A Noninvasive and Real-Time Method for Circulating Tumor Cell Detection by In Vivo Flow Cytometry.

PubMed

Wei, Xunbin; Zhou, Jian; Zhu, Xi; Yang, Xinrong; Yang, Ping; Wang, Qiyan

2017-01-01

The quantification of circulating tumor cells (CTCs) has been considered a potentially powerful tool in cancer diagnosis and prognosis, as CTCs have been shown to appear very early in cancer development. Great efforts have been made to develop methods that were less invasive and more sensitive to detect CTCs earlier. There is growing evidence that CTC clusters have greater metastatic potential than single CTCs. Therefore, the detection of CTC clusters is also important. This chapter is aimed to introduce a noninvasive technique for CTCs detection named in vivo flow cytometry (IVFC), which has been demonstrated to be capable of monitoring CTCs dynamics continuously. Furthermore, IVFC could be helpful for CTC cluster enumeration.

Transforming prevention systems in the United States and the Netherlands using Communities That Care Promising prevention in the eyes of Josine Junger-Tas

PubMed Central

Steketee, Majone; Oesterle, Sabrina; Jonkman, Harrie; Hawkins, J. David; Haggerty, Kevin P.; Aussems, Claire

2013-01-01

Josine Junger-Tas introduced the Communities That Care (CTC) prevention system to the Netherlands as a promising approach to address the growing youth violence and delinquency. Using data from a randomized trial of CTC in the United States and a quasi-experimental study of CTC in the Netherlands, this article describes the results of a comparison of the implementation of CTC in 12 U.S. communities and 5 Dutch neighborhoods. CTC communities in both countries achieved higher stages of a science-based approach to prevention than control communities, but full implementation of CTC in the Netherlands was hampered by the very small list of prevention programs tested and found effective in the Dutch context. PMID:24465089

Monitoring circulating prostate tumor cells after tumor resection by in vivo flow cytometry

NASA Astrophysics Data System (ADS)

Ding, Nan; Zhu, Xi; Xie, Chengying; Wei, Dan; Yang, Zhangru; Suo, Yuanzhen; Wei, Xunbin

2018-02-01

Prostate cancer has already become the biggest threat among all cancer types for male people and many people died because of its bone metastases. Circulating tumor cells (CTCs) can be used as early metastasis marker so that the detection of CTCs in blood is meaningful for early diagnosis and treatment. However, the relationship between these therapies and metastasis has not been fully clarified yet. Hence, we built PC3 subcutaneous tumor model and developed in vivo flow cytometer (IVFC) platform to record the dynamics of CTC before and after tumor resection. We found out that tumor resection can reduce CTC quantities instantaneously while having a good control of metastasis. CTC re-occurred 7 days after surgery, which might be correlated with early disseminated and deposited tumors. In conclusion, in vivo flow cytometry (IVFC) is capable of detecting CTC dynamics in prostate subcutaneous tumor model and this method could facilitate further research about relationship between other cancer therapies and circulating tumor cells.

Screening CT Colonography: Multicenter Survey of Patient Experience, Preference, and Potential Impact on Adherence

PubMed Central

Pooler, B. Dustin; Baumel, Mark J.; Cash, Brooks D.; Moawad, Fouad J.; Riddle, Mark S.; Patrick, Amy M.; Damiano, Mark; Lee, Matthew H.; Kim, David H.; del Rio, Alejandro Muñoz; Pickhardt, Perry J.

