2017-01-01

Health Care associated Infections (HAI) are the most common complications affecting the hospitalized patients. HAI are more common in developing and under developed countries. However, there are no systematic surveillance programs in these countries. To find out the burden, predisposing factors and multidrug resistant organisms causing HAI in a resource limited setting. This prospective observational study was done at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER). Patients aged 13 years or more with stay of more than 48 hours in a 16 bedded Medical Intensive Care Unit (MICU) between November 2011 and April 2013 were included in the study. Patients were prospectively followed up till discharge or death for the development of HAI. Device associated HAI like Ventilator Associated Pneumonia (VAP), Catheter Related-Blood Stream Infection (CR-BSI) and Catheter Associated-Urinary Tract Infections (CA-UTI) were studied. Standard laboratory methods were used for identification of microorganisms causing HAI and to test their antibiotic sensitivity. A total of 346 patients were included in the study with median age of 38 years. Common indications for admission to Medical Intensive Care Unit (MICU) were poisoning (31.5%); neurological illness (23.4%) like Guillian-Barre syndrome, tetanus, meningitis, encephalitis; respiratory illness (14.5%) like pneumonia, acute respiratory distress syndrome and tropical infections (7.2%) like malaria, scrub typhus, leptospirosis. Fifty percent (174/346) patients developed one or more HAI with VAP being the most common. The rates of HAI per 1000 device days for VAP, CR-BSI, CA-UTI were 72.56, 3.98 and 12.4, respectively. Acinetobacter baumannii was the most common organism associated with HAI. Multidrug resistance was seen in 74% of the isolates. The burden of HAI, especially with MDR organisms, in resource constrained setting like ours is alarming. There is urgent need for infection control and monitoring

Exploring quality of life among the elderly in Hai Duong province, Vietnam: a rural–urban dialogue

PubMed Central

Huong, Nguyen Thanh; Hai Ha, Le Thi; Quynh Chi, Nguyen Thai; Hill, Peter S.; Walton, Tara

2012-01-01

Background Quality of life (QoL) is an important health index for the elderly, necessary for assessing interventions, and prioritising medical and social care needs. As the ageing population in Vietnam continues to increase, understanding important dimensions of QoL for the elderly is essential. There is a paucity of research in this area, however, and the available literature focuses on functional capacities. The purpose of this article is to explore perceptions on the dimensions of QoL among the elderly in Vietnam, to use these perceptions to broaden the concept, and to explore similarities and differences between those living in urban compared to rural areas. Method Qualitative methods included in-depth interviews (IDI) with experts in ageing and elderly persons, as well as focus group discussions (FGDs) in three communes in Hai Duong province. IDIs and FGDs were recorded and transcribed. NVivo software was used to analyse the data. Results Thematic analysis identified physical, psychological, social, environmental, religious, and economic as important dimensions of QoL. For elderly participants in both urban and rural areas, physical health, social relations, finances and economics, the physical and social environment, and psychological health were reported as important. Rural participants also identified religious practice as an important dimension of QoL. In terms of relationships, the elderly in urban areas prioritised those with their children, while the elderly in rural areas focussed their concerns on community relationships and economic conditions. Conclusion Isolating individual factors that contribute to QoL among the elderly is difficult given the inter-relations and rich cross-linkages between themes. Elderly participants in urban and rural areas broadly shared perspectives on the themes identified, in particular social relationships, but their experiences diverged around issues surrounding finances and economics, their respective physical and social

Exploring quality of life among the elderly in Hai Duong province, Vietnam: a rural-urban dialogue.

PubMed

Huong, Nguyen Thanh; Hai Ha, Le Thi; Quynh Chi, Nguyen Thai; Hill, Peter S; Walton, Tara

2012-12-22

Quality of life (QoL) is an important health index for the elderly, necessary for assessing interventions, and prioritising medical and social care needs. As the ageing population in Vietnam continues to increase, understanding important dimensions of QoL for the elderly is essential. There is a paucity of research in this area, however, and the available literature focuses on functional capacities. The purpose of this article is to explore perceptions on the dimensions of QoL among the elderly in Vietnam, to use these perceptions to broaden the concept, and to explore similarities and differences between those living in urban compared to rural areas. Qualitative methods included in-depth interviews (IDI) with experts in ageing and elderly persons, as well as focus group discussions (FGDs) in three communes in Hai Duong province. IDIs and FGDs were recorded and transcribed. NVivo software was used to analyse the data. Thematic analysis identified physical, psychological, social, environmental, religious, and economic as important dimensions of QoL. For elderly participants in both urban and rural areas, physical health, social relations, finances and economics, the physical and social environment, and psychological health were reported as important. Rural participants also identified religious practice as an important dimension of QoL. In terms of relationships, the elderly in urban areas prioritised those with their children, while the elderly in rural areas focussed their concerns on community relationships and economic conditions. Isolating individual factors that contribute to QoL among the elderly is difficult given the inter-relations and rich cross-linkages between themes. Elderly participants in urban and rural areas broadly shared perspectives on the themes identified, in particular social relationships, but their experiences diverged around issues surrounding finances and economics, their respective physical and social environments, and the contribution

Targeted Assessment for Prevention of Healthcare-Associated Infections: A New Prioritization Metric

PubMed Central

Soe, Minn M.; Gould, Carolyn V.; Pollock, Daniel; Edwards, Jonathan

2015-01-01

OBJECTIVE To develop a method for calculating the number of healthcare-associated infections (HAIs) that must be prevented to reach a HAI reduction goal and identifying and prioritizing healthcare facilities where the largest reductions can be achieved. SETTING Acute care hospitals that report HAI data to the Centers for Disease Control and Prevention’s National Healthcare Safety Network. METHODS The cumulative attributable difference (CAD) is calculated by subtracting a numerical prevention target from an observed number of HAIs. The prevention target is the product of the predicted number of HAIs and a standardized infection ratio goal, which represents a HAI reduction goal. The CAD is a numeric value that if positive is the number of infections to prevent to reach the HAI reduction goal. We calculated the CAD for catheter-associated urinary tract infections for each of the 3,639 hospitals that reported such data to National Healthcare Safety Network in 2013 and ranked the hospitals by their CAD values in descending order. RESULTS Of 1,578 hospitals with positive CAD values, preventing 10,040 catheter-associated urinary tract infections at 293 hospitals (19%) with the highest CAD would enable achievement of the national 25% catheter-associated urinary tract infection reduction goal. CONCLUSION The CAD is a new metric that facilitates ranking of facilities, and locations within facilities, to prioritize HAI prevention efforts where the greatest impact can be achieved toward a HAI reduction goal. PMID:26310913

Heterosexual anal intercourse among men in Long Beach, California.

PubMed

Hess, Kristen L; Reynolds, Grace L; Fisher, Dennis G

2014-01-01

Anal intercourse poses a greater risk for human immunodeficiency virus (HIV) transmission than vaginal intercourse, and in recent years there has been a growing understanding that heterosexual anal intercourse (HAI) is not uncommon. However, the majority of the anal intercourse literature has focused on men who have sex with men. The little research on HAI has mostly looked at women, with limited work among men. This analysis examined the association between HAI and high-risk behaviors (N = 1,622) and sexual sensation seeking (N = 239) in a sample of men recruited from 2001 to 2012 in Long Beach, California. Almost half of the sample was non-Hispanic Black. The median age was 42 years, 42% were homeless, and 20% reported recent HAI. Men who reported HAI were likely to be Hispanic, were likely to be homeless, had a male partner, engaged in sex exchange, and used cocaine or amphetamines during sex. Men who reported HAI scored higher on the Sexual Sensation Seeking scale. This research supports other work showing the relationship between HAI and high-risk behaviors. More important, it contributes new knowledge by demonstrating the association between HAI and sexual sensation seeking. This research highlights the importance of personality traits when trying to understand sexual behavior and when developing HIV prevention interventions.

Gender differences in heterosexual anal sex practices among women and men in substance abuse treatment.

PubMed

Calsyn, Donald A; Hatch-Maillette, Mary A; Meade, Christina S; Tross, Susan; Campbell, Aimee N C; Beadnell, Blair

2013-09-01

Heterosexual anal intercourse (HAI) is an understudied risk behavior among women and men in substance abuse treatment. Rates of HAI for women (n = 441) and men (n = 539) were identified for any, main and casual partners. More men (32.8 %) than women (27.1 %) reported engaging in HAI in the previous 90 days. These rates are higher than those reported for both men (6.0-15.9 %) and women (3.5-13.0 %) ages 25-59 in the National Survey of Sexual Health and Behavior. Men were significantly more likely to report HAI with their casual partners (34.1 %) than women (16.7 %). In a logistic regression model generated to identify associations between HAI and variables previously shown to be related to high risk sexual behavior, being younger, bisexual, and White were significantly associated with HAI. For men, having more sex partners was also a significant correlate. HAI is a logical target for increased focus in HIV prevention interventions.

Nebraska Prostate Cancer Research Program

DTIC Science & Technology

2014-10-01

orientation on Tuesday of May 28 and continued on Wednesday of May 29. The INBRE Program had a Welcome Barbeque reception in the evening of May 29 and...period.  All CAU students attended Tuesday noon seminar offered by the UNMC Summer Undergraduate Research Program through the entire period...programs.  All CAU students prepared their results in posters.  Our current CAU trainee Ms. Marisha Morris gave a poster presentation in the The

Cost-utility analysis of meaning-centered group psychotherapy for cancer survivors.

PubMed

van der Spek, Nadia; Jansen, Femke; Holtmaat, Karen; Vos, Joël; Breitbart, William; van Uden-Kraan, Cornelia F; Tollenaar, Rob A E M; Cuijpers, Pim; Coupé, Veerle M H; Verdonck-de Leeuw, Irma M

2018-04-06

Meaning-centered group psychotherapy for cancer survivors (MCGP-CS) improves meaning, psychological well-being, and mental adjustment to cancer and reduces psychological distress. This randomized controlled trial was conducted to investigate the cost-utility of MCGP-CS compared with supportive group psychotherapy (SGP) and care-as-usual (CAU). In total, 170 patients were randomized to MCGP-CS, SGP, or CAU. Intervention costs, direct medical and nonmedical costs, productivity losses, and health-related quality of life were measured until 6 months follow-up, using the TIC-P, PRODISQ, data from the hospital information system, and the EQ-5D. The cost-utility was calculated by comparing mean cumulative costs and quality-adjusted life years (QALYs). Mean total costs ranged from €4492 (MCGP-CS) to €5304 (CAU). Mean QALYs ranged .507 (CAU) to .540 (MCGP-CS). MCGP-CS had a probability of 74% to be both less costly and more effective than CAU, and 49% compared with SGP. Sensitivity analyses showed these findings are robust. If society is willing to pay €0 for one gained QALY, MCGP-CS has a 78% probability of being cost-effective compared with CAU. This increases to 85% and 92% at willingness-to-pay thresholds of €10 000 and €30 000, which are commonly accepted thresholds. MCGP-CS is highly likely a cost-effective intervention, meaning that there is a positive balance between the costs and gains of MCGP-CS, in comparison with SGP and CAU. Copyright © 2018 John Wiley & Sons, Ltd.

Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals.

PubMed

Maley, Matthew J; House, James R; Tipton, Michael J; Eglin, Clare M

2015-08-01

Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027-0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043-0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.

Formation of tamoxifen-DNA adducts in multiple organs of adult female cynomolgus monkeys dosed with tamoxifen for 30 days.

PubMed

Schild, Laura J; Divi, Rao L; Beland, Frederick A; Churchwell, Mona I; Doerge, Daniel R; Gamboa da Costa, Gonçalo; Marques, M Matilde; Poirier, Miriam C

2003-09-15

The use of the antiestrogen tamoxifen (TAM) is associated with an increase in endometrial cancer. TAM-induced endometrial carcinogenesis may proceed through a genotoxin-mediated pathway, although the detection of endometrial TAM-DNA adducts in exposed women is still controversial. In this study, a monkey model has been used to investigate the question of TAM-DNA adduct formation in primates. Two methods have been used to determine TAM-DNA adducts: a TAM-DNA chemiluminescence immunoassay (TAM-DNA CIA), using an antiserum that has specificity for (E)-alpha-(deoxyguanosin-N(2)-yl)-tamoxifen (dG-TAM) and (E)-alpha-(deoxyguanosin-N(2)-yl)-N-desmethyltamoxifen (dG-desmethyl-TAM) and electrospray ionization tandem mass spectrometry (ES-MS/MS) coupled with on-line sample preparation and high-performance liquid chromatography (HPLC). Mature (19 year old) cynomolgus monkeys were given either vehicle control (n = 1) or TAM (n = 3) twice daily for a total dose of 2 mg of TAM/kg body weight (bw)/day for 30 days by naso-gastric intubation. Tissues were harvested, and DNA was isolated from uterus, ovary, liver, brain cortex, and kidney. By TAM-DNA CIA, values for uterine TAM-DNA adducts in two monkeys were 0.9 and 1.7 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts in the same animals were 0.4 and 0.5 adducts/10(8) nucleotides. Liver, brain cortex, and kidney DNA samples from the three exposed monkeys had TAM-DNA levels of 2.1-4.2 adducts/10(8) nucleotides, 0.4-5.0 adducts/10(8) nucleotides, and 0.7-2.1 adducts/10(8) nucleotides, respectively. By HPLC-ES-MS/MS, the levels of TAM-DNA adducts detected in all tissues were comparable with those observed by TAM-DNA CIA. Thus, values for uterine TAM-DNA adducts ranged from 0.5 to 1.4 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts, measurable in two monkeys, were 0.2 and 0.3 adducts/10(8) nucleotides. Liver DNA contained the highest TAM-DNA adduct levels (7.0-11.1 adducts/10(8) nucleotides

Healthcare Associated Infections in a Resource Limited Setting

PubMed Central

Doradla, Saikumar; Belgode, Harish Narasimha; Kumar, Harichandra; Swaminathan, Rathinam Palamalai

2017-01-01

Introduction Health Care associated Infections (HAI) are the most common complications affecting the hospitalized patients. HAI are more common in developing and under developed countries. However, there are no systematic surveillance programs in these countries. Aim To find out the burden, predisposing factors and multidrug resistant organisms causing HAI in a resource limited setting. Materials and Methods This prospective observational study was done at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER). Patients aged 13 years or more with stay of more than 48 hours in a 16 bedded Medical Intensive Care Unit (MICU) between November 2011 and April 2013 were included in the study. Patients were prospectively followed up till discharge or death for the development of HAI. Device associated HAI like Ventilator Associated Pneumonia (VAP), Catheter Related-Blood Stream Infection (CR-BSI) and Catheter Associated-Urinary Tract Infections (CA-UTI) were studied. Standard laboratory methods were used for identification of microorganisms causing HAI and to test their antibiotic sensitivity. Results A total of 346 patients were included in the study with median age of 38 years. Common indications for admission to Medical Intensive Care Unit (MICU) were poisoning (31.5%); neurological illness (23.4%) like Guillian-Barre syndrome, tetanus, meningitis, encephalitis; respiratory illness (14.5%) like pneumonia, acute respiratory distress syndrome and tropical infections (7.2%) like malaria, scrub typhus, leptospirosis. Fifty percent (174/346) patients developed one or more HAI with VAP being the most common. The rates of HAI per 1000 device days for VAP, CR-BSI, CA-UTI were 72.56, 3.98 and 12.4, respectively. Acinetobacter baumannii was the most common organism associated with HAI. Multidrug resistance was seen in 74% of the isolates. Conclusion The burden of HAI, especially with MDR organisms, in resource constrained setting like ours is alarming. There

Accuracy of administrative data for surveillance of healthcare-associated infections: a systematic review

PubMed Central

van Mourik, Maaike S M; van Duijn, Pleun Joppe; Moons, Karel G M; Bonten, Marc J M; Lee, Grace M

2015-01-01

Objective Measuring the incidence of healthcare-associated infections (HAI) is of increasing importance in current healthcare delivery systems. Administrative data algorithms, including (combinations of) diagnosis codes, are commonly used to determine the occurrence of HAI, either to support within-hospital surveillance programmes or as free-standing quality indicators. We conducted a systematic review evaluating the diagnostic accuracy of administrative data for the detection of HAI. Methods Systematic search of Medline, Embase, CINAHL and Cochrane for relevant studies (1995–2013). Methodological quality assessment was performed using QUADAS-2 criteria; diagnostic accuracy estimates were stratified by HAI type and key study characteristics. Results 57 studies were included, the majority aiming to detect surgical site or bloodstream infections. Study designs were very diverse regarding the specification of their administrative data algorithm (code selections, follow-up) and definitions of HAI presence. One-third of studies had important methodological limitations including differential or incomplete HAI ascertainment or lack of blinding of assessors. Observed sensitivity and positive predictive values of administrative data algorithms for HAI detection were very heterogeneous and generally modest at best, both for within-hospital algorithms and for formal quality indicators; accuracy was particularly poor for the identification of device-associated HAI such as central line associated bloodstream infections. The large heterogeneity in study designs across the included studies precluded formal calculation of summary diagnostic accuracy estimates in most instances. Conclusions Administrative data had limited and highly variable accuracy for the detection of HAI, and their judicious use for internal surveillance efforts and external quality assessment is recommended. If hospitals and policymakers choose to rely on administrative data for HAI surveillance, continued

Prevalence of Healthcare-Associated Infections and Antimicrobial Use Among Adult Inpatients in Singapore Acute-Care Hospitals: Results From the First National Point Prevalence Survey.

PubMed

Cai, Yiying; Venkatachalam, Indumathi; Tee, Nancy W; Tan, Thean Yen; Kurup, Asok; Wong, Sin Yew; Low, Chian Yong; Wang, Yang; Lee, Winnie; Liew, Yi Xin; Ang, Brenda; Lye, David C; Chow, Angela; Ling, Moi Lin; Oh, Helen M; Cuvin, Cassandra A; Ooi, Say Tat; Pada, Surinder K; Lim, Chong Hee; Tan, Jack Wei Chieh; Chew, Kean Lee; Nguyen, Van Hai; Fisher, Dale A; Goossens, Herman; Kwa, Andrea L; Tambyah, Paul A; Hsu, Li Yang; Marimuthu, Kalisvar

2017-05-15

We conducted a national point prevalence survey (PPS) to determine the prevalence of healthcare-associated infections (HAIs) and antimicrobial use (AMU) in Singapore acute-care hospitals. Trained personnel collected HAI, AMU, and baseline hospital- and patient-level data of adult inpatients from 13 private and public acute-care hospitals between July 2015 and February 2016, using the PPS methodology developed by the European Centre for Disease Prevention and Control. Factors independently associated with HAIs were determined using multivariable regression. Of the 5415 patients surveyed, there were 646 patients (11.9%; 95% confidence interval [CI], 11.1%-12.8%) with 727 distinct HAIs, of which 331 (45.5%) were culture positive. The most common HAIs were unspecified clinical sepsis (25.5%) and pneumonia (24.8%). Staphylococcus aureus (12.9%) and Pseudomonas aeruginosa (11.5%) were the most common pathogens implicated in HAIs. Carbapenem nonsusceptibility rates were highest in Acinetobacter species (71.9%) and P. aeruginosa (23.6%). Male sex, increasing age, surgery during current hospitalization, and presence of central venous or urinary catheters were independently associated with HAIs. A total of 2762 (51.0%; 95% CI, 49.7%-52.3%) patients were on 3611 systemic antimicrobial agents; 462 (12.8%) were prescribed for surgical prophylaxis and 2997 (83.0%) were prescribed for treatment. Amoxicillin/clavulanate was the most frequently prescribed (24.6%) antimicrobial agent. This survey suggested a high prevalence of HAIs and AMU in Singapore's acute-care hospitals. While further research is necessary to understand the causes and costs of HAIs and AMU in Singapore, repeated PPSs over the next decade will be useful to gauge progress at controlling HAIs and AMU. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Prospective study estimating healthcare associated infections in a paediatric hemato-oncology unit of a tertiary care hospital in North India.

PubMed

Gupta, Ayush; Kapil, Arti; Kabra, S K; Lodha, Rakesh; Sood, Seema; Dhawan, Benu; Das, Bimal K; Sreenivas, V

2013-12-01

Healthcare associated infections (HAIs) are responsible for morbidity and mortality among immunocompromised and critically ill patients. We undertook this study to estimate the burden of HAIs in the paediatric cancer patients in a tertiary care hospital in north India. This prospective, observational study, based on active surveillance for a period of 11 months was undertaken in a 4-bedded isolated, cubicle for paediatric cancer patients. Patients who stayed in the cubicle for ≥48 h, were followed prospectively for the development of HAIs. Of the 138 patients, 13 developed 14 episodes of HAIs during the study period. Patient-days calculated were 1273 days. Crude infection rate (CIR) and incidence density (ID) of all HAIs were 9.4/100 patients and 11/1000 patient-days, respectively. Of the 14 episodes of HAIs, seven (50%) were of blood stream infections (HA-BSI), five (36%) of pneumonia (HAP) and two (14%) urinary tract infections (HA-UTI). The CIRs of HA-BSI, HAP and HA-UTI were 5.1, 3.6 and 1.4/100 patients, respectively. The corresponding IDs were 5.5, 3.9 and 1.6/1000 patient-days, respectively. Mean length of stay was significantly higher in patients who developed an HAI [13.8 (range 7-30), median (Interquartile range) 12 (11-14)] vs 7.5 days [range 2-28, median (interquartile range) 7 (5-9); P<0.0001]. Also mortality was significantly higher in patients who developed an HAI [23% (3/13) vs 3% (4/125), P<0.05]. The incidence of HAIs in the paediatric cancer patients in the study was 11/1000 patient days, of which HA-BSIs were the commonest. HAIs were associated with an increase in morbidity and mortality amongst this high risk patient population.

Tamoxifen-DNA adduct formation in monkey and human reproductive organs.

PubMed

Hernandez-Ramon, Elena E; Sandoval, Nicole A; John, Kaarthik; Cline, J Mark; Wood, Charles E; Woodward, Ruth A; Poirier, Miriam C

2014-05-01

The estrogen analog tamoxifen (TAM), used for adjuvant therapy of breast cancer, induces endometrial and uterine tumors in breast cancer patients. Proliferation stimulus of the uterine endometrium is likely involved in tumor induction, but genotoxicity may also play a role. Formation of TAM-DNA adducts in human tissues has been reported but remains controversial. To address this issue, we examined TAM-DNA adducts in uteri from two species of monkeys, Erythrocebus patas (patas) and Macaca fascicularis (macaque), and in human endometrium and myometrium. Monkeys were given 3-4 months of chronic TAM dosing scaled to be equivalent to the daily human dose. In the uteri, livers and brains from the patas (n = 3), and endometrium from the macaques (n = 4), TAM-DNA adducts were measurable by TAM-DNA chemiluminescence immunoassay. Average TAM-DNA adduct values for the patas uteri (23 adducts/10(8) nucleotides) were similar to those found in endometrium of the macaques (19 adducts/10(8) nucleotides). Endometrium of macaques exposed to both TAM and low-dose estradiol (n = 5) averaged 34 adducts/10(8) nucleotides. To examine TAM-DNA persistence in the patas, females (n = 3) were exposed to TAM for 3 months and to no drug for an additional month, resulting in low or non-detectable TAM-DNA in livers and uteri. Human endometrial and myometrial samples from women receiving (n = 8) and not receiving (n = 8) TAM therapy were also evaluated. Women receiving TAM therapy averaged 10.3 TAM-DNA adducts/10(8) nucleotides, whereas unexposed women showed no detectable TAM-DNA. The data indicate that genotoxicity, in addition to estrogen agonist effects, may contribute to TAM-induced human endometrial cancer.

Nursing Workload as a Risk Factor for Healthcare Associated Infections in ICU: A Prospective Study

PubMed Central

Daud-Gallotti, Renata M.; Costa, Silvia F.; Guimarães, Thais; Padilha, Katia Grillo; Inoue, Evelize Naomi; Vasconcelos, Tiago Nery; da Silva Cunha Rodrigues, Fernanda; Barbosa, Edizângela Vasconcelos; Figueiredo, Walquíria Barcelos; Levin, Anna S.

2012-01-01

Introduction Nurse understaffing is frequently hypothesized as a potential risk factor for healthcare-associated infections (HAI). This study aimed to evaluate the role of nursing workload in the occurrence of HAI, using Nursing Activities Score (NAS). Methods This prospective cohort study enrolled all patients admitted to 3 Medical ICUs and one step-down unit during 3 months (2009). Patients were followed-up until HAI, discharge or death. Information was obtained from direct daily observation of medical and nursing rounds, chart review and monitoring of laboratory system. Nursing workload was determined using NAS. Non-compliance to the nurses’ patient care plans (NPC) was identified. Demographic data, clinical severity, invasive procedures, hospital interventions, and the occurrence of other adverse events were also recorded. Patients who developed HAI were compared with those who did not. Results 195 patients were included and 43 (22%) developed HAI: 16 pneumonia, 12 urinary-tract, 8 bloodstream, 2 surgical site, 2 other respiratory infections and 3 other. Average NAS and average proportion of non compliance with NPC were significantly higher in HAI patients. They were also more likely to suffer other adverse events. Only excessive nursing workload (OR: 11.41; p: 0.019) and severity of patient’s clinical condition (OR: 1.13; p: 0.015) remained as risk factors to HAI. Conclusions Excessive nursing workload was the main risk factor for HAI, when evaluated together with other invasive devices except mechanical ventilation. To our knowledge, this study is the first to evaluate prospectively the nursing workload as a potential risk factor for HAI, using NAS. PMID:23300645

Healthcare associated infections in Paediatric Intensive Care Unit of a tertiary care hospital in India: Hospital stay & extra costs.

PubMed

Sodhi, Jitender; Satpathy, Sidhartha; Sharma, D K; Lodha, Rakesh; Kapil, Arti; Wadhwa, Nitya; Gupta, Shakti Kumar

2016-04-01

Healthcare associated infections (HAIs) increase the length of stay in the hospital and consequently costs as reported from studies done in developed countries. The current study was undertaken to evaluate the impact of HAIs on length of stay and costs of health care in children admitted to Paediatric Intensive Care Unit (PICU) of a tertiary care hospital in north India. This prospective study was done in the seven bedded PICU of a large multi-specialty tertiary care hospital in New Delhi, India. A total of 20 children with HAI (cases) and 35 children without HAI (controls), admitted to the PICU during the study period (January 2012 to June 2012), were matched for gender, age, and average severity of illness score. Each patient's length of stay was obtained prospectively. Costs of healthcare were estimated according to traditional and time driven activity based costing methods approach. The median extra length of PICU stay for children with HAI (cases), compared with children with no HAI (controls), was seven days (IQR 3-16). The mean total costs of patients with and without HAI were ' 2,04,787 (US$ 3,413) and ' 56,587 (US$ 943), respectively and the mean difference in the total cost between cases and controls was ' 1,48,200 (95% CI 55,716 to 2,40,685, p<0.01). This study highlights the effect of HAI on costs for PICU patients, especially costs due to prolongation of hospital stay, and suggests the need to develop effective strategies for prevention of HAI to reduce costs of health care.

From the risk analysis to the development of interventions and training for the prevention and control of healthcare associated infections. The experience of G. Pini Orthopedic Institute.

PubMed

Navone, P; Conti, C; Domeniconi, G; Nobile, M

2015-01-01

Health-care associated infections (HAIs) represents a phenomenon of central importance all over Europe. Every year 4,5 millions cases are detected in European Union, with 37.000 related deaths. Surgical-site infections (SSIs) are one of the most common HAIs, that are associated with an increased length of stay, re-operation rate, intensive care admissions rate, and higher mortality rate. G. Pini Orthopedics Institute implemented in the last two years a multimodal strategy for controlling and preventing HAIs, in particular for SSIs. This paper describes the prevention's strategies adopted for prevention of HAIs, at G. Pini Orthopedic Institute. Our findings show that application of a multi modal promotion strategy was associated with an improvement in HAI prevention.

Nitrate accumulation and leaching potential reduced by coupled water and nitrogen management in the Huang-Huai-Hai Plain.

PubMed

Huang, Ping; Zhang, Jiabao; Zhu, Anning; Li, Xiaopeng; Ma, Donghao; Xin, Xiuli; Zhang, Congzhi; Wu, Shengjun; Garland, Gina; Pereira, Engil Isadora Pujol

2018-01-01

Irrigation and nitrogen (N) fertilization in excess of crop requirements are responsible for substantial nitrate accumulation in the soil profile and contamination of groundwater by nitrate leaching during intensive agricultural production. In this on-farm field trial, we compared 16 different water and N treatments on nitrate accumulation and its distribution in the soil profile (0-180cm), nitrate leaching potential, and groundwater nitrate concentration within a summer-maize (Zea mays L.) and winter-wheat (Triticum aestivum L.) rotation system in the Huang-Huai-Hai Plain over five cropping cycles (2006-2010). The results indicated that nitrate remaining in the soil profile after crop harvest and nitrate concentration of soil solutions at two depths (80cm and 180cm) declined with increasing irrigation amounts and increased greatly with increasing N application rates, especially for seasonal N application rates higher than 190kgNha -1 . During the experimental period, continuous torrential rainfall was the main cause for nitrate leaching beyond the root zone (180cm), which could pose potential risks for contamination of groundwater. Nitrate concentration of groundwater varied from 0.2 to 2.9mgL -1 , which was lower than the limit of 10mgL -1 as the maximum safe level for drinking water. In view of the balance between grain production and environmental consequences, seasonal N application rates of 190kgNha -1 and 150kgNha -1 were recommended for winter wheat and summer maize, respectively. Irrigation to the field capacity of 0-40cm and 0-60cm soil depth could be appropriate for maize and wheat, respectively. Therefore, taking grain yields, mineral N accumulation in the soil profile, nitrate leaching potential, and groundwater quality into account, coupled water and N management could provide an opportunity to promote grain production while reducing negative environmental impacts in this region. Copyright © 2017 Elsevier B.V. All rights reserved.

Hepatic DNA adduct dosimetry in rats fed tamoxifen: a comparison of methods.

PubMed

Schild, Laura J; Phillips, David H; Osborne, Martin R; Hewer, Alan; Beland, Frederick A; Churchwell, Mona I; Brown, Karen; Gaskell, Margaret; Wright, Elizabeth; Poirier, Miriam C

2005-03-01

Liver homogenates from rats fed tamoxifen (TAM) in the diet were shared among four different laboratories. TAM-DNA adducts were assayed by high pressure liquid chromatography-electrospray tandem mass spectrometry (HPLC-ES-MS/MS), TAM-DNA chemiluminescence immunoassay (TAM-DNA CIA), and (32)P-postlabeling with either thin layer ((32)P-P-TLC) or liquid chromatography ((32)P-P-HPLC) separation. In the first study, rats were fed a diet containing 500 p.p.m. TAM for 2 months, and the values for measurements of the (E)-alpha-(deoxyguanosin-N(2)-yl)-tamoxifen (dG-N(2)-TAM) adduct in replicate rat livers varied by 3.5-fold when quantified using 'in house' TAM-DNA standards, or other approaches where appropriate. In the second study, rats were fed 0, 50, 250 or 500 p.p.m. TAM for 2 months, and TAM-DNA values were quantified using both 'in house' approaches as well as a newly synthesized [N-methyl-(3)H]TAM-DNA standard that was shared among all the participating groups. In the second study, the total TAM-DNA adduct values varied by 2-fold, while values for the dG-N(2)-TAM varied by 2.5-fold. Ratios of dG-N(2)-TAM:(E)-alpha-(deoxyguanosin-N(2)-yl)-N-desmethyltamoxifen (dG-N(2)-N-desmethyl-TAM) in the second study were approximately 1:1 over the range of doses examined. The study demonstrated a remarkably good agreement for TAM-DNA adduct measurements among the diverse methods employed.

Closure Report for Corrective Action Unit 574: Neptune, Nevada National Security Site, Nevada

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

NSTec Environmental Restoration

Corrective Action Unit (CAU) 574 is identified in the Federal Facility Agreement and Consent Order (FFACO) as 'Neptune' and consists of the following two Corrective Action Sites (CASs), located in Area 12 of the Nevada National Security Site: (1) CAS 12-23-10, U12c.03 Crater (Neptune); and (2) CAS 12-45-01, U12e.05 Crater (Blanca). This Closure Report presents information supporting closure of CAU 574 according to the FFACO (FFACO, 1996 [as amended March 2010]) and the Streamlined Approach for Environmental Restoration Plan for CAU 574 (U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office [NNSA/NSO], 2011). The following activities were performedmore » to support closure of CAU 574: (1) In situ external dose rate measurements were collected using thermoluminescent dosimeters at CAS 12-45-01, U12e.05 Crater (Blanca). (2) Total effective dose rates were determined at both sites by summing the internal and external dose rate components. (3) A use restriction (UR) was implemented at CAS 12-23-10, U12c.03 Crater (Neptune). Areas that exceed the final action level (FAL) of 25 millirems per year (mrem/yr) based on the Occasional Use Area exposure scenario are within the existing use restricted area for CAU 551. The 25-mrem/yr FAL is not exceeded outside the existing CAU 551 UR for any of the exposure scenarios (Industrial Area, Remote Work Area, and Occasional Use Area). Therefore, the existing UR for CAU 551 is sufficient to bound contamination that exceeds the FAL. (4) An administrative UR was implemented at CAS 12-45-01, U12e.05 Crater (Blanca) as a best management practice (BMP). The 25-mrem/yr FAL was not exceeded for the Remote Work Area or Occasional Use Area exposure scenarios; therefore, a UR is not required. However, because the 25-mrem/yr FAL was exceeded for the Industrial Area exposure scenario, an administrative UR was established as a BMP. UR documentation is included as Appendix B. The UR at CAS 12-23-10, U12c.03 Crater

Health care worker perspectives of their motivation to reduce health care-associated infections.

PubMed

McClung, Laura; Obasi, Chidi; Knobloch, Mary Jo; Safdar, Nasia

2017-10-01

Health care-associated infections (HAIs) are largely preventable, but are associated with considerable health care burden. Given the significant cost of HAIs, many health care institutions have implemented bundled interventions to reduce HAIs. These complex behavioral interventions require considerable effort; however, individual behaviors and motivations crucial to successful and sustained implementation have not been adequately assessed. We evaluated health care worker motivations to reduce HAIs. This was a phenomenologic qualitative study of health care workers in different roles within a university hospital, recruited via a snowball strategy. Using constructs from the Consolidated Framework for Implementation Research model, face-to-face semi-structured interviews were used to explore perceptions of health care worker motivation to follow protocols on HAI prevention. Across all types of health care workers interviewed, patient safety and improvement in clinical outcomes were the major motivators to reducing HAIs. Other important motivators included collaborative environment that valued individual input, transparency and feedback at both organizational and individual levels, leadership involvement, and refresher trainings and workshops. We did not find policy, regulatory considerations, or financial penalties to be important motivators. Health care workers perceived patient safety and clinical outcomes as the primary motivators to reduce HAI. Leadership engagement and data-driven interventions with frequent performance feedback were also identified as important facilitators of HAI prevention. Published by Elsevier Inc.

Healthcare-associated infections in a tunisian university hospital: from analysis to action

PubMed Central

Mahjoub, Mohamed; Bouafia, Nebiha; Bannour, Waadia; Masmoudi, Tasnim; Bouriga, Rym; Hellali, Radhia; Cheikh, Asma Ben; Ezzi, Olfa; Abdeljellil, Amel Ben; Mansour, Njah

2015-01-01

Introduction Our study was conducted, in university hospital center (UHC) Farhat Hached of Sousse (city in Tunisian center-east), within healthcare-associated infections (HAI) epidemiological surveillance (ES) program, based, among others, on HAI regular prevalence surveys. Our objectives are to resituate HAI prevalence rate and to identify their risk factors (RF) in order to adjust, in our hospital, prevention programs. Methods It is a transversal descriptive study, including all patients who had been hospitalized for at least 48 hours, measuring prevalence of HAI a “given day”, with only one passage by service. Risk factors were determined using Epiinfo 6.0, by uni-varied analysis, then, logistic regression stepwise descending for the variables whose p Results The study focused on 312 patients. Infected patients prevalence was 12.5% and that of HAI was 14.5%. Infections on peripheral venous catheter (PVC) dominated (42.2%) among all HAI identified. HAI significant RF were neutropenia (p < 10−4) for intrinsic factors, and PVC for extrinsic factors (p = 0,003). Conclusion Predominance of infections on PVC should be subject of specific prevention actions, including retro-information strategy, prospective ES, professional practices evaluation and finally training and increasing awareness of health personnel with hygiene measures. Finally, development of a patient safety culture with personnel ensures best adherence to hygiene measures and HAI prevention. PMID:26113928

Corrective Action Decision Document/Closure Report for Corrective Action Unit 567: Miscellaneous Soil Sites - Nevada National Security Site, Nevada

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

Matthews, Patrick

2014-12-01

This Corrective Action Decision Document/Closure Report presents information supporting the closure of Corrective Action Unit (CAU) 567: Miscellaneous Soil Sites, Nevada National Security Site, Nevada. The purpose of this Corrective Action Decision Document/Closure Report is to provide justification and documentation supporting the recommendation that no further corrective action is needed for CAU 567 based on the implementation of the corrective actions. The corrective actions implemented at CAU 567 were developed based on an evaluation of analytical data from the CAI, the assumed presence of COCs at specific locations, and the detailed and comparative analysis of the CAAs. The CAAs weremore » selected on technical merit focusing on performance, reliability, feasibility, safety, and cost. The implemented corrective actions meet all requirements for the technical components evaluated. The CAAs meet all applicable federal and state regulations for closure of the site. Based on the implementation of these corrective actions, the DOE, National Nuclear Security Administration Nevada Field Office provides the following recommendations: • No further corrective actions are necessary for CAU 567. • The Nevada Division of Environmental Protection issue a Notice of Completion to the DOE, National Nuclear Security Administration Nevada Field Office for closure of CAU 567. • CAU 567 be moved from Appendix III to Appendix IV of the FFACO.« less

Physicochemical, Antioxidant, and Cytotoxic Properties of Xao Tam Phan (Paramignya trimera) Root Extract and Its Fractions.

PubMed

Nguyen, Van Tang; Sakoff, Jennette A; Scarlett, Christopher J

2017-04-01

Xao tam phan (Paramignya trimera (Oliv.) Guillaum) has been used as a medicinal plant for cancer prevention and treatment in recent years. The objective of this study was to determine the physicochemical, antioxidant, and cytotoxic properties of crude P. trimera root (PTR) extract and its fractions using MeOH as a solvent and microwave-assisted extraction as an advanced technique for preparation of the PTR extract. The results showed that the PTR extract had high contents of saponins, phenolics, flavonoids, and proanthocyanidins (7731.05 mg escin equiv. (EE), 238.13 mg gallic acid equiv. (GAE), 81.49 mg rutin equiv., and 58.08 mg catechin equiv. (CE)/g dried extract, resp.). Antioxidant activity of PTR extract was significantly higher (P < 0.05) than those of four its fractions and ostruthin, a key bioactive compound in the P. trimera, while potent cytotoxic capacity of PTR extract on various cancer cell lines in terms of MiaPaCa-2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), MCF-7 (breast), MCF-10A (normal breast), and U87, SJ-G2, SMA (glioblastoma) was observed with GI 50 values ranging from 15 to 32 μg/ml. Cytotoxic potential on pancreatic cancer cells of PTR extract (100 - 200 μg/ml) was significantly higher (P < 0.05) than those of its four fractions (50 μg/ml), ostruthin (20 μg/ml) and gemcitabine (50 nm), and being comparable to a saponin-enriched extract from quillajia bark, a commercial product. Based on the results achieved, we can conclude that the PTR extract is a potential source for application of in the nutraceutical, medical, and pharmaceutical industries. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Differential effect of EGFR inhibitors on tamoxifen-resistant breast cancer cells.

PubMed

Kim, Sangmin; Lee, Jeongmin; Oh, Soo Jin; Nam, Seok Jin; Lee, Jeong Eon

2015-09-01

Although tamoxifen is the most common and effective therapy for treatment of estrogen receptor-α (ER-α) breast cancer patients, resistance of endocrine therapy occurs, either de novo or acquired during therapy. Here, we investigated the clinical value of epidermal growth factor receptor (EGFR) in tamoxifen-resistant (TamR) patients and the differential effect of EGFR inhibitors, neratinib and gefitinib, on TamR breast cancer cell model. The morphology of TamR MCF7 cells showed mesenchymal phenotypes and did not induce cell death by tamoxifen treatment compared with tamoxifen‑sensitive (TamS) MCF7 cells. In addition, mesenchymal marker proteins, including N-cadherin (N-cad), fibronectin (FN), and Slug, significantly increased in TamR cells. In contrast, ER-α and E-cadherin (E-cad) were greatly decreased. We also found that the levels of EGFR and HER2 expression were increased in TamR cells. Furthermore, we observed that EGFR expression was directly involved with poor prognosis of tamoxifen-treated breast cancer patients using the GSE1378 date set. Thus, we treated TamR and TamS cells with EGFR inhibitors, neratinib and gefitinib, respectively. Interestingly, neratinib induced apoptotic cell death of TamR but not gefitinib. Cleaved PARP-1 expression was also increased by neratinib treatment in TamR cells. Therefore, we suggest that neratinib may be a potential therapeutic drug for treating TamR breast cancer.

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

Prather, Paul L.; FrancisDevaraj, FeAna; Dates, Centdrika R.

Highlights: •Tamoxifen produces cytotoxicity via estrogen-receptor (ER) independent mechanisms. •Tamoxifen binds to CB1 and CB2 cannabinoid receptors and acts as an inverse agonist. •CB1 and CB2 receptors are novel molecular targets for Tamoxifen. •ER-independent effects for Tamoxifen may be mediated via CB1 and/or CB2 receptors. -- Abstract: Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam canmore » produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for the ER-independent effects of Tam and its derivatives are poorly understood. Interestingly, similar to Tam and 4OH-Tam, cannabinoids have also been shown to exhibit anti-proliferative and apoptotic effects in ER-negative breast cancer cells, and estrogen can regulate expression levels of cannabinoid receptors (CBRs). Therefore, this study investigated whether CBRs might serve as novel molecular targets for Tam and 4OH-Tam. We report that both compounds bind to CB1 and CB2Rs with moderate affinity (0.9–3 μM). Furthermore, Tam and 4OH-Tam exhibit inverse activity at CB1 and CB2Rs in membrane preparations, reducing basal G-protein activity. Tam and 4OH-Tam also act as CB1/CB2R-inverse agonists to regulate the downstream intracellular effector adenylyl cyclase in intact cells, producing concentration-dependent increases in intracellular cAMP. These results suggest that CBRs are molecular targets for Tam and 4OH-Tam and may contribute to the ER-independent cytotoxic effects reported for these drugs. Importantly, these findings also indicate that Tam and 4OH-Tam might be used as structural scaffolds for development of novel

Streamlined Approach for Environmental Restoration (SAFER) Plan for Corrective Action Unit 411. Double Tracks Plutonium Dispersion (Nellis), Nevada Test and Training Range, Nevada, Revision 0

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

Matthews, Patrick K.

2015-03-01

This Streamlined Approach for Environmental Restoration (SAFER) Plan addresses the actions needed to achieve closure for Corrective Action Unit (CAU) 411, Double Tracks Plutonium Dispersion (Nellis). CAU 411 is located on the Nevada Test and Training Range and consists of a single corrective action site (CAS), NAFR-23-01, Pu Contaminated Soil. There is sufficient information and historical documentation from previous investigations and the 1996 interim corrective action to recommend closure of CAU 411 using the SAFER process. Based on existing data, the presumed corrective action for CAU 411 is clean closure. However, additional data will be obtained during a field investigationmore » to document and verify the adequacy of existing information, and to determine whether the CAU 411 closure objectives have been achieved. This SAFER Plan provides the methodology to gather the necessary information for closing the CAU. The results of the field investigation will be presented in a closure report that will be prepared and submitted to the Nevada Division of Environmental Protection (NDEP) for review and approval. The site will be investigated based on the data quality objectives (DQOs) developed on November 20, 2014, by representatives of NDEP, the U.S. Air Force (USAF), and the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Field Office. The DQO process was used to identify and define the type, amount, and quality of data needed to determine whether CAU 411 closure objectives have been achieved. The following text summarizes the SAFER activities that will support the closure of CAU 411; Collect environmental samples from designated target populations to confirm or disprove the presence of contaminants of concern (COCs) as necessary to supplement existing information; If COCs are no longer present, establish clean closure as the corrective action; If COCs are present, the extent of contamination will be defined and further corrective

The Effects of Cooperative Learning on the Academic Achievement and Knowledge Retention

ERIC Educational Resources Information Center

Tran, Van Dat

2014-01-01

This experimental study investigated the effects of cooperative learning on the achievement and knowledge retention of 110 first-year primary education students toward the psychology subject over the eight weeks of instruction at An Giang University. These tertiary students were divided into two matched groups of 55 to be taught by the same…

76 FR 47149 - Certain Frozen Fish Fillets From the Socialist Republic of Vietnam: Notice of Partial Rescission...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-04

... than August 31, 2011.\\3\\ \\1\\ (1) An Giang Fisheries Import and Export Joint Stock Company (aka Agifish... Vietnam, 68 FR 47909 (August 12, 2003). On September 22, 2010, the Department initiated the August 1, 2009... Revocation, 75 FR 60076, (September 29, 2010). Based upon requests for review from various parties, the...

Effects of flaxseed lignan and oil on bone health of breast-tumor-bearing mice treated with or without tamoxifen.

PubMed

Chen, Jianmin; Saggar, Jasdeep K; Ward, Wendy E; Thompson, Lilian U

2011-01-01

Previous studies showed that flaxseed lignan (secoisolariciresinol diglucoside, SDG) and oil (FO) inhibit established breast tumor growth in athymic mice with or without tamoxifen (TAM) treatment. TAM was found to increase bone mineral content (BMC) and density (BMD) in breast cancer patients. It is not known whether SDG or FO alone or combined with TAM affects bone health. Hence, the effects of SDG and FO, alone or in combination, on BMC, BMD, and biomechanical bone strength in ovariectomized athymic mice with established human breast tumors (MCF-7) treated with or without TAM were studied. In a factorial design, mice were divided into four non-TAM and four TAM groups. Each group consisted of mice fed a basal diet (BD), SDG (1 g/kg), FO (38.5 g/kg) or SDG + FO (combination) diets. The TAM group had TAM implants that provide a 5-mg TAM dose released over 60 d. TAM exerted an overall significant effect in increasing BMC, BMD, and biomechanical strength in femurs and lumbar vertebra. Without TAM treatment, SDG produced significant lower femur BMD (6%) while FO produced lower vertebrae BMC (8%) and BMD (6%). With TAM treatment, SDG and FO did not exert an effect on BMC and BMD at the femur or vertebra. SDG and FO produced no marked effect on biomechanical bone strength with or without TAM treatment. In conclusion, FS components did not significantly attenuate the positive effects on bone induced by TAM in this model system, indicating no apparent adverse effects on bone health.

Pathogen exploitation of an abscisic acid- and jasmonate-inducible MAPK phosphatase and its interception by Arabidopsis immunity.

PubMed

Mine, Akira; Berens, Matthias L; Nobori, Tatsuya; Anver, Shajahan; Fukumoto, Kaori; Winkelmüller, Thomas M; Takeda, Atsushi; Becker, Dieter; Tsuda, Kenichi

2017-07-11

Phytopathogens promote virulence by, for example, exploiting signaling pathways mediated by phytohormones such as abscisic acid (ABA) and jasmonate (JA). Some plants can counteract pathogen virulence by invoking a potent form of immunity called effector-triggered immunity (ETI). Here, we report that ABA and JA mediate inactivation of the immune-associated MAP kinases (MAPKs), MPK3 and MPK6, in Arabidopsis thaliana ABA induced expression of genes encoding the protein phosphatases 2C (PP2Cs), HAI1 , HAI2 , and HAI3 through ABF/AREB transcription factors. These three HAI PP2Cs interacted with MPK3 and MPK6 and were required for ABA-mediated MPK3/MPK6 inactivation and immune suppression. The bacterial pathogen Pseudomonas syringae pv. tomato ( Pto ) DC3000 activates ABA signaling and produces a JA-mimicking phytotoxin, coronatine (COR), that promotes virulence. We found that Pto DC3000 induces HAI1 through COR-mediated activation of MYC2, a master transcription factor in JA signaling. HAI1 dephosphorylated MPK3 and MPK6 in vitro and was necessary for COR-mediated suppression of MPK3/MPK6 activation and immunity. Intriguingly, upon ETI activation, A. thaliana plants overcame the HAI1-dependent virulence of COR by blocking JA signaling. Finally, we showed conservation of induction of HAI PP2Cs by ABA and JA in other Brassicaceae species. Taken together, these results suggest that ABA and JA signaling pathways, which are hijacked by the bacterial pathogen, converge on the HAI PP2Cs that suppress activation of the immune-associated MAPKs. Also, our data unveil interception of JA-signaling activation as a host counterstrategy against the bacterial suppression of MAPKs during ETI.

Healthcare-associated infections in pediatric cancer patients: results of a prospective surveillance study from university hospitals in Germany and Switzerland.

PubMed

Simon, Arne; Ammann, Roland A; Bode, Udo; Fleischhack, Gudrun; Wenchel, Hans-Martin; Schwamborn, Dorothee; Gravou, Chara; Schlegel, Paul-Gerhardt; Rutkowski, Stefan; Dannenberg, Claudia; Körholz, Dieter; Laws, Hans Jürgen; Kramer, Michael H

2008-05-23

Pediatric cancer patients face an increased risk of healthcare-associated infection (HAI). To date, no prospective multicenter studies have been published on this topic. Prospective multicenter surveillance for HAI and nosocomial fever of unknown origin (nFUO) with specific case definitions and standardized surveillance methods. 7 pediatric oncology centers (university facilities) participated from April 01, 2001 to August 31, 2005. During 54,824 days of inpatient surveillance, 727 HAIs and nFUOs were registered in 411 patients. Of these, 263 (36%) were HAIs in 181 patients, for an incidence density (ID) (number of events per 1,000 inpatient days) of 4.8 (95% CI 4.2 to 5.4; range 2.4 to 11.7; P < 0.001), and 464 (64%) were nFUO in 230 patients. Neutropenia at diagnosis correlated significantly with clinical severity of HAI. Of the 263 HAIs, 153 (58%) were bloodstream infections (BSI). Of the 138 laboratory-confirmed BSIs, 123 (89%) were associated with use of a long-term central venous catheter (CVAD), resulting in an overall ID of 2.8 per 1,000 utilization days (95% CI 2.3 to 3.3). The ID was significantly lower in Port-type than in Hickman-type CVADs. The death of 8 children was related to HAI, including six cases of aspergillosis. The attributable mortality was 3.0% without a significant association to neutropenia at time of NI diagnosis. Our study confirmed that pediatric cancer patients are at an increased risk for specific HAIs. The prospective surveillance of HAI and comparison with cumulative multicenter results are indispensable for targeted prevention of these adverse events of anticancer treatment.

Anti-tumour strategies aiming to target tumour-associated macrophages

PubMed Central

Tang, Xiaoqiang; Mo, Chunfen; Wang, Yongsheng; Wei, Dandan; Xiao, Hengyi

2013-01-01

Tumour-associated macrophages (TAMs) represent a predominant population of inflammatory cells that present in solid tumours. TAMs are mostly characterized as alternatively activated M2-like macrophages and are known to orchestrate nearly all stages of tumour progression. Experimental investigations indicate that TAMs contribute to drug-resistance and radio-protective effects, and clinical evidence shows that an elevated number of TAMs and their M2 profile are correlated with therapy failure and poor prognosis in cancer patients. Recently, many studies on TAM-targeted strategies have made significant progress and some pilot works have achieved encouraging results. Among these, connections between some anti-tumour drugs and their influence on TAMs have been suggested. In this review, we will summarize recent advances in TAM-targeted strategies for tumour therapy. Based on the proposed mechanisms, those strategies are grouped into four categories: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival; (iii) enhancing M1-like tumoricidal activity of TAMs; (iv) blocking M2-like tumour-promoting activity of TAMs. It is desired that further attention be drawn to this research field and more effort be made to promote TAM-targeted tumour therapy. PMID:23113570

Climatic effects of irrigation over the Huang-Huai-Hai Plain in China simulated by the weather research and forecasting model: Simulated Irrigation Effects in China

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

Yang, Ben; Zhang, Yaocun; Qian, Yun

In this study, we apply the Weather Research and Forecasting model coupled with an operational-like irrigation scheme to investigate the climatic effects of irrigation over the Huang-Huai-Hai plain (3HP) in China. Multiple numerical experiments with irrigation off/on during spring, summer and both spring and summer are conducted, respectively. Our results show that the warm bias in surface temperature and dry bias in soil moisture are reduced over the 3HP region during growing seasons when irrigation is turned on in the model. Air temperature during non-growing seasons is also affected by irrigation due to the persistent effects of soil moisture onmore » land-air energy exchanges and ground heat storage. Irrigation can induce a cooler planetary boundary layer (PBL) during growing seasons, causing a wetter PBL with more low-level clouds during spring but relatively dryer PBL in summer. Further analyses indicate that the dryer summer is highly related to the changes in the East Asian summer monsoon (EASM) circulation that is modified by irrigation effect. Spring irrigation may induce a decreased land-ocean thermal contrast, leading to a possible weaker EASM. Summer irrigation, however, evidently cools the atmosphere column and forces a southward shift of the upper-level jet, which results in more precipitation in Yangtze River basin but less over southern and northern China during summer.« less

Return to Activity at Altitude After High-Altitude Illness

PubMed Central

DeWeber, Kevin; Scorza, Keith

2010-01-01

Context: Sports and other activities at high altitude are popular, yet they pose the unique risk for high-altitude illness (HAI). Once those who have suffered from a HAI recover, they commonly desire or need to perform the same activity at altitude in the immediate or distant future. Evidence Acquisition: As based on key text references and peer-reviewed journal articles from a Medline search, this article reviews the pathophysiology and general treatment principles of HAI. Results: In addition to the type of HAI experienced and the current level of recovery, factors needing consideration in the return-to-play plan include physical activity requirements, flexibility of the activity schedule, and available medical equipment and facilities. Most important, adherence to prudent acclimatization protocols and gradual ascent recommendations (when above 3000 m, no more than 600-m net elevation gain per day, and 1 rest day every 1 to 2 ascent days) is powerful in its preventive value and thus strongly recommended. When these are not practical, prophylactic medications (acetazolamide, dexamethasone, salmeterol, nifedipine, or phosphodiesterase inhibitors, depending on the type of prior HAI) may be prescribed and can reduce the risk of illness. Athletes with HAI should be counseled that physical and mental performance may be adversely affected if activity at altitude continues before recovery is complete and that there is a risk of progression to a more serious HAI. Conclusion: With a thoughtful plan, most recurrent HAI in athletes can be prevented. PMID:23015950

Public health law for the collection and reporting of health care–associated infections

PubMed Central

Meier, Benjamin Mason; Stone, Patricia W.; Gebbie, Kristine M.

2015-01-01

Background State-based laws for reporting of health care-associated infections (HAI) have developed and changed dramatically in recent years, affecting the costs of reporting and impact on infection rates. It is necessary for practitioners of infection control to understand these changing legal frameworks and their application to practice. Methods Employing systematic state-based research, the researchers have documented legislation and administrative regulations for institution-specific HAI reporting, using this information to create a comprehensive resource on state-based laws for mandatory HAI reporting. Results As of August 27, 2007, 24 states have adopted laws requiring reporting of HAI rates, with an additional 7 states currently considering legislation that would require HAI reporting and 19 states employing detailed regulation in the absence of any current legislative authorization specific to HAI. This study documents (1) which states require reporting of HAI and, if so, whether this is done by legislation or administrative regulation; (2) whether the specific HAIs to be reported are identified in state law or codified generally as “diseases of public health importance,” with reporting specified by administrative regulation; and (3) what reporting policies and procedures are detailed in law. Conclusion Through analysis of the collected information, the researchers have examined the degree to which states have modernized their respective public health laws to approach mandatory reporting by way of general legislation regarding “matters of public health importance” and subsequent detailed administrative regulation to specify those matters. PMID:18926306

Public health law for the collection and reporting of health care-associated infections.

PubMed

Meier, Benjamin Mason; Stone, Patricia W; Gebbie, Kristine M

2008-10-01

State-based laws for reporting of health care-associated infections (HAI) have developed and changed dramatically in recent years, affecting the costs of reporting and impact on infection rates. It is necessary for practitioners of infection control to understand these changing legal frameworks and their application to practice. Employing systematic state-based research, the researchers have documented legislation and administrative regulations for institution-specific HAI reporting, using this information to create a comprehensive resource on state-based laws for mandatory HAI reporting. As of August 27, 2007, 24 states have adopted laws requiring reporting of HAI rates, with an additional 7 states currently considering legislation that would require HAI reporting and 19 states employing detailed regulation in the absence of any current legislative authorization specific to HAI. This study documents (1) which states require reporting of HAI and, if so, whether this is done by legislation or administrative regulation; (2) whether the specific HAIs to be reported are identified in state law or codified generally as "diseases of public health importance," with reporting specified by administrative regulation; and (3) what reporting policies and procedures are detailed in law. Through analysis of the collected information, the researchers have examined the degree to which states have modernized their respective public health laws to approach mandatory reporting by way of general legislation regarding "matters of public health importance" and subsequent detailed administrative regulation to specify those matters.

Predicting healthcare associated infections using patients' experiences

NASA Astrophysics Data System (ADS)

Pratt, Michael A.; Chu, Henry

2016-05-01

Healthcare associated infections (HAI) are a major threat to patient safety and are costly to health systems. Our goal is to predict the HAI performance of a hospital using the patients' experience responses as input. We use four classifiers, viz. random forest, naive Bayes, artificial feedforward neural networks, and the support vector machine, to perform the prediction of six types of HAI. The six types include blood stream, urinary tract, surgical site, and intestinal infections. Experiments show that the random forest and support vector machine perform well across the six types of HAI.

Tumor-Associated Macrophages Associate with Cerebrospinal Fluid Interleukin-10 and Survival in Primary Central Nervous System Lymphoma (PCNSL).

PubMed

Sasayama, Takashi; Tanaka, Kazuhiro; Mizowaki, Takashi; Nagashima, Hiroaki; Nakamizo, Satoshi; Tanaka, Hirotomo; Nishihara, Masamitsu; Mizukawa, Katsu; Hirose, Takanori; Itoh, Tomoo; Kohmura, Eiji

2016-07-01

Increased tumor-associated macrophages (TAMs) have been reported to be associated with poor prognosis in various tumors; however, the importance of TAMs in primary central nervous system lymphoma (PCNSL) has not been clarified. In 47 patients with PCNSL who were treated with high-dose methotrexate (MTX) and radiotherapy, the relationships between the infiltration levels of TAMs and the clinicopathological parameters were analyzed. Univariate analysis of the Cox proportional hazards model using continuous scales revealed that increased CD68 positive (+) TAMs was significantly associated with inferior progression-free survival (PFS) (P = 0.04), and trends were observed for the increased CD163(+)  TAMs and having shorter PFS (P = 0.05). However, increased TAMs were not associated with overall survival. Because TAMs are known to produce various cytokines, we examined the relationships between cerebrospinal fluid (CSF) cytokines and TAMs. CSF interleukin-6 (IL-6) and soluble IL-2 receptor were not correlated with the infiltration rate of TAMs; however, CSF IL-10 level was correlated with infiltration levels of CD68 and CD163(+)  TAMs. We also confirmed the expression of IL-10 in CD68(+)  and CD163(+)  TAMs by double immunostaining analysis. Our results indicate that a high level of IL-10 in CSF may be positively associated with the infiltration level of TAMs in PCNSLs. © 2015 International Society of Neuropathology.

Using Positive Deviance in the prevention and control of MRSA infections in a Colombian hospital: a time-series analysis.

PubMed

Escobar, N M Olarte; Márquez, I A Valderrama; Quiroga, J Avila; Trujillo, T Goretty; González, F; Aguilar, M I Garzón; Escobar-Pérez, J

2017-04-01

Positive Deviance (PD) is a process to achieve a social and cultural change. This strategy has been used for the control of methicillin-resistant Staphylococcus aureus (MRSA) infection in some health institutions in the United States, but has rarely been adopted in institutions from developing countries where resources are limited. We describe our experience of PD in the control of healthcare-associated infections (HAIs) due to MRSA in a Colombian hospital with the aim of reducing HAI rates through a cultural change in processes. A time-series study was conducted based on the MRSA-HAI rate and the number of months with zero MRSA infections before and after application of PD (2001-2012). On comparing the pre-intervention and intervention periods, the mean overall rates of MRSA-HAI was 0·62 and 0·36, respectively (P = 0·0005); the number of months with zero MRSA-HAIs were 3/70 and 12/74 (odds ratio 0·264, 95% confidence interval 0·078-0·897); the percentage of MRSA-HAIs was 53·2% and 41·0%. These results are consistent with other published data. Implementation of PD was associated with a significant reduction of MRSA-HAIs, it did not involve high costs and the changes have been lasting.

Corrective Action Decision Document for Corrective Action Unit 563: Septic Systems, Nevada Test Site, Nevada, Revision 0

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

Grant Evenson

2008-02-01

This Corrective Action Decision Document has been prepared for Corrective Action Unit (CAU) 563, Septic Systems, in accordance with the Federal Facility Agreement and Consent Order (FFACO, 1996; as amended January 2007). The corrective action sites (CASs) for CAU 563 are located in Areas 3 and 12 of the Nevada Test Site, Nevada, and are comprised of the following four sites: •03-04-02, Area 3 Subdock Septic Tank •03-59-05, Area 3 Subdock Cesspool •12-59-01, Drilling/Welding Shop Septic Tanks •12-60-01, Drilling/Welding Shop Outfalls The purpose of this Corrective Action Decision Document is to identify and provide the rationale for the recommendation of a correctivemore » action alternative (CAA) for the four CASs within CAU 563. Corrective action investigation (CAI) activities were performed from July 17 through November 19, 2007, as set forth in the CAU 563 Corrective Action Investigation Plan (NNSA/NSO, 2007). Analytes detected during the CAI were evaluated against appropriate final action levels (FALs) to identify the contaminants of concern (COCs) for each CAS. The results of the CAI identified COCs at one of the four CASs in CAU 563 and required the evaluation of CAAs. Assessment of the data generated from investigation activities conducted at CAU 563 revealed the following: •CASs 03-04-02, 03-59-05, and 12-60-01 do not contain contamination at concentrations exceeding the FALs. •CAS 12-59-01 contains arsenic and chromium contamination above FALs in surface and near-surface soils surrounding a stained location within the site. Based on the evaluation of analytical data from the CAI, review of future and current operations at CAS 12-59-01, and the detailed and comparative analysis of the potential CAAs, the following corrective actions are recommended for CAU 563.« less

Corrective Action Investigation Plan for Corrective Action Unit 413: Clean Slate II Plutonium Dispersion (TTR) Tonopah Test Range, Nevada, Revision 1

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

Matthews, Patrick; Burmeister, Mark; Gallo, Patricia

Corrective Action Unit (CAU) 413 is located on the Tonopah Test Range, which is approximately 130 miles northwest of Las Vegas, Nevada, and approximately 40 miles southeast of Tonopah, Nevada. The CAU 413 site consists of the release of radionuclides to the surface and shallow subsurface from the conduct of the Clean Slate II (CSII) storage–transportation test conducted on May 31, 1963. CAU 413 includes one corrective action site (CAS), TA-23-02CS (Pu Contaminated Soil). The known releases at CAU 413 are the result of the atmospheric deposition of contamination from the 1963 CSII test. The CSII test was a non-nuclearmore » detonation of a nuclear device located inside a reinforced concrete bunker covered with 2 feet of soil. This test dispersed radionuclides, primarily plutonium, on the ground surface. The presence and nature of contamination at CAU 413 will be evaluated based on information collected from a corrective action investigation (CAI). The investigation is based on the data quality objectives (DQOs) developed on June 17, 2015, by representatives of the Nevada Division of Environmental Protection; the U.S. Air Force; and the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Field Office. The DQO process was used to identify and define the type, amount, and quality of data needed to develop and evaluate appropriate corrective actions for CAU 413. The CAI will include radiological surveys, geophysical surveys, collection and analyses of soil samples, and assessment of investigation results. The collection of soil samples will be accomplished using both probabilistic and judgmental sampling approaches. To facilitate site investigation and the evaluation of DQO decisions, the releases at CAU 413 have been divided into seven study groups.« less

Corrective Action Investigation Plan for Corrective Action Unit 414: Clean Slate III Plutonium Dispersion (TTR) Tonopah Test Range, Nevada, Revision 1

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

Matthews, Patrick

Corrective Action Unit (CAU) 414 is located on the Tonopah Test Range, which is approximately 130 miles northwest of Las Vegas, Nevada, and approximately 40 miles southeast of Tonopah, Nevada. The CAU 414 site consists of the release of radionuclides to the surface and shallow subsurface from the conduct of the Clean Slate III (CSIII) storage–transportation test conducted on June 9, 1963. CAU 414 includes one corrective action site (CAS), TA-23-03CS (Pu Contaminated Soil). The known releases at CAU 414 are the result of the atmospheric dispersal of contamination from the 1963 CSIII test. The CSIII test was a nonnuclearmore » detonation of a nuclear device located inside a reinforced concrete bunker covered with 8 feet of soil. This test dispersed radionuclides, primarily uranium and plutonium, on the ground surface. The presence and nature of contamination at CAU 414 will be evaluated based on information collected from a corrective action investigation (CAI). The investigation is based on the data quality objectives (DQOs) developed on June 7, 2016, by representatives of the Nevada Division of Environmental Protection; the U.S. Air Force; and the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Field Office. The DQO process was used to identify and define the type, amount, and quality of data needed to develop and evaluate appropriate corrective action alternatives for CAU 414.« less

Novel Shape-Stabilized Phase Change Materials Composed of Polyethylene Glycol/Nonsurfactant-Templated Mesoporous Silica: Preparation and Thermal Properties

NASA Astrophysics Data System (ADS)

Chen, Yan; Zhu, Yingying; Wang, Jinbao; Lv, Mengjiao; Zhang, Xiongjie; Gao, Junkai; Zhang, Zijun; Lei, Hao

2017-12-01

A novel shape-stabilized phase change material (PEG/TAMS), fabricated using tannic acid-templated mesoporous silica (TAMS) as a support for polyethylene glycol, was developed for thermal energy storage. The method used to synthesize TAMS was simple, cost effective, environmentally friendly, and free of surfactant. The characterization results indicated that PEG was physically absorbed to TAMS and that TAMS had no influence on the crystal structure of PEG. According to the TGA thermograms, PEG/TAMS has excellent thermal stability and can be applied over a wide temperature range. Additionally, the differential scanning calorimetry results suggested that PEG/TAMS has good thermal properties and that its fusion and solidification enthalpies reached 114.7 J/g and 102.4 J/g, respectively. The results indicated that PEG/TAMS has great potential for practical applications.

Direct, Differential Effects of Tamoxifen, 4-Hydroxytamoxifen, and Raloxifene on Cardiac Myocyte Contractility and Calcium Handling

PubMed Central

Asp, Michelle L.; Martindale, Joshua J.; Metzger, Joseph M.

2013-01-01

Tamoxifen (Tam), a selective estrogen receptor modulator, is in wide clinical use for the treatment and prevention of breast cancer. High Tam doses have been used for treatment of gliomas and cancers with multiple drug resistance, but long QT Syndrome is a side effect. Tam is also used experimentally in mice for inducible gene knockout in numerous tissues, including heart; however, the potential direct effects of Tam on cardiac myocyte mechanical function are not known. The goal of this study was to determine the direct, acute effects of Tam, its active metabolite 4-hydroxytamoxifen (4OHT), and related drug raloxifene (Ral) on isolated rat cardiac myocyte mechanical function and calcium handling. Tam decreased contraction amplitude, slowed relaxation, and decreased Ca2+ transient amplitude. Effects were primarily observed at 5 and 10 μM Tam, which is relevant for high dose Tam treatment in cancer patients as well as Tam-mediated gene excision in mice. Myocytes treated with 4OHT responded similarly to Tam-treated cells with regard to both contractility and calcium handling, suggesting an estrogen-receptor independent mechanism is responsible for the effects. In contrast, Ral increased contraction and Ca2+ transient amplitudes. At 10 μM, all drugs had a time-dependent effect to abolish cellular contraction. In conclusion, Tam, 4OHT, and Ral adversely and differentially alter cardiac myocyte contractility and Ca2+ handling. These findings have important implications for understanding the Tam-induced cardiomyopathy in gene excision studies and may be important for understanding effects on cardiac performance in patients undergoing high-dose Tam therapy. PMID:24205315

3-D imaging of temporal and spatial development of Puccinia striiformis haustoria in wheat.

PubMed

Sørensen, Chris K; Justesen, Annemarie F; Hovmøller, Mogens S

2012-01-01

Differentiation of haustoria on primary infection hyphae of the fungal pathogen Puccinia striiformis was studied in wheat seedlings with two-photon microscopy in combination with a classical staining technique. Our results showed a significant increase in the average haustorium size 22, 44, 68, 92 and 116 h after inoculation (hai). After 116 hai no significant change was observed until 336 hai. Haustorium morphology also changed significantly during the time of infection. Initially small spherical haustoria were seen, but as they grew the haustoria gradually became apically branched. At 22 hai all observed haustoria were spherical, but at 44 hai most haustoria had an irregular structure, and at 92 hai all observed haustoria appeared branched. Along with the changes of the haustorial body the haustorial neck changed from narrow and slender to having an expanded appearance with a rough and invaginated structure. The structural changes were similar in two susceptible wheat varieties, 514W and Cartago, although the mean haustorium size was larger in 514W than in Cartago at all intervals.

Health anxiety and depression in patients with fibromyalgia syndrome.

PubMed

Uçar, Mehmet; Sarp, Ümit; Karaaslan, Özgül; Gül, Ali Irfan; Tanik, Nermin; Arik, Hasan Onur

2015-10-01

To investigate health anxiety and depressive symptoms in patients with fibromyalgia syndrome (FMS). Patients with FMS and healthy control subjects were recruited. All participants completed the Health Anxiety Inventory Short Form (HAI-SF) and Beck Depression Inventory (BDI). Pain was assessed in patients with FMS using the Fibromyalgia Impact Questionnaire (FIQ) and Visual Analogue Scale (VAS). This study involved 95 patients with FMS (15 male) and 95 healthy controls (17 male). Mean ± SD HAI-SF and BDI scores were significantly higher in patients with FMS = than in controls=. HAI-SF scores were 23.50 ± 10.78 and 9.38 ± 4.24 respectively; BDI scores were 18.64 ± 10.11 and 6.21 ± 4.05 respectively. There were highly significant correlations between FIQ and HAI-SF, FIQ and BDI, and HAI-SF and BDI. Patients with FMS had significantly higher HAI-SF and BDI scores than healthy controls. Psychiatric support is essential for patients with FMS. Treatment should include biological, psychological and social approaches. © The Author(s) 2015.

CLOSURE REPORT FOR CORRECTIVE ACTION UNIT 204: STORAGE BUNKERS, NEVADA TEST SITE, NEVADA

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

NONE

Corrective Action Unit (CAU) 330 consists of four Corrective Action Sites (CASs) located in Areas 6, 22, and 23 of the Nevada Test Site (NTS). The unit is listed in the Federal Facility Agreement and Consent Order (FFACO, 1996) as CAU 330: Areas 6, 22, and 23 Tanks and Spill Sites. CAU 330 consists of the following CASs: CAS 06-02-04, Underground Storage Tank (UST) and Piping CAS 22-99-06, Fuel Spill CAS 23-01-02, Large Aboveground Storage Tank (AST) Farm CAS 23-25-05, Asphalt Oil Spill/Tar Release

Burden of Six Healthcare-Associated Infections on European Population Health: Estimating Incidence-Based Disability-Adjusted Life Years through a Population Prevalence-Based Modelling Study

PubMed Central

Eckmanns, Tim; Abu Sin, Muna; Ducomble, Tanja; Harder, Thomas; Sixtensson, Madlen; Velasco, Edward; Weiß, Bettina; Kramarz, Piotr; Monnet, Dominique L.; Kretzschmar, Mirjam E.; Suetens, Carl

2016-01-01

Background Estimating the burden of healthcare-associated infections (HAIs) compared to other communicable diseases is an ongoing challenge given the need for good quality data on the incidence of these infections and the involved comorbidities. Based on the methodology of the Burden of Communicable Diseases in Europe (BCoDE) project and 2011–2012 data from the European Centre for Disease Prevention and Control (ECDC) point prevalence survey (PPS) of HAIs and antimicrobial use in European acute care hospitals, we estimated the burden of six common HAIs. Methods and Findings The included HAIs were healthcare-associated pneumonia (HAP), healthcare-associated urinary tract infection (HA UTI), surgical site infection (SSI), healthcare-associated Clostridium difficile infection (HA CDI), healthcare-associated neonatal sepsis, and healthcare-associated primary bloodstream infection (HA primary BSI). The burden of these HAIs was measured in disability-adjusted life years (DALYs). Evidence relating to the disease progression pathway of each type of HAI was collected through systematic literature reviews, in order to estimate the risks attributable to HAIs. For each of the six HAIs, gender and age group prevalence from the ECDC PPS was converted into incidence rates by applying the Rhame and Sudderth formula. We adjusted for reduced life expectancy within the hospital population using three severity groups based on McCabe score data from the ECDC PPS. We estimated that 2,609,911 new cases of HAI occur every year in the European Union and European Economic Area (EU/EEA). The cumulative burden of the six HAIs was estimated at 501 DALYs per 100,000 general population each year in EU/EEA. HAP and HA primary BSI were associated with the highest burden and represented more than 60% of the total burden, with 169 and 145 DALYs per 100,000 total population, respectively. HA UTI, SSI, HA CDI, and HA primary BSI ranked as the third to sixth syndromes in terms of burden of disease

The effectiveness of UV-C radiation for facility-wide environmental disinfection to reduce health care-acquired infections.

PubMed

Napolitano, Nathanael A; Mahapatra, Tanmay; Tang, Weiming

2015-12-01

Health care-acquired infections (HAIs) constitute an increasing threat for patients worldwide. Potential contributors of HAIs include environmental surfaces in health care settings, where ultraviolet-C radiation (UV-C) is commonly used for disinfection. This UV-C intervention-based pilot study was conducted in a hospital setting to identify any change in the incidence of HAIs before and after UV-C intervention, and to determine the effectiveness of UV-C in reducing pathogens. In a hospital in Culver City, CA, during 2012-2013, bactericidal doses of UV-C radiation (254 nm) were delivered through a UV-C-based mobile environmental decontamination unit. The UV-C dosing technology and expertise of the specifically trained personnel were provided together as a dedicated service model by a contracted company. The incidence of HAIs before and after the intervention period were determined and compared. The dedicated service model dramatically reduced HAIs (incidence difference, 1.3/1000 patient-days, a 34.2% reduction). Reductions in the total number and incidence proportions (28.8%) of HAIs were observed after increasing and maintaining the coverage of UV-C treatments. The dedicated service model was found to be effective in decreasing the incidence of HAIs, which could reduce disease morbidity and mortality in hospitalized patients. This model provides a continuously monitored and frequently UV-C-treated patient environment. This approach to UV-C disinfection was associated with a decreased incidence of HAIs. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Estimating the proportion of healthcare-associated infections that are reasonably preventable and the related mortality and costs.

PubMed

Umscheid, Craig A; Mitchell, Matthew D; Doshi, Jalpa A; Agarwal, Rajender; Williams, Kendal; Brennan, Patrick J

2011-02-01

To estimate the proportion of healthcare-associated infections (HAIs) in US hospitals that are "reasonably preventable," along with their related mortality and costs. To estimate preventability of catheter-associated bloodstream infections (CABSIs), catheter-associated urinary tract infections (CAUTIs), surgical site infections (SSIs), and ventilator-associated pneumonia (VAP), we used a federally sponsored systematic review of interventions to reduce HAIs. Ranges of preventability included the lowest and highest risk reductions reported by US studies of "moderate" to "good" quality published in the last 10 years. We used the most recently published national data to determine the annual incidence of HAIs and associated mortality. To estimate incremental cost of HAIs, we performed a systematic review, which included costs from studies in general US patient populations. To calculate ranges for the annual number of preventable infections and deaths and annual costs, we multiplied our infection, mortality, and cost figures with our ranges of preventability for each HAI. As many as 65%-70% of cases of CABSI and CAUTI and 55% of cases of VAP and SSI may be preventable with current evidence-based strategies. CAUTI may be the most preventable HAI. CABSI has the highest number of preventable deaths, followed by VAP. CABSI also has the highest cost impact; costs due to preventable cases of VAP, CAUTI, and SSI are likely less. Our findings suggest that 100% prevention of HAIs may not be attainable with current evidence-based prevention strategies; however, comprehensive implementation of such strategies could prevent hundreds of thousands of HAIs and save tens of thousands of lives and billions of dollars.

Surveillance of healthcare-associated infections in Piemonte, Italy: results from a second regional prevalence study

PubMed Central

2014-01-01

Background A prevalence survey of healthcare-associated infections (HAIs) was previously performed in the Piemonte region in 2000. In the decade following the survey, many studies were performed at both the regional and hospital levels, and training courses were developed to address issues highlighted by the survey. In 2010, a second regional prevalence study was performed. The aim of this paper is to present the results of the second prevalence study and discuss them within the context of the HAI prevention and control programmes that have been implemented in the decade since the original survey was conducted. Methods The study involved all public hospitals in the Piemonte region. Uni- and multivariate analyses were performed to assess the main risk factors associated with HAIs, including both overall and site-specific infections. Results A total of 7841 patients were enrolled: 6.8% were affected by at least one HAI. The highest prevalence of HAIs was found in intensive care units (18.0%, 95% CI 14.0-22.6), while UTIs presented the highest relative frequency (26.7%), followed by respiratory tract infections (21.9%). The age of the patient, hospital size and urinary and central venous catheter status were significantly associated with HAIs. Conclusions The study results showed an increase in HAI prevalence, despite prevention and control efforts, as well as training implemented after the first regional survey. Nevertheless, these data are consistent with the current literature. Furthermore, despite its limits, the prevalence approach remains an important means for involving healthcare workers, emphasising HAIs and revealing critical problems that need be addressed. PMID:24899239

The national response for preventing healthcare-associated infections: research and adoption of prevention practices.

PubMed

Kahn, Katherine L; Mendel, Peter; Leuschner, Kristin J; Hiatt, Liisa; Gall, Elizabeth M; Siegel, Sari; Weinberg, Daniel A

2014-02-01

Healthcare-associated infections (HAIs) have long been the subject of research and prevention practice. When findings show potential to significantly impact outcomes, clinicians, policymakers, safety experts, and stakeholders seek to bridge the gap between research and practice by identifying mechanisms and assigning responsibility for translating research to practice. This paper describes progress and challenges in HAI research and prevention practices, as explained through an examination of Health and Human Services (HHS) Action Plan's goals, inputs, and implementation in each area. We used the Context-Input-Process-Product evaluation model, together with an HAI prevention system framework, to assess the transformative processes associated with HAI research and adoption of prevention practices. Since the introduction of the Action Plan, HHS has made substantial progress in prioritizing research projects, translating findings from those projects into practice, and designing and implementing research projects in multisite practice settings. Research has emphasized the basic science and epidemiology of HAIs, the identification of gaps in research, and implementation science. The basic, epidemiological, and implementation science communities have joined forces to better define mechanisms and responsibilities for translating HAI research into practice. Challenges include the ongoing need for better evidence about intervention effectiveness, the growing implementation burden on healthcare providers and organizations, and challenges implementing certain practices. Although these HAI research and prevention practice activities are complex spanning multiple system functions and properties, HHS is making progress so that the right methods for addressing complex HAI problems at the interface of patient safety and clinical practice can emerge.

Multimodal Interfaces: Literature Review of Ecological Interface Design, Multimodal Perception and Attention, and Intelligent Adaptive Multimodal Interfaces

DTIC Science & Technology

2010-05-01

Multimodal Interfaces Literature Review of Ecological Interface Design , Multimodal Perception and Attention, and Intelligent... Design , Multimodal Perception and Attention, and Intelligent Adaptive Multimodal Interfaces Wayne Giang, Sathya Santhakumaran, Ehsan Masnavi, Doug...Advanced Interface Design Laboratory, E2-1303N 200 University Avenue West Waterloo, Ontario Canada N2L 3G1 Contract Project Manager: Dr. Catherine

Tumor-associated macrophages induce the expression of FOXQ1 to promote epithelial-mesenchymal transition and metastasis in gastric cancer cells.