2013-01-01

OBJECTIVE Prior research indicates CT colonography (CTC) would be a cost-effective colorectal cancer (CRC) screening test if widespread availability were to increase overall CRC screening adherence rates. The primary aims of this multicenter study were to evaluate patient experience and satisfaction with CTC screening and compare preference against screening colonoscopy. MATERIALS AND METHODS A 12-question survey instrument measuring pretest choice, experience, and satisfaction was given to a consecutive cohort of adults undergoing CTC screening in three disparate screening settings: university academic center, military medical center, and community practice. The study cohort was composed of individuals voluntarily participating in clinical CTC screening programs. RESULTS A total of 1417 patients responded to the survey. The top reasons for choosing CTC for screening included “noninvasiveness” (68.0%), “avoidance of sedation/anesthesia” (63.1%), “ability to drive after the test” (49.2%), “avoidance of optical colonoscopy risks” (46.9%), and “identifying abnormalities outside the colon” (43.3%). Only 7.2% of patients reported pain during the CTC examination and only 2.5% reported greater than moderate discomfort. Of 441 patients who had experienced both CTC and optical colonoscopy, 77.1% preferred CTC and 13.8% preferred optical colonoscopy. Of all patients, 29.6% indicated that they may not have undergone optical colonoscopy screening if CTC were not available. Of all patients, 92.9% labeled their overall experience with CTC as “excellent” or “good,” and 93.0% indicated they would choose CTC for their next screening. CONCLUSION Respondents reported a very high satisfaction level with CTC, and those who had experienced both modalities indicated a preference for CTC over optical colonoscopy. These results suggest that CTC has the potential to increase adherence to CRC screening guidelines if widely available. PMID:22623549

Effects of the communities that care prevention system on youth reports of protective factors.

PubMed

Kim, B K Elizabeth; Gloppen, Kari M; Rhew, Isaac C; Oesterle, Sabrina; Hawkins, J David

2015-07-01

Many interventions seeking to reduce problem behaviors and promote healthy youth development target both risk and protective factors, yet few studies have examined the effect of preventive interventions on overall levels of protection community wide. In a community-randomized controlled trial, this study tested the effect of Communities That Care (CTC) on protective factors in 24 communities across seven states. Data on protective factors were collected from a panel of 4407 youths in CTC and control communities followed from grade 5 through grade 8. Hierarchical linear modeling compared mean levels of 15 protective factors derived from the social development model in CTC and control communities in grade 8, adjusted for individual and community characteristics and baseline levels of protective factors in grade 5. Global test statistics were calculated to examine effects on protection overall and by domain. Analyses across all protective factors found significantly higher levels of overall protection in CTC compared to control communities. Analyses by domain found significantly higher levels of protection in CTC than control communities in the community, school, and peer/individual domains, but not in the family domain. Significantly higher levels of opportunities for prosocial involvement in the community, recognition for prosocial involvement in school, interaction with prosocial peers, and social skills among CTC compared to control youth contributed to the overall and domain-specific results. This is consistent with CTC's theory of change, which posits that strengthening protective factors is a mechanism through which CTC prevents behavior problems.

Cost analysis of colorectal cancer screening with CT colonography in Italy.

PubMed

Mantellini, Paola; Lippi, Giuseppe; Sali, Lapo; Grazzini, Grazia; Delsanto, Silvia; Mallardi, Beatrice; Falchini, Massimo; Castiglione, Guido; Carozzi, Francesca Maria; Mascalchi, Mario; Milani, Stefano; Ventura, Leonardo; Zappa, Marco

2018-06-01

Unit costs of screening CT colonography (CTC) can be useful for cost-effectiveness analyses and for health care decision-making. We evaluated the unit costs of CTC as a primary screening test for colorectal cancer in the setting of a randomized trial in Italy. Data were collected within the randomized SAVE trial. Subjects were invited to screening CTC by mail and requested to have a pre-examination consultation. CTCs were performed with 64- and 128-slice CT scanners after reduced or full bowel preparation. Activity-based costing was used to determine unit costs per-process, per-participant to screening CTC, and per-subject with advanced neoplasia. Among 5242 subjects invited to undergo screening CTC, 1312 had pre-examination consultation and 1286 ultimately underwent CTC. Among 129 subjects with a positive CTC, 126 underwent assessment colonoscopy and 67 were ultimately diagnosed with advanced neoplasia (i.e., cancer or advanced adenoma). Cost per-participant of the entire screening CTC pathway was €196.80. Average cost per-participant for the screening invitation process was €17.04 and €9.45 for the pre-examination consultation process. Average cost per-participant of the CTC execution and reading process was €146.08 and of the diagnostic assessment colonoscopy process was €24.23. Average cost per-subject with advanced neoplasia was €3777.30. Cost of screening CTC was €196.80 per-participant. Our data suggest that the more relevant cost of screening CTC, amenable of intervention, is related to CTC execution and reading process.

Capture of mesothelioma cells with 'universal' CTC-chip.

PubMed

Yoneda, Kazue; Chikaishi, Yasuhiro; Kuwata, Taiji; Ohnaga, Takashi; Tanaka, Fumihiro

2018-02-01

Malignant mesothelioma (MM) is a highly aggressive malignant tumor, predominantly associated with job-related exposure to asbestos. Development of effective and non-invasive modalities for diagnosis is an important issue in occupational medicine. Circulating tumor cells (CTCs), which are tumor cells that are shed from primary tumors and circulate in the peripheral blood, may be detected at an earlier stage than malignant tumors, and detection of CTCs may provide a novel insight into the diagnosis of MM. In a previous study evaluating clinical utility of CTCs, detected with a widely used system 'CellSearch', the authors indicated a significant however insufficient capability in the diagnosis of MM, suggesting need for a more sensitive system. Accordingly, the authors developed a novel microfluidic system to capture CTCs (CTC-chip), and demonstrated that the CTC-chip effectively captured MM cells (ACC-MESO-4) spiked in the blood by conjugating an anti-podoplanin antibody. The results of the present study demonstrated that the CTC-chip coated with the anti-podoplanin antibody captured another MM cell (ACC-MESO-1). However, the capture efficiencies were lower than those for ACC-MESO-4. In addition, an anti-mesothelin antibody was used to capture CTCs, however the CTC-chip coated with the anti-mesothelin antibody failed to effectively capture MM cells, possibly due to low mesothelin expression. Overall, the CTC-chip may capture specific types of CTCs by conjugating any antibody against an antigen expressed on CTCs, and may be a useful system for the diagnosis of malignant tumors, including MM.

Circulating tumor cells (CTCs) in malignant pleural mesothelioma (MPM).

PubMed

Yoneda, Kazue; Tanaka, Fumihiro; Kondo, Nobuyuki; Hashimoto, Masaki; Takuwa, Teruhisa; Matsumoto, Seiji; Okumura, Yoshitomo; Tsubota, Noriaki; Sato, Ayuko; Tsujimura, Tohru; Kuribayashi, Kozo; Fukuoka, Kazuya; Tabata, Chiharu; Nakano, Takashi; Hasegawa, Seiki

2014-12-01

To investigate the diagnostic and prognostic value of circulating tumor cells (CTCs), a potential surrogate of micrometastasis, in malignant pleural mesothelioma (MPM). We prospectively evaluated CTCs in 7.5 mL of peripheral blood sampled from patients with a suspicion of MPM. A semiautomated system was used to capture CTCs with an antibody against the epithelial cell adhesion molecule. Of 136 eligible patients, 32 were finally diagnosed with nonmalignant diseases (NM), and 104 had MPM. CTCs were detected in 32.7 % (34 of 104) of MPM patients but in only 9.4 % (3 of 32) of NM patients (P = 0.011). The CTC count was significantly higher in MPM patients than in NM patients (P = 0.007), and a receiver operating characteristic (ROC) curve analysis showed an insufficient capability of the CTC test in discrimination between MPM and NM, with an area under ROC curve of 0.623 (95 % confidence interval, 0.523-0.723; P = 0.036). Among MPM patients, CTCs were more frequently detected in patients with epithelioid subtype (39.7 %, 31 of 78) than in those with nonepithelioid subtypes (11.5 %, 3 of 26; P = 0.016). Positive CTCs (CTC count ≥ 1) were a significant factor to predict a poor prognosis among epithelioid patients (median overall survival, 22.3 months for positive CTCs vs. 12.6 months for negative CTCs; P = 0.004) and not in nonepithelioid patients (P = 0.649). A multivariate analysis showed that positive CTCs were a significant and independent factor to predict a poor prognosis (hazard ratio, 2.904; 95 % confidence interval, 1.530-5.511; P = 0.001) for epithelioid MPM patients. CTC was a promising marker in diagnosis and prediction of prognosis in MPM, especially in epithelioid MPM.