PubMed

Guo, Jian; Yan, Yan; Yan, Yu; Guo, Qinyue; Zhang, Mingxin; Zhang, Jia; Goltzman, David

2017-10-01

Gastric cancer (GC) is one of the most common malignancies, and is the second leading cause of cancer-related deaths worldwide. Macrophages infiltrated in the tumor microenvironment (TME) called tumor-associated macrophages (TAMs) are key orchestrators in TME. In GC, it has been reported that infiltration of TAMs is associated with epithelial-mesenchymal transition (EMT)-related proteins in human GC tissues, but the exactly mechanism has not been clarified. In the present study, we aimed to elucidate the underlying mechanism of TAMs on GC cells. THP-1 cells were used to investigate the effects of TAMs on GC cells. The effects of invasion and migration induced by coculture with TAMs were investigated by Transwell invasion and wound healing assays. The expression of EMT-related genes and forkhead box Q1 (FOXQ1) were examined in MKN45 and MKN74 cells after being co-cultured with TAMs. The density of TAMs and the expression of FOXQ1 were analyzed by immunohistochemistry in GC tissues. Our results revealed that, co-culture with TAMs promoted the invasion and migration of GC cells. Co-culture with TAMs induced EMT in GC cells. FOXQ1 is essential for TAM-induced EMT and metastasis in GC cells. Furthermore, silencing of FOXQ1 blocked the effect of TAM-enhanced EMT and metastasis of GC cells. High expression of CD68 was correlated with positive FOXQ1 expression (r=0.613; P<0.001) in clinical GC samples. Our data provided evidence that TAMs promote EMT, invasion and migration of GC cells via FOXQ1. Therefore, the TAM/FOXQ1 axis may represent a novel target for GC cells.

Healthcare associated infections in neonatal intensive care unit and its correlation with environmental surveillance.

PubMed

Kumar, Sanjay; Shankar, Binoy; Arya, Sugandha; Deb, Manorma; Chellani, Harish

Healthcare-associated infections (HAI) are frequent complications in neonatal intensive care units (NICU) with varying risk factors and bacteriological profile. There is paucity of literature comparing the bacteriological profile of organisms causing HAI with the environmental surveillance isolates. Therefore, this study aimed to evaluate demographic profile, risk factors and outcome of HAI in NICU and correlate with environmental surveillance. Three hundred newborns with signs and symptoms of sepsis were enrolled in the study group and their profile, risk factors and outcome were compared with the control group. Univariate analysis and multivariable logistic regression were performed. Environmental surveillance results were compared to the bacteriological profile of HAIs. We identified lower gestational age, male gender and apgar score less than 7 at 5min, use of peripheral vascular catheter & ventilator along with their duration as significant risk factors. Mortality rate was 29% in the study group (p<0.05). The HAI site distribution showed blood-stream infections (73%) to be the most common followed by pneumonia (12%) and meningitis (10%). Gram positive cocci were the most common isolates in HAI as well as environmental surveillance. The bacteriological profile of HAI correlates with the environmental surveillance report thus insisting for periodic surveillance and thereby avoiding irrational antibiotic usage. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Healthcare-associated infections in intensive care units: epidemiology and infection control in low-to-middle income countries.

PubMed

Alp, Emine; Damani, Nizam

2015-10-29

Healthcare-associated infections (HAIs) are major patient safety problems in hospitals, especially in intensive care units (ICUs). Patients in ICUs are prone to HAIs due to reduced host defense mechanisms, low compliance with infection prevention and control (IPC) measures due to lack of education and training, and heavy workload and low staffing levels, leading to cross-transmission of microorganisms from patient to patient. Patients with HAIs have prolonged hospital stays, and have high morbidity and mortality, thus adding economic burden on the healthcare system. For various reasons, in low-to-middle income countries (LMICs), the scale of the problem is huge; each year, many people die from HAIs. In this review, epidemiology of HAIs and infection prevention and control measures in ICUs is discussed, with especial emphasis on LMICs. High rates of HAIs caused by multidrug-resistant organisms (MDROs) are serious problems in ICUs in LMICs. In view of increasing prevalence of MDROs, LMICs should establish effective IPC infrastructure, appoint IPC teams, and provide adequate training and resources. These resources to establish and appoint IPC teams can be released by avoiding ritualistic, wasteful, and unsafe IPC practices, and by diverting resources to implement basic IPC measures, including early detection of infection, isolation of patients, application of appropriate IPC precautions, adherence to hand hygiene, and implementation of HAIs care bundles and basic evidence-based practices.

Implementation in the midst of complexity: Using ethnography to study health care-associated infection prevention and control.

PubMed

Knobloch, Mary Jo; Thomas, Kevin V; Patterson, Erin; Zimbric, Michele L; Musuuza, Jackson; Safdar, Nasia

2017-10-01

Contextual factors associated with health care settings make reducing health care-associated infections (HAIs) a complex task. The aim of this article is to highlight how ethnography can assist in understanding contextual factors that support or hinder the implementation of evidence-based practices for reducing HAIs. We conducted a review of ethnographic studies specifically related to HAI prevention and control in the last 5 years (2012-2017). Twelve studies specific to HAIs and ethnographic methods were found. Researchers used various methods with video-reflexive sessions used in 6 of the 12 studies. Ethnography was used to understand variation in data reporting, identify barriers to adherence, explore patient perceptions of isolation practices and highlight the influence of physical design on infection prevention practices. The term ethnography was used to describe varied research methods. Most studies were conducted outside the United States, and authors indicate insights gained using ethnographic methods (whether observations, interviews, or reflexive video recording) as beneficial to unraveling the complexities of HAI prevention. Ethnography is well-suited for HAI prevention, especially video-reflexive ethnography, for activating patients and clinicians in infection control work. In this era of increasing pressure to reduce HAIs within complex work systems, ethnographic methods can promote understanding of contextual factors and may expedite translation evidence to practice. Published by Elsevier Inc.

Morphological and molecular review of Jacob's Mountain Stream Keelback Opisthotropis jacobi Angel Bourret, 1933 (Squamata: Natricidae) with description of a sibling species from northern Vietnam.

PubMed

Ziegler, Thomas; David, Patrick; Ziegler, Tim N; Pham, Cuong T; Nguyen, Truong Q; Le, Minh D

2018-01-21

New morphological data including hemipenis morphology is provided for Opisthotropis jacobi, a poorly known Mountain Stream Keelback from Vietnam and China, based on three newly collected individuals from Sa Pa (Lao Cai Province) and Tam Dao (Vinh Phuc Province) in northern Vietnam. In addition, morphological data from Vietnam is summarized based on the original description (Angel Bourret 1933), on the overview book by Bourret (1936) and on a number of smaller, little-known contributions by the latter author along with re-examination of specimens deposited in the herpetological collection of the Muséum national d'Histoire naturelle, Paris. We also sequenced a fragment of the mitochondrial cytochrome b from the newly collected specimens of the Jacob's Mountain Stream Keelback and performed molecular analyses of new and existing data of the genus. A recently discovered Opisthotropis population from Tay Yen Tu Nature Reserve in Bac Giang Province, northern Vietnam, which at the first glance resembled O. jacobi morphologically, is shown to diverge both genetically and morphologically from the existing species and is herein described as a new species. Opisthotropis voquyi sp. nov. is characterized by the combination of the following characters: internasal not in contact with loreal; one preocular; usually two postoculars; one anterior temporal; one posterior temporal; 7 or 8, rarely 9 supralabials; 25 maxillary teeth; subcaudals 74-86; 15 dorsal scale rows at neck, at midbody and before vent; body scales smooth or only with few faint keels; and dorsal scales being greyish, greyish-brown or brown in preservative, posteriorly more or less edged with pale greyish-brown. Phylogenetically, the new species is supported as a sister taxon to O. jacobi, but the two taxa are approximately 10% divergent based on cytochrome b data.

Closure Report for Corrective Action Unit 536: Area 3 Release Site, Nevada Test Site, Nevada

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

NSTec Environmental Restoration

Corrective Action Unit (CAU) 536 is located in Area 3 of the Nevada Test Site. CAU 536 is listed in the Federal Facility Agreement and Consent Order of 1996 as Area 3 Release Site, and comprises a single Corrective Action Site (CAS): {sm_bullet} CAS 03-44-02, Steam Jenny Discharge The Nevada Division of Environmental Protection (NDEP)-approved corrective action alternative for CAS 03-44-02 is clean closure. Closure activities included removing and disposing of total petroleum hydrocarbon (TPH)- and polyaromatic hydrocarbon (PAH)-impacted soil, soil impacted with plutonium (Pu)-239, and concrete pad debris. CAU 536 was closed in accordance with the NDEP-approved CAU 536more » Corrective Action Plan (CAP), with minor deviations as approved by NDEP. The closure activities specified in the CAP were based on the recommendations presented in the CAU 536 Corrective Action Decision Document (U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office, 2004). This Closure Report documents CAU 536 closure activities. During closure activities, approximately 1,000 cubic yards (yd3) of hydrocarbon waste in the form of TPH- and PAH-impacted soil and debris, approximately 8 yd3 of Pu-239-impacted soil, and approximately 100 yd3 of concrete debris were generated, managed, and disposed of appropriately. Additionally, a previously uncharacterized, buried drum was excavated, removed, and disposed of as hydrocarbon waste as a best management practice. Waste minimization techniques, such as the utilization of laboratory analysis to characterize and classify waste streams, were employed during the performance of closure« less

Corrective Action Decision Document/Corrective Action Plan for Corrective Action Unit 573: Alpha Contaminated Sites Nevada National Security Site, Nevada, Revision 0

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

Matthews, Patrick

CAU 573 comprises the following corrective action sites (CASs): • 05-23-02, GMX Alpha Contaminated Area • 05-45-01, Atmospheric Test Site - Hamilton These two CASs include the release at the Hamilton weapons-related tower test and a series of 29 atmospheric experiments conducted at GMX. The two CASs are located in two distinctly separate areas within Area 5. To facilitate site investigation and data quality objective (DQO) decisions, all identified releases (i.e., CAS components) were organized into study groups. The reporting of investigation results and the evaluation of DQO decisions are at the release level. The corrective action alternatives (CAAs) weremore » evaluated at the FFACO CAS level. The purpose of this CADD/CAP is to evaluate potential CAAs, provide the rationale for the selection of recommended CAAs, and provide the plan for implementation of the recommended CAA for CAU 573. Corrective action investigation (CAI) activities were performed from January 2015 through November 2015, as set forth in the CAU 573 Corrective Action Investigation Plan (CAIP). Analytes detected during the CAI were evaluated against appropriate final action levels (FALs) to identify the contaminants of concern. Assessment of the data generated from investigation activities conducted at CAU 573 revealed the following: • Radiological contamination within CAU 573 does not exceed the FALs (based on the Occasional Use Area exposure scenario). • Chemical contamination within CAU 573 does not exceed the FALs. • Potential source material—including lead plates, lead bricks, and lead-shielded cables—was removed during the investigation and requires no additional corrective action.« less

Corrective Action Decision Document/Corrective Action Plan for Corrective Action Unit 104: Area 7 Yucca Flat Atmospheric Test Sites Nevada National Security Site, Nevada, Revision 0

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

Patrick Matthews

2012-10-01

CAU 104 comprises the following corrective action sites (CASs): • 07-23-03, Atmospheric Test Site T-7C • 07-23-04, Atmospheric Test Site T7-1 • 07-23-05, Atmospheric Test Site • 07-23-06, Atmospheric Test Site T7-5a • 07-23-07, Atmospheric Test Site - Dog (T-S) • 07-23-08, Atmospheric Test Site - Baker (T-S) • 07-23-09, Atmospheric Test Site - Charlie (T-S) • 07-23-10, Atmospheric Test Site - Dixie • 07-23-11, Atmospheric Test Site - Dixie • 07-23-12, Atmospheric Test Site - Charlie (Bus) • 07-23-13, Atmospheric Test Site - Baker (Buster) • 07-23-14, Atmospheric Test Site - Ruth • 07-23-15, Atmospheric Test Site T7-4 •more » 07-23-16, Atmospheric Test Site B7-b • 07-23-17, Atmospheric Test Site - Climax These 15 CASs include releases from 30 atmospheric tests conducted in the approximately 1 square mile of CAU 104. Because releases associated with the CASs included in this CAU overlap and are not separate and distinguishable, these CASs are addressed jointly at the CAU level. The purpose of this CADD/CAP is to evaluate potential corrective action alternatives (CAAs), provide the rationale for the selection of recommended CAAs, and provide the plan for implementation of the recommended CAA for CAU 104. Corrective action investigation (CAI) activities were performed from October 4, 2011, through May 3, 2012, as set forth in the CAU 104 Corrective Action Investigation Plan.« less

Colchicum autumnale in Patients with Goitre with Euthyroidism or Mild Hyperthyroidism: Indications for a Therapeutic Regulative Effect—Results of an Observational Study

PubMed Central

Scheffer, Christian; Debus, Marion; Heckmann, Christian; Cysarz, Dirk; Girke, Matthias

2016-01-01

Introduction. Goitre with euthyroid function or with subclinical or mild hyperthyroidism due to thyroid autonomy is common. In anthroposophic medicine various thyroid disorders are treated with Colchicum autumnale (CAU). We examined the effects of CAU in patients with goitre of both functional states. Patients and methods. In an observational study, 24 patients with goitre having suppressed thyroid stimulating hormone (TSH) levels with normal or slightly elevated free thyroxine (fT4) and free triiodothyronine (fT3) (group 1, n = 12) or normal TSH, fT3, and fT4 (group 2, n = 12) were included. After 3 months and after 6 to 12 months of CAU treatment, we investigated clinical pathology using the Hyperthyroid Symptom Scale (HSS), hormone status (TSH, fT4, and fT3), and thyroidal volume (tV). Results. After treatment with CAU, in group 1 the median HSS decreased from 4.5 (2.3–11.8) to 2 (1.3–3) (p < 0.01) and fT3 decreased from 3.85 (3.5–4.78) to 3.45 (3.3–3.78) pg/mL (p < 0.05). In group 2 tV (13.9% (18.5%–6.1%)) and TSH (p < 0.01) were reduced. Linear regression for TSH and fT3 in both groups indicated a regulative therapeutic effect of CAU. Conclusions. CAU positively changed the clinical pathology of subclinical hyperthyroidism and thyroidal volume in patients with euthyroid goitre by normalization of the regulation of thyroidal hormones. PMID:26955394

Colchicum autumnale in Patients with Goitre with Euthyroidism or Mild Hyperthyroidism: Indications for a Therapeutic Regulative Effect-Results of an Observational Study.

PubMed

Scheffer, Christian; Debus, Marion; Heckmann, Christian; Cysarz, Dirk; Girke, Matthias

2016-01-01

Introduction. Goitre with euthyroid function or with subclinical or mild hyperthyroidism due to thyroid autonomy is common. In anthroposophic medicine various thyroid disorders are treated with Colchicum autumnale (CAU). We examined the effects of CAU in patients with goitre of both functional states. Patients and methods. In an observational study, 24 patients with goitre having suppressed thyroid stimulating hormone (TSH) levels with normal or slightly elevated free thyroxine (fT4) and free triiodothyronine (fT3) (group 1, n = 12) or normal TSH, fT3, and fT4 (group 2, n = 12) were included. After 3 months and after 6 to 12 months of CAU treatment, we investigated clinical pathology using the Hyperthyroid Symptom Scale (HSS), hormone status (TSH, fT4, and fT3), and thyroidal volume (tV). Results. After treatment with CAU, in group 1 the median HSS decreased from 4.5 (2.3-11.8) to 2 (1.3-3) (p < 0.01) and fT3 decreased from 3.85 (3.5-4.78) to 3.45 (3.3-3.78) pg/mL (p < 0.05). In group 2 tV (13.9% (18.5%-6.1%)) and TSH (p < 0.01) were reduced. Linear regression for TSH and fT3 in both groups indicated a regulative therapeutic effect of CAU. Conclusions. CAU positively changed the clinical pathology of subclinical hyperthyroidism and thyroidal volume in patients with euthyroid goitre by normalization of the regulation of thyroidal hormones.

Corrective Action Decision Document/Corrective Action Plan for Corrective Action Unit 97: Yucca Flat/Climax Mine Nevada National Security Site, Nevada, Revision 1

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

Farnham, Irene

This corrective action decision document (CADD)/corrective action plan (CAP) has been prepared for Corrective Action Unit (CAU) 97, Yucca Flat/Climax Mine, Nevada National Security Site (NNSS), Nevada. The Yucca Flat/Climax Mine CAU is located in the northeastern portion of the NNSS and comprises 720 corrective action sites. A total of 747 underground nuclear detonations took place within this CAU between 1957 and 1992 and resulted in the release of radionuclides (RNs) in the subsurface in the vicinity of the test cavities. The CADD portion describes the Yucca Flat/Climax Mine CAU data-collection and modeling activities completed during the corrective action investigationmore » (CAI) stage, presents the corrective action objectives, and describes the actions recommended to meet the objectives. The CAP portion describes the corrective action implementation plan. The CAP presents CAU regulatory boundary objectives and initial use-restriction boundaries identified and negotiated by DOE and the Nevada Division of Environmental Protection (NDEP). The CAP also presents the model evaluation process designed to build confidence that the groundwater flow and contaminant transport modeling results can be used for the regulatory decisions required for CAU closure. The UGTA strategy assumes that active remediation of subsurface RN contamination is not feasible with current technology. As a result, the corrective action is based on a combination of characterization and modeling studies, monitoring, and institutional controls. The strategy is implemented through a four-stage approach that comprises the following: (1) corrective action investigation plan (CAIP), (2) CAI, (3) CADD/CAP, and (4) closure report (CR) stages.« less

Up-regulation of HOXB cluster genes are epigenetically regulated in tamoxifen-resistant MCF7 breast cancer cells.

PubMed

Yang, Seoyeon; Lee, Ji-Yeon; Hur, Ho; Oh, Ji Hoon; Kim, Myoung Hee

2018-05-28

Tamoxifen (TAM) is commonly used to treat estrogen receptor (ER)-positive breast cancer. Despite the remarkable benefits, resistance to TAM presents a serious therapeutic challenge. Since several HOX transcription factors have been proposed as strong candidates in the development of resistance to TAM therapy in breast cancer, we generated an in vitro model of acquired TAM resistance using ER-positive MCF7 breast cancer cells (MCF7-TAMR), and analyzed the expression pattern and epigenetic states of HOX genes. HOXB cluster genes were uniquely up-regulated in MCF7-TAMR cells. Survival analysis of in slico data showed the correlation of high expression of HOXB genes with poor response to TAM in ER-positive breast cancer patients treated with TAM. Gain- and loss-of-function experiments showed that the overexpression of multi HOXB genes in MCF7 renders cancer cells more resistant to TAM, whereas the knockdown restores TAM sensitivity. Furthermore, activation of HOXB genes in MCF7-TAMR was associated with histone modifications, particularly the gain of H3K9ac. These findings imply that the activation of HOXB genes mediate the development of TAM resistance, and represent a target for development of new strategies to prevent or reverse TAM resistance.

Basic research supported developments of chemotherapy in nonresectable isolated colorectal liver metastases to a protocol of hepatic artery infusion using mitoxantrone, 5-FU + folinic acid and mitomycin C.

PubMed

Link, K H; Kornmann, M; Leder, G; Pillasch, A F; Sunelaitis, E; Schatz, M; Pressmar, J; Beger, H G

1999-02-01

Since the developments in systemic chemotherapy of metastasized colorectal cancer have not resulted in substantial gains in survival times, we wished to improve the course of isolated nonresectable colorectal liver metastases (CPLM) by hepatic arterial infusion treatment. Patients (pts) with CRLM have a worse fate than those pts whose liver metastases could be resected. Systemic (i.v.) chemotherapy for CRLM/colorectal metastases does not improve survival to a relevant level (median survival time (med. surv.) after 5-Fluorouracil + Folinic Acid (5-FU + FA) i.v.: 6.4-14.3 months (m)). Hepatic artery infusion (HAI) with 5-Fluorode-oxyuridine (5-FUDR) has been demonstrated in a metaanalysis of randomized trials to be superior to i.v. treatment/palliative care (med. surv.: 15 vs. 10 m). The benefit of HAI with 5-FUDR, although recommended as treatment for CRLM, is severely compromised by the 5-FUDR induced hepatotoxicity, leading eventually to sclerosing cholangitis (SC)/liver scirrhosis. We have stepwise developed a protocol for HAI of CRLM, which is superior to HAI with 5-FUDR, and, most evidently, to systemic chemotherapy. Between 1982-1997, 222 CR (L) M patients were treated within subsequent protocols (Table). In protocol A, 68 CRLM pts received HAI with 5-FUDR (A1: nonrandomized pts; A2: randomized pts). In protocol B (randomized pts.), 46 pts received 5-FUDR i.a. (via HAI) + i.v. In protocol C, systemic chemotherapy with 5-FU + FA was conducted in 34 pts with metastasized colorectal cancers, including CRLM. In protocol D 5-FU + FA was delivered via HAI in 25 pts with CRLM. In protocol E, based on in vitro phase II studies and the results of protocol D, Mitoxantrone and Mitomycin C were added to 5-FU + FA (MFFM). Fifty (50) CRLM pts received HAI with MFFM. The response rates, med. surv. times, systemic toxicity and SC rates are shown in the table. HAI with MFFM produced objective responses in 66%, the med. surv. was 27.4 m, and no SC occurred. The ports surgically

Definition of healthcare-associated influenza: A review and results from an international survey.

PubMed

Munier-Marion, Elodie; Bénet, Thomas; Vanhems, Philippe

2017-09-01

To describe definitions of healthcare-associated influenza (HAI) in recent literature and in hospitals participating in a survey of Society for Healthcare Epidemiology of America (SHEA) Research Network (SRN) members. A review with PubMed search was undertaken to retrieve articles published between 2008 and 2016, focusing on the subject headings "influenza, human" and "cross infection." Definitions of clinical influenza-like illness (ILI) and HAI were identified. An invitation to participate in the survey was sent to 218 SRN members via email. Of 75 articles on HAI included in the review, 30 presented a standardized definition of clinical ILI based on fever (100%), cough (80%), and sore throat (70%). Forty studies (53%) contained a standardized HAI definition, grounded on threshold delay from admission in 29 of them, this delay ranging from 48 to 196 hour (median: 72 hour). Fifty-five SRN members responded to the survey, with a standardized definition of HAI adopted by 76% of them. This definition was based on clinical features for 24%, virological features for 31%, and both for 45%. Fever (mean threshold: 38.0°C) was part of the definition for 82%. The features required most frequently in the clinical definition were cough (46%) and sore throat (26%). Median threshold delay between admission and symptoms onset adopted for HAI definition was 48 hour (range: 24-96 hour). This work underlined the heterogeneity of HAI definitions in different countries. A standardized definition would be helpful to evaluate HAI spread, outcomes in patients and healthcare systems, and the impact of prevention measures, including vaccination. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Antimicrobial-Resistant Pathogens Associated With Healthcare-Associated Infections: Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011-2014.

PubMed

Weiner, Lindsey M; Webb, Amy K; Limbago, Brandi; Dudeck, Margaret A; Patel, Jean; Kallen, Alexander J; Edwards, Jonathan R; Sievert, Dawn M

2016-11-01

OBJECTIVE To describe antimicrobial resistance patterns for healthcare-associated infections (HAIs) that occurred in 2011-2014 and were reported to the Centers for Disease Control and Prevention's National Healthcare Safety Network. METHODS Data from central line-associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonias, and surgical site infections were analyzed. These HAIs were reported from acute care hospitals, long-term acute care hospitals, and inpatient rehabilitation facilities. Pooled mean proportions of pathogens that tested resistant (or nonsusceptible) to selected antimicrobials were calculated by year and HAI type. RESULTS Overall, 4,515 hospitals reported that at least 1 HAI occurred in 2011-2014. There were 408,151 pathogens from 365,490 HAIs reported to the National Healthcare Safety Network, most of which were reported from acute care hospitals with greater than 200 beds. Fifteen pathogen groups accounted for 87% of reported pathogens; the most common included Escherichia coli (15%), Staphylococcus aureus (12%), Klebsiella species (8%), and coagulase-negative staphylococci (8%). In general, the proportion of isolates with common resistance phenotypes was higher among device-associated HAIs compared with surgical site infections. Although the percent resistance for most phenotypes was similar to earlier reports, an increase in the magnitude of the resistance percentages among E. coli pathogens was noted, especially related to fluoroquinolone resistance. CONCLUSION This report represents a national summary of antimicrobial resistance among select HAIs and phenotypes. The distribution of frequent pathogens and some resistance patterns appear to have changed from 2009-2010, highlighting the need for continual, careful monitoring of these data across the spectrum of HAI types. Infect Control Hosp Epidemiol 2016;1-14.

Healthcare-associated infections among pediatric oncology patients in Pakistan: risk factors and outcome.

PubMed

Siddiqui, Naveed-ur-Rehman; Wali, Rabia; Haque, Anwar-ul; Fadoo, Zehra

2012-05-14

Pediatric oncology patients are at increased risk of contracting healthcare-associated infections (HAIs), which are responsible for increased morbidity and mortality rates as well as treatment costs.  This study aimed to identify the frequency of HAIs among pediatric oncology patients and their outcome. Pediatric oncology patients admitted between January 2009 and June 2010 in a pediatric ward at Aga Khan University Hospital, Karachi, Pakistan, who developed HAIs, were analyzed. A total of 90 HAIs were identified in 32 patients in 70 admissions. The HAI rate among pediatric oncology patients was 3.1/100 admission episodes. Bloodstream infections (63 episodes, 90.0%) were the most common, followed by urinary tract infection (two episodes, 2.9%). Gram-positive infections were seen in 54 (60%) patients, followed by Gram-negative infection in 34 (37.8%), and fungi in 2 (2.8%) cases. Coagulase negative staphylococci was the most common Gram-positive and Escherichia coli and Pseudomonas aeruginosa were most common Gram-negative infections. Mortality rate among pediatric oncology patients who developed HAIs was 12.5% (4/32). Total parental nutrition use and length of stay longer than 30 days were the identified risk factors associated with increased mortality among pediatric oncology patients who developed HAIs. We report an HAI rate among pediatric oncology patients of 3.1/100 admission episodes with a mortality rate of 12.5% in Pakistan. Further studies should be done, especially in the developing world, to identify the risk factors associated with increased mortality among pediatric oncology patients so that adequate measures can be taken to reduce the mortality among these patients.

Reducing the risk of healthcare‐associated infections through Lean Six Sigma: The case of the medicine areas at the Federico II University Hospital in Naples (Italy)

PubMed Central

Cesarelli, Mario; Montuori, Paolo; Santillo, Liberatina Carmela; Triassi, Maria

2017-01-01

Abstract Rationale, aims, and objectives Lean Six Sigma (LSS) has been recognized as an effective management tool for improving healthcare performance. Here, LSS was adopted to reduce the risk of healthcare‐associated infections (HAIs), a critical quality parameter in the healthcare sector. Methods Lean Six Sigma was applied to the areas of clinical medicine (including general medicine, pulmonology, oncology, nephrology, cardiology, neurology, gastroenterology, rheumatology, and diabetology), and data regarding HAIs were collected for 28,000 patients hospitalized between January 2011 and December 2016. Following the LSS define, measure, analyse, improve, and control cycle, the factors influencing the risk of HAI were identified by using typical LSS tools (statistical analyses, brainstorming sessions, and cause‐effect diagrams). Finally, corrective measures to prevent HAIs were implemented and monitored for 1 year after implementation. Results Lean Six Sigma proved to be a useful tool for identifying variables affecting the risk of HAIs and implementing corrective actions to improve the performance of the care process. A reduction in the number of patients colonized by sentinel bacteria was achieved after the improvement phase. Conclusions The implementation of an LSS approach could significantly decrease the percentage of patients with HAIs. PMID:29098756

Corrective Action Decision Document/Closure Report for Corrective Action Unit 252: Area 25 Engine Test Stand 1 Decontamination Pad, Nevada Test Site, Nevada

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

DOE /NV

This Corrective Action Decision Document/Closure Report (CADD/CR) has been prepared for Corrective Action Unit (CAU) 252: Area 25 Engine Test Stand-1 Decontamination Pad, in accordance with the Federal Facility Agreement and Consent Order (FFACO). Located at the Nevada Test Site in Nevada, CAU 252 consists of only one Corrective Action Site (25-07-04, Decontamination Pad). This CADD/CR identifies and rationalizes the U.S. Department of Energy, Nevada Operations Office's (DOE/NV's) recommendation that no corrective action is deemed necessary at CAU 252. The Corrective Action Decision Document and Closure Report have been combined into one report because the potential contaminants of concern weremore » either not detected during the corrective action investigation or were only present at naturally occurring concentrations. Based on the field results, neither corrective action or a corrective action plan is required at this site. A Notice of Completion to DOE/NV is being requested from the Nevada Division of Environmental Protection for closure of CAU 252, as well as a request that this site be moved from Appendix III to Appendix IV of the FFACO. Further, no use restrictions are required to be placed on this CAU.« less

CLOSURE REPORT FOR CORRECTIVE ACTION UNIT165: AREA 25 AND 26 DRY WELL AND WASH DOWN AREAS, NEVADA TEST SITE, NEVADA

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

BECHTEL NEVADA

This Closure Report (CR) documents the closure activities for Corrective Action Unit (CAU) 165, Area 25 and 26 Dry Well and Washdown Areas, according to the Federal Facility Agreement and Consent Order (FFACO) of 1996. CAU 165 consists of 8 Corrective Action Sites (CASs) located in Areas 25 and 26 of the Nevada Test Site (NTS). The NTS is located approximately 105 kilometers (65 miles) northwest of Las Vegas, nevada. Site closure activities were performed according to the Nevada Division of Environmental Protection (NDEP)-approved Corrective Action Plan (CAP) for CAU 165. CAU 165 consists of the following CASs: (1) CASmore » 25-07-06, Train Decontamination Area; (2) CAS 25-07-07, Vehicle Washdown; (3) CAS 25-20-01, Lab Drain Dry Well; (4) CAS 25-47-01, Reservoir and French Drain; (5) CAS 25-51-02, Drywell; (6) CAS 25-59-01, Septic System; (7) CAS 26-07-01, Vehicle Washdown Station; and (8) CAS 26-59-01, Septic System. CAU 165, Area 25 and 26 Dry Well and Washdown Areas, consists of eight CASs located in Areas 25 and 26 of the NTS. The approved closure alternatives included No Further Action, Clean Closure, and Closure in Place with Administrative Controls.« less

Corrective Action Plan for Corrective Action Unit 262: Area 25 Septic Systems and Underground Discharge Point, Nevada Test Site, Nevada

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

K. B. Campbell

This Corrective Action Plan (CAP) provides selected corrective action alternatives and proposes the closure methodology for Corrective Action Unit (CAU) 262, Area 25 Septic Systems and Underground Discharge Point. CAU 262 is identified in the Federal Facility Agreement and Consent Order (FFACO) of 1996. Remediation of CAU 262 is required under the FFACO. CAU 262 is located in Area 25 of the Nevada Test Site (NTS), approximately 100 kilometers (km) (62 miles [mi]) northwest of Las Vegas, Nevada. The nine Corrective Action Sites (CASs) within CAU 262 are located in the Nuclear Rocket Development Station complex. Individual CASs are locatedmore » in the vicinity of the Reactor Maintenance, Assembly, and Disassembly (R-MAD); Engine Maintenance, Assembly, and Disassembly (E-MAD); and Test Cell C compounds. CAU 262 includes the following CASs as provided in the FFACO (1996); CAS 25-02-06, Underground Storage Tank; CAS 25-04-06, Septic Systems A and B; CAS 25-04-07, Septic System; CAS 25-05-03, Leachfield; CAS 25-05-05, Leachfield; CAS 25-05-06, Leachfield; CAS 25-05-08, Radioactive Leachfield; CAS 25-05-12, Leachfield; and CAS 25-51-01, Dry Well. Figures 2, 3, and 4 show the locations of the R-MAD, the E-MAD, and the Test Cell C CASs, respectively. The facilities within CAU 262 supported nuclear rocket reactor engine testing. Activities associated with the program were performed between 1958 and 1973. However, several other projects used the facilities after 1973. A significant quantity of radioactive and sanitary waste was produced during routine operations. Most of the radioactive waste was managed by disposal in the posted leachfields. Sanitary wastes were disposed in sanitary leachfields. Septic tanks, present at sanitary leachfields (i.e., CAS 25-02-06,2504-06 [Septic Systems A and B], 25-04-07, 25-05-05,25-05-12) allowed solids to settle out of suspension prior to entering the leachfield. Posted leachfields do not contain septic tanks. All CASs located in CAU 262

Corrective Action Decision Document/Corrective Action Plan for Corrective Action Unit 413: Clean Slate II Plutonium Dispersion (TTR) Tonopah Test Range, Nevada. Revision 0

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

Matthews, Patrick

This Corrective Action Decision Document/Corrective Action Plan provides the rationale and supporting information for the selection and implementation of corrective actions at Corrective Action Unit (CAU) 413, Clean Slate II Plutonium Dispersion (TTR). CAU 413 is located on the Tonopah Test Range and includes one corrective action site, TA-23-02CS. CAU 413 consists of the release of radionuclides to the surface and shallow subsurface from the Clean Slate II (CSII) storage–transportation test conducted on May 31, 1963. The CSII test was a non-nuclear detonation of a nuclear device located inside a concrete bunker covered with 2 feet of soil. To facilitatemore » site investigation and the evaluation of data quality objectives decisions, the releases at CAU 413 were divided into seven study groups: 1 Undisturbed Areas 2 Disturbed Areas 3 Sedimentation Areas 4 Former Staging Area 5 Buried Debris 6 Potential Source Material 7 Soil Mounds Corrective action investigation (CAI) activities, as set forth in the CAU 413 Corrective Action Investigation Plan, were performed from June 2015 through May 2016. Radionuclides detected in samples collected during the CAI were used to estimate total effective dose using the Construction Worker exposure scenario. Corrective action was required for areas where total effective dose exceeded, or was assumed to exceed, the radiological final action level (FAL) of 25 millirem per year. The results of the CAI and the assumptions made in the data quality objectives resulted in the following conclusions: The FAL is exceeded in surface soil in SG1, Undisturbed Areas; The FAL is assumed to be exceeded in SG5, Buried Debris, where contaminated debris and soil were buried after the CSII test; The FAL is not exceeded at SG2, SG3, SG4, SG6, or SG7. Because the FAL is exceeded at CAU 413, corrective action is required and corrective action alternatives (CAAs) must be evaluated. For CAU 413, three CAAs were evaluated: no further action, clean

Tamoxifen metabolite isomer separation and quantification by liquid chromatography-tandem mass spectrometry.

PubMed

Jaremko, Malgorzata; Kasai, Yumi; Barginear, Myra F; Raptis, George; Desnick, Robert J; Yu, Chunli

2010-12-15

Tamoxifen (Tam), the antiestrogen used to treat estrogen receptor-positive breast cancer is a pro-drug that is converted to its major active metabolites, endoxifen and 4-hydroxy-tamoxifen (4-OH-Tam) by various biotransformation enzymes of which cytochrome P450-2D6 (CYP2D6) is key. The usual Tam dose is 20 mg daily; however, the plasma active metabolite concentrations vary due to common genetic variants encoding the biotransformation enzymes and environmental factors (e.g., concomitant drugs) that inhibit these enzymes. Effective treatment depends on adequate Tam conversion to its active isomers. To monitor metabolite plasma levels, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to separate and quantitate Tam, N-desmethyl-tamoxifen (ND-Tam), and tamoxifen-N-oxide (Tam-N-oxide), and the E, Z, and Z' isomers of endoxifen and 4-OH-Tam. Known standards were used to identify each metabolite/isomer. Quantitation of these metabolites in plasma was linear from 0.6 to 2000 nM. Intra- and inter-assay reproducibilities were 0.2-8.4% and 0.6-6.3%, respectively. Accuracy determined by spike experiments with known standards was 86-103%. Endoxifen, 4-OH-Tam, and their isomers were stable in fresh frozen plasma for ≥6 months. This method provides the first sensitive, specific, accurate, and reproducible quantitation of Tam and its metabolite isomers for monitoring Tam-treated breast cancer patients.

Impact of thermal time shift on wheat phenology and yield under warming climate in the Huang-Huai-Hai Plain, China

NASA Astrophysics Data System (ADS)

Xiao, Dengpan; Qi, Yongqing; Li, Zhiqiang; Wang, Rende; Moiwo, Juana P.; Liu, Fengshan

2017-03-01

Given climate change can potentially influence crop phenology and subsequent yield, an investigation of relevant adaptation measures could increase the understanding and mitigation of these responses in the future. In this study, field observations at 10 stations in the Huang-Huai-Hai Plain of China (HHHP) are used in combination with the Agricultural Production Systems Simulator (APSIM)-Wheat model to determine the effect of thermal time shift on the phenology and potential yield of wheat from 1981-2009. Warming climate speeds up winter wheat development and thereby decreases the duration of the wheat growth period. However, APSIM-Wheat model simulation suggests prolongation of the period from flowering to maturity (Gr) of winter wheat by 0.2-0.8 d•10yr-1 as the number of days by which maturity advances, which is less than that by which flowering advances. Based on computed thermal time of the two critical growth phases of wheat, total thermal time from floral initiation to flowering (TT_floral_initiation) increasesd in seven out of the 10 investigated stations. Alternatively, total thermal time from the start of grainfilling to maturity (TT_start_ grain_fill) increased in all investigated stations, except Laiyang. It is thus concluded that thermal time shift during the past three decades (1981-2009) prolongs Gr by 0.2-3.0 d•10yr-1 in the study area. This suggests that an increase in thermal time (TT) of the wheat growth period is critical for mitigating the effect of growth period reduction due to warming climatic condition. Furthermore, climate change reduces potential yield of winter wheat in 80% of the stations by 2.3-58.8 kg•yr-1. However, thermal time shift (TTS) increases potential yield of winter wheat in most of the stations by 3.0-51.0 kg•yr-1. It is concluded that wheat cultivars with longer growth periods and higher thermal requirements could mitigate the negative effects of warming climate on crop production in the study area.

Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer.

PubMed

Nonomura, Norio; Takayama, Hitoshi; Nakayama, Masashi; Nakai, Yasutomo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Aozasa, Katsuyuki; Tsujimura, Akira

2011-06-01

• To evaluate tumour-associated macrophage (TAM) infiltration in prostate biopsy specimens as a possible prognostic factor for prostate cancer (PCa) after hormonal therapy. • Immunostaining of TAMs in prostate biopsy specimens was performed using a monoclonal antibody CD68 for 71 patients having PCa treated with hormonal therapy. • Six microscopic (×400) fields around the cancer foci were selected for TAM counting. • The median value of serum prostate-specific antigen (PSA) was 50.1 ng/mL, and the median TAM count was 22. • Recurrence-free survival was significantly better in patients with fewer TAMs (<22) than in those with higher numbers of TAMs (≥22) (P < 0.001). • TAM count was higher in those with higher serum PSA (PSA), higher Gleason score, clinical T stage or those with PSA failure. Cox multivariate analysis showed that TAM count is one of the prognostic factors for PCa treated by hormonal therapy (P < 0.0001). • TAM infiltration in prostate needle biopsy specimens is a useful predictive factor for PSA failure or progression of PCa after hormonal therapy. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

Hai Long | NREL

Science.gov Websites

research interests are broadly in computational modeling for renewable energy generation and energy ions transport in fuel cell and bioenergetics enzymes, and functional membrane structure modeling and University Featured Publications Hydroxide Degradation Pathways for Imidazolium Cations: A DFT Study, J. Phys

Phase I Contaminant Transport Parameters for the Groundwater Flow and Contaminant Transport Model of Corrective Action Unit 97: Yucca Flat/Climax Mine, Nevada Test Site, Nye County, Nevada, Revision 0

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

John McCord

2007-09-01

This report documents transport data and data analyses for Yucca Flat/Climax Mine CAU 97. The purpose of the data compilation and related analyses is to provide the primary reference to support parameterization of the Yucca Flat/Climax Mine CAU transport model. Specific task objectives were as follows: • Identify and compile currently available transport parameter data and supporting information that may be relevant to the Yucca Flat/Climax Mine CAU. • Assess the level of quality of the data and associated documentation. • Analyze the data to derive expected values and estimates of the associated uncertainty and variability. The scope of thismore » document includes the compilation and assessment of data and information relevant to transport parameters for the Yucca Flat/Climax Mine CAU subsurface within the context of unclassified source-term contamination. Data types of interest include mineralogy, aqueous chemistry, matrix and effective porosity, dispersivity, matrix diffusion, matrix and fracture sorption, and colloid-facilitated transport parameters.« less

Closure Report for Corrective Action Unit 465: Hydronuclear Nevada National Security Site, Nevada, Revision 0

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

Mark Burmeister and Patrick Matthews

2012-11-01

The corrective action sites (CASs) within CAU 465 are located within Areas 6 and 27 of the NNSS. CAU 465 comprises the following CASs: • 00-23-01, Hydronuclear Experiment, located in Area 27 of the NNSS and known as the Charlie site. • 00-23-02, Hydronuclear Experiment, located in Area 27 of the NNSS and known as the Dog site. • 00-23-03, Hydronuclear Experiment, located in Area 27 of the NNSS and known as the Charlie Prime and Anja sites. • 06-99-01, Hydronuclear, located in Area 6 of the NNSS and known as the Trailer 13 site. The purpose of this CRmore » is to provide documentation supporting the completed corrective actions and provide data confirming that the closure objectives for CASs within CAU 465 were met. From September 2011 through July 2012, closure activities were performed as set forth in the Streamlined Approach for Environmental Restoration Plan for CAU 465: Hydronuclear, Nevada National Security Site, Nevada.« less

Site Matters: Multisite Randomized Trial of Motivational Enhancement Therapy in Community Drug Abuse Clinics

PubMed Central

Ball, Samuel A.; Martino, Steve; Nich, Charla; Frankforter, Tami L.; Van Horn, Deborah; Crits-Christoph, Paul; Woody, George E.; Obert, Jeanne L.; Farentinos, Christiane; Carroll, Kathleen M.