A Prognostic Gene Expression Profile That Predicts Circulating Tumor Cell Presence in Breast Cancer Patients

PubMed Central

Molloy, Timothy J.; Roepman, Paul; Naume, Bjørn; van't Veer, Laura J.

2012-01-01

The detection of circulating tumor cells (CTCs) in the peripheral blood and microarray gene expression profiling of the primary tumor are two promising new technologies able to provide valuable prognostic data for patients with breast cancer. Meta-analyses of several established prognostic breast cancer gene expression profiles in large patient cohorts have demonstrated that despite sharing few genes, their delineation of patients into “good prognosis” or “poor prognosis” are frequently very highly correlated, and combining prognostic profiles does not increase prognostic power. In the current study, we aimed to develop a novel profile which provided independent prognostic data by building a signature predictive of CTC status rather than outcome. Microarray gene expression data from an initial training cohort of 72 breast cancer patients for which CTC status had been determined in a previous study using a multimarker QPCR-based assay was used to develop a CTC-predictive profile. The generated profile was validated in two independent datasets of 49 and 123 patients and confirmed to be both predictive of CTC status, and independently prognostic. Importantly, the “CTC profile” also provided prognostic information independent of the well-established and powerful ‘70-gene’ prognostic breast cancer signature. This profile therefore has the potential to not only add prognostic information to currently-available microarray tests but in some circumstances even replace blood-based prognostic CTC tests at time of diagnosis for those patients already undergoing testing by multigene assays. PMID:22384245

Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture.

PubMed

Grillet, Fanny; Bayet, Elsa; Villeronce, Olivia; Zappia, Luke; Lagerqvist, Ebba Louise; Lunke, Sebastian; Charafe-Jauffret, Emmanuelle; Pham, Kym; Molck, Christina; Rolland, Nathalie; Bourgaux, Jean François; Prudhomme, Michel; Philippe, Claire; Bravo, Sophie; Boyer, Jean Christophe; Canterel-Thouennon, Lucile; Taylor, Graham Roy; Hsu, Arthur; Pascussi, Jean Marc; Hollande, Frédéric; Pannequin, Julie

2017-10-01

Although counting of circulating tumour cells (CTC) has attracted a broad interest as potential markers of tumour progression and treatment response, the lack of functional characterisation of these cells had become a bottleneck in taking these observations to the clinic. Our objective was to culture these cells in order to understand them and exploit their therapeutic potential to the full. Here, hypothesising that some CTC potentially have cancer stem cell (CSC) phenotype, we generated several CTC lines from the blood of patients with advanced metastatic colorectal cancer (CRC) based on their self-renewal abilities. Multiple standard tests were then employed to characterise these cells. Our CTC lines self-renew, express CSC markers and have multilineage differentiation ability, both in vitro and in vivo . Patient-derived CTC lines are tumorigenic in subcutaneous xenografts and are also able to colonise the liver after intrasplenic injection. RNA sequencing analyses strikingly demonstrate that drug metabolising pathways represent the most upregulated feature among CTC lines in comparison with primary CRC cells grown under similar conditions. This result is corroborated by the high resistance of the CTC lines to conventional cytotoxic compounds. Taken together, our results directly demonstrate the existence of patient-derived colorectal CTCs that bear all the functional attributes of CSCs. The CTC culture model described here is simple and takes <1 month from blood collection to drug testing, therefore, routine clinical application could facilitate access to personalised medicine. ClinicalTrial.gov NCT01577511. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Sustainability of the Communities That Care prevention system by coalitions participating in the Community Youth Development Study.

PubMed

Gloppen, Kari M; Arthur, Michael W; Hawkins, J David; Shapiro, Valerie B

2012-09-01

Community prevention coalitions are a common strategy to mobilize stakeholders to implement tested and effective prevention programs to promote adolescent health and well-being. This article examines the sustainability of Communities That Care (CTC) coalitions approximately 20 months after study support for the intervention ended. The Community Youth Development Study is a community-randomized trial of the CTC prevention system. Using data from 2007 and 2009 coalition leader interviews, this study reports changes in coalition activities from a period of study support for CTC (2007) to 20 months following the end of study support for CTC (2009), measured by the extent to which coalitions continued to meet specific benchmarks. Twenty months after study support for CTC implementation ended, 11 of 12 CTC coalitions in the Community Youth Development Study still existed. The 11 remaining coalitions continued to report significantly higher scores on the benchmarks of phases 2 through 5 of the CTC system than did prevention coalitions in the control communities. At the 20-month follow-up, two-thirds of the CTC coalitions reported having a paid staff person. This study found that the CTC coalitions maintained a relatively high level of implementation fidelity to the CTC system 20 months after the study support for the intervention ended. However, the downward trend in some of the measured benchmarks indicates that continued high-quality training and technical assistance may be important to ensure that CTC coalitions maintain a science-based approach to prevention, and continue to achieve public health impacts on adolescent health and behavior outcomes. Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

International study on inter-reader variability for circulating tumor cells in breast cancer.

PubMed

Ignatiadis, Michail; Riethdorf, Sabine; Bidard, François-Clement; Vaucher, Isabelle; Khazour, Mustapha; Rothé, Françoise; Metallo, Jessica; Rouas, Ghizlane; Payne, Rachel E; Coombes, Raoul; Teufel, Ingrid; Andergassen, Ulrich; Apostolaki, Stella; Politaki, Eleni; Mavroudis, Dimitris; Bessi, Silvia; Pestrin, Marta; Di Leo, Angelo; Campion, Michael; Reinholz, Monica; Perez, Edith; Piccart, Martine; Borgen, Elin; Naume, Bjorn; Jimenez, Jose; Aura, Claudia; Zorzino, Laura; Cassatella, Maria; Sandri, Maria; Mostert, Bianca; Sleijfer, Stefan; Kraan, Jaco; Janni, Wolfgang; Fehm, Tanja; Rack, Brigitte; Terstappen, Leon; Repollet, Madeline; Pierga, Jean-Yves; Miller, Craig; Sotiriou, Christos; Michiels, Stefan; Pantel, Klaus

2014-04-23

Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch® system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement. CellSearch® images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2- vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (κ) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test. For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median κ of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and <3CTCs (median 87%, range 66 to 95%) compared to M0 and ≥3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2- vs HER2+), the median agreement was 87% (range 51 to 95%) with a median κ of 0.74 (range 0.25 to 0.90). The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required.

CT colonography: accuracy, acceptance, safety and position in organised population screening.

PubMed

de Haan, Margriet C; Pickhardt, Perry J; Stoker, Jaap

2015-02-01

Colorectal cancer (CRC) is the second most common cancer and second most common cause of cancer-related deaths in Europe. The introduction of CRC screening programmes using stool tests and flexible sigmoidoscopy, have been shown to reduce CRC-related mortality substantially. In several European countries, population-based CRC screening programmes are ongoing or being rolled out. Stool tests like faecal occult blood testing are non-invasive and simple to perform, but are primarily designed to detect early invasive cancer. More invasive tests like colonoscopy and CT colonography (CTC) aim at accurately detecting both CRC and cancer precursors, thus providing for cancer prevention. This review focuses on the accuracy, acceptance and safety of CTC as a CRC screening technique and on the current position of CTC in organised population screening. Based on the detection characteristics and acceptability of CTC screening, it might be a viable screening test. The potential disadvantage of radiation exposure is probably overemphasised, especially with newer technology. At this time-point, it is not entirely clear whether the detection of extracolonic findings at CTC is of net benefit and is cost effective, but with responsible handling, this may be the case. Future efforts will seek to further improve the technique, refine appropriate diagnostic algorithms and study cost-effectiveness. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Patient experiences of colonoscopy, barium enema and CT colonography: a qualitative study.