2007-01-01

The effectiveness of motivational enhancement therapy (MET) in comparison with counseling as usual (CAU) for increasing retention and reducing substance use was evaluated in a multisite randomized clinical trial. Participants were 461 outpatients treated by 31 therapists within 1 of 5 outpatient substance abuse programs. There were no retention differences between the 2 brief intervention conditions. Although both 3-session interventions resulted in reductions in substance use during the 4-week therapy phase, MET resulted in sustained reductions during the subsequent 12 weeks whereas CAU was associated with significant increases in substance use over this follow-up period. This finding was complicated by program site main effects and higher level interactions. MET resulted in more sustained substance use reductions than CAU among primary alcohol users, but no difference was found for primary drug users. An independent evaluation of session audiotapes indicated that MET and CAU were highly and comparably discriminable across sites. PMID:17663610

Site matters: multisite randomized trial of motivational enhancement therapy in community drug abuse clinics.

PubMed

Ball, Samuel A; Martino, Steve; Nich, Charla; Frankforter, Tami L; Van Horn, Deborah; Crits-Christoph, Paul; Woody, George E; Obert, Jeanne L; Farentinos, Christiane; Carroll, Kathleen M

2007-08-01

The effectiveness of motivational enhancement therapy (MET) in comparison with counseling as usual (CAU) for increasing retention and reducing substance use was evaluated in a multisite randomized clinical trial. Participants were 461 outpatients treated by 31 therapists within 1 of 5 outpatient substance abuse programs. There were no retention differences between the 2 brief intervention conditions. Although both 3-session interventions resulted in reductions in substance use during the 4-week therapy phase, MET resulted in sustained reductions during the subsequent 12 weeks whereas CAU was associated with significant increases in substance use over this follow-up period. This finding was complicated by program site main effects and higher level interactions. MET resulted in more sustained substance use reductions than CAU among primary alcohol users, but no difference was found for primary drug users. An independent evaluation of session audiotapes indicated that MET and CAU were highly and comparably discriminable across sites.

Underground Test Area Activity Preemptive Review Guidance Nevada National Security Site, Nevada, Revision 0

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

Farnham, Irene; Rehfeldt, Kenneth

Preemptive reviews (PERs) of Underground Test Area (UGTA) Activity corrective action unit (CAU) studies are an important and long-maintained quality improvement process. The CAU-specific PER committees provide internal technical review of ongoing work throughout the CAU lifecycle. The reviews, identified in the UGTA Quality Assurance Plan (QAP) (Sections 1.3.5.1 and 3.2), assure work is comprehensive, accurate, in keeping with the state of the art, and consistent with CAU goals. PER committees review various products, including data, documents, software/codes, analyses, and models. PER committees may also review technical briefings including Federal Facility Agreement and Consent Order (FFACO)-required presentations to the Nevadamore » Division of Environmental Protection (NDEP) and presentations supporting key technical decisions (e.g., investigation plans and approaches). PER committees provide technical recommendations to support regulatory decisions that are the responsibility of the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Field Office (NNSA/NFO) and NDEP.« less

Optimizing tamoxifen-inducible Cre/loxp system to reduce tamoxifen effect on bone turnover in long bones of young mice.

PubMed

Zhong, Zhendong A; Sun, Weihua; Chen, Haiyan; Zhang, Hongliang; Lay, Yu-An E; Lane, Nancy E; Yao, Wei

2015-12-01

For tamoxifen-dependent Cre recombinase, also known as CreER recombinase, tamoxifen (TAM) is used to activate the Cre to generate time- and tissue-specific mouse mutants. TAM is a potent CreER system inducer; however, TAM is also an active selective estrogen receptor modulator (SERM) that can influence bone homeostasis. The purpose of this study was to optimize the TAM dose for Cre recombinase activation while minimizing the effects of TAM on bone turnover in young growing mice. To evaluate the effects of TAM on bone turnover and bone mass, 1-month-old wild-type male and female mice were intraperitoneally injected with TAM at 0, 1, 10 or 100mg/kg/day for four consecutive days, or 100, 300 mg/kg/day for one day. The distal femurs were analyzed one month after the last TAM injection by microCT, mechanical test, and surface-based bone histomorphometry. Similar doses of TAM were used in Col1 (2.3 kb)-CreERT2; mT/mG reporter male mice to evaluate the dose-dependent efficacy of Cre-ER activation in bone tissue. A TAM dose of 100 mg/kg × 4 days significantly increased trabecular bone volume/total volume (BV/TV) of the distal femur, femur length, bone strength, and serum bone turnover markers compared to the 0mg control group. In contrast, TAM doses ≤ 10 mg/kg did not significantly change any of these parameters compared to the 0mg group, although a higher bone strength was observed in the 10mg group. Surface-based histomorphometry revealed that the 100mg/kg dose of TAM dose significantly increased trabecular bone formation and decreased periosteal bone formation at 1-week post-TAM treatment. Using the reporter mouse model Col1-CreERT2; mT/mG, we found that 10mg/kg TAM induced Col1-CreERT2 activity in bone at a comparable level to the 100mg/kg dose. TAM treatment at 100mg/kg/day × 4 days significantly affects bone homeostasis, resulting in an anabolic bone effect on trabecular bone in 1-month-old male mice. However, a lower dose of TAM at 10 mg/kg/day × 4 days can

77 FR 73424 - Certain Frozen Fish Fillets From the Socialist Republic of Vietnam: Partial Rescission of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-10

...The Department of Commerce (``the Department'') is conducting an administrative review of the antidumping duty order on certain frozen fish fillets (``fish fillets'') from the Socialist Republic of Vietnam (``Vietnam'').\\1\\ The Department is rescinding the review with respect to An Giang Fisheries Import & Export Joint Stock Company (``Agifish''). The period of review (``POR'') is August 1, 2010, through July 31, 2011. ---------------------------------------------------------------------------

Health economic evaluation of an infection prevention and control program: are quality and patient safety programs worth the investment?

PubMed

Raschka, Stefanie; Dempster, Linda; Bryce, Elizabeth

2013-09-01

The effect of regional consolidation of an infection prevention and control (IPC) program on reduction of selected health care-acquired infections (HAIs), the economic burden of these illnesses, and where the potential for greatest financial benefit in reducing infection rates lies was assessed. Cost-benefit analysis (in Canadian $) was used to evaluate the effectiveness of a regional IPC program in preventing incident cases of HAIs. The costs of managing these infections, as well as the operational costs of the IPC program were compared against reductions in HAI rates over a 4-year period. Benefits were calculated as cost avoided by reducing HAI cases year over year. The Health Authority spent more than $66.3 million managing 24,937 HAI cases over the 4-year evaluation period. Urinary tract infections, methicillin-resistant Staphylococcus aureus, and bacteremias incurred the greatest costs. A reduction of 4,739 HAI cases led to avoided costs of $9.1 million in 4 years; the IPC program budget was $6.7 million during this period. Regionalization of the IPC program with standardized policies, procedures, and initiatives led to a 19% reduction in selected HAIs over 4 years and a cost avoidance of at least $9 million. This was particularly evident in years 3 and 4 of the program when $7.2 million (79% of the total) savings were realized. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Epidemiology and economic impact of health care-associated infections and cost-effectiveness of infection control measures at a Thai university hospital.

PubMed

Rattanaumpawan, Pinyo; Thamlikitkul, Visanu

2017-02-01

Data on clinical and economic impact of health care-associated infections (HAIs) from resource limited countries are limited. We aimed to determine epidemiology and economic impact of HAIs and cost-effectiveness of infection prevention and control measures in a resource-limited setting. A retrospective cohort study was conducted among hospitalized patients at Siriraj Hospital, Thailand. Results from the cohort were subsequently used to conduct cost-effective analysis (CEA) to compare the comprehensive implementation of individualized bundling infection control measures (IBICMs) with regular infection control care. From February-May 2013, there were 515 hospitalizations (497 patients) with 7,848 hospitalization days. Cumulative incidence of HAIs was 23.30%, and the incidence rate of HAIs was 18.66 ± 44.19 per 1,000 hospitalization days. Hospital mortality among those with and without HAIs was 33.33% and 20.00%, respectively (P < .001). The adjusted cost attributable to HAIs was $704.72 ± $226.73 (P < .001). CEA identified IBICMs as a non-dominated strategy, with an incremental cost-effectiveness ratio of -$20,444.62 per life saved. HAI is significantly related with higher hospital mortality, longer length of stay, and higher hospitalization costs. IBICMs were confirmed to be cost-effective at Siriraj Hospital. Implementing this intervention could improve care quality and save costs. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Antibody responses to natural influenza A/H1N1/09 disease or following immunization with adjuvanted vaccines, in immunocompetent and immunocompromised children.

PubMed

Meier, Sara; Bel, Michael; L'huillier, Arnaud; Crisinel, Pierre-Alex; Combescure, Christophe; Kaiser, Laurent; Grillet, Stéphane; Pósfay-Barbe, Klara; Siegrist, Claire-Anne

2011-04-27

To compare antibody responses elicited by influenza A/H1N1/09 disease and immunization with adjuvanted vaccines, in immunocompetent or immunocompromised children. Prospective parallel cohort field study enrolling children with confirmed influenza A/H1N1/09 disease or immunized with 1 (immunocompetent) or 2 (immunocompromised) doses of influenza A/H1N1/09 squalene-based AS03- or MF59-adjuvanted vaccines. Antibody geometric mean titers (GMT) were measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays 4-6 weeks after vaccination/disease. Vaccine adverse events were self-recorded in a 7-day diary. Antibody titers were as high in 48 immunocompetent children after a single immunization (HAI and MN seroprotection rates: 98%; HAI-GMT: 395, MN-GMT: 370) as in 51 convalescent children (seroprotection rates: 98% (HAI) and 92% (MN); GMT: 350 (HAI) and 212 (MN). Twenty-seven immunocompromised children reached slightly lower seroprotection rates (HAI: 89%, MN: 85%) but similar antibody titers (HAI-GMT: 306, MN-GMT: 225) after 2 immunizations. Adverse events increased with age (P=0.01) and were more frequent with Pandemrix® than Focetria® (P=0.03). Similarly high seroresponses may be expected in immunocompetent children after a single dose of adjuvanted vaccines as responses of convalescent children. Two vaccine doses were sufficient for most immunocompromised children. NCT0102293 and NCT01022905. Copyright © 2011 Elsevier Ltd. All rights reserved.

Psychosocial and Psychophysiological Effects of Human-Animal Interactions: The Possible Role of Oxytocin

PubMed Central

Beetz, Andrea; Uvnäs-Moberg, Kerstin; Julius, Henri; Kotrschal, Kurt

2012-01-01

During the last decade it has become more widely accepted that pet ownership and animal assistance in therapy and education may have a multitude of positive effects on humans. Here, we review the evidence from 69 original studies on human-animal interactions (HAI) which met our inclusion criteria with regard to sample size, peer-review, and standard scientific research design. Among the well-documented effects of HAI in humans of different ages, with and without special medical, or mental health conditions are benefits for: social attention, social behavior, interpersonal interactions, and mood; stress-related parameters such as cortisol, heart rate, and blood pressure; self-reported fear and anxiety; and mental and physical health, especially cardiovascular diseases. Limited evidence exists for positive effects of HAI on: reduction of stress-related parameters such as epinephrine and norepinephrine; improvement of immune system functioning and pain management; increased trustworthiness of and trust toward other persons; reduced aggression; enhanced empathy and improved learning. We propose that the activation of the oxytocin system plays a key role in the majority of these reported psychological and psychophysiological effects of HAI. Oxytocin and HAI effects largely overlap, as documented by research in both, humans and animals, and first studies found that HAI affects the oxytocin system. As a common underlying mechanism, the activation of the oxytocin system does not only provide an explanation, but also allows an integrative view of the different effects of HAI. PMID:22866043

Post-Closure Report for Closed Resource Conservation and Recovery Act Corrective Action Units, Nevada National Security Site, Nevada, for Fiscal Year 2014

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

Silvas, Alissa J.

2015-01-01

This report serves as the combined annual report for post-closure activities for several Corrective Action Units (CAUs). The locations of the sites are shown in Figure 1. This report covers fiscal year 2014 (October 2013–September 2014). The post-closure requirements for these sites are described in Resource Conservation and Recovery Act Permit Number NEV HW0101 and summarized in each CAU-specific section in Section 1.0 of this report. The results of the inspections, a summary of maintenance activities, and an evaluation of monitoring data are presented in this report. Site inspections are conducted semiannually at CAUs 90 and 91 and quarterly atmore » CAUs 92, 110, 111, and 112. Additional inspections are conducted at CAU 92 if precipitation occurs in excess of 0.50 inches (in.) in a 24-hour period and at CAU 111 if precipitation occurs in excess of 1.0 in. in a 24-hour period. Inspections include an evaluation of the condition of the units, including covers, fences, signs, gates, and locks. In addition to visual inspections, soil moisture monitoring, vegetation evaluations, and subsidence surveys are conducted at CAU 110. At CAU 111, soil moisture monitoring, vegetation evaluations, subsidence surveys, direct radiation monitoring, air monitoring, radon flux monitoring, and groundwater monitoring are conducted. The results of the vegetation surveys and an analysis of the soil moisture monitoring data at CAU 110 are presented in this report. Results of additional monitoring at CAU 111 are documented annually in the Nevada National Security Site Waste Management Monitoring Report Area 3 and Area 5 Radioactive Waste Management Sites and in the Nevada National Security Site Data Report: Groundwater Monitoring Program Area 5 Radioactive Waste Management Site, which will be prepared in approximately June 2015. All required inspections, maintenance, and monitoring were conducted in accordance with the post-closure requirements of the permit. It is recommended to

Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer

PubMed Central

Yin, Mingzhu; Li, Xia; Tan, Shu; Zhou, Huanjiao Jenny; Ji, Weidong; Bellone, Stefania; Xu, Xiaocao; Zhang, Haifeng; Santin, Alessandro D.; Lou, Ge

2016-01-01

Tumor-associated macrophages (TAMs) can influence ovarian cancer growth, migration, and metastasis, but the detailed mechanisms underlying ovarian cancer metastasis remain unclear. Here, we have shown a strong correlation between TAM-associated spheroids and the clinical pathology of ovarian cancer. Further, we have determined that TAMs promote spheroid formation and tumor growth at early stages of transcoelomic metastasis in an established mouse model for epithelial ovarian cancer. M2 macrophage–like TAMs were localized in the center of spheroids and secreted EGF, which upregulated αMβ2 integrin on TAMs and ICAM-1 on tumor cells to promote association between tumor cells and TAM. Moreover, EGF secreted by TAMs activated EGFR on tumor cells, which in turn upregulated VEGF/VEGFR signaling in surrounding tumor cells to support tumor cell proliferation and migration. Pharmacological blockade of EGFR or antibody neutralization of ICAM-1 in TAMs blunted spheroid formation and ovarian cancer progression in mouse models. These findings suggest that EGF secreted from TAMs plays a critical role in promoting early transcoelomic metastasis of ovarian cancer. As transcoelomic metastasis is also associated with many other cancers, such as pancreatic and colon cancers, our findings uncover a mechanism for TAM-mediated spheroid formation and provide a potential target for the treatment of ovarian cancer and other transcoelomic metastatic cancers. PMID:27721235

Pharmacokinetics of endoxifen and tamoxifen in female mice: implications for comparative in vivo activity studies.

PubMed

Reid, Joel M; Goetz, Matthew P; Buhrow, Sarah A; Walden, Chad; Safgren, Stephanie L; Kuffel, Mary J; Reinicke, Kathryn E; Suman, Vera; Haluska, Paul; Hou, Xiaonan; Ames, Matthew M

2014-12-01

Reduced CYP2D6 metabolism and low Z-endoxifen (ENDX) concentrations may increase the risk of breast cancer recurrence in tamoxifen (TAM)-treated women. Little is known regarding the differences between TAM and ENDX murine pharmacokinetics or the effect of administration route on plasma concentrations of each drug. The pharmacokinetics of TAM and ENDX were characterized in female mice. For subcutaneous [s.c.] and oral TAM (4, 10 and 20 mg/kg), TAM AUC increased in a linear manner, but concentrations of the active metabolites [ENDX and 4-hydroxytamoxifen (4HT)] remained low. For oral TAM (20 mg), 4HT concentrations were tenfold greater (>25 ng/ml) than achievable in TAM-treated humans. Both oral (10-200 mg/kg) and s.c. (2.5-25 mg/kg) ENDX·HCl resulted in a greater than dose-proportional increase in AUC, with eightfold greater ENDX concentrations than an equivalent TAM dose. ENDX accumulated in plasma after 5-day dosing of 25 or 100 mg/kg ENDX·HCl and exceeded target concentrations of 0.1 and 1.0 μM, respectively, by twofold to fourfold. In murine models, oral ENDX yields substantially higher ENDX concentrations, compared to TAM. The low 4HT and ENDX concentrations observed in mice receiving s.c. TAM mirror the TAM pharmacokinetics in humans with impaired CYP2D6 metabolism. These data support the ongoing development of ENDX as a novel agent for the endocrine treatment of ER-positive breast cancer.

Comparison of the safety and immunogenicity of live attenuated and inactivated hepatitis A vaccine in healthy Chinese children aged 18 months to 16 years: results from a randomized, parallel controlled, phase IV study.

PubMed

Ma, F; Yang, J; Kang, G; Sun, Q; Lu, P; Zhao, Y; Wang, Z; Luo, J; Wang, Z

2016-09-01

For large-scale immunization of children with hepatitis A (HA) vaccines in China, accurately designed studies comparing the safety and immunogenicity of the live attenuated HA vaccine (HA-L) and inactivated HA vaccine (HA-I) are necessary. A randomized, parallel controlled, phase IV clinical trial was conducted with 6000 healthy children aged 18 months to 16 years. HA-L or HA-I was administered at a ratio of 1: 1 to randomized selected participants. The safety and immunogenicity were evaluated. Both HA-L and HA-I were well tolerated by all participants. The immunogenicity results showed that the seroconversion rates (HA-L versus HA-I: 98.0% versus 100%, respectively, p >0.05), and geometric mean concentrations in participants negative for antibodies against HA virus IgG (anti-HAV IgG) before vaccination did not differ significantly between the two types of vaccines (HA-L versus HA-I first dose: 898.9 versus 886.2 mIU/mL, respectively, p >0.05). After administration of the booster dose of HA-I, the geometric mean concentrations of anti-HAV IgG (HA-I booster dose: 2591.2 mIU/mL) was higher than that after the first dose (p <0.05) and that reported in participants administered HA-L (p <0.05). Additionally, 12 (25%) of the 48 randomized selected participants who received HA-L tested positive for HA antigen in stool samples. Hence, both HA-L and HA-I could provide acceptable immunogenicity in children. The effects of long-term immunogenicity after natural exposure to wild-type HA virus and the possibility of mutational shifts of the live vaccine virus in the field need to be studied in more detail. Copyright © 2016. Published by Elsevier Ltd.

1,25-Dihydroxyvitamin D Deficiency Is Associated With Preterm Birth in African American and Caucasian Women

PubMed Central

Menon, Ramkumar; Fortunato, Stephen J.; Brou, Lina; Lee, Jae-Eun; Al-Hendy, Ayman

2014-01-01

Vitamin (vit) D deficiency and preterm birth (PTB) are more prevalent among African American (AA) women compared to caucasian (Cau) women. Because vit D is important in regulating cell-mediated immune responses, vit D insufficiency or deficiency during pregnancy may enhance inflammation in pregnant women and increase the risk of PTB. In this study, circulatory levels of 25-hydroxy (OH) and 1,25-dihydroxy (OH)2 vit D were measured using chemiluminescence and radioimmunoassay techniques, respectively, in AA (n = 108) and Cau (n = 84) women who delivered at term and preterm. The results from this study suggest that the serum levels of the 25-(OH) vit D concentrations tend to decrease (P = .06) in the Cau women who delivered at preterm compared to those delivering at term. However, the 25-(OH) vit D levels in Cau and AA between term and preterm deliveries were not significantly different. The serum levels of 1,25-(OH)2 vit D were found to be significantly lower in AA women compared to Cau women (P < .02) at term, and in the Cau (P < .01) and AA (P < .04) women delivering at preterm compared to those delivering at term. One-way analysis of variance demonstrated that 1,25-(OH)2 vit D levels were significantly lower in participants delivering at preterm (<34 weeks and between 34 and 37 weeks) compared to those delivering at term (>37 weeks).These results suggest that low levels of serum 1,25-(OH)2 vit D are associated with PTB, and vit D can potentially be used as a novel diagnostic marker in the detection of PTB. PMID:23793474

Face-to-face stacks of trinuclear gold(I) trihalides with benzene, hexafluorobenzene, and borazine: impact of aromaticity on stacking interactions.

PubMed

Tsipis, Athanassios C; Stalikas, Alexandros V

2013-01-18

The interplay of electrostatics, charge transfer, and dispersion forces contributing to the interaction energies in 1:1, 1:2, and 2:1 binary stacks of the c-Au(3)(μ(2)-X)(3) (X = F, Cl, Br, I) clusters with benzene, hexafluorobenzene, or borazine were investigated by employing a multitude of electronic structure computational techniques. The molecular and electronic structures, stabilities, bonding features, and magnetotropicity of [c-Au(3)(μ(2)-X)(3)](n)(L)(m) (X = halide; L = C(6)H(6), C(6)F(6), B(3)N(3)H(6); n, m ≤ 2) columnar binary stacks have been investigated by DFT calculations employing the M05-2X functional. The novel binary stacks could be considered as the building blocks of extended columnar supramolecular assemblies formulated as {[c-Au(3)(μ(2)-X)(3)](C(6)H(6))}(∞), {[c-Au(3)(μ(2)-X)(3)](2)(C(6)F(6))}(∞), and {[c-Au(3)(μ(2)-X)(3)](B(3)N(3)H(6))(2)}(∞). In all binary stacks, with a few exceptions, the plane of the alternating c-Au(3)(μ(2)-X)(3) and L (C(6)H(6), C(6)F(6), B(3)N(3)H(6)) stacking participants adopt an almost parallel face-to-face (pff) orientation. The observed trends in the intermolecular distances R in the [c-Au(3)(μ(2)-X)(3)](n)(L)(m) (X = halide; L = C(6)H(6), C(6)F(6), B(3)N(3)H(6); n, m ≤ 2) columnar binary stacks are explained by the diverse intermolecular interactions characterizing the stacks, since the three ligands L and the c-Au(3)(μ(2)-X)(3) cyclic trinuclear clusters (CTCs) exhibit diverse physical properties being important determinants of the intermolecular interactions (consisting of covalent, electrostatic, and dispersion forces). The properties considered are the zz tensor components of quadrupole moment, Q(zz), polarizability, α(zz), nucleus-independent chemical shift, NICS(zz)(1), along with the molecular electrostatic potential, MEP(0), and surface area (S). Energy decomposition analysis (EDA) at the revPBE-D3/TZ2P level revealed that the dominant term in the stacking interactions arises mainly

Assessment of Nanobiotechnology-Targeted siRNA Designed to Inhibit NF-kappaB Classical And Alternative Signaling in Breast Tumor Macrophages

DTIC Science & Technology

2012-07-01

tumor microenvironment we intend to deliver siRNA specifically to tumor- associated-macrophages ( TAMs ). Therefore, the proposed work seeks to synthesize...characterize and assess multifunctional nanoparticles for siRNA delivery specifically to tumor-associated-macrophages ( TAMs ). The nanoparticles...knockdown protein expression of NF-κB modulators with exceptional specificity for TAMs . TAM -specific nanoparticle targeting offers an innovative approach

Arrested development of the myxozoan parasite, Myxobolus cerebralis, in certain populations of mitochondrial 16S lineage III Tubifex tubifex.

PubMed

Baxa, D V; Kelley, G O; Mukkatira, K S; Beauchamp, K A; Rasmussen, C; Hedrick, R P

2008-01-01

Laboratory populations of Tubifex tubifex from mitochondrial (mt)16S ribosomal DNA (rDNA) lineage III were generated from single cocoons of adult worms releasing the triactinomyxon stages (TAMs) of the myxozoan parasite, Myxobolus cerebralis. Subsequent worm populations from these cocoons, referred to as clonal lines, were tested for susceptibility to infection with the myxospore stages of M. cerebralis. Development and release of TAMs occurred in five clonal lines, while four clonal lines showed immature parasitic forms that were not expelled from the worm (non-TAM producers). Oligochaetes from TAM- and non-TAM-producing clonal lines were confirmed as lineage III based on mt16S rDNA and internal transcribed spacer region 1 (ITS1) sequences, but these genes did not differentiate these phenotypes. In contrast, random amplified polymorphic DNA analyses of genomic DNA demonstrated unique banding patterns that distinguished the phenotypes. Cohabitation of parasite-exposed TAM- and non-TAM-producing phenotypes showed an overall decrease in expected TAM production compared to the same exposure dose of the TAM-producing phenotype without cohabitation. These studies suggest that differences in susceptibility to parasite infection can occur in genetically similar T. tubifex populations, and their coexistence may affect overall M. cerebralis production, a factor that may influence the severity of whirling disease in wild trout populations.

Enhancement of anticancer effect of interferon-γ gene transfer against interferon-γ-resistant tumor by depletion of tumor-associated macrophages.

PubMed

Kiyota, Tsuyoshi; Takahashi, Yuki; Watcharanurak, Kanitta; Nishikawa, Makiya; Ohara, Saori; Ando, Mitsuru; Watanabe, Yoshihiko; Takakura, Yoshinobu

2014-05-05

Tumor-associated macrophages (TAMs) negatively affect the therapeutic effects of anticancer agents. To examine the role of TAMs in interferon (IFN)-γ gene therapy, we selected two types of solid tumors, which varied in the number of TAMs, and investigated the effects of IFN-γ gene transfer on tumor growth. Many TAMs were detected in the solid tumors of murine adenocarcinoma colon-26 cells, whereas few TAMs were detected in murine melanoma B16-BL6 cells. IFN-γ gene transfer hardly suppressed the growth of colon-26 tumors, whereas it was effective in suppressing the growth of B16-BL6 tumors. The antiproliferative effects of IFN-γ on cultured colon-26 cells were similar to those on cultured B16-BL6 cells. To evaluate the role of TAMs, we injected clodronate liposomes (CLs) modified with poly(ethylene glycol) (PEG) to functionally deplete TAMs in tumor-bearing mice. Repeated injections of PEG-CLs significantly retarded the growth of colon-26 tumors and combination with IFN-γ gene transfer further inhibited the growth. In contrast, PEG-CLs hardly retarded the growth of B16-BL6 tumors. These results clearly indicate that TAM depletion is effective in enhancing the therapeutic effect of IFN-γ in TAM-repleted and IFN-γ-resistant tumors.

Streamlined Approach for Environmental Restoration Plan for Corrective Action Unit 489: WWII UXO Sites, Tonopah Test Range, Nevada; May 2005

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

Bechtel Nevada; U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office

2005-05-01

This Streamlined Approach for Environmental Restoration Plan provides the details for the closure of Corrective Action Unit (CAU) 489: WWII UXO Sites, Tonopah Test Range. CAU 489 is located at the Tonopah Test Range and is currently listed in Appendix III of the Federal Facility Agreement and Consent Order of 1996.

Introduction of software tools for epidemiological surveillance in infection control in Colombia.

PubMed

Hernández-Gómez, Cristhian; Motoa, Gabriel; Vallejo, Marta; Blanco, Víctor M; Correa, Adriana; de la Cadena, Elsa; Villegas, María Virginia

2015-01-01

Healthcare-Associated Infections (HAI) are a challenge for patient safety in the hospitals. Infection control committees (ICC) should follow CDC definitions when monitoring HAI. The handmade method of epidemiological surveillance (ES) may affect the sensitivity and specificity of the monitoring system, while electronic surveillance can improve the performance, quality and traceability of recorded information. To assess the implementation of a strategy for electronic surveillance of HAI, Bacterial Resistance and Antimicrobial Consumption by the ICC of 23 high-complexity clinics and hospitals in Colombia, during the period 2012-2013. An observational study evaluating the introduction of electronic tools in the ICC was performed; we evaluated the structure and operation of the ICC, the degree of incorporation of the software HAI Solutions and the adherence to record the required information. Thirty-eight percent of hospitals (8/23) had active surveillance strategies with standard criteria of the CDC, and 87% of institutions adhered to the module of identification of cases using the HAI Solutions software. In contrast, compliance with the diligence of the risk factors for device-associated HAIs was 33%. The introduction of ES could achieve greater adherence to a model of active surveillance, standardized and prospective, helping to improve the validity and quality of the recorded information.

Reducing the risk of healthcare-associated infections through Lean Six Sigma: The case of the medicine areas at the Federico II University Hospital in Naples (Italy).

PubMed

Improta, Giovanni; Cesarelli, Mario; Montuori, Paolo; Santillo, Liberatina Carmela; Triassi, Maria

2018-04-01

Lean Six Sigma (LSS) has been recognized as an effective management tool for improving healthcare performance. Here, LSS was adopted to reduce the risk of healthcare-associated infections (HAIs), a critical quality parameter in the healthcare sector. Lean Six Sigma was applied to the areas of clinical medicine (including general medicine, pulmonology, oncology, nephrology, cardiology, neurology, gastroenterology, rheumatology, and diabetology), and data regarding HAIs were collected for 28,000 patients hospitalized between January 2011 and December 2016. Following the LSS define, measure, analyse, improve, and control cycle, the factors influencing the risk of HAI were identified by using typical LSS tools (statistical analyses, brainstorming sessions, and cause-effect diagrams). Finally, corrective measures to prevent HAIs were implemented and monitored for 1 year after implementation. Lean Six Sigma proved to be a useful tool for identifying variables affecting the risk of HAIs and implementing corrective actions to improve the performance of the care process. A reduction in the number of patients colonized by sentinel bacteria was achieved after the improvement phase. The implementation of an LSS approach could significantly decrease the percentage of patients with HAIs. © 2017 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.

Introduction of software tools for epidemiological surveillance in infection control in Colombia

PubMed Central

Motoa, Gabriel; Vallejo, Marta; Blanco, Víctor M; Correa, Adriana; de la Cadena, Elsa; Villegas, María Virginia

2015-01-01

Introduction: Healthcare-Associated Infections (HAI) are a challenge for patient safety in the hospitals. Infection control committees (ICC) should follow CDC definitions when monitoring HAI. The handmade method of epidemiological surveillance (ES) may affect the sensitivity and specificity of the monitoring system, while electronic surveillance can improve the performance, quality and traceability of recorded information. Objective: To assess the implementation of a strategy for electronic surveillance of HAI, Bacterial Resistance and Antimicrobial Consumption by the ICC of 23 high-complexity clinics and hospitals in Colombia, during the period 2012-2013. Methods: An observational study evaluating the introduction of electronic tools in the ICC was performed; we evaluated the structure and operation of the ICC, the degree of incorporation of the software HAI Solutions and the adherence to record the required information. Results: Thirty-eight percent of hospitals (8/23) had active surveillance strategies with standard criteria of the CDC, and 87% of institutions adhered to the module of identification of cases using the HAI Solutions software. In contrast, compliance with the diligence of the risk factors for device-associated HAIs was 33%. Conclusions: The introduction of ES could achieve greater adherence to a model of active surveillance, standardized and prospective, helping to improve the validity and quality of the recorded information. PMID:26309340

Keeping It Local: Dispersal Limitations of Coral Larvae to the High Latitude Coral Reefs of the Houtman Abrolhos Islands.

PubMed

Markey, Kathryn L; Abdo, Dave A; Evans, Scott N; Bosserelle, Cyprien

2016-01-01

In 2011 the first recorded bleaching event for the high latitude Houtman Abrolhos Islands (HAI) coral communities was documented. This bleaching event highlighted the question of whether a supply of 'heat tolerant' coral recruits from the tropical north would be sufficient to provide a level of resistance for these reefs to future warming events. Using Lagrangian modelling we showed that due to its regional isolation, large-scale larval input from potential tropical northern source populations to the HAI is unlikely, despite the southward flowing Leeuwin current. Successful recruitment to artificial substrates was recorded following the bleaching event. However, this was negligible (0.4 ± 0.1 recruits per tile) compared to 2013 post impact recruitment (128.8 ± 15.8 recruits per tile). Our data therefore provides preliminary evidence suggesting that the connectivity of the HAI with coral communities in the north is limited, and population maintenance and recovery is likely driven primarily by self-recruitment. Given the low thermal tolerance of the HAI coral communities, the dominance of Acropora, and the apparent reliance on self-recruitment, an increased frequency of thermally anomalous conditions at the HAI (such as experienced in 2011) has the potential to reduce the long-term stability of the HAI coral populations and species that depend upon them.

Teamwork in the NICU setting and its association with healthcare-associated infections in very low birth weight infants

PubMed Central

Profit, Jochen; Sharek, Paul J.; Kan, Peiyi; Rigdon, Joseph; Desai, Manisha; Nisbet, Courtney C.; Tawfik, Daniel S.; Thomas, Eric J.; Lee, Henry C.; Sexton, J. Bryan

2018-01-01

Background and Objective Teamwork may affect clinical care in the neonatal intensive care unit (NICU) setting. The objective of this study was to assess teamwork climate across NICUs and to test scale level and item level associations with healthcare-associated infection (HAI) rates in very low birth weight (VLBW) infants. Methods Cross-sectional study of the association between HAI rates, defined as any bacterial or fungal infection during the birth hospitalization, among 6663 VLBW infants cared for in 44 NICUs between 2010 and 2012. NICU HAI rates were correlated with teamwork climate ratings obtained in 2011 from 2073 of 3294 eligible (response rate 63%) NICU health professionals. The relation between HAI rates and NICU teamwork climate was assessed using logistic regression models including NICU as a random effect. Results Across NICUs, 36 to 100% (mean 66%) of respondents reported good teamwork. HAI rates were significantly and independently associated with teamwork climate (OR [95% CI] 0.82 [0.73-0.92], p = 0.005), such that the odds of an infant contracting a HAI decreased by 18% with each 10% rise in NICU respondents reporting good teamwork. Conclusion Improving teamwork may be an important element in infection control efforts. PMID:28395366

Clinical and molecular epidemiology of community-acquired methicillin-resistant Staphylococcus aureus infections among children with risk factors for health care-associated infection: 2001-2003.

PubMed

Zaoutis, Theoklis E; Toltzis, Philip; Chu, Jaclyn; Abrams, Tara; Dul, Michael; Kim, Jason; McGowan, Karin L; Coffin, Susan E

2006-04-01

Methicillin-resistant Staphylococcus aureus (MRSA) has recently emerged as a common cause of infection in children in many parts of the world. The epidemiology of community-acquired MRSA (CA-MRSA) among healthy children has been recently described. However, little is known about CA-MRSA in children with underlying medical conditions. To compare the clinical and molecular epidemiology of CA-MRSA in children with and without risk factors for health care-associated infections (RF-HAI). We conducted a 3-year retrospective cohort study of children with CA-MRSA infection. RF-HAI, including hospitalization within the past year, indwelling medical devices or chronic medical condition, were identified by chart review. Genetic relatedness of CA-MRSA strains was assessed by pulsed field gel electrophoresis. Polymerase chain reaction was used to detect Panton-Valentine leukocidin and determine staphylococcal chromosomal cassette carrying the mecA methicillin-resistant gene (SCCmec) type. We identified 446 episodes of community-acquired S. aureus infections, of which 134 (30%) were caused by MRSA. During the 3-year study period, the proportion of S. aureus infections caused by MRSA rose from 15% (12 of 80) to 40% (93 of 235) (P < 0.001) with the increase noted predominately in children with skin and soft tissue infections. RF-HAI were identified in 56 (42%) patients with CA-MRSA. Among subjects with CA-MRSA, children with RF-HAI were more likely to have had an invasive infection than healthy children (32% versus 5%; P < 0.001). CA-MRSA isolates from children with RF-HAI were similar to those without RF-HAI; all laboratory-retained CA-MRSA isolates harbored the SCCmec type IV cassette, and almost all isolates were susceptible to trimethoprim-sulfamethoxazole and clindamycin. However, pulsed field gel electrophoresis revealed greater molecular diversity among CA-MRSA isolates recovered from children with RF-HAI compared with those from otherwise healthy children (P = 0

Autophagy-induced RelB/p52 activation mediates tumour-associated macrophage repolarisation and suppression of hepatocellular carcinoma by natural compound baicalin

PubMed Central

Tan, H-Y; Wang, N; Man, K; Tsao, S-W; Che, C-M; Feng, Y

2015-01-01

The plasticity of tumour-associated macrophages (TAMs) has implicated an influential role in hepatocellular carcinoma (HCC). Repolarisation of TAM towards M1 phenotype characterises an immune-competent microenvironment that favours tumour regression. To investigate the role and mechanism of TAM repolarisation in suppression of HCC by a natural compound baicalin, Orthotopic HCC implantation model was used to investigate the effect of baicalin on HCC; liposome-clodronate was introduced to suppress macrophage populations in mice; bone marrow-derived monocytes (BMDMs) were induced to unpolarised, M1-like, M2-like macrophages and TAM using different conditioned medium. We observed that oral administration of baicalin (50 mg/kg) completely blocked orthotopic growth of implanted HCC. Suppression of HCC by baicalin was diminished when mice macrophage was removed by clodronate treatment. Baicalin induced repolarisation of TAM to M1-like phenotype without specific toxicity to either phenotype of macrophages. Baicalin initiated TAM reprogramming to M1-like macrophage, and promoted pro-inflammatory cytokines production. Co-culturing of HCC cells with baicalin-treated TAMs resulted in reduced proliferation and motility in HCC. Baicalin had minimal effect on derivation of macrophage polarisation factors by HCC cells, while directly induced repolarisation of TAM and M2-like macrophage. This effect was associated with elevated autophagy, and transcriptional activation of RelB/p52 pathway. Suppression of autophagy or RelB abolished skewing of baicalin-treated TAM. Autophagic degradation of TRAF2 in baicalin-treated TAM might be responsible for RelB/p52 activation. Our findings unveil the essential role of TAM repolarisation in suppressive effect of baicalin on HCC, which requires autophagy-associated activation of RelB/p52. PMID:26492375

Reduced health care-associated infections in an acute care community hospital using a combination of self-disinfecting copper-impregnated composite hard surfaces and linens.

PubMed

Sifri, Costi D; Burke, Gene H; Enfield, Kyle B

2016-12-01

The purpose of this study was to determine the effectiveness of copper-impregnated composite hard surfaces and linens in an acute care hospital to reduce health care-associated infections (HAIs). We performed a quasiexperimental study with a control group, assessing development of HAIs due to multidrug resistant organisms (MDROs) and Clostridium difficile in the acute care units of a community hospital following the replacement of a 1970s-era clinical wing with a new wing outfitted with copper-impregnated composite hard surfaces and linens. The study was conducted over a 25.5-month time period that included a 3.5-month washout period. HAI rates obtained from the copper-containing new hospital wing (14,479 patient-days; 72 beds) and the unmodified hospital wing (19,177 patient-days) were compared with those from the baseline period (46,391 patient-days). The new wing had 78% (P = .023) fewer HAIs due to MDROs or C difficile, 83% (P = .048) fewer cases of C difficile infection, and 68% (P = .252) fewer infections due to MDROs relative to the baseline period. No changes in rates of HAI were observed in the unmodified hospital wing. Copper-impregnated composite hard surfaces and linens may be useful technologies to prevent HAIs in acute care hospital settings. Additional studies are needed to determine whether reduced HAIs can be attributed to the use of copper-containing antimicrobial hard and soft surfaces. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Engaging patients in the prevention of health care-associated infections: a survey of patients' awareness, knowledge, and perceptions regarding the risks and consequences of infection with methicillin-resistant Staphylococcus aureus and Clostridium difficile.