PubMed

Von Wagner, C; Knight, K; Halligan, S; Atkin, W; Lilford, R; Morton, D; Wardle, J

2009-01-01

Previous studies of patient experience with bowel screening tests, in particular CT colonography (CTC), have superimposed global rating scales and not explored individual experience in detail. To redress this, we performed qualitative interviews in order to characterize patient expectations and experiences in depth. Following ethical permission, 16 patients undergoing CTC, 18 undergoing colonoscopy and 15 undergoing barium enema agreed to a semi-structured interview by a health psychologist. Interviews were recorded, responses transcribed and themes extracted with the aim of assimilating individual experiences to facilitate subsequent development and interpretation of quantitative surveys of overall satisfaction with each diagnostic test. Transcript analysis identified three principal themes: physical sensations, social interactions and information provision. Physical sensations differed for each test but were surprisingly well tolerated overall. Social interactions with staff were perceived as very important in colouring the whole experience, particularly in controlling the feelings of embarrassment, which was critical for all procedures. Information provision was also an important determinant of experience. Verbal feedback was most common during colonoscopy and invariably reassuring. However, patients undergoing CTC received little visual or verbal feedback and were often confused regarding the test outcome. Barium enema had no specific advantage over other tests. Qualitative interviews provided important perspectives on patient experience. Our data demonstrated that models describing the quality of medical encounters are applicable to single diagnostic episodes. Staff interactions and information provision were particularly important. We found advantages specific to both CTC and colonoscopy but none for barium enema. CTC could benefit greatly from improved information provision following examination.

Detection and characterization of invasive circulating tumor cells derived from men with metastatic castration-resistant prostate cancer.

PubMed

Friedlander, Terence W; Ngo, Vy T; Dong, Huan; Premasekharan, Gayatri; Weinberg, Vivian; Doty, Shaun; Zhao, Qiang; Gilbert, Elizabeth G; Ryan, Charles J; Chen, Wen-Tien; Paris, Pamela L

2014-05-15

The Vitatex cell-adhesion matrix (CAM) platform allows for isolation of invasive circulating tumor cells (iCTCs). Here we sought to determine the utility of prostate-specific membrane antigen (PSMA) as a metastatic castration-resistant prostate cancer (mCRPC) iCTC biomarker, to identify solitary cells and clusters of iCTCs expressing either epithelial, mesenchymal, or stem cell markers, and to explore the feasibility of iCTC epigenomic analysis. CTCs were isolated and enumerated simultaneously using the Vitatex and CellSearch platforms in 23 men with mCRPC. CAM-avid iCTCs were identified as nucleated cells capable of CAM uptake, but without detectable expression of hematopoietic lineage (HL) markers including CD45. iCTCs were enumerated immunocytochemically (ICC) and by flow cytometry. Whole-genome methylation status was determined for iCTCs using the Illumina HumanMethylation27 BeadChip. Thirty-four samples were collected for iCTC analysis. A median of 27 (range 0-800) and 23 (range 2-390) iCTCs/mL were detected by ICC and flow, respectively. In a subset of 20 samples, a median of seven CTCs/mL (range 0-85) were detected by the CellSearch platform compared to 26 by the CAM platform. iCTC clusters were observed in 17% of samples. iCTCs expressing PSMA as well as markers of EMT and stemness were detectable. The iCTC methylation profile highly resembled mCRPC. More CTCs were recovered using the CAM platform than the CellSearch platform, and the CAM platform allowed for the detection of iCTC clusters, iCTCs expressing EMT and stem-cell markers, and characterization of the iCTC methylome. Correlation with clinical data in future studies may yield further insight into the functional significance of these findings. © 2013 UICC.

International study on inter-reader variability for circulating tumor cells in breast cancer

PubMed Central

2014-01-01

Introduction Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch® system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement. Methods CellSearch® images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2- vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (κ) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test. Results For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median κ of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and <3CTCs (median 87%, range 66 to 95%) compared to M0 and ≥3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2- vs HER2+), the median agreement was 87% (range 51 to 95%) with a median κ of 0.74 (range 0.25 to 0.90). Conclusions The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required. PMID:24758318

CT colonography with reduced bowel preparation after incomplete colonoscopy in the elderly.