PubMed

Ottum, Andrew; Sethi, Ajay K; Jacobs, Elizabeth; Zerbel, Sara; Gaines, Martha E; Safdar, Nasia

2013-04-01

Methicillin-resistant Staphylococcus aureus (MRSA) infections and Clostridium difficile infections (CDI) are major health care-associated infections (HAIs). Little is known about patients' knowledge of these HAIs. Therefore, we surveyed patients to determine awareness, knowledge, and perceptions of MRSA infections and CDI. An interviewer-administered questionnaire. A tertiary care academic medical center. Adult patients who met at least one of the following criteria: at risk of CDI or MRSA infection, current CDI or colonization or current MRSA infection or colonization, or history of CDI or MRSA infection. Two unique surveys were developed and administered to 100 patients in 2011. Overall, 76% of patients surveyed were aware of MRSA, whereas 44% were aware of C difficile. The strongest predictor of patients' awareness of these infections was having a history of HAI. Patients with a history of HAI were significantly more likely to have heard of both MRSA (odds ratio, 13.29; 95% confidence interval, 2.84-62.14; P = .001) and C difficile (odds ratio, 9.78; 95% confidence interval, 2.66-35.95; P = .001), than those patients without a history of HAI. There was also a significant positive association between having a history of HAI and greater knowledge of the risk factors, health consequences, and prevention techniques relative to CDI and MRSA infections. There are additional opportunities to engage patients about the risks and consequences of MRSA and CDIs, particularly those without a history of HAI. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Temporal trends of healthcare associated infections and antimicrobial use in 2011-2013, observed with annual point prevalence surveys in Ferrara University Hospital, Italy.

PubMed

Antonioli, P; Manzalini, M C; Stefanati, A; Bonato, B; Verzola, A; Formaglio, A; Gabutti, G

2016-09-01

Healthcare associated infections (HAIs) and misuse of antimicrobials (AMs) represent a growing public health problem. The Point Prevalence Surveys (PPSs) find available information to be used for specific targeted interventions and evaluate their effects. The objective of this study was to estimate the prevalence of HAIs and AM use, to describe types of infections, causative pathogens and to compare data collected through three PPSs in Ferrara University Hospital (FUH), repeated in 3 different years (2011-2013). The population-based sample consists of all patients admitted to every acute care and rehabilitation Department in a single day. ECDC Protocol and Form for PPS of HAI and AM use, Version 4.2, July 2011. Risk factor analysis was performed using logistic regression. 1,239 patients were observed. Overall, HAI prevalence was 9.6%; prevalence was higher in Intensive Care Units; urinary tract infections were the most common HAIs in all 3 surveys; E.coli was the most common pathogen; AM use prevalence was 51.1%; AMs most frequently administered were fluoroquinolones, combinations of penicillins and third-generation cephalosporins. According to the regression model, urinary catheter (OR: 2.5) and invasive respiratory device (OR: 2.3) are significantly associated risk factors for HAIs (p < 0.05). PPSs are a sensitive and effective method of analysis. Yearly repetition is a useful way to maintain focus on the topic of HAIs and AM use, highlighting how changes in practices impact on the outcome of care and providing useful information to implement intervention programs targeted on specific issues.

Healthcare associated infection: good practices, knowledge and the locus of control in heatlhcare professionals.

PubMed

Taffurelli, Chiara; Sollami, Alfonso; Camera, Carmen; Federa, Francesca; Grandi, Annise; Marino, Marcella; Marrosu, Tiziano; Sarli, Leopoldo

2017-07-18

  The incidence of Healthcare Associated Infections (HAI) is an important indicator of the quality of care. The behaviors associated with the prevention of infections are not only supported by rational knowledge or motivation, but are mediated by social, emotional and often stereotyped behaviors. The awarness of the good practices related to HAI, may be a factor. Other studies, identify how the perception of the problem in healthcare professionals is often influenced by a tendency towards an external Locus of Control: the patient, the family, the other wards, other care settings. The aim of this study is to investigate the perception of healthcare professionals. In particular they have been measured their  awarness of the good practices, perceptions of the potential contamination level of some commonly used objects, knowledge about the management of invasive devices, Locus of Control.   A cross-sectional correlational design was utilized.  An ad hoc questionnaire was interviewed by 222 health professionals nurses and physicians in a northern hospital of Italy. The percentage of professionals who have attended training courses over the last 5 years was quite high, both for upgrades on HAI (78.7%) and Vascular Catheters (78.8%), while the percentage of professionals who updated on bladder catheterization (59.46%) was lower. The mean  score of good practice awareness towards HAI (5.06), is high. The perception of the potential level of contamination of some devices had a  mean ranging from 4.62 (for the drip) to 5.26 (for the door handle). The average value of the Locus of Control (43.54) indicates that participants demonstrated a value that is midway between External and Internal. The correlation test analysis revealed no significant relationships among professionals'age, knowledge about HAI, or infection related venus catheter. Also, results revealed that there were statistically significant positive relationships between professionals' Good Practices

Longitudinal Household Trends in Access to Improved Water Sources and Sanitation in Chi Linh Town, Hai Duong Province, Viet Nam and Associated Factors.

PubMed

Tuyet-Hanh, Tran Thi; Long, Tran Khanh; Van Minh, Hoang; Huong, Le Thi Thanh

2016-01-01

This study aims to characterize household trends in access to improved water sources and sanitaton in Chi Linh Town, Hai Duong Province, Vietnam, and to identify factors affecting those trends. Data were extracted from the Chi Linh Health and Demographic Surveillance System (CHILILAB HDSS) database from 2004-2014, which included household access to improved water sources, household access to improved sanitation, and household demographic data. Descriptive statistical analysis and multinominal logistic regression were used. The results showed that over a 10-year period (2004-2014), the proportion of households with access to improved water and improved sanitation increased by 3.7% and 28.3%, respectively. As such, the 2015 Millennium Development Goal targets for safe drinking water and basic sanitation were met. However, 13.5% of households still had unimproved water and sanitation. People who are retired, work in trade or services, or other occupations were 1.49, 1.97, and 1.34 times more likely to have access to improved water and sanitation facilities than farming households, respectively ( p < 0.001). Households living in urban areas were 1.84 times more likely than those living in rural areas to have access to improved water sources and improved sanitation facilities (OR =1.84; 95% CI = 1.73-1.96). Non-poor households were 2.12 times more likely to have access to improved water sources and improved sanitation facilities compared to the poor group (OR = 2.12; 95% CI = 2.00-2.25). More efforts are required to increase household access to both improved water and sanitation in Chi Linh Town, focusing on the 13.5% of households currently without access. Similar to situations observed elsewhere in Vietnam and other low- and middle- income countries, there is a need to address socio-economic factors that are associated with inadequate access to improved water sources and sanitation facilities.

Cost-utility of collaborative care for major depressive disorder in primary care in the Netherlands.

PubMed

Goorden, Maartje; Huijbregts, Klaas M L; van Marwijk, Harm W J; Beekman, Aartjan T F; van der Feltz-Cornelis, Christina M; Hakkaart-van Roijen, Leona

2015-10-01

Major depression is a great burden on society, as it is associated with high disability/costs. The aim of this study was to evaluate the cost-utility of Collaborative Care (CC) for major depressive disorder compared to Care As Usual (CAU) in a primary health care setting from a societal perspective. A cluster randomized controlled trial was conducted, including 93 patients that were identified by screening (45-CC, 48-CAU). Another 57 patients were identified by the GP (56-CC, 1-CAU). The outcome measures were TiC-P, SF-HQL and EQ-5D, respectively measuring health care utilization, production losses and general health related quality of life at baseline three, six, nine and twelve months. A cost-utility analysis was performed for patients included by screening and a sensitivity analysis was done by also including patients identified by the GP. The average annual total costs was €1131 (95% C.I., €-3158 to €750) lower for CC compared to CAU. The average quality of life years (QALYs) gained was 0.02 (95% C.I., -0.004 to 0.04) higher for CC, so CC was dominant from a societal perspective. Taking a health care perspective, CC was less cost-effective due to higher costs, €1173 (95% C.I., €-216 to €2726), of CC compared to CAU which led to an ICER of 53,717 Euro/QALY. The sensitivity analysis showed dominance of CC. The cost-utility analysis from a societal perspective showed that CC was dominant to CAU. CC may be a promising treatment for depression in the primary care setting. Further research should explore the cost-effectiveness of long-term CC. Netherlands Trial Register ISRCTN15266438. Copyright © 2015 Elsevier Inc. All rights reserved.

Closure Report for Corrective Action Unit 516: Septic Systems and Discharge Points

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

NSTec Environmental Restoration

Corrective Action Unit (CAU) 516 is located in Areas 3, 6, and 22 of the Nevada Test Site. CAU 516 is listed in the Federal Facility Agreement and Consent Order of 1996 as Septic Systems and Discharge Points, and is comprised of six Corrective Action Sites (CASs): {sm_bullet} CAS 03-59-01, Bldg 3C-36 Septic System {sm_bullet} CAS 03-59-02, Bldg 3C-45 Septic System {sm_bullet} CAS 06-51-01, Sump and Piping {sm_bullet} CAS 06-51-02, Clay Pipe and Debris {sm_bullet} CAS 06-51-03, Clean Out Box and Piping {sm_bullet} CAS 22-19-04, Vehicle Decontamination Area The Nevada Division of Environmental Protection (NDEP)-approved corrective action alternative for CASsmore » 06-51-02 and 22-19-04 is no further action. The NDEP-approved corrective action alternative for CASs 03-59-01, 03-59-02, 06-51-01, and 06-51-03 is clean closure. Closure activities included removing and disposing of total petroleum hydrocarbon (TPH)-impacted septic tank contents, septic tanks, distribution/clean out boxes, and piping. CAU 516 was closed in accordance with the NDEP-approved CAU 516 Corrective Action Plan (CAP). The closure activities specified in the CAP were based on the recommendations presented in the CAU 516 Corrective Action Decision Document (U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office, 2004). This Closure Report documents CAU 516 closure activities. During closure activities, approximately 186 tons of hydrocarbon waste in the form of TPH-impacted soil and debris, as well as 89 tons of construction debris, were generated and managed and disposed of appropriately. Waste minimization techniques, such as field screening of soil samples and the utilization of laboratory analysis to characterize and classify waste streams, were employed during the performance of closure work.« less

Corrective Action Decision Document/Closure Report for Corrective Action 405: Area 3 Septic Systems, Tonopah Test Range, Nevada Rev. No.: 0, April 2002

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

IT Coroporation, Las Vegas, NV

2002-04-17

This Corrective Action Decision Document/Closure Report (CADD/CR) has been prepared for Corrective Action Unit (CAU) 405, Area 3 Septic Systems, in accordance with the Federal Facility Agreement and Consent Order. Located on the Tonopah Test Range (TTR) approximately 235 miles north of Las Vegas, Nevada, CAU 405 consists of three Corrective Action Sites (CASs): 03-05-002-SW03, Septic Waste System (aka: Septic Waste System [SWS] 3); 03-05-002-SW04, Septic Waste System (aka: SWS 4); 03-05-002-SW07, Septic Waste System (aka: SWS 7). The CADD and CR have been combined into one report because no further action is recommended for this CAU, and this reportmore » provides specific information necessary to support this recommendation. The CAU consists of three leachfields and associated collection systems that were installed in or near Area 3 for wastewater disposal. These systems were used until a consolidated sewer system was installed in 1990. Historically, operations within various buildin gs in and near Area 3 of the TTR generated sanitary and industrial wastewaters. There is a potential that contaminants of concern (COCs) were present in the wastewaters and were disposed of in septic tanks and leachfields. The justification for closure of this CAU without further action is based on process knowledge and the results of the investigative activities. Closure activities were performed at these CASs between January 14 and February 2, 2002, and included the removal and proper disposal of media containing regulated constituents and proper closure of septic tanks. No further action is appropriate because all necessary activities have been completed. No use restrictions are required to be imposed for these sites since the investigation showed no evidence of COCs identified in the soil for CAU 405.« less

[Current status of urological training in Latin America.

PubMed

Angulo, Javier C; Figueroa, Carlos; Gómez, Reynaldo; Martins, Francisco; Corrales, Juan Guillermo; Secin, Fernando; López-Secchi, Gerardo; León, Antonio; Torrico, Marcelo; Reis, Leonardo O; Plata, Mauricio; Sotomayor, Mariano; Gutiérrez-Aceves, Jorge

2018-01-01

Achieving residents' medical training of quality is a constant concern in the Confederación Americana de Urología (CAU), the third Urological Society worldwide. We aim to analyze the diversity of state training programs, with the intention to identify opportunities for global improvement within them and also to analyse the professional reality in different countries. Data from 2nd and 3rd Foro Educativo CAU regarding postgraduate training and labour implications are reviewed. This information is complemented by the opinion of representatives involved with the academic training in Confederación Americana de Urología, who have analyzed the reality and current status of the urological training through a 10-question survey that describes different aspects of residency program in the countries confederated in CAU. A total of 3,000 graduate doctors train as residents in Urology at the CAU environment. Each year 670 residents begin their training program in Latin America, Spain and Portugal, a territory that serves nearly 650 million people, with an active professional force of around 16.800 professionals. Detailed data on training, employment and supporting reality in the countries that comprise the CAU are presented. We also discuss the proportion of residents who carry out research and doctorate during the residency program. Finally, we examine the proportion of professionals who receive specific training at the end of their residence, the relative importance of this training and what are the most popular environments to carry it out. Current postgraduate training in CAU environment is heterogeneous in their programs, as well as in the modes of accreditation and recertification. Academic activities do not seem to be properly valued. However, specific training offers better expectations of professional development.

Arrested development of the myxozoan parasite, Myxobolus cerebralis, in certain populations of mitochondrial 16S lineage III Tubifex tubifex

USGS Publications Warehouse

Baxa, D.V.; Kelley, G.O.; Mukkatira, K.S.; Beauchamp, K.A.; Rasmussen, C.; Hedrick, R.P.

2008-01-01

Laboratory populations of Tubifex tubifex from mitochondrial (mt)16S ribosomal DNA (rDNA) lineage III were generated from single cocoons of adult worms releasing the triactinomyxon stages (TAMs) of the myxozoan parasite, Myxobolus cerebralis. Subsequent worm populations from these cocoons, referred to as clonal lines, were tested for susceptibility to infection with the myxospore stages of M. cerebralis. Development and release of TAMs occurred in five clonal lines, while four clonal lines showed immature parasitic forms that were not expelled from the worm (non-TAM producers). Oligochaetes from TAM- and non-TAM-producing clonal lines were confirmed as lineage III based on mt16S rDNA and internal transcribed spacer region 1 (ITS1) sequences, but these genes did not differentiate these phenotypes. In contrast, random amplified polymorphic DNA analyses of genomic DNA demonstrated unique banding patterns that distinguished the phenotypes. Cohabitation of parasite-exposed TAM- and non-TAM-producing phenotypes showed an overall decrease in expected TAM production compared to the same exposure dose of the TAM-producing phenotype without cohabitation. These studies suggest that differences in susceptibility to parasite infection can occur in genetically similar T. tubifex populations, and their coexistence may affect overall M. cerebralis production, a factor that may influence the severity of whirling disease in wild trout populations. ?? 2007 Springer-Verlag.

Proteomic identification of E6AP as a molecular target of tamoxifen in MCF7 cells.

PubMed

Lochab, Savita; Pal, Pooja; Kanaujiya, Jitendra K; Tripathi, Shashi B; Kapoor, Isha; Bhatt, Madan L B; Sanyal, Sabyasachi; Behre, Gerhard; Trivedi, Arun K

2012-05-01

Tamoxifen (Tam) is most widely used selective estrogen receptor modulator (SERM) for treatment of hormone-responsive breast cancer. Despite being regularly used in clinical therapy for breast cancer since 1971, the mechanism of Tam action remains largely unclear. In order to gain insights into Tam-mediated antibreast cancer actions, we applied 2DE and MS based proteomics approach to identify target proteins of Tam. We identified E6-associated protein, i.e. E6AP (UBE3A) among others to be regulated by Tam that otherwise is upregulated in breast tumors. We confirmed our 2DE finding by immunoblotting and further show that Tam leads to inhibition of E6AP expression presumably by promoting its autoubiquitination, which is coupled with nuclear export and subsequent proteasome-mediated degradation. Furthermore, we show that Tam- and siE6AP-mediated inhibition of E6AP leads to enhanced G0-G1 growth arrest and apoptosis, which is also evident from significant upregulation of cytochrome-c, Bax, p21, and PARP cleavage. Taken together, our data suggest that, Tam-targeted E6AP inhibition is in fact required for Tam-mediated antibreast cancer actions. Thus, E6AP may be a therapeutic target in breast cancer. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Alliance in Motivational Enhancement Therapy and Counseling as Usual for Substance Use Problems

ERIC Educational Resources Information Center

Crits-Christoph, Paul; Gallop, Robert; Temes, Christina M.; Woody, George; Ball, Samuel A.; Martino, Steve; Carroll, Kathleen M.

2009-01-01

Data from a community-based multicenter study of motivational enhancement therapy (MET) and counseling as usual (CAU) for outpatient substance users were used to examine questions about the role of the alliance in MET and CAU. Most (94%) of the sample met diagnostic criteria for abuse or dependence (primarily alcohol and/or cocaine). Sixteen…

GPER promotes tamoxifen-resistance in ER+ breast cancer cells by reduced Bim proteins through MAPK/Erk-TRIM2 signaling axis.

PubMed

Yin, Heng; Zhu, Qing; Liu, Manran; Tu, Gang; Li, Qing; Yuan, Jie; Wen, Siyang; Yang, Guanglun

2017-10-01

Tamoxifen resistance is a major clinical challenge in breast cancer treatment. Our previous studies find that GPER and its down-stream signaling play a pivotal role in the development of tamoxifen (TAM) resistance. cDNA array analysis indicated a set of genes associated with cell apoptosis are aberrant in GPER activated and TAM-resistant MCF-7R cells compared with TAM-sensitive MCF-7 cells. Among these genes, Bim (also named BCL2-L11), a member of the BH3-only pro-apoptotic protein family is significantly decreased, and TRIM RING finger protein TRIM2 (a ubiquitin ligase) is highly expressed in MCF-7R. To understand the mechanism of TAM-resistance in GPER activated ER+ breast cancer, the function of TRIM2 and Bim inducing cell apoptosis was studied. By using immunohistochemical and western blot analysis, there is an adverse correlation between TRIM2 and Bim in TAM-resistant breast tumor tissues and MCF-7R cells. Knockdown Bim in TAM-sensitive MCF-7 cells or overexpression of Bim in TAM-resistant MCF-7 cells significantly changed its sensibility to TAM through altering the levels of cleaved PARP and caspase-3. Activation of GPER and its downstream signaling MAPK/ERK, not PI3K/AKT, led to enhanced TRIM2 protein levels and affected the binding between TRIM2 and Bim which resulted in a reduced Bim in TAM-resistant breast cancer cells. Thus, the present study provides a novel insight to TAM-resistance in ER-positive breast cancer cells.

CORRECTIVE ACTION PLAN FOR CORRECTIVE ACTION UNIT 516: SEPTIC SYSTEMS AND DISCHARGE POINTS, NEVADA TEST SITE, NEVADA

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

BECHTEL NEVADA; U.S. DEPARTMENT OF ENERGY, NATIONAL NUCLEAR SECURITY ADMINISTRATION NEVADA SITE OFFICE

2005-08-01

Corrective Action Unit (CAU) 516, Septic Systems and Discharge Points, is listed in the ''Federal Facility Agreement and Consent Order'' (FFACO) of 1996 (FFACO, 1996). CAU 516 consists of six Corrective Action Sites (CASs) located in Areas 3, 6, and 22 of the Nevada Test Site (NTS), which is located approximately 65 miles northwest of Las Vegas, Nevada (Figure 1). CAU 516 is comprised of the following six CASs: (1) 03-59-01 Building 3C-36 Septic System; (2) 03-59-02 Building 3C-45 Septic System; (3) 06-51-01 Sump and Piping; (4) 06-51-02 Clay Pipe and Debris; (5) 06-51-03 Clean-Out Box and Piping; and (6)more » 22-19-04 Vehicle Decontamination Area. Details on site history and site characterization results for CAU 516 are provided in the approved Corrective Action Investigation Plan (CAIP), (U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office [NNSA/NSO], 2003), and the approved Corrective Action Decision Document (CADD) (NNSA/NSO, 2004).« less

Corrective Action Investigation Plan for Corrective Action Unit 573: Alpha Contaminated Sites, Nevada National Security Site, Nevada, Revision 0

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

Matthews, Patrick

2014-05-01

Corrective Action Unit (CAU) 573 is located in Area 5 of the Nevada National Security Site, which is approximately 65 miles northwest of Las Vegas, Nevada. CAU 573 is a grouping of sites where there has been a suspected release of contamination associated with non-nuclear experiments and nuclear testing. This document describes the planned investigation of CAU 573, which comprises the following corrective action sites (CASs): • 05-23-02, GMX Alpha Contaminated Area • 05-45-01, Atmospheric Test Site - Hamilton These sites are being investigated because existing information on the nature and extent of potential contamination is insufficient to evaluate andmore » recommend corrective action alternatives.« less

Application of TAM III to study sensitivity of soil organic matter degradation to temperature

NASA Astrophysics Data System (ADS)

Vikegard, Peter; Barros, Nieves; Piñeiro, Verónica

2014-05-01

Traditionally, studies of soil biodegradation are based on CO2 dissipation rates. CO2 is a product of aerobic degradation of labile organic substrates like carbohydrates. That limits the biodegradation concept to just one of the soil organic matter fractions. This feature is responsible for some problems to settle the concept of soil organic matter (SOM) recalcitrance and for controversial results defining sensitivity of SOM to temperature. SOM consists of highly complex macromolecules constituted by fractions with different chemical nature and redox state affecting the chemical nature of biodegradation processes. Biodegradation of fractions more reduced than carbohydrates take place through metabolic pathways that dissipate less CO2 than carbohydrate respiration, that may not dissipate CO2, or that even may uptake CO2. These compounds can be considered more recalcitrant and with lower turnover times than labile SOM just because they are degraded at lower CO2 rates that may be just a consequence of the metabolic path. Nevertheless, decomposition of every kind of organic substrate always releases heat. For this reason, the measurement of the heat rate by calorimetry yields a more realistic measurement of the biodegradation of the SOM continuum. TAM III is one of the most recent calorimeters designed for directly measuring in real time the heat rate associated with any degradation process. It is designed as a multichannel system allowing the concomitant measurement of to up 24 samples at isothermal conditions or through a temperature scanning mode from 18 to 100ºC, allowing the continous measure of any sample at controlled non-isothermal conditions. The temperature scanning mode was tested in several soil samples collected at different depths to study their sensitivity to temperature changes from 18 to 35 ºC calculating the Q10 and the activation energy (EA) by the Arrhenius equation. It was attempted to associate the obtained EA values with the soil thermal

Educational interventions to improve knowledge and skills of interns towards prevention and control of hospital-associated infections.

PubMed

Dogra, Sandeep; Mahajan, Ruchita; Jad, Beena; Mahajan, Bella

2015-08-01

We believe that there is significant educational deficit amongst interns regarding up-to-date formal knowledge and skills on healthcare-associated infections (HAIs) which might compromise patient safety. This urgently requires curriculum innovations to ensure their formal training on HAIs prevention and control. Education of interns to improve their knowledge and skills toward HAIs prevention and control. This pilot study was conducted in interns using a multimodal approach consisting of a combination of videos, PowerPoint presentation, and hands-on demonstration to provide applied and practical teaching on prevention and control of HAIs. Pre- and post-test assessment of knowledge, attitude, and skills was carried out by multiple choice questions, 5-point Likert scale, and Objective Structured Practical Examination respectively. Paired t-test. A statistically significant improvement in the overall score rates between pre- and post-test of intern's was seen, suggesting that educational programs have a positive effect. Intern's felt benefitted from interventions focused on HAIs prevention and control and hoped that such sessions are integrated in the regular undergraduate curriculum. A majority of the students felt that their learning style assessment matched well with their own perception of learning preference. Assessment drives learning; hence strengthening the contribution of health-care workers to HAIs prevention programs should include measures that enhance knowledge, improve skills and develop appropriate attitudes, resulting in safety and quality of patient care.

The European Centre for Disease Prevention and Control (ECDC) pilot point prevalence survey of healthcare-associated infections and antimicrobial use.

PubMed

Zarb, P; Coignard, B; Griskeviciene, J; Muller, A; Vankerckhoven, V; Weist, K; Goossens, Mm; Vaerenberg, S; Hopkins, S; Catry, B; Monnet, Dl; Goossens, H; Suetens, C

2012-11-15

A standardised methodology for a combined point prevalence survey (PPS) on healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals developed by the European Centre for Disease Prevention and Control was piloted across Europe. Variables were collected at national, hospital and patient level in 66 hospitals from 23 countries. A patient-based and a unit-based protocol were available. Feasibility was assessed via national and hospital questionnaires. Of 19,888 surveyed patients, 7.1% had an HAI and 34.6% were receiving at least one antimicrobial agent. Prevalence results were highest in intensive care units, with 28.1% patients with HAI, and 61.4% patients with antimicrobial use. Pneumonia and other lower respiratory tract infections (2.0% of patients; 95% confidence interval (CI): 1.8–2.2%) represented the most common type (25.7%) of HAI. Surgical prophylaxis was the indication for 17.3% of used antimicrobials and exceeded one day in 60.7% of cases. Risk factors in the patient-based protocol were provided for 98% or more of the included patients and all were independently associated with both presence of HAI and receiving an antimicrobial agent. The patient-based protocol required more work than the unit-based protocol, but allowed collecting detailed data and analysis of risk factors for HAI and antimicrobial use.

Teamwork in the NICU Setting and Its Association with Health Care-Associated Infections in Very Low-Birth-Weight Infants.

PubMed

Profit, Jochen; Sharek, Paul J; Kan, Peiyi; Rigdon, Joseph; Desai, Manisha; Nisbet, Courtney C; Tawfik, Daniel S; Thomas, Eric J; Lee, Henry C; Sexton, J Bryan

2017-08-01

Background and Objective  Teamwork may affect clinical care in the neonatal intensive care unit (NICU) setting. The objective of this study was to assess teamwork climate across NICUs and to test scale-level and item-level associations with health care-associated infection (HAI) rates in very low-birth-weight (VLBW) infants. Methods  Cross-sectional study of the association between HAI rates, defined as any bacterial or fungal infection during the birth hospitalization, among 6,663 VLBW infants cared for in 44 NICUs between 2010 and 2012. NICU HAI rates were correlated with teamwork climate ratings obtained in 2011 from 2,073 of 3,294 eligible NICU health professionals (response rate 63%). The relation between HAI rates and NICU teamwork climate was assessed using logistic regression models including NICU as a random effect. Results  Across NICUs, 36 to 100% (mean 66%) of respondents reported good teamwork. HAI rates were significantly and independently associated with teamwork climate (odds ratio, 0.82; 95% confidence interval, 0.73-0.92, p  = 0.005), such that the odds of an infant contracting a HAI decreased by 18% with each 10% rise in NICU respondents reporting good teamwork. Conclusion  Improving teamwork may be an important element in infection control efforts. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The national response for preventing healthcare-associated infections: data and monitoring.

PubMed

Kahn, Katherine L; Weinberg, Daniel A; Leuschner, Kristin J; Gall, Elizabeth M; Siegel, Sari; Mendel, Peter

2014-02-01

Historically, the ability to accurately track healthcare-associated infections (HAIs) was hindered due to a lack of coordination among data sources and shortcomings in individual data sources. This paper presents the results of the evaluation of the HAI data and the monitoring component of the Action Plan, focusing on context (goals), inputs, and processes. We used the Content-Input-Process-Product framework, together with the HAI prevention system framework, to describe the transformative processes associated with data and monitoring efforts. Six HAI priority conditions in the 2009 Action Plan created a focus for the selection of goals and activities. Key Action Plan decisions included a phased-in data and monitoring approach, commitment to linking the selection of priority HAIs to highly visible national 5-year prevention targets, and the development of a comprehensive HAI database inventory. Remaining challenges relate to data validation, resources, and the opportunity to integrate electronic health and laboratory records with other provider data systems. The Action Plan's data and monitoring program has developed a sound infrastructure that builds upon technological advances and embodies a firm commitment to prioritization, coordination and alignment, accountability and incentives, stakeholder engagement, and an awareness of the need for predictable resources. With time, and adequate resources, it is likely that the investment in data-related infrastructure during the Action Plan's initial years will reap great rewards.

Closure Report for Corrective Action Unit 356: Mud Pits and Disposal Sites, Nevada Test Site, Nevada with Errata Sheet

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

NNSA /NV

2002-11-12

This Closure Report (CR) has been prepared for Corrective Action Unit (CAU) 356, Mud Pits and Disposal Sites, in accordance with the Federal Facility Agreement and Consent Order. This CAU is located in Areas 3 and 20 of the Nevada Test Site (NTS) approximately 65 miles northwest of Las Vegas, Nevada. Corrective Action Unit 356 consists of seven Corrective Action Sites (CASs): 03-04-01, Area 3 Change House Septic System; 03-09-01, Mud Pit Spill Over; 03-09-03, Mud Pit; 03-09-04, Mud Pit; 03-09-05, Mud Pit; 20-16-01, Landfill; and 20-22-21, Drums. This CR identifies and rationalizes the U.S. Department of Energy (DOE), Nationalmore » Nuclear Security Administration Nevada Operations Office's (NNSA/NV's) recommendation that no further corrective action and closure in place is deemed necessary for CAU 356. This recommendation is based on the results of field investigation/closure activities conducted November 20, 2001, through January 3, 2002, and March 11 to 14, 2002. These activities were conducted in accordance with the Streamlined Approach for Environmental Restoration Plan (SAFER) for CAU 356. For CASs 03-09-01, 03-09-03, 20-16-01, and 22-20-21, analytes detected in soil during the corrective action investigation were evaluated against Preliminary Action Levels (PALs) and it was determined that no Contaminants of Concern (COCs) were present. Therefore, no further action is necessary for the soil at these CASs. For CASs 03-04-01, 03-09-04, and 03-09-05, analytes detected in soil during the corrective action investigation were evaluated against PALs and identifies total petroleum hydrocarbons (TPHs) and radionuclides (i.e., americium-241 and/or plutonium 239/240) as COCs. The nature, extent, and concentration of the TPH and radionuclide COCs were bounded by sampling and shown to be relatively immobile. Therefore, closure in place is recommended for these CASs in CAU 356. Further, use restrictions are not required at this CAU beyond the NTS use restrictions

Clinical relevance of hepsin and hepatocyte growth factor activator inhibitor type 2 expression in renal cell carcinoma.

PubMed

Betsunoh, Hironori; Mukai, Shoichiro; Akiyama, Yutaka; Fukushima, Tsuyoshi; Minamiguchi, Naoki; Hasui, Yoshihiro; Osada, Yukio; Kataoka, Hiroaki

2007-04-01

Cell surface proteolysis is important for the generation of bioactive proteins mediating tumor progression. Recent studies suggest that the membrane-anchored cell surface proteinases matriptase and hepsin have significant roles in tumors. We analyzed the expression and clinical relevance of matriptase and hepsin, and their inhibitors hepatocyte growth factor activator inhibitor type 1 (HAI-1) and type 2 (HAI-2) in 66 cases of conventional renal cell carcinomas (RCC). The mRNA level was evaluated in paired samples from tumor and non-tumorous renal tissues by real-time reverse transcription-polymerase chain reaction. As matriptase and hepsin potently activate the proform of hepatocyte growth factor (HGF), the expression of HGF and its receptor, c-Met, was also analyzed. Although upregulation of matriptase was observed occasionally in RCC, the expression level was not associated with prognostic parameters. Hepsin was downregulated in RCC, particularly in early stage disease, but upregulated in advanced stages. There was a trend of higher hepsin expression in RCC with distant metastasis, and Kaplan-Meier survival curves showed that high hepsin expression was associated with reduced overall survival (P<0.01, log-rank test). Moreover, multivariate analysis indicated that hepsin was an independent prognostic factor. Overexpression of HGF or c-Met also showed reduced overall survival. We also observed a tendency of low HAI-2 expression with reduced overall survival and a statistical association between high hepsin and low HAI-2 level. No associations were observed between matriptase and HAI-1 and HAI-2. Our findings suggest that the balance between hepsin and its inhibitor, HAI-2, may have prognostic value in RCC.

Kinetics during the redox biotransformation of pollutants mediated by immobilized and soluble humic acids.

PubMed

Cervantes, Francisco J; Martínez, Claudia M; Gonzalez-Estrella, Jorge; Márquez, Arturo; Arriaga, Sonia

2013-03-01

The aim of this study was to elucidate the kinetic constraints during the redox biotransformation of the azo dye, Reactive Red 2 (RR2), and carbon tetrachloride (CT) mediated by soluble humic acids (HAs) and immobilized humic acids (HAi), as well as by the quinoid model compounds, anthraquinone-2,6-disulfonate (AQDS) and 1,2-naphthoquinone-4-sulfonate (NQS). The microbial reduction of both HAs and HAi by anaerobic granular sludge (AGS) was the rate-limiting step during decolorization of RR2 since the reduction of RR2 by reduced HAi proceeded at more than three orders of magnitute faster than the electron-transferring rate observed during the microbial reduction of HAi by AGS. Similarly, the reduction of RR2 by reduced AQDS proceeded 1.6- and 1.9-fold faster than the microbial reduction of AQDS by AGS when this redox mediator (RM) was supplied in soluble and immobilized form, respectively. In contrast, the reduction of NQS by AGS occurred 1.6- and 19.2-fold faster than the chemical reduction of RR2 by reduced NQS when this RM was supplied in soluble and immobilized form, respectively. The microbial reduction of HAs and HAi by a humus-reducing consortium proceeded 1,400- and 790-fold faster than the transfer of electrons from reduced HAs and HAi, respectively, to achieve the reductive dechlorination of CT to chloroform. Overall, the present study provides elucidation on the rate-limiting steps involved in the redox biotransformation of priority pollutants mediated by both HAs and HAi and offers technical suggestions to overcome the kinetic restrictions identified in the redox reactions evaluated.

Effects of water temperature and substrate type on spore production and release in eastern Tubifex tubifex worms infected with Myxobolus cerebralis

USGS Publications Warehouse

Blazer, V.S.; Waldrop, T.B.; Schill, W.B.; Densmore, Christine L.; Smith, D.

2003-01-01

Eastern Tubifex tubifex worms were exposed to Myxobolus cerebralis spores at 9, 13, 17, and 20 C in 1-L jars that contained sand, mud, or leaf litter as substrata. Beginning 60 days after exposure, water from each jar was filtered daily and examined for the presence of waterborne triactinomyxon spores (TAMs). On discovering a single TAM from an experimental jar, 48 T. tubifex worms from that jar were placed individually into 24-well plates. Spores released from individual infected T. tubifex worms were quantified to determine the first day of TAM release from infected worms, the infection rate, the total number of TAMs released per worm, and the duration of release. No TAMs were found in any of the jars incubated at 20 C or in uninfected, control worms at any temperature. The total number of TAMs released by infected worms in mud and sand was highest at 13 C compared with other temperatures. Infection rates among individual worms increased with temperature between 9 and 17 C. Higher temperatures (up to 17 C) induced earlier TAM releases among infected worms, and substratum did not influence this production parameter. The average duration of TAM release decreased as the temperature increased from 9 to 17 C, and there was a significant effect of substratum in the groups maintained at 13 and 17 C. In all temperature treatments between 9 and 17 C, the duration of release was least in the worms maintained in leaf litter, as was the total number of TAMs released during the experimental period and the median number of TAMs per production day.

Biocompatible mannosylated endosomal-escape nanoparticles enhance selective delivery of short nucleotide sequences to tumor associated macrophages

NASA Astrophysics Data System (ADS)

Ortega, Ryan A.; Barham, Whitney J.; Kumar, Bharat; Tikhomirov, Oleg; McFadden, Ian D.; Yull, Fiona E.; Giorgio, Todd D.

2014-12-01

Tumor associated macrophages (TAMs) can modify the tumor microenvironment to create a pro-tumor niche. Manipulation of the TAM phenotype is a novel, potential therapeutic approach to engage anti-cancer immunity. siRNA is a molecular tool for knockdown of specific mRNAs that is tunable in both strength and duration. The use of siRNA to reprogram TAMs to adopt an immunogenic, anti-tumor phenotype is an attractive alternative to ablation of this cell population. One current difficulty with this approach is that TAMs are difficult to specifically target and transfect. We report here successful utilization of novel mannosylated polymer nanoparticles (MnNP) that are capable of escaping the endosomal compartment to deliver siRNA to TAMs in vitro and in vivo. Transfection with MnNP-siRNA complexes did not significantly decrease TAM cell membrane integrity in culture, nor did it create adverse kidney or liver function in mice, even at repeated doses of 5 mg kg-1. Furthermore, MnNP effectively delivers labeled nucleotides to TAMs in mice with primary mammary tumors. We also confirmed TAM targeting in the solid tumors disseminated throughout the peritoneum of ovarian tumor bearing mice following injection of fluorescently labeled MnNP-nucleotide complexes into the peritoneum. Finally, we show enhanced uptake of MnNP in lung metastasis associated macrophages compared to untargeted particles when using an intubation delivery method. In summary, we have shown that MnNP specifically and effectively deliver siRNA to TAMs in vivo.

NF-κB RelA renders tumor-associated macrophages resistant to and capable of directly suppressing CD8+ T cells for tumor promotion.

PubMed

Li, Liwen; Han, Lei; Sun, Fan; Zhou, Jingjiao; Ohaegbulam, Kim C; Tang, Xudong; Zang, Xingxing; Steinbrecher, Kris A; Qu, Zhaoxia; Xiao, Gutian

2018-01-01

Activation of the inflammatory transcription factor NF-κB in tumor-associated macrophages (TAMs) is assumed to contribute to tumor promotion. However, whether and how NF-κB drives the antitumor macrophages to become pro-tumorigenic have not been determined in any cancer type yet. Similarly, how TAMs repress CD8 + cytotoxic T lymphocytes (CTLs) remains largely unknown, although their importance in regulatory T (Treg) cell regulation and tumor promotion has been well appreciated. Here, using an endogenous lung cancer model we uncover a direct crosstalk between TAMs and CTLs. TAMs suppress CTLs through the T-cell inhibitory molecule B7x (B7-H4/B7S1) in a cell-cell contact manner, whereas CTLs kill TAMs in a tumor antigen-specific manner. Remarkably, TAMs secrete the known T-cell suppressive cytokine interleukin-10 (IL-10) to activate, but not to repress, CTLs. Notably, one major role of cell-intrinsic NF-κB RelA is to drive TAMs to suppress CTLs for tumor promotion. It induces B7x expression in TAMs directly, and restricts IL-10 expression indirectly by repressing expression of the NF-κB cofactor Bcl3 and subsequent Bcl3/NF-κB1-mediated transcription of IL-10. It also renders TAMs resistant to CTLs by up-regulating anti-apoptotic genes. These studies help understand how immunity is shaped in lung tumorigenesis, and suggest a RelA-targeted immunotherapy for this deadliest cancer.

A Comprehensive Proteomics Analysis Reveals a Secretory Path- and Status-Dependent Signature of Exosomes Released from Tumor-Associated Macrophages.

PubMed

Zhu, Yinghui; Chen, Xianwei; Pan, Qingfei; Wang, Yang; Su, Siyuan; Jiang, Cuicui; Li, Yang; Xu, Ningzhi; Wu, Lin; Lou, Xiaomin; Liu, Siqi

2015-10-02

Exosomes are 30-120 nm-sized membrane vesicles of endocytic origin that are released into the extracellular environment and play roles in cell-cell communication. Tumor-associated macrophages (TAMs) are important constituents of the tumor microenvironment; thus, it is critical to study the features and complex biological functions of TAM-derived exosomes. Here, we constructed a TAM cell model from a mouse macrophage cell line, Ana-1, and performed comparative proteomics on exosomes, exosome-free media, and cells between TAMs and Ana-1. Proteomic analysis between exosome and exosome-free fractions indicated that the functions of exosome dominant proteins were mainly enriched in RNA processing and proteolysis. TAM status dramatically affected the abundances of 20S proteasome subunits and ribosomal proteins in their exosomes. The 20S proteasome activity assay strongly indicated that TAM exosomes possessed higher proteolytic activity. In addition, Ana-1- and TAM-derived exosomes have different RNA profiles, which may result from differential RNA processing proteins. Taken together, our comprehensive proteomics study provides novel views for understanding the complicated roles of macrophage-derived exosomes in the tumor microenvironment.

Interactions of the anticancer drug tamoxifen with lipid membranes

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

Khadka, Nawal K.; Cheng, Xiaolin; Ho, Chian Sing

Interactions of the hydrophobic anticancer drug tamoxifen (TAM) with lipid model membranes were studied using calcein-encapsulated vesicle leakage, attenuated total reflection Fourier transform infrared (FTIR) spectroscopy, small-angle neutron scattering (SANS), atomic force microscopy (AFM) based force spectroscopy, and all-atom molecular dynamics (MD) simulations. The addition of TAM enhances membrane permeability, inducing calcein to translocate from the interior to the exterior of lipid vesicles. A large decrease in the FTIR absorption band’s magnitude was observed in the hydrocarbon chain region, suggesting suppressed bond vibrational dynamics. Bilayer thickening was determined from SANS data. Force spectroscopy measurements indicate that the lipid bilayer areamore » compressibility modulus KA is increased by a large amount after the incorporation of TAM. MD simulations show that TAM decreases the lipid area and increases chain order parameters. Moreover, orientational and positional analyses show that TAM exhibits a highly dynamic conformation within the lipid bilayer. Lastly, our detailed experimental and computational studies of TAM interacting with model lipid membranes shed new light on membrane modulation by TAM.« less

Interactions of the anticancer drug tamoxifen with lipid membranes

DOE PAGES

Khadka, Nawal K.; Cheng, Xiaolin; Ho, Chian Sing; ...

2015-05-19

Interactions of the hydrophobic anticancer drug tamoxifen (TAM) with lipid model membranes were studied using calcein-encapsulated vesicle leakage, attenuated total reflection Fourier transform infrared (FTIR) spectroscopy, small-angle neutron scattering (SANS), atomic force microscopy (AFM) based force spectroscopy, and all-atom molecular dynamics (MD) simulations. The addition of TAM enhances membrane permeability, inducing calcein to translocate from the interior to the exterior of lipid vesicles. A large decrease in the FTIR absorption band’s magnitude was observed in the hydrocarbon chain region, suggesting suppressed bond vibrational dynamics. Bilayer thickening was determined from SANS data. Force spectroscopy measurements indicate that the lipid bilayer areamore » compressibility modulus KA is increased by a large amount after the incorporation of TAM. MD simulations show that TAM decreases the lipid area and increases chain order parameters. Moreover, orientational and positional analyses show that TAM exhibits a highly dynamic conformation within the lipid bilayer. Lastly, our detailed experimental and computational studies of TAM interacting with model lipid membranes shed new light on membrane modulation by TAM.« less

Circumventing Therapeutic Resistance and the Emergence of Disseminated Breast Cancer Cells Through Non-Invasive Optical Imaging

DTIC Science & Technology

2014-07-01

vesicle degradation in vivo. Lastly, we have established four pairs of parental and isogenic matched tamoxifen ( tam )-resistant cell lines (MCF7, T47D...members of the HER receptor family (EGFR/HER1; HER2; HER3) are upregulated with the development of tam -resistance; furthermore, differences in receptor...Figure 4 Increased HER receptor expression in response to tam -treated MDA-MB-361 cells and tam -resistant 361 cells. Steady-state levels of the

Southeast Asia Report.

DTIC Science & Technology

1987-03-26

Members 102 ECONOMIC PLANNING, TRADE, AND FINANCE Increase in Consumer, Export Goods Urged (Pham Thanh; NHAN DAN, 2 Jan 87) 103 Reasons for...Economic Management 121 Kien Giang Increases Handicrafts 121 Population, Relocation Labor 121 AGRICULTURE Potential Economic Resources Available in Sea...imperative that ac- tion be taken to increase tax or reduce expenditure. Instead, they believe he won’t follow either option and may, in- deed

How to Manage and Control Healthcare Associated Infections

NASA Astrophysics Data System (ADS)

Wijaya, L.

2018-03-01

Healthcare associated infections (HAI) are the major complications of modern medical therapy. The most important HAIs are related to invasive devices including central line- associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), ventilator-associated pneumonia (VAP) and surgical-site infections (SSI). Excessive use of antibiotics has also led to the emergence and the global dissemination of antibiotic resistant bacteria over the last few decades. Reducing HAIs will involve a multi-modal approach to infection control practices as well as antibiotic stewardship program.

Drought evolution characteristics and precipitation intensity changes during alternating dry-wet changes in the Huang-Huai-Hai River basin

NASA Astrophysics Data System (ADS)

Yan, D. H.; Wu, D.; Huang, R.; Wang, L. N.; Yang, G. Y.

2013-07-01

Abrupt drought-flood change events caused by atmospheric circulation anomalies have occurred frequently and widely in recent years, which has caused great losses and casualties in China. In this paper, we focus on investigating whether there will be a rainfall occurrence with higher intensity after a drought period in the Huang-Huai-Hai River basin. Combined with the Chinese climate divisions and the basin's DEM (digital elevation model), the basin is divided into seven sub-regions by means of cluster analysis of the basin meteorological stations using the self-organizing map (SOM) neural network method. Based on the daily precipitation data of 171 stations for the years 1961-2011, the changes of drought times with different magnitudes are analyzed, and the number of consecutive days without precipitation is used to identify the drought magnitudes. The first precipitation intensity after a drought period is analyzed with the Pearson-III frequency curve, then the relationship between rainfall intensity and different drought magnitudes is observed, as are the changes of drought times for different years. The results of the study indicated that the occurrence times of different drought levels show an overall increasing trend; there is no clear interdecadal change shown, but the spatial difference is significant. (2) As the drought level increases, the probability of extraordinary rainstorm becomes lower, and the frequency of occurrence of spatial changes in different precipitation intensities vary. In the areas I and II, as the drought level increases, the occurrence frequency of different precipitation intensities first shows a decreasing trend, which becomes an increasing trend when extraordinary drought occurs. In the area III, IV and V, the probability of the different precipitation intensities shows an overall decreasing trend. The areas VI and VII are located at the mountains with high altitudes where the variation of different precipitation intensities with the

The effect of tamoxifen and raloxifene on estrogen metabolism and endometrial cancer risk.

PubMed

Williams-Brown, Marian Y; Salih, Sana M; Xu, Xia; Veenstra, Timothy D; Saeed, Muhammad; Theiler, Shaleen K; Diaz-Arrastia, Concepcion R; Salama, Salama A

2011-09-01

Selective estrogen receptor modulators (SERMs) demonstrate differential endometrial cancer (EC) risk. While tamoxifen (TAM) use increases the risk of endometrial hyperplasia and malignancy, raloxifene (RAL) has neutral effects on the uterus. How TAM increases the risk of EC and why TAM and RAL differentially modulate the risk for EC, however, remain elusive. Here, we tested the hypothesis that TAM increases the risk for EC, at least in part, by enhancing the local estrogen biosynthesis and directing estrogen metabolism towards the formation of genotoxic and hormonally active estrogen metabolites. In addition, the differential effects of TAM and RAL in EC risk are attributed to their differential effect on estrogen metabolism/metabolites. The endometrial cancer cell line (Ishikawa cells) and the nonmalignant immortalized human endometrial glandular cell line (EM1) were used for the study. The profile of estrogen/estrogen metabolites (EM), depurinating estrogen-DNA adducts, and the expression of estrogen-metabolizing enzymes in cells treated with 17β-estradiol (E2) alone or in combination with TAM or RAL were investigated using high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS(2)), ultraperformance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS), and Western blot analysis, respectively. TAM significantly increased the total EM and enhanced the formation of hormonally active and carcinogenic estrogen metabolites, 4-hydroxestrone (4-OHE1) and 16α-hydroxyestrone, with concomitant reduction in the formation of antiestrogenic and anticarcinogenic 2-hydroxyestradiol and 2-methoxyestradiol. Furthermore, TAM increased the formation of depurinating estrogen-DNA adducts 4-OHE1 [2]-1-N7Guanine and 4-OHE1 [2]-1-N3 Adenine. TAM-induced alteration in EM and depurinating DNA adduct formation is associated with altered expression of estrogen metabolizing enzymes CYP1A1, CYP1B1, COMT, NQO1, and SF-1 as revealed by

Detecting borderline infection in an automated monitoring system for healthcare-associated infection using fuzzy logic.

PubMed

de Bruin, Jeroen S; Adlassnig, Klaus-Peter; Blacky, Alexander; Koller, Walter

2016-05-01

Many electronic infection detection systems employ dichotomous classification methods, classifying patient data as pathological or normal with respect to one or several types of infection. An electronic monitoring and surveillance system for healthcare-associated infections (HAIs) known as Moni-ICU is being operated at the intensive care units (ICUs) of the Vienna General Hospital (VGH) in Austria. Instead of classifying patient data as pathological or normal, Moni-ICU introduces a third borderline class. Patient data classified as borderline with respect to an infection-related clinical concept or HAI surveillance definition signify that the data nearly or partly fulfill the definition for the respective concept or HAI, and are therefore neither fully pathological nor fully normal. Using fuzzy sets and propositional fuzzy rules, we calculated how frequently patient data are classified as normal, borderline, or pathological with respect to infection-related clinical concepts and HAI definitions. In dichotomous classification methods, borderline classification results would be confounded by normal. Therefore, we also assessed whether the constructed fuzzy sets and rules employed by Moni-ICU classified patient data too often or too infrequently as borderline instead of normal. Electronic surveillance data were collected from adult patients (aged 18 years or older) at ten ICUs of the VGH. All adult patients admitted to these ICUs over a two-year period were reviewed. In all 5099 patient stays (4120 patients) comprising 49,394 patient days were evaluated. For classification, a part of Moni-ICU's knowledge base comprising fuzzy sets and rules for ten infection-related clinical concepts and four top-level HAI definitions was employed. Fuzzy sets were used for the classification of concepts directly related to patient data; fuzzy rules were employed for the classification of more abstract clinical concepts, and for top-level HAI surveillance definitions. Data for each

International Nosocomial Infection Control Consortium Findings of Device-Associated Infections Rate in an Intensive Care Unit of a Lebanese University Hospital

PubMed Central

Kanj, SS; Kanafani, ZA; Sidani, N; Alamuddin, L; Zahreddine, N; Rosenthal, VD

2012-01-01

Objectives: To determine the rates of device-associated healthcare-associated infections (DA-HAI), microbiological profile, bacterial resistance, length of stay (LOS), excess mortality and hand hygiene compliance in one intensive care unit (ICU) of a hospital member of the International Infection Control Consortium (INICC) in Beirut, Lebanon. Materials and Methods: An open label, prospective cohort, active DA-HAI surveillance study was conducted on adults admitted to a tertiary-care ICU in Lebanon from November 2007 to March 2010. The protocol and methodology implemented were developed by INICC. Data collection was performed in the participating ICUs. Data uploading and analyses were conducted at INICC headquarters on proprietary software. DA-HAI rates were recorded by applying the definitions of the National Healthcare Safety Network (NHSN) at the US Centers for Disease Control and Prevention (CDC). We analyzed the DA-HAI, mechanical ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CLA-BSI), and catheter-associated urinary tract infection (CAUTI) rates, microorganism profile, excess LOS, excess mortality, and hand hygiene compliance. Results: A total of 666 patients hospitalized for 5,506 days acquired 65 DA-HAIs, an overall rate of 9.8% [(95% confidence interval (CI) 7.6–12.3], and 11.8 (95% CI 9.1–15.0) DA-HAIs per 1000 ICU-days. The CLA-BSI rate was 5.2 (95% CI 2.8–8.7) per 1000 catheter-days; the VAP rate was 8.1 (95% CI 5.5–11.7) per 1000 ventilator-days; and the CAUTI rate was 4.1 (95% CI 2.6–6.2) per 1000 catheter-days. LOS of patients was 7.3 days for those without DA-HAI, 13.8 days for those with CLA-BSI, 18.8 days for those with VAP. Excess mortality was 40.9% [relative risk (RR) 3.14; P 0.004] for CLA-BSI. Mortality of VAP and CAUTI was not significantly different from patients without DA-HAI. Escherichia coli was the most common isolated microorganism. Overall hand hygiene compliance was 84.9% (95% CI 82

The network approach for prevention of healthcare-associated infections: long-term effect of participation in the Duke Infection Control Outreach Network.

PubMed

Anderson, Deverick J; Miller, Becky A; Chen, Luke F; Adcock, Linda H; Cook, Evelyn; Cromer, A Lynn; Louis, Susan; Thacker, Paul A; Sexton, Daniel J

2011-04-01

To describe the rates of several key outcomes and healthcare-associated infections (HAIs) among hospitals that participated in the Duke Infection Control Outreach Network (DICON). Prospective, observational cohort study of patients admitted to 24 community hospitals from 2003 through 2009. The following data were collected and analyzed: incidence of central line-associated bloodstream infections (CLABSIs), ventilator-associated pneumonia (VAP), catheter-associated urinary tract infections (CAUTIs), and HAIs caused by methicillin-resistant Staphylococcus aureus (MRSA); employee exposures to bloodborne pathogens (EBBPs); physician EBBPs; patient-days; central line-days; ventilator-days; and urinary catheter-days. Poisson regression was used to determine whether incidence rates of these HAIs and exposures changed during the first 5 and 7 years of participation in DICON; nonrandom clustering of each outcome was controlled for. Cost saved and lives saved were calculated on the basis of published estimates. In total, we analyzed 6.5 million patient-days, 4,783 EBPPs, 2,948 HAIs due to MRSA, and 2,076 device-related infections. Rates of employee EBBPs, HAIs due to MRSA, and device-related infections decreased significantly during the first 5 years of participation in DICON (P< .05 for all models; average decrease was approximately 50%); in contrast, physician EBBPs remained unchanged. In aggregate, 210 CLABSIs, 312 cases of VAP, 332 CAUTIs, 1,042 HAIs due to MRSA, and 1,016 employee EBBPs were prevented. Each hospital saved approximately $100,000 per year of participation, and collectively the hospitals may have prevented 52-105 deaths from CLABSI or VAP. The 7-year analysis demonstrated that these trends continued with further participation. Hospitals with long-term participation in an infection control network decreased rates of significant HAIs by approximately 50%, decreased costs, and saved lives.

Circumventing Therapeutic Resistance and the Emergence of Disseminated Breast Cancer Cells Through Non-Invasive Optical Imaging

DTIC Science & Technology

2014-07-01

vivo. Lastly, we have established four pairs of parental and isogenic matched tamoxifen ( tam )-resistant cell lines (MCF7, T47D, MDA-MB-361 and HCC1428...receptor family (EGFR/HER1; HER2; HER3) are upregulated with the development of tam -resistance; furthermore, differences in receptor expression between ER...Increased HER receptor expression in response to tam -treated MDA-MB-361 cells and tam -resistant 361 cells. Steady-state levels of the indicated proteins

A point prevalence survey of health care-associated infections in Canadian pediatric inpatients.

PubMed

Rutledge-Taylor, Katie; Matlow, Anne; Gravel, Denise; Embree, Joanne; Le Saux, Nicole; Johnston, Lynn; Suh, Kathryn; Embil, John; Henderson, Elizabeth; John, Michael; Roth, Virginia; Wong, Alice; Shurgold, Jayson; Taylor, Geoff

2012-08-01

Health care-associated infections (HAIs) cause considerable morbidity and mortality to hospitalized patients. The objective of this point prevalence study was to assess the burden of HAIs in the Canadian pediatric population, updating results reported from a similar study conducted in 2002. A point prevalence survey of pediatric inpatients was conducted in February 2009 in 30 pediatric or combined adult/pediatric hospitals. Data pertaining to one 24-hour period were collected, including information on HAIs, microorganisms isolated, antimicrobials prescribed, and use of additional (transmission based) precautions. The following prevalent infections were included: pneumonia, urinary tract infection, bloodstream infection, surgical site infection, viral respiratory infection, Clostridium difficile infection, viral gastroenteritis, and necrotizing enterocolitis. One hundred eighteen patients had 1 or more HAI, corresponding to a prevalence of 8.7% (n = 118 of 1353, 95% confidence interval: 7.2-10.2). Six patients had 2 infections. Bloodstream infections were the most frequent infection in neonates (3.0%), infants (3.1%), and children (3.5%). Among all patients surveyed, 16.3% were on additional precautions, and 40.1% were on antimicrobial agents, whereas 40.7% of patients with a HAI were on additional precautions, and 89.0% were on antimicrobial agents. Overall prevalence of HAI in 2009 has remained similar to the prevalence reported from 2002. The unchanged prevalence of these infections nonetheless warrants continued vigilance on their prevention and control. Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

Health care-associated infections in Iran: A national update for the year 2015.

PubMed

Eshrati, Babak; Masoumi Asl, Hossein; Afhami, Shirin; Pezeshki, Zahra; Seifi, Arash

2018-06-01

A national surveillance system for health care-associated infections (HAIs) in Iran is relatively new, and an update on incidence and mortality rates can aid clinicians and stakeholders in development of new guidelines and imperative modifications to be made. Data were extracted from the national HAIs surveillance software for more than 7 million hospitalizations during 2015. Data regarding age, gender, deaths, ward of admission, and microbiologic findings were collected and analyzed. From 491 hospitals, 7,018,393 hospitalizations were reported during 2015; 82,950 patients had been diagnosed with at least 1 HAI, 6,355 of whom died (crude fatality rate, 7.7). Men comprised 51.4% of the patients. The incidence rate was calculated to be 1.18. Urinary tract infections and pneumonia were the most commonly reported infections (27.9% and 23.8%) and 33% of patients were older than age 65 years. Intensive care units had the highest incidence rates, followed by burn units with incidence rates close to 9. Highest percentages of deaths were reported among patients with an HAI in the intensive care unit (20.6%) and those with pneumonia (39.6%). Although the underreporting of HAIs hinders accurate calculation of incidence, the present study provides a general update. The results can help in modification of national guidelines and appropriate choice of antimicrobial agents in the management of HAIs. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Simulation on Change Law of Runoff, Sediment and Non-point Source Nitrogen and Phosphorus Discharge under Different Land uses Based on SWAT Model: A Case Study of Er hai Lake Small Watershed

NASA Astrophysics Data System (ADS)

Tong, Xiao Xia; Lai Cui, Yuan; Chen, Man Yu; Hu, Bo; Xu, Wen Sheng

2018-05-01

The Er yuan watershed of Er hai district is chosen as the research area, the law of runoff and sediment and non-point source nitrogen and phosphorus discharges under different land uses during 2001 to 2014 are simulated based on SWAT model. Results of simulation indicate that the order of total runoff yield of different land use type from high to low is grassland, paddy fields, dry land. Specifically, the order of surface runoff yield from high to low is paddy fields, dry land, grassland, the order of lateral runoff yield from high to low is paddy fields, dry land, grassland, the order of groundwater runoff yield from high to low is grassland, paddy fields, dry land. The orders of sediment and nitrogen and phosphorus yield per unit area of different land use type are the same, grassland> paddy fields> dry land. It can be seen, nitrogen and phosphorus discharges from paddy fields and dry land are the main sources of agricultural non-point pollution of the irrigated area. Therefore, reasonable field management measures which can decrease the discharge of nitrogen and phosphorus of paddy fields and dry land are the key to agricultural non-point source pollution prevention and control.

Acceptance of Internet Banking Systems among Young Managers

NASA Astrophysics Data System (ADS)

Ariff, Mohd Shoki Md; M, Yeow S.; Zakuan, Norhayati; Zaidi Bahari, Ahamad

2013-06-01

The aim of this paper is to determine acceptance of internet banking system among potential young users, specifically future young managers. The relationships and the effects of computer self-efficacy (CSE) and extended technology acceptance model (TAM) on the behavioural intention (BI) to use internet banking system were examined. Measurement of CSE, TAM and BI were adapted from previous studies. However construct for TAM has been extended by adding a new variable which is perceived credibility (PC). A survey through questionnaire was conducted to determine the acceptance level of CSE, TAM and BI. Data were obtained from 275 Technology Management students, who are pursuing their undergraduate studies in a Malaysia's public university. The confirmatory factor analysis performed has identified four variables as determinant factors of internet banking acceptance. The first variable is computer self-efficacy (CSE), and another three variables from TAM constructs which are perceived usefulness (PU), perceived ease of use (PE) and perceived credibility (PC). The finding of this study indicated that CSE has a positive effect on PU and PE of the Internet banking systems. Respondents' CSE was positively affecting their PC of the systems, indicating that the higher the ability of one in computer skills, the higher the security and privacy issues of PC will be concerned. The multiple regression analysis indicated that only two construct of TAM; PU and PC were significantly associated with BI. It was found that the future managers' CSE indirectly affects their BI to use the internet banking systems through PU and PC of TAM. TAM was found to have direct effects on respondents' BI to use the systems. Both CSE and the PU and PC of TAM were good predictors in understanding individual responses to information technology. The role of PE of the original TAM to predict the attitude of users towards the use of information technology systems was surprisingly insignificant.

Investigation of discriminant metabolites in tamoxifen-resistant and choline kinase-alpha-downregulated breast cancer cells using 1H-nuclear magnetic resonance spectroscopy.

PubMed

Kim, Hoe Suk; Tian, Lianji; Kim, Hyeonjin; Moon, Woo Kyung

2017-01-01

Metabolites linked to changes in choline kinase-α (CK-α) expression and drug resistance, which contribute to survival and autophagy mechanisms, are attractive targets for breast cancer therapies. We previously reported that autophagy played a causative role in driving tamoxifen (TAM) resistance of breast cancer cells (BCCs) and was also promoted by CK-α knockdown, resulting in the survival of TAM-resistant BCCs. There is no comparative study yet about the metabolites resulting from BCCs with TAM-resistance and CK-α knockdown. Therefore, the aim of this study was to explore the discriminant metabolic biomarkers responsible for TAM resistance as well as CK-α expression, which might be linked with autophagy through a protective role. A total of 33 intracellular metabolites, including a range of amino acids, energy metabolism-related molecules and others from cell extracts of the parental cells (MCF-7), TAM-resistant cells (MCF-7/TAM) and CK-α knockdown cells (MCF-7/shCK-α, MCF-7/TAM/shCK-α) were analyzed by proton nuclear magnetic resonance spectroscopy (1H-NMRS). Principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) revealed the existence of differences in the intracellular metabolites to separate the 4 groups: MCF-7 cells, MCF-7/TAM cells, MCF-7-shCK-α cells, and MCF-7/TAM/shCK-α cells. The metabolites with VIP>1 contributed most to the differentiation of the cell groups, and they included fumarate, UA (unknown A), lactate, myo-inositol, glycine, phosphocholine, UE (unknown E), glutamine, formate, and AXP (AMP/ADP/ATP). Our results suggest that these altered metabolites would be promising metabolic biomarkers for a targeted therapeutic strategy in BCCs that exhibit TAM-resistance and aberrant CK-α expression, which triggers a survival and drug resistance mechanism.

Antitumor effect of nuclear factor-κB decoy transfer by mannose-modified bubble lipoplex into macrophages in mouse malignant ascites

PubMed Central

Kono, Yusuke; Kawakami, Shigeru; Higuchi, Yuriko; Maruyama, Kazuo; Yamashita, Fumiyoshi; Hashida, Mitsuru

2014-01-01

Patients with malignant ascites (MAs) display several symptoms, such as dyspnea, nausea, pain, and abdominal tenderness, resulting in a significant reduction in their quality of life. Tumor-associated macrophages (TAMs) play a crucial role in MA progression. Because TAMs have a tumor-promoting M2 phenotype, conversion of the M2 phenotypic function of TAMs would be promising for MA treatment. Nuclear factor-κB (NF-κB) is a master regulator of macrophage polarization. Here, we developed targeted transfer of a NF-κB decoy into TAMs by ultrasound (US)-responsive, mannose-modified liposome/NF-κB decoy complexes (Man-PEG bubble lipoplexes) in a mouse peritoneal dissemination model of Ehrlich ascites carcinoma. In addition, we investigated the effects of NF-κB decoy transfection into TAMs on MA progression and mouse survival rates. Intraperitoneal injection of Man-PEG bubble lipoplexes and US exposure transferred the NF-κB decoy into TAMs effectively. When the NF-κB decoy was delivered into TAMs by this method in the mouse peritoneal dissemination model, mRNA expression of the Th2 cytokine interleukin (IL)-10 in TAMs was decreased significantly. In contrast, mRNA levels of Th1 cytokines (IL-12, tumor necrosis factor-α, and IL-6) were increased significantly. Moreover, the expression level of vascular endothelial growth factor in ascites was suppressed significantly, and peritoneal angiogenesis showed a reduction. Furthermore, NF-κB decoy transfer into TAMs significantly decreased the ascitic volume and number of Ehrlich ascites carcinoma cells in ascites, and prolonged mouse survival. In conclusion, we transferred a NF-κB decoy efficiently by Man-PEG bubble lipoplexes with US exposure into TAMs, which may be a novel approach for MA treatment. PMID:24850474

'Real-time' burden of community and healthcare-related infections in medical and rehabilitation patients in a public hospital in Auckland, New Zealand.

PubMed

Read, Kerry; Bhally, Hansan; Sapsford, Sabrina; Sapsford, Thomas

2015-12-04

To determine the prevalence and spectrum of infections on admission, or acquired during hospitalisation (HAI) at Waitakere Hospital, Auckland. A questionnaire was completed on two separate days for all adult in-patients admitted to medical and rehabilitation wards for greater than 24 hours. Information obtained included patient characteristics, the presence and type of infection on admission or acquired during hospitalisation, as well as information on indwelling devices. Infection was the admitting diagnosis in 81 (41%) of 195 patients reviewed, with lower respiratory tract infection (LRTI) diagnosed in 50%, urine infections in 22% and cellulitis 18%. Only 40% LRTIs were supported by radiology or microbiological criteria. Twenty-five HAIs occurred in 21 patients (cumulative and point prevalence of 10.7% and 5.0% respectively). Urinary tract infection (UTI) was the most common HAI in 13 patients (62%), including 4 catheter-related infections. Patients with HAI were older and appeared to have had longer hospital stays, and higher urinary catheter usage. This study highlights the ongoing high burden of infections contributing to hospitalisation of adult patients in a developed country. The prevalence of HAI, patient characteristics and risk factors are comparable to previous studies in similar settings.

Triple negative breast cancer: Key role of Tumor-Associated Macrophages in regulating the activity of anti-PD-1/PD-L1 agents.

PubMed

Santoni, Matteo; Romagnoli, Emanuela; Saladino, Tiziana; Foghini, Laura; Guarino, Stefania; Capponi, Marco; Giannini, Massimo; Cognigni, Paolo Decembrini; Ferrara, Gerardo; Battelli, Nicola

2018-01-01

Triple-negative breast cancer (TNBC) is associated with a poor prognosis, due to its aggressive behaviour and lack of effective targeted therapies. Immunocheckpoint inhibitors, such as anti-programmed cell death 1 (PD-1) and anti-PD-ligand(L)1 agents, are in course of investigation in TNBC, used alone or in combination with other systemic or local approaches. However, the high cost of these drugs and the lack of validated predictive biomarkers support the development of strategies aimed to overcome resistance and optimize the efficacy of these approaches. Tumor-Associated Macrophages (TAMs) derive from peripheral blood monocytes recruited into the TNBC microenvironment and, in response to several stimuli, undergo M1 (classical) or M2 (alternative) activation. In TNBC, TAMs promote tumor growth and progression by several mechanisms that include the secretion of inhibitory cytokines, the reduction of effector functions of Tumor Infiltrating Lymphocytes (TILs) and the promotion of Regulatory T cell (Treg). Interestingly, TAMs have been shown to directly and indirectly modulate PD-1/PD-L1 expression in tumor environment. On this scenario, several TAM-centered strategies have been proposed, such as the suppression of TAM recruitment, the depletion of their number, the switch of M2 TAMs into antitumor M1 phenotype and the inhibition of TAM-associated molecules. In this review, we will illustrate the activity of TAMs and associated molecules in TNBC, focusing on their role in modulating the expression of PD-1/PD-L1 and on the emerging TAM-tailored strategies for TNBC patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Liposomal formulation of {alpha}-tocopheryl maleamide: In vitro and in vivo toxicological profile and anticancer effect against spontaneous breast carcinomas in mice

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

Turanek, Jaroslav; Wang Xiufang; Knoetigova, Pavlina

2009-06-15

The vitamin E analogue {alpha}-tocopheryl succinate ({alpha}-TOS) is an efficient anti-cancer drug. Improved efficacy was achieved through the synthesis of {alpha}-tocopheryl maleamide ({alpha}-TAM), an esterase-resistant analogue of {alpha}-tocopheryl maleate. In vitro tests demonstrated significantly higher cytotoxicity of {alpha}-TAM towards cancer cells (MCF-7, B16F10) compared to {alpha}-TOS and other analogues prone to esterase-catalyzed hydrolysis. However, in vitro models demonstrated that {alpha}-TAM was cytotoxic to non-malignant cells (e.g. lymphocytes and bone marrow progenitors). Thus we developed lyophilized liposomal formulations of both {alpha}-TOS and {alpha}-TAM to solve the problem with cytotoxicity of free {alpha}-TAM (neurotoxicity and anaphylaxis), as well as the low solubilitymore » of both drugs. Remarkably, neither acute toxicity nor immunotoxicity implicated by in vitro tests was detected in vivo after application of liposomal {alpha}-TAM, which significantly reduced the growth of cancer cells in hollow fiber implants. Moreover, liposomal formulation of {alpha}-TAM and {alpha}-TOS each prevented the growth of tumours in transgenic FVB/N c-neu mice bearing spontaneous breast carcinomas. Liposomal formulation of {alpha}-TAM demonstrated anti-cancer activity at levels 10-fold lower than those of {alpha}-TOS. Thus, the liposomal formulation of {alpha}-TAM preserved its strong anti-cancer efficacy while eliminating the in vivo toxicity found of the free drug applied in DMSO. Liposome-based targeted delivery systems for analogues of vitamin E are of interest for further development of efficient and safe drug formulations for clinical trials.« less

Haemagglutination inhibition antibody levels one year after natural measles infection and vaccination.

PubMed

Eghafona, N O; Ahmad, A A; Ezeokoli, C D; Emejuaiwe, S O

1991-01-01

An assessment of haemagglutination inhibition antibody (HAI) titres of 1,163 children, comprising 739 recipients of live measles vaccines and 424 patients with natural measles infection after 1 year was made in this investigation. Statistical analysis revealed a significant difference in the levels of HAI antibodies. Of the vaccinated children a significant 67.45% showed antibody titres of less than or equal to 1:16, while only 23.48% of children with natural measles showed these antibody titres. The importance and implication of such HAI antibody titres is discussed.

Screening and Characterization of Lactic Acid Bacteria Strains with Anti-inflammatory Activities through in vitro and Caenorhabditis elegans Model Testing

PubMed Central

Park, Mi Ri; Kim, Younghoon; Lee, Myung-Ki

2015-01-01

The present study was conducted to screen candidate probiotic strains for anti-inflammatory activity. Initially, a nitric oxide (NO) assay was used to test selected candidate probiotic strains for anti-inflammatory activity in cultures of the murine macrophage cell line, RAW 264.7. Then, the in vitro probiotic properties of the strains, including bile tolerance, acid resistance, and growth in skim milk media, were investigated. We also performed an in vitro hydrophobicity test and an intestinal adhesion assay using Caenorhabditis elegans as a surrogate in vivo model. From our screening, we obtained 4 probiotic candidate lactic acid bacteria (LAB) strains based on their anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell cultures and the results of the in vitro and in vivo probiotic property assessments. Molecular characterization using 16S rDNA sequencing analysis identified the 4 LAB strains as Lactobacillus plantarum. The selected L. plantarum strains (CAU1054, CAU1055, CAU1064, and CAU1106) were found to possess desirable in vitro and in vivo probiotic properties, and these strains are good candidates for further investigations in animal models and human clinical studies to elucidate the mechanisms underlying their anti-inflammatory activities. PMID:26761805

The Effectiveness of Parent Management Training-Oregon Model in Clinically Referred Children with Externalizing Behavior Problems in The Netherlands.

PubMed

Thijssen, Jill; Vink, Gerko; Muris, Peter; de Ruiter, Corine

2017-02-01

The present study examined the effectiveness of parent management training-Oregon model (PMTO) as a treatment for children with externalizing behavior problems in The Netherlands. Clinically referred children (N = 146) aged 4-11 years and their parents were partly randomized to either PMTO (n = 91) or Care As Usual (CAU; n = 55). Families were assessed at four time points: at pretreatment, and after 6, 12, and 18 months. Results showed that both PMTO and CAU were effective in reducing child externalizing behavior, parenting stress and parental psychopathology, with no significant differences between the two treatment conditions. PMTO and CAU interventions also produced some improvements in self-reported parenting skills, but not in observed parenting skills. According to the Reliable Change Index, 16.9 and 45.8 % of the children within the PMTO group showed full recovery or improvement in externalizing behavior, respectively, versus 9.7 and 42.8 % in the CAU condition. Finally, the effect size of PMTO on parent-reported externalizing behavior problems as found in the present study was comparable to that found in previous studies evaluating PMTO as an intervention for this type of child psychopathology.

The Structure of L-Tyrosine 2,3-Aminomutase frmo the C-1027 Enediyne Antitumor Antibiotic Biosynthetic Pathway

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

Christianson,C.; Montavon, T.; Van Lanen, S.

2007-01-01

The SgcC4 L-tyrosine 2,3-aminomutase (SgTAM) catalyzes the formation of (S)-{beta}-tyrosine in the biosynthetic pathway of the enediyne antitumor antibiotic C-1027. SgTAM is homologous to the histidine ammonia lyase family of enzymes whose activity is dependent on the methylideneimidazole-5-one (MIO) cofactor. Unlike the lyase enzymes, SgTAM catalyzes additional chemical transformations resulting in an overall stereospecific 1,2-amino shift in the substrate L-tyrosine to generate (S)-{beta}-tyrosine. Previously, we provided kinetic, spectroscopic, and mutagenesis data supporting the presence of MIO in the active site of SgTAM [Christenson, S. D.; Wu, W.; Spies, A.; Shen, B.; and Toney, M. D. (2003) Biochemistry 42, 12708-12718]. Heremore » we report the first X-ray crystal structure of an MIO-containing aminomutase, SgTAM, and confirm the structural homology of SgTAM to ammonia lyases. Comparison of the structure of SgTAM to the L-tyrosine ammonia lyase from Rhodobacter sphaeroides provides insight into the structural basis for aminomutase activity. The results show that SgTAM has a closed active site well suited to retain ammonia and minimize the formation of lyase elimination products. The amino acid determinants for substrate recognition and catalysis can be predicted from the structure, setting the framework for detailed mechanistic investigations.« less

8-bromo-7-methoxychrysin Reversed M2 Polarization of Tumor-associated Macrophages Induced by Liver Cancer Stem-like Cells.

PubMed

Sun, Shuwen; Cui, Yinghong; Ren, Kaiqun; Quan, Meifang; Song, Zhenwei; Zou, Hui; Li, Duo; Zheng, Yu; Cao, Jianguo

2017-01-01

Hepatocellular carcinoma (HCC) is related to chronic liver inflammation. M2 polarization of tumor-associated macrophages (TAMs) in the tumor microenvironment promotes liver cancer stem-like cell (LCSLC) self-renewal capability and carcinogenicity. Therefore, reversing M2 polarization of TAMs could be an effective approach to cure HCC. To evaluate whether 8-bromo-7-methoxychrysin (BrMC) has an effect on M2 polarization of TAMs. LCSLC and conditional medium were obtained by sphere forming assay. Identification of LCSLC were analyzed by sphere forming, wound-healing and invasion assay. TAM and effects of BrMC on it were validated by immunofluorescence staining, ELISA and griess assay. Expressions of cancer stem cell and macrophage marker were analyzed by western blotting. Our results showed that BrMC significantly suppressed the expression of the M2 macrophage marker CD163. Furthermore, BrMC influenced the secretion profile of cytokines of TAMs. Mechanistically, BrMC reversed M2 polarization of TAMs due to inhibition of NF-κB activation. BrMC may be a potentially novel flavonoid agent that can be applied for disrupting the interaction of LCSLCs and TAMs.

Computer-assisted update of a consumer health vocabulary through mining of social network data.

PubMed

Doing-Harris, Kristina M; Zeng-Treitler, Qing

2011-05-17

Consumer health vocabularies (CHVs) have been developed to aid consumer health informatics applications. This purpose is best served if the vocabulary evolves with consumers' language. Our objective was to create a computer assisted update (CAU) system that works with live corpora to identify new candidate terms for inclusion in the open access and collaborative (OAC) CHV. The CAU system consisted of three main parts: a Web crawler and an HTML parser, a candidate term filter that utilizes natural language processing tools including term recognition methods, and a human review interface. In evaluation, the CAU system was applied to the health-related social network website PatientsLikeMe.com. The system's utility was assessed by comparing the candidate term list it generated to a list of valid terms hand extracted from the text of the crawled webpages. The CAU system identified 88,994 unique terms 1- to 7-grams ("n-grams" are n consecutive words within a sentence) in 300 crawled PatientsLikeMe.com webpages. The manual review of the crawled webpages identified 651 valid terms not yet included in the OAC CHV or the Unified Medical Language System (UMLS) Metathesaurus, a collection of vocabularies amalgamated to form an ontology of medical terms, (ie, 1 valid term per 136.7 candidate n-grams). The term filter selected 774 candidate terms, of which 237 were valid terms, that is, 1 valid term among every 3 or 4 candidates reviewed. The CAU system is effective for generating a list of candidate terms for human review during CHV development.

Oral administration of Lactococcus chungangensis inhibits 2,4-dinitrochlorobenzene-induced atopic-like dermatitis in NC/Nga mice.

PubMed

Choi, Woo Jin; Konkit, Maytiya; Kim, Yena; Kim, Mi-Kyung; Kim, Wonyong

2016-09-01

Interest is increasing in the potentially beneficial role of probiotics in the prevention and treatment of atopic diseases. In this study, we investigated the protective effects of Lactococcus chungangensis CAU 28(T) against atopic dermatitis using murine macrophage RAW 264.7 cells, human keratinocyte HaCaT cells, human mast cell line HMC-1 cells, and a 2,4-dinitrochlorobenzene-induced atopic dermatitis model (NC/Nga mice). The results showed that L. chungangensis CAU 28(T) exhibited potent antiinflammatory activity by inhibiting the production of the proinflammatory mediators nitric oxide and prostaglandin E2 in lipopolysaccharide-stimulated RAW 264.7 cells. Treatment with L. chungangensis CAU 28(T) reduced the release of β-hexosaminidase and histamine in HMC-1 cells stimulated with mast cell activator compound 48/80. In addition, the back skin and ears of NC/Nga mice exhibited reduced histological manifestations of atopic skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration. Oral administration of L. chungangensis CAU 28(T) suppressed the production of IL-4, IL-5, IL-12, IFN-γ, tumor necrosis factor-α, and thymus- and activation-regulated chemokine (TARC) in skin lesions, indicating that it strongly drives the local immune system with efficacy comparable to that of tacrolimus, a topical immunomodulatory drug used for the treatment of atopic dermatitis. The findings indicate that L. chungangensis CAU 28(T) could be a novel probiotic candidate for controlling the symptoms of atopic dermatitis. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Amelioration of tamoxifen-induced liver injury in rats by grape seed extract, black seed extract and curcumin.

PubMed

El-Beshbishy, Hesham A; Mohamadin, Ahmed M; Nagy, Ayman A; Abdel-Naim, Ashraf B

2010-03-01

Liver injury was induced in female rats using tamoxifen (TAM). Grape seeds (Vitis vinifera) extract (GSE), black seed (Nigella sativa) extract (NSE), curcumin (CUR) or silymarin (SYL) were orally administered to TAM-intoxicated rats. Liver histopathology of TAM-intoxicated:rats showed pathological changes. TAM-intoxication elicited declines in liver antioxidant enzymes levels (glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase), reduced glutathione (GSH) and GSH/GSSG ratio plus the hepatic elevations in lipid peroxides, oxidized glutathione (GSSG), tumor necrosis factor-alpha (TNF-alpha) and serum liver enzymes; alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase and gamma glutamyl transferase levels. Oral intake of NSE, GSE, CUR or SYL to TAM-intoxicated rats, attenuated histopathological changes and corrected all parameters mentioned above. Improvements were prominent in case of NSE (similarly SYL) > CUR > GSE. Data indicated that NSE, GSE or CUR act as free radicals scavengers and protect TAM-induced liver injury in rats.

Targeting tumor-associated macrophages by anti-tumor Chinese materia medica.

PubMed

Pu, Wei-Ling; Sun, Li-Kang; Gao, Xiu-Mei; Rüegg, Curzio; Cuendet, Muriel; Hottiger, Micheal O; Zhou, Kun; Miao, Lin; Zhang, Yun-Sha; Gebauer, Margaret

2017-10-01

Tumor-associated macrophages (TAMs) play a key role in all stages of tumorigenesis and tumor progression. TAMs secrete different kinds of cytokines, chemokines, and enzymes to affect the progression, metastasis, and resistance to therapy depending on their state of reprogramming. Therapeutic benefit in targeting TAMs suggests that macrophages are attractive targets for cancer treatment. Chinese materia medica (CMM) is an important approach for treating cancer in China and in the Asian region. According to the theory of Chinese medicine (CM) and its practice, some prescriptions of CM regulate the body's internal environment possibly including the remodeling the tumor microenvironment (TME). Here we briefly summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis and immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM's dual-regulatory and multi-targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy.

Closure Report for Corrective Action Unit 562: Waste Systems, Nevada National Security Site, Nevada

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

NSTec Environmental Restoration

2012-08-15

This Closure Report (CR) presents information supporting closure of Corrective Action Unit (CAU) 562, Waste Systems, and provides documentation supporting the completed corrective actions and confirmation that closure objectives for CAU 562 were met. This CR complies with the requirements of the Federal Facility Agreement and Consent Order (FFACO) that was agreed to by the State of Nevada; the U.S. Department of Energy (DOE), Environmental Management; the U.S. Department of Defense; and DOE, Legacy Management (FFACO, 1996 as amended). CAU 562 consists of the following 13 Corrective Action Sites (CASs), located in Areas 2, 23, and 25 of the Nevadamore » National Security Site: · CAS 02-26-11, Lead Shot · CAS 02-44-02, Paint Spills and French Drain · CAS 02-59-01, Septic System · CAS 02-60-01, Concrete Drain · CAS 02-60-02, French Drain · CAS 02-60-03, Steam Cleaning Drain · CAS 02-60-04, French Drain · CAS 02-60-05, French Drain · CAS 02-60-06, French Drain · CAS 02-60-07, French Drain · CAS 23-60-01, Mud Trap Drain and Outfall · CAS 23-99-06, Grease Trap · CAS 25-60-04, Building 3123 Outfalls Closure activities began in October 2011 and were completed in April 2012. Activities were conducted according to the Corrective Action Plan for CAU 562 (U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office [NNSA/NSO], 2011). The corrective actions included No Further Action and Clean Closure. Closure activities generated sanitary waste and hazardous waste. Some wastes exceeded land disposal limits and required offsite treatment prior to disposal. Other wastes met land disposal restrictions and were disposed in appropriate onsite or offsite landfills. NNSA/NSO requests the following: · A Notice of Completion from the Nevada Division of Environmental Protection to NNSA/NSO for closure of CAU 562 · The transfer of CAU 562 from Appendix III to Appendix IV, Closed Corrective Action Units, of the FFACO« less

Intensive home treatment for patients in acute psychiatric crisis situations: a multicentre randomized controlled trial.

PubMed

Cornelis, Jurgen; Barakat, Ansam; Dekker, Jack; Schut, Tessy; Berk, Sandra; Nusselder, Hans; Ruhl, Nikander; Zoeteman, Jeroen; Van, Rien; Beekman, Aartjan; Blankers, Matthijs

2018-02-27

Hospitalization is a common method to intensify care for patients experiencing a psychiatric crisis. A short-term, specialised, out-patient crisis intervention by a Crisis Resolution Team (CRT) in the Netherlands, called Intensive Home Treatment (IHT), is a viable intervention which may help reduce hospital admission days. However, research on the (cost-)effectiveness of alternatives to hospitalisation such as IHT are scarce. In the study presented in this protocol, IHT will be compared to care-as-usual (CAU) in a randomized controlled trial (RCT). CAU comprises low-intensity outpatient care and hospitalisation if necessary. In this RCT it is hypothesized that IHT will reduce inpatient days by 33% compared to CAU while safety and clinical outcomes will be non-inferior. Secondary hypotheses are that treatment satisfaction of patients and their relatives are expected to be higher in the IHT condition compared to CAU. A 2-centre, 2-arm Zelen double consent RCT will be employed. Participants will be recruited in the Amsterdam area, the Netherlands. Clinical assessments will be carried out at baseline and at 6, 26 and 52 weeks post treatment allocation. The primary outcome measure is the number of admission days. Secondary outcomes include psychological well-being, safety and patients' and their relatives' treatment satisfaction. Alongside this RCT an economic evaluation will be carried out to assess the cost-effectiveness and cost-utility of IHT compared to CAU. RCTs on the effectiveness of crisis treatment in psychiatry are scarce and including patients in studies performed in acute psychiatric crisis care is a challenge due to the ethical and practical hurdles. The Zelen design may offer a feasible opportunity to carry out such an RCT. If our study finds that IHT is a safe and cost-effective alternative for CAU it may help support a further decrease of in-patient bed days and may foster the widespread implementation of IHT by mental health care organisations

CORRECTIVE ACTION DECISION DOCUMENT FOR CORRECTIVE ACTION UNIT 383: AREA 12 E-TUNNEL SITES, NEVADA TEST SITE, REV. NO. 0

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

Mark McLane

2005-03-01

This Corrective Action Decision Document (CADD) was prepared by the Defense Threat Reduction Agency (DTRA) and the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO). The recommendations and corrective actions described within this document apply to the future closure of Corrective Action Unit (CAU) 383, Area 12 E-Tunnel Sites, which is a joint DTRA and NNSA/NSO site. The CAU consists of three (3) Corrective Action Sites (CASs): CAS 12-06-06 (Muckpile); CAS 12-25-02 (Oil Spill); and CAS 12-28-02 (Radioactive Material). In addition to these CASs, E-Tunnel Ponds One, Two, and Three, and the Drainage Area above themore » ponds were included since closure of the Muckpile will impact these areas. This CADD is consistent with the requirements of the ''Federal Facility Agreement and Consent Order'' agreed to by the State of Nevada, the U.S. Department of Energy, and the U.S. Department of Defense. The DTRA point of contact is the Nevada Operations Office, Environmental Project Manager; currently Ms. Tiffany A. Lantow. The NNSA/NSO point of contact is the Environmental Restoration, Industrial Sites Project Manager; currently Ms. Janet Appenzeller-Wing. The purpose of this CADD is to identify and provide the rationale for the selection of a recommended corrective action alternative for CAU 383. This document presents the recommended corrective action for CAU 383 (E-Tunnel Sites); however, implementation may be affected by the corrective action (to be determined) for CAU 551 (Area 12 Muckpiles) due to the close proximity of B, C, D, and F-Tunnels. The scope of this CADD consists of the following tasks: (1) Develop corrective action objectives; (2) Identify corrective action alternative screening criteria; (3) Develop corrective action alternatives; (4) Perform detailed and comparative evaluations of the corrective action alternatives in relation to the corrective action objectives and screening criteria; and (5) Recommend and

Southeast Asia Report, No. 1300, Vietnam, Tap Chi Cong San, No. 3, March 1983

DTIC Science & Technology

1983-06-14

Countryside and the New Life (pp 49-53) ( True Giang) 62 -a - IIII - ASIA - 107] The Imperialists and Reactionaries Cannot Reverse the Situation (PP...and, at the same time, establish the system of centralism, which is to be understood as true democracy and which encompasses the capability—a...energies and the fighting determination of troops. If they did not become the true masters of the 51 battlefield and did not have a flesh and

77 FR 34935 - Certain Frozen Warmwater Shrimp From the Socialist Republic of Vietnam: Notice of Court Decision...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-12

...: Amanda Foods (Vietnam) Ltd.; Bac Lieu Fisheries Joint Stock Company; Cadovimex Seafood Import- Export and Processing Joint Stock Company; Cafatex Fishery Joint Stock Corporation; Cam Ranh Seafoods Processing... Export Frozen Seafood Processing Joint Stock Company (``Minh Hai Jostoco''); Minh Hai Joint-Stock...

Closure Report for Corrective Action Unit 415: Project 57 No. 1 Plutonium Dispersion (NTTR) Nevada Test and Training Range, Nevada, Revision 0 with ROTC-1

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

Cabble, Kevin J.; Boehlecke, Robert F.

This Closure Report (CR) presents information supporting the closure of Corrective Action Unit (CAU) 415: Project 57 No. 1 Plutonium Dispersion, which is located on Range 4808A of the Nevada Test and Training Range (NTTR). This CR complies with the requirements of the Federal Facility Agreement and Consent Order (FFACO) that was agreed to by the State of Nevada; U.S. Department of Energy (DOE), Environmental Management; U.S. Department of Defense; and DOE, Legacy Management. CAU 415 comprises one corrective action site (CAS): NAFR-23-02, Pu Contaminated Soil. The purpose of this CR is to provide justification and documentation supporting the recommendationmore » that no further corrective action is needed for CAU 415 based on the implementation of the corrective action of Closure in Place.« less

Tumor-associated macrophages: implications in cancer immunotherapy.

PubMed

Petty, Amy J; Yang, Yiping

2017-03-01

Tumor-associated macrophages (TAMs), representing most of the leukocyte population in solid tumors, demonstrate great phenotypic heterogeneity and diverse functional capabilities under the influence of the local tumor microenvironment. These anti-inflammatory and protumorigenic macrophages modulate the local microenvironment to facilitate tumor growth and metastasis. In this review, we examine the origin of TAMs and the complex regulatory networks within the tumor microenvironment that facilitate the polarization of TAMs toward a protumoral phenotype. More extensively, we evaluate the mechanisms by which TAMs mediate angiogenesis, metastasis, chemotherapeutic resistance and immune evasion. Lastly, we will highlight novel interventional strategies targeting TAMs in preclinical studies and in early clinical trials that have significant potential in improving efficacy of current chemotherapeutic and/or immunotherapeutic approaches.

Magnetic Resonance Imaging of Tumor Associated Macrophages: Clinical Translation.

PubMed

Aghighi, Maryam; Theruvath, Ashok Joseph; Pareek, Anuj; Pisani, Laura; Alford, Raphael; Muehe, Anne Monika; Sethi, Tarsheen K; Holdsworth, Samantha J; Hazard, Florette K; Gratzinger, Dita; Luna-Fineman, Sandra; Advani, Ranjana H; Spunt, Sheri L; Daldrup-Link, Heike E

2018-05-15

Tumor associated macrophages (TAM) in malignant tumors have been linked to tumor aggressiveness and represent a new target for cancer immunotherapy. As new TAM-targeted immunotherapies are entering clinical trials, it is important to detect and quantify TAM with non-invasive imaging techniques. The purpose of this study was to determine if ferumoxytol-enhanced MRI can detect TAM in lymphomas and bone sarcomas of pediatric patients and young adults. In a first-in-patient , IRB-approved prospective clinical trial, 25 pediatric and young adult patients with lymphoma or bone sarcoma underwent ferumoxytol-enhanced MRI. To confirm ferumoxytol enhancement, five pilot patients (2 lymphoma, 3 bone sarcoma) underwent pre- and post-contrast MRI. Subsequently, 20 patients (10 lymphoma, 10 bone sarcoma) underwent ferumoxytol-enhanced MRI 24-48 hours after intravenous injection, followed by tumor biopsy/resection and macrophage staining. To determine if ferumoxytol-MRI can differentiate tumors with different TAM content, we compared T2* relaxation times of lymphomas and bone sarcomas. Tumor T2* values of 20 patients were correlated with CD68+ and CD163+ TAM quantities on histopathology. Significant ferumoxytol tumor enhancement was noted on post-contrast scans compared to pre-contrast scans ( P = 0.036). Bone sarcomas and lymphomas demonstrated significantly different MRI enhancement and TAM density ( P < 0.05). Within each tumor group, T2* signal enhancement on MR images correlated significantly with the density of CD68+ and CD163+ TAM ( P < 0.05). Ferumoxytol-enhanced MRI is immediately clinically applicable and could be used to stratify patients with TAM-rich tumors to immune-targeted therapies and to monitor tumor response to these therapies. Copyright ©2018, American Association for Cancer Research.

In Vitro and In Vivo Effects of Jia-Wei-Xiao-Yao-San in Human Breast Cancer MCF-7 Cells Treated With Tamoxifen.

PubMed

Chen, Jiun-Liang; Chang, Chun-Ju; Wang, Jir-You; Wen, Che-Sheng; Tseng, Ling-Ming; Chang, Wen-Chi; Noomhorm, Nattanant; Liu, Hui-Ju; Chen, Wei-Shone; Chiu, Jen-Hwey; Shyr, Yi-Ming

2014-05-01

There is epidemiological evidence that Jia-Wei-Xiao-Yao-San (JWXYS) is the most common Chinese medicine decoction coprescribed with tamoxifen (Tam) when breast cancer is treated by hormonal therapy. However, whether there is interaction between JWXYS and Tam remains to be clarified. The aim of this study was to investigate the in vitro and in vivo effects of JWXYS on human breast cancer MCF-7 cells treated with Tam. In vitro cultured MCF-7 cells were cotreated with JWXYS and Tam. This was followed by MTT ([4,5-cimethylthiazol-2-yl]- 2,5-diphenyl tetrazolium bromide) assays and cell cycle analysis to assess cell proliferation; Western blot analysis was used to analyze the expression of various proteins involved in growth-related signal pathways. In addition, immunohistochemistry was used to detect autophagy among the cancer cells. In vivo analysis used female athymic nude mice implanted with MCF-7 cells; these mice were randomly assigned to 6 groups. All mice were killed humanely after 21 days of treatment; body weight, tumor volume, and tumor weight were then measured. JWXYS was not cytotoxic to MCF-7 cells, based on the fact that there were no statistically significant changes between the JWXYS + Tam groups and the Tam-alone group in cell numbers, cell cycle progression, and cell proliferation signals, the latter including the expression levels of AKT, ERK, P38, p27(Kip1), and light chain (LC3)-I, II. Furthermore, using the MCF-7 xenograft mouse model, there were no significant changes between the JWXYS (1.3-3.9 gm/kg) + Tam groups and the Tam-alone group in terms of tumor weight and the protein expression levels of AKT, ERK, P38, and p27 (Kip1). However, there was a significant decrease in LC3-II protein expression with the low-dose JWXYS + Tam group but not with the middle- or high-dose JWXYS + Tam groups compared with the Tam-alone group. Based on in vitro studies and in vivo functional studies, there is no obvious interaction between JWXYS and Tam. However

Combined Plasma Elevation of CRP, Intestinal-Type Fatty Acid-Binding Protein (I-FABP), and sCD14 Identify Older Patients at High Risk for Health Care-Associated Infections.

PubMed

Paillaud, Elena; Bastuji-Garin, Sylvie; Plonquet, Anne; Foucat, Emile; Fournier, Bénédicte; Boutin, Emmanuelle; Le Thuaut, Aurélie; Levy, Yves; Hue, Sophie

2018-01-16

We hypothesized that low-grade inflammation was driven by microbial translocation and associated with an increased risk of health care-associated infections (HAIs). We included 121 patients aged 75 years or over in this prospective cohort study. High-sensitivity C-reactive protein (hs-CRP), I-FABP, and sCD14-as markers for low-grade inflammation, intestinal epithelial barrier integrity, and monocyte activation, respectively-were measured at admission. HAIs occurred during hospitalization in 62 (51%) patients. Elevated hs-CRP (≥6.02 mg/L, ie, the median) was associated with a significantly higher HAI risk when I-FABP was in the highest quartile (odds ratio [OR], 4; 95% confidence interval [95% CI], 1.39-11.49; p = .010). In patients with hs-CRP elevation and highest-quartile I-FABP, sCD14 elevation (≥0.65 µg/mL, ie, the median) was associated with an 11-fold higher HAI risk (OR, 10.8; 95% CI, 2.28-51.1; p = .003). Multivariate analyses adjusted for invasive procedures and comorbidities did not change the associations linking the three markers to the HAI risk. Increased levels of hs-CRP, I-FABP, and sCD14 may reflect loss of intestinal epithelial barrier integrity with microbial translocation leading to monocyte activation and low-grade inflammation. In our cohort, these markers identified patients at high risk for HAIs. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Reducing health care-associated infections by implementing separated environmental cleaning management measures by using disposable wipes of four colors.

PubMed

Wong, Swee Siang; Huang, Cheng Hua; Yang, Chiu Chu; Hsieh, Yi Pei; Kuo, Chen Ni; Chen, Yi Ru; Chen, Li Ching

2018-01-01

Environmental cleaning is a fundamental principle of infection control in health care settings. We determined whether implementing separated environmental cleaning management measures in MICU reduced the density of HAI. We performed a 4-month prospective cohort intervention study between August and December 2013, at the MICU of Cathay General hospital. We arranged a training program for all the cleaning staff regarding separated environmental cleaning management measures by using disposable wipes of four colors to clean the patients' bedside areas, areas at a high risk of contamination, paperwork areas, and public areas. Fifteen high-touch surfaces were selected for cleanliness evaluation by using the adenosine triphosphate (ATP) bioluminescence test. Then data regarding HAI densities in the MICU were collected during the baseline, intervention, and late periods. A total of 120 ATP readings were obtained. The total number of clean high-touch surfaces increased from 13% to 53%, whereas that of unclean high-touch surface decreased from 47% to 20%. The densities of HAI were 14.32‰ and 14.90‰ during the baseline and intervention periods, respectively. The HAI density did not decrease after the intervention period, but it decreased to 9.07‰ during the late period. Implementing separated environmental cleaning management measures by using disposable wipes of four colors effectively improves cleanliness in MICU environments. However, no decrease in HAI density was observed within the study period. Considering that achieving high levels of hand-hygiene adherence is difficult, improving environmental cleaning is a crucial adjunctive measure for reducing the incidence of HAIs.

48 CFR 1201.301 - Policy.

Code of Federal Regulations, 2011 CFR

2011-10-01

... the Transportation Acquisition Manual (TAM). OA procedures necessary to implement or supplement the (FAR) 48 CFR chapter 1, (TAR) 48 CFR chapter 12, or TAM may be issued by the Head of the Contracting... procedures may be more restrictive or require higher approval levels than those permitted by the TAM unless...

Tumor-associated macrophages promote neuroblastoma via STAT3 phosphorylation and up-regulation of c-MYC

PubMed Central

Hadjidaniel, Michael D.; Muthugounder, Sakunthala; Hung, Long T.; Sheard, Michael A.; Shirinbak, Soheila; Chan, Randall Y.; Nakata, Rie; Borriello, Lucia; Malvar, Jemily; Kennedy, Rebekah J.; Iwakura, Hiroshi; Akamizu, Takashi; Sposto, Richard; Shimada, Hiroyuki; DeClerck, Yves A.; Asgharzadeh, Shahab

2017-01-01

Tumor-associated macrophages (TAMs) are strongly associated with poor survival in neuroblastomas that lack MYCN amplification. To study TAM action in neuroblastomas, we used a novel murine model of spontaneous neuroblastoma lacking MYCN amplification, and observed recruitment and polarization of TAMs, which in turn enhanced neuroblastoma proliferation and growth. In both murine and human neuroblastoma cells, we found that TAMs increased STAT3 activation in neuroblastoma cells and transcriptionally up-regulated the MYC oncogene. Analysis of human neuroblastoma tumor specimens revealed that MYC up-regulation correlates with markers of TAM infiltration. In an IL6ko neuroblastoma model, the absence of IL-6 protein had no effect on tumor development and prevented neither STAT3 activation nor MYC up-regulation. In contrast, inhibition of JAK-STAT activation using AZD1480 or the clinically admissible inhibitor ruxolitinib significantly reduced TAM-mediated growth of neuroblastomas implanted subcutaneously in NOD scid gamma mice. Our results point to a unique mechanism in which TAMs promote tumor cells that lack amplification of an oncogene common to the malignancy by up-regulating transcriptional expression of a distinct oncogene from the same gene family, and underscore the role of IL-6-independent activation of STAT3 in this mechanism. Amplification of MYCN or constitutive up-regulation of MYC protein is observed in approximately half of high-risk tumors; our findings indicate a novel role of TAMs as inducers of MYC expression in neuroblastomas lacking independent oncogene activation. PMID:29207662

Hypomethylation associated enhanced transcription of trefoil factor-3 mediates tamoxifen-stimulated oncogenicity of ER+ endometrial carcinoma cells.

PubMed

Pandey, Vijay; Zhang, Min; Chong, Qing-Yun; You, Mingliang; Raquib, Ainiah Rushdiana; Pandey, Amit K; Liu, Dong-Xu; Liu, Liang; Ma, Lan; Jha, Sudhakar; Wu, Zheng-Sheng; Zhu, Tao; Lobie, Peter E

2017-09-29

Tamoxifen (TAM) is widely used as an adjuvant therapy for women with breast cancer (BC). However, TAM possesses partial oestrogenic activity in the uterus and its use has been associated with an increased incidence of endometrial carcinoma (EC). The molecular mechanism for these observations is not well understood. Herein, we demonstrated that forced expression of Trefoil factor 3 ( TFF3) , in oestrogen receptor-positive (ER+) EC cells significantly increased cell cycle progression, cell survival, anchorage-independent growth, invasiveness and tumour growth in xenograft models. Clinically, elevated TFF3 protein expression was observed in EC compared with normal endometrial tissue, and its increased expression in EC was significantly associated with myometrial invasion. TAM exposure increased expression of TFF3 in ER+ EC cells and its elevated expression resulted in increased oncogenicity and invasiveness. TAM-stimulated expression of TFF3 in EC cells was associated with hypomethylation of the TFF3 promoter sequence and c-JUN/SP1-dependent transcriptional activation. In addition, small interfering ( si) RNA -mediated depletion or polyclonal antibody inhibition of TFF3 significantly abrogated oncogenicity and invasiveness in EC cells consequent to TAM induction or forced expression of TFF3. Hence, TAM-stimulated upregulation of TFF3 in EC cells was critical in promoting EC progression associated with TAM treatment. Importantly, inhibition of TFF3 function might be an attractive molecular modality to abrogate the stimulatory effects of TAM on endometrial tissue and to limit the progression of EC.

The Prognostic and Clinicopathological Significance of Tumor-Associated Macrophages in Patients with Gastric Cancer: A Meta-Analysis.

PubMed

Yin, Songcheng; Huang, Jinyu; Li, Zhan; Zhang, Junyan; Luo, Jiazi; Lu, Chunyang; Xu, Hao; Xu, Huimian

2017-01-01

Comprehensive studies have investigated the prognostic and clinicopathological value of tumor-associated macrophages (TAMs) in gastric cancer patients, yet results remain controversial. Therefore, we performed a meta-analysis to clarify this issue. PubMed, Embase, and the Cochrane Library databases were searched to identify eligible studies. We extracted hazard ratios (HRs) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) to estimate the effect sizes. In addition, subgroup analysis and sensitivity analysis were also conducted. A total of 19 studies involving 2242 patients were included. High generalised TAMs density was significantly associated with poor overall survival (OS) (HR 1.49, 95% CI 1.15-1.95). Subgroup analysis revealed that CD68+ TAMs had no significant effect on OS (HR 1.38, 95% CI 1.00-1.91). High M1 TAMs density was correlated with better OS (HR 0.45, 95% CI 0.32-0.65). By contrast, high density of M2 TAMs was correlated with a poor prognosis for OS (HR 1.48, 95% CI 1.25-1.75). Furthermore, high M2 TAMs density was correlated with larger tumor size, diffuse Lauren type, poor histologic differentiation, deeper tumor invasion, lymph node metastasis, and advanced TNM stage. Overall, this meta-analysis reveal that although CD68+ TAMs infiltration has the neutral prognostic effects on OS, the M1/M2 polarization of TAMs are predicative factor of prognosis in gastric cancer patients.

Tamoxifen resistance and metastasis of human breast cancer cells were mediated by the membrane-associated estrogen receptor ER-α36 signaling in vitro.

PubMed

Gu, Wenwen; Dong, Nian; Wang, Peng; Shi, Changgen; Yang, Jun; Wang, Jian

2017-04-01

The drug resistance and tumor metastasis have been the main obstacles for the longer-term therapeutic effects of tamoxifen (TAM) on estrogen receptor-positive (ER + ) breast cancer, but the mechanisms underlying the TAM resistance are still unclear. Here, we demonstrated that the membrane-associated estrogen receptor ER-α36 signaling, but not the G protein-coupled estrogen receptor 1 (GPER1) signaling, might be involved in the TAM resistance and metastasis of breast cancer cells. In this study, a model of ER + breast cancer cell MCF-7 that involves the up-regulated expression of ER-α36 and unchanged expression of ER-α66 and GPER1 was established via the removal of insulin from the cell culture medium. The mechanism of TAM resistance in the ER + breast cancer cell line MCF-7 was investigated, and the results showed that the stimulating effect of insulin on susceptibility of MCF-7 to TAM was mediated by ER-α36 and that the expression level of ER-α36 in TAM-resistant MCF-7 cells was also significantly increased. Both TAM and estradiol (E2) could promote the migration of triple negative (ER-α66 - /PR - /HER2 - ) and ER-α36 + /GPER1 + breast cancer cells MDA-MB-231. The migration of MDA-MB-231 cells was inhibited by the down-regulated intracellular expression of ER-α36 by transient transfection of specific small interfering RNA, whereas no effect of GPER1 down-regulation was observed. Meanwhile, the effect of TAM on the migration of ER-α36-down-regulated MDA-MB-231 cells was also reduced. Furthermore, it was found that TAM enhanced the distribution of integrin β1 on the cell surface but did not affect the expression of integrin β1 in MDA-MB-231 cells. Collectively, these data suggested that ER-α36 signaling might play critical roles in acquired and de novo TAM resistance and metastasis of breast cancer, and ER-α36 might present a potential biomarker of TAM resistance in the clinical diagnosis and treatment of ER + breast cancer.

Peroxidase-mediated dealkylation of tamoxifen, detected by electrospray ionization-mass spectrometry, and activation to form DNA adducts.

PubMed

Gaikwad, Nilesh W; Bodell, William J

2012-01-15

Tamoxifen (TAM) is extensively used for the treatment and prevention of breast cancer. Associated with TAM treatment is a two- to eightfold increase in risk of endometrial cancer. To understand the mechanisms associated with this increased risk several pathways for TAM metabolism and DNA adduct formation have been studied. The purpose of this study was to investigate the role of peroxidase enzymes in the metabolism of TAM and its activation to form DNA adducts. Using advanced tandem mass spectrometry we have investigated the peroxidase-mediated metabolism of TAM. Incubation of TAM with horseradish peroxidase (HRP) and H(2)O(2) produced multiple metabolites. Electrospray ionization-MS/MS analysis of the metabolites demonstrated a peak at 301.3m/z with daughter ions at 183.0, 166.9, 128.9, and 120.9m/z, which identified the metabolite as metabolite E (ME). The levels of ME were significantly inhibited by the addition of ascorbic acid to the incubation mixture. Co-incubation of either TAM or ME and DNA with HRP and H(2)O(2) produced three DNA adducts with a RAL of 1.97±0.01×10(-7) and 8.45±2.7×10(-7). Oxidation of ME with MnO(2) produced metabolite E quinone methide (MEQM). Furthermore, incubation of either TAM or ME with HRP and H(2)O(2) resulted in formation of MEQM. Reaction of calf thymus DNA with MEQM produced three DNA adducts with a RAL of 9.8±1.0×10(-7). Rechromatography analyses indicated that DNA adducts 1, 2, and 3 formed in the HRP activation of either TAM or ME were the same as those formed by the chemical reaction of DNA with MEQM. The results of these studies demonstrate that peroxidase enzymes can both metabolize TAM to form the primary metabolite ME and activate ME to a quinone methide intermediate, which reacts with DNA to form adducts. It is possible that peroxidase enzymes or peroxidase-like activity in endometrium could contribute to the formation of DNA damage and genotoxic effects in endometrium after TAM administration. Published by

Harnessing the cross-talk between tumor cells and tumor-associated macrophages with a nano-drug for modulation of glioblastoma immune microenvironment.

PubMed

Li, Tong-Fei; Li, Ke; Wang, Chao; Liu, Xin; Wen, Yu; Xu, Yong-Hong; Zhang, Quan; Zhao, Qiu-Ya; Shao, Ming; Li, Yan-Ze; Han, Min; Komatsu, Naoki; Zhao, Li; Chen, Xiao

2017-12-28

Glioblastoma (GBM) is the most frequent and malignant brain tumor with a high mortality rate. The presence of a large population of macrophages (Mφ) in the tumor microenvironment is a prominent feature of GBM and these so-called tumor-associated Mφ (TAM) closely interact with the GBM cells to promote the survival, progression and therapy resistance of the GBM. Various therapeutic strategies have been devised either targeting the GBM cells or the TAM but few have addressed the cross-talks between the two cell populations. The present study was carried out to explore the possibility of exploiting the cross-talks between the GBM cells (GC) and TAM for modulation of the GBM microenvironment through using Nano-DOX, a drug composite based on nanodiamonds bearing doxorubicin. In the in vitro work on human cell models, Nano-DOX-loaded TAM were first shown to be viable and able to infiltrate three-dimensional GC spheroids and release cargo drug therein. GC were then demonstrated to encourage Nano-DOX-loaded TAM to unload Nano-DOX back into GC which consequently emitted damage-associated molecular patterns (DAMPs) that are powerful immunostimulatory agents as well as indicators of cell damage. Nano-DOX was next proven to be a more potent inducer of GC DAMPs emission than doxorubicin. As a result, Nano-DOX-damaged GC exhibited an enhanced ability to attract both TAM and Nano-DOX-loaded TAM. Most remarkably, Nano-DOX-damaged GC reprogrammed the TAM from a pro-GBM phenotype to an anti-GBM phenotype that suppressed GC growth. Finally, the in vivo relevance of the in vitro findings was tested in animal study. Mice bearing orthotopic human GBM xenografts were intravenously injected with Nano-DOX-loaded mouse TAM which were found releasing drug in the GBM xenografts 24h after injection. GC damage was evidenced by the induction of DAMPs emission within the xenografts and a shift of TAM phenotype was detected as well. Taken together, our results demonstrate a novel way with

Cancer-promoting tumor-associated macrophages: new vistas and open questions.

PubMed

Mantovani, Alberto; Germano, Giovanni; Marchesi, Federica; Locatelli, Marco; Biswas, Subhra K

2011-09-01

Tumor-associated macrophages (TAMs) are key components of the tumor macroenvironment. Cancer- and host cell-derived signals generally drive the functions of TAMs towards an M2-like polarized, tumor-propelling mode; however, when appropriately re-educated. TAMs also have the potential to elicit tumor destructive reactions. Here, we discuss recent advances regarding the immunobiology of TAMs and highlight open questions including the mechanisms of their accumulation (recruitment versus proliferation), their diversity and how to best therapeutically target these cells. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification of barriers and research opportunities to improve the effective and efficient application of adjunct UVC surface disinfection in healthcare

NASA Astrophysics Data System (ADS)

Martinello, Richard A.; Miller, Shelly L.; Fabian, M. Patricia; Peccia, Jordan

2018-02-01

Healthcare associated infections (HAI) affect approximately 1 of every 25 hospitalized patients, lead to substantial morbidity and mortality, degrade patient experience and are costly. Risks for HAI are multifactorial and it is known that microbial contamination of the healthcare environment increases risk for HAI. Portable ultraviolet-C (UVC) surface disinfection as an adjunct to standard hospital disinfection has been shown to decrease both surface microbial contamination and HAI. However, there remain significant gaps in the understanding of the efficient and effective application of UVC in healthcare. Specific barriers identified are: 1) the variability in size, shape, and surface materials of hospital rooms as well as the presence of medical devices and furniture, which impacts the amount of UVC energy delivered to surfaces and its disinfection efficiency; 2) the significant resources needed to acquire and efficiently use UVC equipment and achieve the desired patient benefits- a particular challenge for complex healthcare facilities with limited operating margins; and 3) the lack of implementation guidance and industry standard methods for measuring the UVC output and antimicrobial effects from the multiple commercial UVC options available. An improved understanding of the efficient and effective use of UVC surface disinfection in healthcare and the implementation of standard device industry metrics may lead to increased use and decrease the burden of HAI.

Prevention of common healthcare-associated infections in humanitarian hospitals.

PubMed

Murphy, Richard A; Chua, Arlene C

2016-08-01

Humanitarian medical organizations focus on vulnerable patients with increased risk for healthcare-associated infections (HAIs) and are obligated to minimize them in inpatient departments (IPDs). However, in doing so humanitarian groups face considerable obstacles. This report will focus on approaches to reducing common HAIs that the authors have found to be helpful in humanitarian settings. HAIs are common in humanitarian contexts but there are few interventions or guidelines adapted for use in poor and conflict-affected settings to improve prevention and guide surveillance. Based on existing recommendations and studies, it appears prudent that all humanitarian IPDs introduce a basic infection prevention infrastructure, assure high adherence to hand hygiene with wide accessibility to alcohol-based hand rub, and develop pragmatic surveillance based on clinically evident nosocomial infection. Although microbiology remains out of reach for most humanitarian hospitals, rapid tests offer the possibility of improving the diagnosis of HAIs in humanitarian hospitals in the decade ahead. There is a dearth of new studies that can direct efforts to prevent HAIs in IPDs in poor and conflict-affected areas and there is a need for practical, field-adapted guidelines from professional societies, and international bodies to guide infection prevention efforts in humanitarian environments.

National infection prevention and control programmes: Endorsing quality of care.

PubMed

Stempliuk, Valeska; Ramon-Pardo, Pilar; Holder, Reynaldo

2014-01-01

Core components Health care-associated infections (HAIs) are a major cause of morbidity and mortality. In addition to pain and suffering, HAIs increase the cost of health care and generates indirect costs from loss of productivity for patients and society as a whole. Since 2005, the Pan American Health Organization has provided support to countries for the assessment of their capacities in infection prevention and control (IPC). More than 130 hospitals in 18 countries were found to have poor IPC programmes. However, in the midst of many competing health priorities, IPC programmes are not high on the agenda of ministries of health, and the sustainability of national programmes is not viewed as a key point in making health care systems more consistent and trustworthy. Comprehensive IPC programmes will enable countries to reduce the mobility, mortality and cost of HAIs and improve quality of care. This paper addresses the relevance of national infection prevention and control (NIPC) programmes in promoting, supporting and reinforcing IPC interventions at the level of hospitals. A strong commitment from national health authorities in support of national IPC programmes is crucial to obtaining a steady decrease of HAIs, lowering health costs due to HAIs and ensuring safer care.

Healthcare-associated infections and their prevention after extensive flooding.

PubMed

Apisarnthanarak, Anucha; Warren, David K; Mayhall, Clovus Glen

2013-08-01

This review will focus on the epidemiology of healthcare-associated infections (HAIs) after extensive blackwater flooding as well as preventive measures. There is evidence suggesting an increased incidence of HAIs and pseudo-outbreaks due to molds after extensive flooding in healthcare facilities. However, there is no strong evidence of an increased incidence of typical nosocomial infections (i.e., ventilator-associated pneumonia, healthcare-associated pneumonia, central line-associated bloodstream infection and catheter-associated urinary tract infections). The prevalence of multidrug-resistant organisms may decrease after extensive flooding, due to repeated and thorough environmental cleaning prior to re-opening hospitals. Contamination of hospital water sources by enteric Gram-negative bacteria (e.g., Aeromonas species), Legionella species and nontuberculous Mycobacterium species in flood-affected hospitals has been reported. Surveillance is an important initial step to detect potential outbreaks/pseudo-outbreaks of HAIs. Hospital preparedness policies before extensive flooding, particularly with environmental cleaning and mold remediation, are key to reducing the risk of flood-related HAIs. These policies are still lacking in most hospitals in countries that have experienced or are at risk for extensive flooding, which argues for nationwide policies to strengthen preparedness planning. Additional studies are needed to evaluate the epidemiology of flood-related HAIs and the optimal surveillance and control methods following extensive flooding.

Leadership rounds to reduce health care-associated infections.

PubMed

Knobloch, Mary Jo; Chewning, Betty; Musuuza, Jackson; Rees, Susan; Green, Christopher; Patterson, Erin; Safdar, Nasia

2018-03-01

Evidence-based guidelines exist to reduce health care-associated infections (HAIs). Leadership rounds are one tool leaders can use to ensure compliance with guidelines, but have not been studied specifically for the reduction of HAIs. This study examines HAI leadership rounds at one facility. We explored unit-based HAI leadership rounds led by 2 hospital leaders at a large academic hospital. Leadership rounds were observed on 19 units, recorded, and coded to identify themes. Themes were linked to the Consolidated Framework for Implementation Research and used to guide interviews with frontline staff members. Staff members disclosed unit-specific problems and readily engaged in problem-solving with top hospital leaders. These themes appeared over 350 times within 22 rounds. Findings revealed that leaders used words that demonstrated fallibility and modeled curiosity, 2 factors associated with learning climate and psychologic safety. These 2 themes appeared 115 and 142 times, respectively. The flexible nature of the rounds appeared to be conducive for reflection and evaluation, which was coded 161 times. Each interaction between leaders and frontline staff can foster psychologic safety, which can lead to open problem-solving to reduce barriers to implementation. Discovering specific communication and structural factors that contribute to psychologic safety may be powerful in reducing HAIs. Published by Elsevier Inc.

Could Histoplasma capsulatum Be Related to Healthcare-Associated Infections?

PubMed Central

Carreto-Binaghi, Laura Elena; Damasceno, Lisandra Serra; Mendes-Giannini, Maria José Soares; Zancopé-Oliveira, Rosely Maria; Taylor, Maria Lucia

2015-01-01

Healthcare-associated infections (HAI) are described in diverse settings. The main etiologic agents of HAI are bacteria (85%) and fungi (13%). Some factors increase the risk for HAI, particularly the use of medical devices; patients with severe cuts, wounds, and burns; stays in the intensive care unit, surgery, and hospital reconstruction works. Several fungal HAI are caused by Candida spp., usually from an endogenous source; however, cross-transmission via the hands of healthcare workers or contaminated devices can occur. Although other medically important fungi, such as Blastomyces dermatitidis, Paracoccidioides brasiliensis, and Histoplasma capsulatum, have never been considered nosocomial pathogens, there are some factors that point out the pros and cons for this possibility. Among these fungi, H. capsulatum infection has been linked to different medical devices and surgery implants. The filamentous form of H. capsulatum may be present in hospital settings, as this fungus adapts to different types of climates and has great dispersion ability. Although conventional pathogen identification techniques have never identified H. capsulatum in the hospital environment, molecular biology procedures could be useful in this setting. More research on H. capsulatum as a HAI etiologic agent is needed, since it causes a severe and often fatal disease in immunocompromised patients. PMID:26106622

Dectin-1 Activation by a Natural Product β-Glucan Converts Immunosuppressive Macrophages into an M1-like Phenotype

PubMed Central

Liu, Min; Luo, Fengling; Ding, Chuanlin; Albeituni, Sabrin; Hu, Xiaoling; Ma, Yunfeng; Cai, Yihua; McNally, Lacey; Sanders, Mary Ann; Jain, Dharamvir; Kloecker, Goetz; Bousamra, Michael; Zhang, Huang-ge; Higashi, Richard M.; Lane, Andrew N.; Fan, Teresa W-M.; Yan, Jun

2015-01-01

Tumor-associated macrophages (TAM) with an M2-like phenotype have been linked to tumor-elicited inflammation, immunosuppression, and resistance to chemotherapies in cancer, thus representing an attractive target for an effective cancer immunotherapy. Here, we demonstrate that particulate yeast-derived β-glucan, a natural polysaccharide compound, converts polarized M2 macrophages or immunosuppressive TAM into an M1-like phenotype with potent immuno-stimulating activity. This process is associated with macrophage metabolic reprograming with enhanced glycolysis, krebs cycle and glutamine utilization. In addition, particulate β-glucan converts immunosuppressive TAM via the C-type lectin receptor dectin-1-induced Syk-Card9-Erk pathway. Further in vivo studies show that oral particulate β-glucan treatment significantly delays tumor growth, which is associated with in vivo TAM phenotype conversion and enhanced effector T cell activation. Mice injected with particulate β-glucan-treated TAM mixed with tumor cells have significantly reduced tumor burden with less blood vascular vessels compared to those with TAM plus tumor cell injection. In addition, macrophage depletion significantly reduced the therapeutic efficacy of particulate β-glucan in tumor-bearing mice. These findings have established a new paradigm for macrophage polarization and immunosuppressive TAM conversion and shed the light on the action mode of β-glucan treatment in cancer. PMID:26453753

CDDO-Me Redirects Activation of Breast Tumor Associated Macrophages.

PubMed

Ball, Michael S; Shipman, Emilie P; Kim, Hyunjung; Liby, Karen T; Pioli, Patricia A

2016-01-01

Tumor-associated macrophages can account for up to 50% of the tumor mass in breast cancer patients and high TAM density is associated with poor clinical prognosis. Because TAMs enhance tumor growth, development, and metastatic potential, redirection of TAM activation may have significant therapeutic benefit. Our studies in primary human macrophages and murine breast TAMs suggest that the synthetic oleanane triterpenoid CDDO-methyl ester (CDDO-Me) reprograms the activation profile of TAMs from tumor-promoting to tumor-inhibiting. We show that CDDO-Me treatment inhibits expression of IL-10 and VEGF in stimulated human M2 macrophages and TAMs but increases expression of TNF-α and IL-6. Surface expression of CD206 and CD163, which are characteristic of M2 activation, is significantly attenuated by CDDO-Me. In contrast, CDDO-Me up-regulates surface expression of HLA-DR and CD80, which are markers of M1 activation, and importantly potentiates macrophage activation of autologous T cells but inhibits endothelial cell vascularization. These results show for the first time that CDDO-Me redirects activation of M2 macrophages and TAMs from immune-suppressive to immune-stimulatory, and implicate a role for CDDO-Me as an immunotherapeutic in the treatment of breast and potentially other types of cancer.

CDDO-Me Redirects Activation of Breast Tumor Associated Macrophages

PubMed Central

Ball, Michael S.; Shipman, Emilie P.; Kim, Hyunjung; Liby, Karen T.; Pioli, Patricia A.

2016-01-01

Tumor-associated macrophages can account for up to 50% of the tumor mass in breast cancer patients and high TAM density is associated with poor clinical prognosis. Because TAMs enhance tumor growth, development, and metastatic potential, redirection of TAM activation may have significant therapeutic benefit. Our studies in primary human macrophages and murine breast TAMs suggest that the synthetic oleanane triterpenoid CDDO-methyl ester (CDDO-Me) reprograms the activation profile of TAMs from tumor-promoting to tumor-inhibiting. We show that CDDO-Me treatment inhibits expression of IL-10 and VEGF in stimulated human M2 macrophages and TAMs but increases expression of TNF-α and IL-6. Surface expression of CD206 and CD163, which are characteristic of M2 activation, is significantly attenuated by CDDO-Me. In contrast, CDDO-Me up-regulates surface expression of HLA-DR and CD80, which are markers of M1 activation, and importantly potentiates macrophage activation of autologous T cells but inhibits endothelial cell vascularization. These results show for the first time that CDDO-Me redirects activation of M2 macrophages and TAMs from immune-suppressive to immune-stimulatory, and implicate a role for CDDO-Me as an immunotherapeutic in the treatment of breast and potentially other types of cancer. PMID:26918785

Nanomedicine Strategies to Target Tumor-Associated Macrophages

PubMed Central

Binnemars-Postma, Karin; Storm, Gert; Prakash, Jai

2017-01-01

In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different subtypes, each of which has a different function. While classically activated M1 macrophages are involved in inflammatory and malignant processes, activated M2 macrophages are more involved in the wound-healing processes occurring in tumors. Tumor-associated macrophages (TAM) display M2 macrophage characteristics and support tumor growth and metastasis by matrix remodeling, neo-angiogenesis, and suppressing local immunity. Due to their detrimental role in tumor growth and metastasis, selective targeting of TAM for the treatment of cancer may prove to be beneficial in the treatment of cancer. Due to the plastic nature of macrophages, their activities may be altered to inhibit tumor growth. In this review, we will discuss the therapeutic options for the modulation and targeting of TAM. Different therapeutic strategies to deplete, inhibit recruitment of, or re-educate TAM will be discussed. Current strategies for the targeting of TAM using nanomedicine are reviewed. Passive targeting using different nanoparticle systems is described. Since TAM display a number of upregulated surface proteins compared to non-TAM, specific targeting using targeting ligands coupled to nanoparticles is discussed in detail. PMID:28471401

48 CFR 1201.104 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Transportation Acquisition Manual (TAM): (1) Statute; (2) (FAR) 48 CFR chapter 1 or other applicable regulation; (3) (TAR) 48 CFR chapter 12; (4) DOT Orders; and (5) TAM. (c) The Maritime Administration may depart... CFR chapter 1, (TAR) 48 CFR chapter 12 and TAM do not apply to the Federal Aviation Administration as...

Validating the Technology Acceptance Model in the Context of the Laboratory Information System-Electronic Health Record Interface System

ERIC Educational Resources Information Center

Aquino, Cesar A.

2014-01-01

This study represents a research validating the efficacy of Davis' Technology Acceptance Model (TAM) by pairing it with the Organizational Change Readiness Theory (OCRT) to develop another extension to the TAM, using the medical Laboratory Information Systems (LIS)--Electronic Health Records (EHR) interface as the medium. The TAM posits that it is…

48 CFR 1201.104 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Transportation Acquisition Manual (TAM): (1) Statute; (2) (FAR) 48 CFR chapter 1 or other applicable regulation; (3) (TAR) 48 CFR chapter 12; (4) DOT Orders; and (5) TAM. (c) The Maritime Administration may depart... CFR chapter 1, (TAR) 48 CFR chapter 12 and TAM do not apply to the Federal Aviation Administration as...

Characterization of dynamics in complex lyophilized formulations: I. Comparison of relaxation times measured by isothermal calorimetry with data estimated from the width of the glass transition temperature region.

PubMed

Chieng, Norman; Mizuno, Masayasu; Pikal, Michael

2013-10-01

The purposes of this study are to characterize the relaxation dynamics in complex freeze dried formulations and to investigate the quantitative relationship between the structural relaxation time as measured by thermal activity monitor (TAM) and that estimated from the width of the glass transition temperature (ΔT(g)). The latter method has advantages over TAM because it is simple and quick. As part of this objective, we evaluate the accuracy in estimating relaxation time data at higher temperatures (50 °C and 60 °C) from TAM data at lower temperature (40 °C) and glass transition region width (ΔT(g)) data obtained by differential scanning calorimetry. Formulations studied here were hydroxyethyl starch (HES)-disaccharide, HES-polyol, and HES-disaccharide-polyol at various ratios. We also re-examine, using TAM derived relaxation times, the correlation between protein stability (human growth hormone, hGH) and relaxation times explored in a previous report, which employed relaxation time data obtained from ΔT(g). Results show that most of the freeze dried formulations exist in single amorphous phase, and structural relaxation times were successfully measured for these systems. We find a reasonably good correlation between TAM measured relaxation times and corresponding data obtained from estimates based on ΔT(g), but the agreement is only qualitative. The comparison plot showed that TAM data are directly proportional to the 1/3 power of ΔT(g) data, after correcting for an offset. Nevertheless, the correlation between hGH stability and relaxation time remained qualitatively the same as found with using ΔT(g) derived relaxation data, and it was found that the modest extrapolation of TAM data to higher temperatures using ΔT(g) method and TAM data at 40 °C resulted in quantitative agreement with TAM measurements made at 50 °C and 60 °C, provided the TAM experiment temperature, is well below the Tg of the sample. Copyright © 2013 Elsevier B.V. All rights

Characterization of Dynamics in Complex Lyophilized Formulations: I. Comparison of Relaxation Times Measured by Isothermal Calorimetry with Data Estimated from the Width of the Glass Transition Temperature Region

PubMed Central

Chieng, Norman; Mizuno, Masayasu; Pikal, Michael

2013-01-01

The purposes of this study are to characterize the relaxation dynamics in complex freeze dried formulations and to investigate the quantitative relationship between the structural relaxation time as measured by thermal activity monitor (TAM) and that estimated from the width of the glass transition temperature (ΔTg). The latter method has advantages over TAM because it is simple and quick. As part of this objective, we evaluate the accuracy in estimating relaxation time data at higher temperatures (50°C and 60°C) from TAM data at lower temperature (40°C) and glass transition region width (ΔTg) data obtained by differential scanning calorimetry. Formulations studied here were hydroxyethyl starch (HES)-disaccharide, HES-polyol and HES-disaccharide-polyol at various ratios. We also re-examine, using TAM derived relaxation times, the correlation between protein stability (human growth hormone, hGH) and relaxation times explored in a previous report, which employed relaxation time data obtained from ΔTg. Results show that most of the freeze dried formulations exist in single amorphous phase, and structural relaxation times were successfully measured for these systems. We find a reasonably good correlation between TAM measured relaxation times and corresponding data obtained from estimates based on ΔTg, but the agreement is only qualitative. The comparison plot showed that TAM data is directly proportional to the 1/3 power of ΔTg data, after correcting for an offset. Nevertheless, the correlation between hGH stability and relaxation time remained qualitatively the same as found with using ΔTg derived relaxation data, and it was found that the modest extrapolation of TAM data to higher temperatures using ΔTg method and TAM data at 40°C resulted in quantitative agreement with TAM measurements made at 50 °C and 60 °C, provided the TAM experiment temperature is well below the Tg of the sample. PMID:23608636

Tamoxifen induces the expression of maspin through estrogen receptor-alpha.

PubMed

Liu, Zesheng; Shi, Heidi Y; Nawaz, Zafar; Zhang, Ming

2004-06-08

Maspin (mammary serine protease inhibitor) is a tumor suppressor gene that plays an important role in inhibiting tumor growth, invasion and metastasis. Maspin expression is down regulated at transcription level in primary and metastatic breast tumor cells. Previous studies on hormonal regulation of maspin prompt us to test whether an estrogen antagonist tamoxifen (TAM) can exert its anti-tumor function by up regulating maspin gene expression. For this purpose, we first tested whether maspin promoter could be activated in normal and several breast tumor cells. We then carried out a series of promoter analysis in which estrogen receptors and TAM were reconstituted in an in vitro cell culture system. Here we report our new finding that tumor suppresser gene maspin is one of the TAM target genes. TAM induces a maspin/luciferase reporter in cell culture and this induction requires the presence of (estrogen receptor alpha) ERalpha but not estrogen receptor-beta (ERbeta). Maspin promoter deletion and mutation analysis showed that the cis element(s) within a region between -90and+87 bp but not the HRE site (-272 bp) was involved in TAM induction of maspin expression. TAM bound ERalpha may directly control maspin gene expression through the interaction with cofactor (s). Analysis using several ERalpha mutants showed that the N-terminal A/B motif (AF-1) was critical for maspin basal level transcription activation. An ERalpha mutant with point mutations at DNA binding domain abolished estrogen induction of an ERE-luciferase reporter but was still active in activating maspin promoter by TAM. LBD-AF2 domain was required for ERalpha-dependent TAM induction. Deletion of LBD-AF2 or a point mutation in the ERalpha LBD-AF2 region (LBDmtL539A) completely abolished the activation of maspin promoter, suggesting that TAM induction of maspin involves the recruitment of cofactor(s) by ERalpha to the maspin promoter region. This finding indicates that one of the pathways for cancer

Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection.

PubMed

Zhang, Heng; Wang, Xuefei; Shen, Zhenbin; Xu, Jiejie; Qin, Jing; Sun, Yihong

2015-10-01

Tumor-associated macrophages (TAMs), the most predominant tumor-infiltrating immune cells, are emerging prognostic factors and therapeutic targets for personalized therapy against malignant neoplasms. We aimed to evaluate the prognostic significance of diametrically polarized TAMs in gastric cancer and generate a predictive nomogram to refine a risk stratification system. We evaluated polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68, CD11c, and CD206 in 180 consecutive gastric cancer patients from Zhongshan Hospital, Shanghai, China. Prognostic values were assessed in these patients. We created a predictive nomogram by integrating polarized TAMs with the TNM staging system for overall survival of gastric cancer patients. CD68(+) TAMs display polarized programs comprising CD11c(+) proinflammatory macrophages (M1) and CD206(+) immunosuppressive macrophages (M2) that configure versatile infiltration files in gastric cancer. CD11c(+) TAMs negatively correlated with lymph node metastasis (p = 0.012), whereas CD206(+) TAMs correlated with the Lauren classification (p = 0.031). No prognostic difference was observed for overall survival for CD68 density (high vs low, p = 0.1031), whereas high versus low CD11c density (p < 0.0001) and low vs high CD206 density (p = 0.0105) indicate better overall survival. Multivariate Cox regression analysis identified CD11c and CD206 as independent prognostic factors (p < 0.001 and p = 0.030, respectively), which could be integrated with the TNM staging system to generate a predictive nomogram for patient outcomes. Infiltration of polarized TAMs, a novel identified independent prognostic factor, could be combined with the TNM stage to refine a risk stratification system and better stratify patients with different prognosis. Tipping TAMs to an antitumoral phenotype might be a promising therapeutic target for postoperative treatment.

Involvement of multiple cellular pathways in regulating resistance to tamoxifen in BIK-suppressed MCF-7 cells.

PubMed

Viedma-Rodríguez, Rubí; Ruiz Esparza-Garrido, Ruth; Baiza-Gutman, Luis Arturo; Velázquez-Flores, Miguel Ángel; García-Carrancá, Alejandro; Salamanca-Gómez, Fabio; Arenas-Aranda, Diego

2015-09-01

Majority of women with estrogen receptor (ER)-positive breast cancers initially respond to hormone therapies such as tamoxifen (TAM; antagonist of estrogen). However, many tumors eventually become resistant to TAM. Therefore, understanding the various cellular components involved in causing resistance to TAM is of paramount importance in designing novel entities for efficacious hormone therapy. Previously, we found that suppression of BIK gene expression induced TAM resistance in MCF-7 breast cancer cells. In order to understand the response of these cells to TAM and its association with resistance, a microarray analysis of gene expression was performed in the BIK-suppressed MCF-7 cells and compared it to the TAM-only-treated cells (controls). Several genes participating in various cellular pathways were identified. Molecules identified in the drug resistance pathway were 14-3-3z or YWHAZ, WEE1, PRKACA, NADK, and HSP90AA 1. Further, genes involved in cell cycle control, apoptosis, and cell proliferation were also found differentially expressed in these cells. Transcriptional and translational analysis of key molecules such as STAT2, AKT 3, and 14-3-3z revealed similar changes at the messenger RNA (mRNA) as well as at the protein level. Importantly, there was no cytotoxic effect of TAM on BIK-suppressed MCF-7 cells. Further, these cells were not arrested at the G0-G1 phase of the cell cycle although 30 % of BIK-suppressed cells were arrested at the G2 phase of the cycle on TAM treatment. Furthermore, we found a relevant interaction between 14-3-3z and WEE1, suggesting that the cytotoxic effect of TAM was prevented in BIK-suppressed cells because this interaction leads to transitory arrest in the G2 phase leading to the repair of damaged DNA and allowing the cells to proliferate.

Quantitative monitoring of tamoxifen in human plasma extended to 40 metabolites using liquid-chromatography high-resolution mass spectrometry: new investigation capabilities for clinical pharmacology.

PubMed

Dahmane, Elyes; Boccard, Julien; Csajka, Chantal; Rudaz, Serge; Décosterd, Laurent; Genin, Eric; Duretz, Bénédicte; Bromirski, Maciej; Zaman, Khalil; Testa, Bernard; Rochat, Bertrand

2014-04-01

Liquid-chromatography (LC) high-resolution (HR) mass spectrometry (MS) analysis can record HR full scans, a technique of detection that shows comparable selectivity and sensitivity to ion transitions (SRM) performed with triple-quadrupole (TQ)-MS but that allows de facto determination of "all" ions including drug metabolites. This could be of potential utility in in vivo drug metabolism and pharmacovigilance studies in order to have a more comprehensive insight in drug biotransformation profile differences in patients. This simultaneous quantitative and qualitative (Quan/Qual) approach has been tested with 20 patients chronically treated with tamoxifen (TAM). The absolute quantification of TAM and three metabolites in plasma was realized using HR- and TQ-MS and compared. The same LC-HR-MS analysis allowed the identification and relative quantification of 37 additional TAM metabolites. A number of new metabolites were detected in patients' plasma including metabolites identified as didemethyl-trihydroxy-TAM-glucoside and didemethyl-tetrahydroxy-TAM-glucoside conjugates corresponding to TAM with six and seven biotransformation steps, respectively. Multivariate analysis allowed relevant patterns of metabolites and ratios to be associated with TAM administration and CYP2D6 genotype. Two hydroxylated metabolites, α-OH-TAM and 4'-OH-TAM, were newly identified as putative CYP2D6 substrates. The relative quantification was precise (<20 %), and the semiquantitative estimation suggests that metabolite levels are non-negligible. Metabolites could play an important role in drug toxicity, but their impact on drug-related side effects has been partially neglected due to the tremendous effort needed with previous MS technologies. Using present HR-MS, this situation should evolve with the straightforward determination of drug metabolites, enlarging the possibilities in studying inter- and intra-patients drug metabolism variability and related effects.

Effect of tamoxifen, methoxyprogesterone acetate and combined treatment on cellular proliferation and apoptosis in SKOV3/DDP cells via the regulation of vascular endothelial growth factor.

PubMed

Wen, Lv; Hong, Ding; Yanyin, Wu; Mingyue, Zhang; Baohua, Li

2013-05-01

The aim of this study was to investigate the effect of tamoxifen (TAM), methoxyprogesterone acetate (MPA) and their combined treatment on cisplatin-resistant ovarian cancer SKOV3/DDP cells, as well as the potential mechanisms. MTT assay was used to investigate the effect of different concentrations (0.01, 0.1, 1, 10 and 100 μM) of TAM, MPA and their combined treatment on the proliferation of cisplatin-resistant ovarian cancer SKOV3/DDP cells. Flow cytometry was employed to analyze the cell cycle and apoptosis rate of SKOV3/DDP cells treated with medium concentration (10 μM) of TAM, MPA and their combined treatment. Change in the protein level of vascular endothelial growth factor (VEGF) in response to drug treatments was measured using Western-blot. The proliferation of SKOV3/DDP cells was inhibited by 1, 10 and 100 μM of TAM or MPA in a dose-dependent manner. Compared to the control group, 10 μM TAM could significantly arrest SKOV3/DDP cells in the G0/G1 stage and induce apoptosis (p < 0.01). However, 10 μM MPA only promoted cell apoptosis, while exhibited little effect on the cell cycle. We further found that 10 μM TAM could remarkably reduce the protein expression of VEGF, while 10 μM MPA only induce a slight reduction. Strikingly, the combined treatment of TAM and MPA exhibited additive effect on the proliferation, cell cycle, apoptosis rate and VEGF expression of SKOV3/DDP cells. We found that TAM, MPA and their combined treatment exhibited significant inhibitory effect on the cisplatin-resistant ovarian cancer SKOV3/DDP cells. Hence, TAM and MPA could be potential cytotoxic drugs to treat cisplatin-resistant patients with advanced ovarian cancer.

Examining the Moderating Effect of Individual-Level Cultural Values on Users' Acceptance of E-Learning in Developing Countries: A Structural Equation Modeling of an Extended Technology Acceptance Model

ERIC Educational Resources Information Center

Tarhini, Ali; Hone, Kate; Liu, Xiaohui; Tarhini, Takwa

2017-01-01

In this study, we examine the effects of individual-level culture on the adoption and acceptance of e-learning tools by students in Lebanon using a theoretical framework based on the Technology Acceptance Model (TAM). To overcome possible limitations of using TAM in developing countries, we extend TAM to include "subjective norms" (SN)…

Computer-Assisted Update of a Consumer Health Vocabulary Through Mining of Social Network Data

PubMed Central

2011-01-01

Background Consumer health vocabularies (CHVs) have been developed to aid consumer health informatics applications. This purpose is best served if the vocabulary evolves with consumers’ language. Objective Our objective was to create a computer assisted update (CAU) system that works with live corpora to identify new candidate terms for inclusion in the open access and collaborative (OAC) CHV. Methods The CAU system consisted of three main parts: a Web crawler and an HTML parser, a candidate term filter that utilizes natural language processing tools including term recognition methods, and a human review interface. In evaluation, the CAU system was applied to the health-related social network website PatientsLikeMe.com. The system’s utility was assessed by comparing the candidate term list it generated to a list of valid terms hand extracted from the text of the crawled webpages. Results The CAU system identified 88,994 unique terms 1- to 7-grams (“n-grams” are n consecutive words within a sentence) in 300 crawled PatientsLikeMe.com webpages. The manual review of the crawled webpages identified 651 valid terms not yet included in the OAC CHV or the Unified Medical Language System (UMLS) Metathesaurus, a collection of vocabularies amalgamated to form an ontology of medical terms, (ie, 1 valid term per 136.7 candidate n-grams). The term filter selected 774 candidate terms, of which 237 were valid terms, that is, 1 valid term among every 3 or 4 candidates reviewed. Conclusion The CAU system is effective for generating a list of candidate terms for human review during CHV development. PMID:21586386

Closure Report for Corrective Action Unit 151: Septic Systems and Discharge Area, Nevada Test Site, Nevada

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

NSTec Environmental Restoration

2008-04-01

Corrective Action Unit (CAU) 151 is identified in the Federal Facility Agreement and Consent Order (FFACO) as Septic Systems and Discharge Area. CAU 151 consists of the following eight Corrective Action Sites (CASs), located in Areas 2, 12, and 18 of the Nevada Test Site, approximately 65 miles northwest of Las Vegas, Nevada: (1) CAS 02-05-01, UE-2ce Pond; (2) CAS 12-03-01, Sewage Lagoons (6); (3) CAS 12-04-01, Septic Tanks; (4) CAS 12-04-02, Septic Tanks; (5) CAS 12-04-03, Septic Tank; (6) CAS 12-47-01, Wastewater Pond; (7) CAS 18-03-01, Sewage Lagoon; and (8) CAS 18-99-09, Sewer Line (Exposed). CAU 151 closure activitiesmore » were conducted according to the FFACO (FFACO, 1996; as amended February 2008) and the Corrective Action Plan for CAU 151 (U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office, 2007) from October 2007 to January 2008. The corrective action alternatives included no further action, clean closure, and closure in place with administrative controls. CAU 151 closure activities are summarized in Table 1. Closure activities generated liquid remediation waste, sanitary waste, hydrocarbon waste, and mixed waste. Waste generated was appropriately managed and disposed. Waste that is currently staged onsite is being appropriately managed and will be disposed under approved waste profiles in permitted landfills. Waste minimization activities included waste characterization sampling and segregation of waste streams. Some waste exceeded land disposal restriction limits and required offsite treatment prior to disposal. Other waste meeting land disposal restrictions was disposed of in appropriate onsite or offsite landfills. Waste disposition documentation is included as Appendix C.« less

Economic evaluation of an intervention program with the aim to improve at-work productivity for workers with rheumatoid arthritis.

PubMed

Noben, Cindy; Vilsteren, Myrthe van; Boot, Cécile; Steenbeek, Romy; Schaardenburg, Dirkjan van; Anema, Johannes R; Evers, Silvia; Nijhuis, Frans; Rijk, Angelique de

2017-05-25

Evaluating the cost effectiveness and cost utility of an integrated care intervention and participatory workplace intervention for workers with rheumatoid arthritis (RA) to improve their work productivity. Twelve month follow-up economic evaluation alongside a randomized controlled trial (RCT) within specialized rheumatology treatment centers. Adults diagnosed with RA between 18-64 years, in a paid job for at least eight hours per week, experiencing minor difficulties in work functioning were randomized to the intervention (n = 75) or the care-as-usual (CAU) group (n = 75). Effect outcomes were productivity and quality of life (QALYs). Costs associated with healthcare, patient and family, productivity, and intervention were calculated from a societal perspective. Cost effectiveness and cost utility were assessed to indicate the incremental costs and benefits per additional unit of effect. Subgroup and sensitivity analyses evaluated the robustness of the findings. At-work productivity loss was about 4.6 hours in the intervention group and 3.5 hours in the care as usual (CAU) group per two weeks. Differences in QALY were negligible; 0.77 for the CAU group and 0.74 for the intervention group. In total, average costs after twelve months follow-up were highest in the intervention group (€7,437.76) compared to the CAU group (€5,758.23). The cost-effectiveness and cost-utility analyses show that the intervention was less effective and (often) more expensive when compared to CAU. Sensitivity analyses supported these findings. The integrated care intervention and participatory workplace intervention for workers with RA provides gains neither in productivity at the workplace nor in quality of life. These results do not justify the additional costs.

Economic evaluation of an intervention program with the aim to improve at-work productivity for workers with rheumatoid arthritis

PubMed Central

Noben, Cindy; van Vilsteren, Myrthe; Boot, Cécile; Steenbeek, Romy; van Schaardenburg, Dirkjan; Anema, Johannes R.; Evers, Silvia; Nijhuis, Frans; de Rijk, Angelique

2017-01-01

Objectives: Evaluating the cost effectiveness and cost utility of an integrated care intervention and participatory workplace intervention for workers with rheumatoid arthritis (RA) to improve their work productivity. Methods: Twelve month follow-up economic evaluation alongside a randomized controlled trial (RCT) within specialized rheumatology treatment centers. Adults diagnosed with RA between 18-64 years, in a paid job for at least eight hours per week, experiencing minor difficulties in work functioning were randomized to the intervention (n = 75) or the care-as-usual (CAU) group (n = 75). Effect outcomes were productivity and quality of life (QALYs). Costs associated with healthcare, patient and family, productivity, and intervention were calculated from a societal perspective. Cost effectiveness and cost utility were assessed to indicate the incremental costs and benefits per additional unit of effect. Subgroup and sensitivity analyses evaluated the robustness of the findings. Results: At-work productivity loss was about 4.6 hours in the intervention group and 3.5 hours in the care as usual (CAU) group per two weeks. Differences in QALY were negligible; 0.77 for the CAU group and 0.74 for the intervention group. In total, average costs after twelve months follow-up were highest in the intervention group (€7,437.76) compared to the CAU group (€5,758.23). The cost-effectiveness and cost-utility analyses show that the intervention was less effective and (often) more expensive when compared to CAU. Sensitivity analyses supported these findings. Discussion: The integrated care intervention and participatory workplace intervention for workers with RA provides gains neither in productivity at the workplace nor in quality of life. These results do not justify the additional costs. PMID:28381814

Healthcare-associated infections: infection prevention and control within the Accreditation Canada Qmentum Program.

PubMed

Nicklin, Wendy; Greco, Paula; Mitchell, Jonathan I

2009-01-01

Gardam, Lemieux, Reason, van Dijk and Goel argue that healthcare-associated infections (HAIs) are "a pressing and imminent concern in the context of patient safety." Accreditation Canada supports the position taken by these authors. The prevention and control of two HAIs of great concern, methicillin-resistant Staphylococcus aureus and Clostridium difficile, are an integral part of the Accreditation Canada program. A coordinated approach to combating HAIs and developing a culture of infection prevention and control is necessary, one that involves front-line healthcare professionals, senior leadership, national and provincial partners and the public. Since 2005, Accreditation Canada has increasingly strengthened the accreditation program in this area through a number of new strategies, including enhanced standards, required organizational practices, performance measures and indicators and the introduction of education programs. Optimizing the value of accreditation through an integrative approach with organizations' quality improvement programs will contribute to effectively combating HAIs and developing a culture of infection prevention and control.

The Medicare Policy of Payment Adjustment for Health Care-Associated Infections: Perspectives on Potential Unintended Consequences

PubMed Central

Hartmann, Christine W.; Hoff, Timothy; Palmer, Jennifer A.; Wroe, Peter; Dutta-Linn, M. Maya; Lee, Grace

2014-01-01

In 2008, the Centers for Medicare & Medicaid Services introduced a new policy to adjust payment to hospitals for health care-associated infections (HAIs) not present on admission. Interviews with 36 hospital infection preventionists across the United States explored the perspectives of these key stakeholders on the potential unintended consequences of the current policy. Responses were analyzed using an iterative coding process where themes were developed from the data. Participants’ descriptions of unintended impacts of the policy centered around three themes. Results suggest the policy has focused more attention on targeted HAIs and has affected hospital staff; relatively fewer systems changes have ensued. Some consequences of the policy, such as infection preventionists having less time to devote to HAIs other than those in the policy or having less time to implement prevention activities, may have undesirable effects on HAI rates if hospitals do not recognize and react to potential time and resource gaps. PMID:21810797

Tirandamycin biosynthesis is mediated by co-dependent oxidative enzymes

NASA Astrophysics Data System (ADS)

Carlson, Jacob C.; Li, Shengying; Gunatilleke, Shamila S.; Anzai, Yojiro; Burr, Douglas A.; Podust, Larissa M.; Sherman, David H.

2011-08-01

Elucidation of natural product biosynthetic pathways provides important insights into the assembly of potent bioactive molecules, and expands access to unique enzymes able to selectively modify complex substrates. Here, we show full reconstitution, in vitro, of an unusual multi-step oxidative cascade for post-assembly-line tailoring of tirandamycin antibiotics. This pathway involves a remarkably versatile and iterative cytochrome P450 monooxygenase (TamI) and a flavin adenine dinucleotide-dependent oxidase (TamL), which act co-dependently through the repeated exchange of substrates. TamI hydroxylates tirandamycin C (TirC) to generate tirandamycin E (TirE), a previously unidentified tirandamycin intermediate. TirE is subsequently oxidized by TamL, giving rise to the ketone of tirandamycin D (TirD), after which a unique exchange back to TamI enables successive epoxidation and hydroxylation to afford, respectively, the final products tirandamycin A (TirA) and tirandamycin B (TirB). Ligand-free, substrate- and product-bound crystal structures of bicovalently flavinylated TamL oxidase reveal a likely mechanism for the C10 oxidation of TirE.

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

NONE

Corrective Action Unit (CAU) 390 consists four Corrective Action Sites (CASs) located in Areas 9, 10, and 12 of the Nevada Test Site. The closure activities performed at the CASs include: (1) CAS 09-99-03, Wax, Paraffin: 2 cubic yards of drilling polymer was removed on June 20,2005, and transported to the Area 9 Landfill for disposal. (2) CAS 10-99-01, Epoxy Tar Spill: 2 cubic feet of asphalt waste was removed on June 20,2005, and transported to the Area 9 Landfill for disposal. (3) CAS 10-99-03, Tar Spills: 3 cubic yards of deteriorated asphalt waste was removed on June 20,2005, andmore » transported to the Area 9 Landfill for disposal. (4) CAS 12-25-03, Oil Stains (2); Container: Approximately 16 ounces of used oil were removed from ventilation equipment on June 28,2005, and recycled. One CAS 10-22-19, Drums, Stains, was originally part of CAU 390 but was transferred out of CAU 390 and into CAU 550, Drums, Batteries, and Lead Materials. The transfer was approved by the Nevada Division of Environmental Protection on August 19,2005, and a copy of the approval letter is included in Appendix D of this report.« less

Minor long-term effects 3-4 years after the ReDO™ intervention for women with stress-related disorders: A focus on sick leave rate, everyday occupations and well-being.

PubMed

Eklund, Mona

2017-01-01

The Redesigning Daily Occupations (ReDO™) work rehabilitation method has been found effective, compared with care as usual (CAU), for women with stress-related disorders. To conduct a long-term follow-up of former ReDO™ and CAU participants with respect to sick leave, well-being and everyday occupations 3-4 years after completed work rehabilitation. Forty-two women in each group participated. An index day was decided to estimate sick-leave rate, retrieved from register data. Fifty-five women also participated in a telephone interview addressing well-being, everyday occupations and life events. Both groups had reduced their sick-leave rate further, but no difference between the groups was established. The ReDO™ women perceived a better balance in the work domain of everyday occupations, whereas the CAU group reported more over-occupation. No differences were found on well-being. The groups had experienced similar important life events, affecting the women's work and private lives. Previous stress and anxiety predicted sick leave at the long-term follow-up. Although the ReDO™ intervention had speeded up return to work in the immediate follow-up perspective, the CAU had caught up in the longer term. Still, the ReDO™ women exhibited better balance in the work domain.

Evidence of previous but not current transmission of chikungunya virus in southern and central Vietnam: Results from a systematic review and a seroprevalence study in four locations.

PubMed

Quan, Tran Minh; Phuong, Huynh Thi; Vy, Nguyen Ha Thao; Thanh, Nguyen Thi Le; Lien, Nguyen Thi Nam; Hong, Tran Thi Kim; Dung, Pham Ngoc; Chau, Nguyen Van Vinh; Boni, Maciej F; Clapham, Hannah E

2018-02-01

Arbovirus infections are a serious concern in tropical countries due to their high levels of transmission and morbidity. With the outbreaks of chikungunya (CHIKV) in surrounding regions in recent years and the fact that the environment in Vietnam is suitable for the vectors of CHIKV, the possibility of transmission of CHIKV in Vietnam is of great interest. However, information about CHIKV activity in Vietnam remains limited. In order to address this question, we performed a systematic review of CHIKV in Vietnam and a CHIKV seroprevalence survey. The seroprevalence survey tested for CHIKV IgG in population serum samples from individuals of all ages in 2015 from four locations in Vietnam. The four locations were An Giang province (n = 137), Ho Chi Minh City (n = 136), Dak Lak province (n = 137), and Hue City (n = 136). The findings give us evidence of some CHIKV activity: 73/546 of overall samples were seropositive (13.4%). The age-adjusted seroprevalences were 12.30% (6.58-18.02), 13.42% (7.16-19.68), 7.97% (3.56-12.38), and 3.72% (1.75-5.69) in An Giang province, Ho Chi Minh City, Dak Lak province, and Hue City respectively. However, the age-stratified seroprevalence suggests that the last transmission ended around 30 years ago, consistent with results from the systematic review. We see no evidence for on-going transmission in three of the locations, though with some evidence of recent exposure in Dak Lak, most likely due to transmission in neighbouring countries. Before the 1980s, when transmission was occurring, we estimate on average 2-4% of the population were infected each year in HCMC and An Giang and Hue (though transmision ended earlier in Hue). We estimate lower transmission in Dak Lak, with around 1% of the population infected each year. In conclusion, we find evidence of past CHIKV transmission in central and southern Vietnam, but no evidence of recent sustained transmission. When transmission of CHIKV did occur, it appeared to be widespread and affect a

Evidence of previous but not current transmission of chikungunya virus in southern and central Vietnam: Results from a systematic review and a seroprevalence study in four locations

PubMed Central

Phuong, Huynh Thi; Vy, Nguyen Ha Thao; Thanh, Nguyen Thi Le; Lien, Nguyen Thi Nam; Hong, Tran Thi Kim; Dung, Pham Ngoc; Chau, Nguyen Van Vinh; Boni, Maciej F.; Clapham, Hannah E.

2018-01-01

Background Arbovirus infections are a serious concern in tropical countries due to their high levels of transmission and morbidity. With the outbreaks of chikungunya (CHIKV) in surrounding regions in recent years and the fact that the environment in Vietnam is suitable for the vectors of CHIKV, the possibility of transmission of CHIKV in Vietnam is of great interest. However, information about CHIKV activity in Vietnam remains limited. Methodology In order to address this question, we performed a systematic review of CHIKV in Vietnam and a CHIKV seroprevalence survey. The seroprevalence survey tested for CHIKV IgG in population serum samples from individuals of all ages in 2015 from four locations in Vietnam. Principal findings The four locations were An Giang province (n = 137), Ho Chi Minh City (n = 136), Dak Lak province (n = 137), and Hue City (n = 136). The findings give us evidence of some CHIKV activity: 73/546 of overall samples were seropositive (13.4%). The age-adjusted seroprevalences were 12.30% (6.58–18.02), 13.42% (7.16–19.68), 7.97% (3.56–12.38), and 3.72% (1.75–5.69) in An Giang province, Ho Chi Minh City, Dak Lak province, and Hue City respectively. However, the age-stratified seroprevalence suggests that the last transmission ended around 30 years ago, consistent with results from the systematic review. We see no evidence for on-going transmission in three of the locations, though with some evidence of recent exposure in Dak Lak, most likely due to transmission in neighbouring countries. Before the 1980s, when transmission was occurring, we estimate on average 2–4% of the population were infected each year in HCMC and An Giang and Hue (though transmision ended earlier in Hue). We estimate lower transmission in Dak Lak, with around 1% of the population infected each year. Conclusion In conclusion, we find evidence of past CHIKV transmission in central and southern Vietnam, but no evidence of recent sustained transmission. When

Resource Conservation and Recovery Act closure report: Area 2 Bitcutter and Postshot Containment Shops Injection Wells, Correction Action Unit 90

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

NONE

This Closure Report provides documentation of the activities conducted during the Resource Conservation and Recovery Act (RCRA) closure of the Bitcutter and Postshot Containment Shops Injection Wells located in Area 2 of the Nevada Test Site (NTS), Oak Spring Quadrangle (USGS, 1986), Township 10 South, Range 53 East, Nye County, Nevada. This report discusses the Bitcutter Shop Inside Injection Well (CAU 90-A) closure-in-place and the Bitcutter Shop Outside Injection Well (CAU 90-B) and Postshot Containment Shop Injection Well (CAU 90-C) clean closures. This Closure Report provides background information about the unit, the results of the characterization activities and actions conductedmore » to determine the closure design. It also provides a discussion of the drainage analysis, preliminary closure activities, final closure activities, waste management activities, and the Post-Closure Care requirements.« less

Rejecting Admission Offers to a Selective Math and Science School

ERIC Educational Resources Information Center

Jones, Brent M.

2014-01-01

An exploratory study of applicants who rejected admission to the Texas Academy of Mathematics and Science (TAMS) is described in this article. TAMS is a residential early college entry program at the University of North Texas in Denton. Up to 600 mathematically talented sophomores apply to TAMS each year and among the 200 selectees, a predictable…

Effect of alpha(1)-acid glycoprotein on the pharmacokinetics of tamsulosin in rats treated with turpentine oil.

PubMed

Matsushima, H; Watanabe, T; Higuchi, S

2000-04-01

The pharmacokinetics of tamsulosin (TAM) was investigated using male Sprague-Dawley rats in which plasma alpha(1)-acid glycoprotein (alpha(1)-AGP) levels were elevated by the subcutaneous injection of 0.2 mL/kg of turpentine oil. alpha(1)-AGP levels increased about eight times after turpentine oil treatment, causing a threefold decrease in plasma unbound fraction (f(u)) of TAM. When 0.3 mg/kg of TAM was dosed intravenously, total and nonrenal clearances (CL(tot) and CL(nr)) in turpentine-treated rats were 47% and 44% lower than those in nontreated controls, respectively. The area under the concentration-time curve of plasma unbound TAM (AUC(inf,u)) was lower than that in the control. When 1 mg/kg of TAM was dosed orally, oral clearance (CL(oral)) in alpha1-AGP-induced rats was 65% lower than in the control. The AUC(inf,u) and unbound oral clearance (CL(oral,u)) were nearly equal in both groups. Moreover, a positive correlation was observed between fu and CL(oral) of TAM (r(2) = 0.603, P < 0.01), whereas no correlation was observed between f(u) and CL(oral,u). The absolute bioavailability (BA) increased from 19.2% to 46.9% by induction of alpha(1)-AGP. These results suggest that decreased f(u) caused by the elevation of plasma alpha(1)-AGP level affects the pharmacokinetics of TAM, but does not affect the CL(oral,u,) which represents the hepatic metabolism of TAM. Copyright 2000 Wiley-Liss, Inc.

Developing analytical approaches to explore the connection between endocrine-active pharmaceuticals in water to effects in fish

USGS Publications Warehouse

Jones-Lepp, Tammy L.; Taniguchi-Fu, Randi L.; Morgan, Jade; Nance Jr., Trevor; Ward, Matthew; Alvarez, David A.; Mills, Lesley

2015-01-01

The emphasis of this research project was to develop and optimize a solid-phase extraction method and highperformance liquid chromatography-electrospray ionizationmass spectrometry method, such that a linkage between the detection of endocrine-active pharmaceuticals (EAPs) in the aquatic environment and subsequent effects on fish populations could eventually be studied. Four EAPs were studied: tamoxifen (TAM), exemestane (EXE), letrozole (LET), anastrozole (ANA); and three TAM metabolites: 4- hydroxytamoxifen, e/z endoxifen, and n-desmethyl tamoxifen. In aqueous matrices, the use of isotopically labeled standards for the EAPs allowed for the generation of good recoveries, greater than 80 %, and low relative standard deviations (% RSDs) (3 to 27 %). TAM metabolites had lower recoveries in the spiked water matrices: 35 to 93 % in waste/source water compared to 58 to 110 % in DI water. The precision in DI water was acceptable ranging from 8 to 38 % RSD. However, the precision in real environmental wastewaters could be poor, ranging from 15 to 120 % RSD, dependent upon unique matrix effects. In plasma, the overall recoveries of the EAPs were acceptable: 88 to 110 %, with %RSDs of 6 to 18 % (Table 3). The spiked recoveries of the TAM metabolites from plasma were good, ranging from 77 to 120 %, with %RSDs ranging from 27 to 32 %. Two of the TAM metabolites, 4- hydroxytamoxifen and n-desmethyl tamoxifen, were confirmed in most of the environmental aqueous samples. The discovery of TAM metabolites demonstrates that the source of the TAM metabolites, TAM, is constant, introducing a pseudo-persistence of this chemical into the environment.

Addendum to the Closure Report for Corrective Action Unit 411: Double Tracks Plutonium Dispersion (Nellis), Nevada Test and Training Range, Nevada, Revision 0

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