PubMed

Iafrate, F; Hassan, C; Zullo, A; Stagnitti, A; Ferrari, R; Spagnuolo, A; Laghi, A

2008-07-01

We prospectively assessed the feasibility and acceptance of computerized tomographic colonography (CTC) without bowel cathartic preparation in elderly patients after incomplete colonoscopy. A total of 136 patients underwent CTC without cathartic preparation. The time delay between conventional colonoscopy and CTC ranged between 3 and 20 days, depending on the clinical situation. Before CTC, fecal tagging was achieved by adding diatrizoate meglumine and diatrizoate sodium to regular meals. CTCs were interpreted using a primary two-dimensional (2D) approach and 3D images for further characterization. Patients were interviewed before and 2 weeks after CTC to assess preparation acceptance. CTC was feasible and technically successful in all the 136 patients. Fecal tagging was judged as excellent in 113 (83%) patients and sufficient in 23 (17%). Average CT image interpretation time was 14.8 min. Six (4.4%) cases of colorectal cancer and nine (6.6%) large polyps were detected, as well as 23 (11.3%) extracolonic findings of high clinical importance. No major side effect occurred, although 25% patients reported minor side effects, especially diarrhea. Overall, 76/98 patients replied that they would be willing to repeat the test if necessary. CTC without cathartic preparation is a technically feasible and safe procedure to complete a colonic study in the elderly, prompting its use in clinical practice.

The kinetics of the arginine deiminase pathway in the meat starter culture Lactobacillus sakei CTC 494 are pH-dependent.

PubMed

Rimaux, T; Vrancken, G; Pothakos, V; Maes, D; De Vuyst, L; Leroy, F

2011-05-01

Lactobacillus sakei is frequently present as the dominant lactic acid bacterium in spontaneously fermented meat products, demonstrating its competitiveness in and adaptation to the meat environment. Since meat is generally low in carbohydrate content, the ability to utilize other energy sources to generate ATP, such as arginine via the arginine deiminase (ADI) pathway, represents a competitive benefit. In this study, the kinetics of growth and arginine conversion capabilities of Lb. sakei CTC 494 were analyzed, and a model was set up to describe the influence of pH on growth and arginine conversion. A series of in vitro batch fermentations using reconstituted MRS medium at different constant pH values (pH 4.50-pH 7.75) was performed. Arginine conversion through the ADI pathway, which was activated from the stationary growth phase on, resulted in the production of both citrulline and ornithine for all pH conditions tested. However, the pattern and the ratio of the end-products of the ADI pathway were influenced by pH. For certain pH values (between pH 5.0 and 6.5), a further conversion of citrulline into ornithine was found when all arginine was depleted. Characterization of responses of the ADI pathway in Lb. sakei CTC 494 to environmental conditions will allow a better understanding and control of this important starter culture in meat fermentations. Copyright © 2010 Elsevier Ltd. All rights reserved.

Detection of Circulating Tumour Cells in Urothelial Cancers and Clinical Correlations: Comparison of Two Methods

PubMed Central

Fina, Emanuela; Necchi, Andrea; Bottelli, Stefano; Reduzzi, Carolina; Pizzamiglio, Sara; Iacona, Chiara; Daidone, Maria Grazia

2017-01-01

Circulating tumour cells (CTC) are identified exploiting their protein/gene expression patterns or distinct size compared to blood cells. Data on CTC in bladder cancer (BC) are still scarce. We comparatively analyzed CTC enrichment by AdnaTest ProstateCancerSelect (AT) and ScreenCell®Cyto (SC) kits, combined with identification by EPCAM, MUC1, and ERBB2 expression and by cytological criteria, respectively, in 19 nonmetastatic (M0) and 47 metastatic (M+) BC patients, at baseline (T0) and during treatment (T1). At T0, CTC positivity rates by AT were higher in M+ compared to M0 cases (57.4% versus 25%, p = 0.041). EPCAM was detected in 75% of CTC-positive samples by AT, showing increasing expression levels from T0 to T1 (median (interquartile range, IQR): 0.18 (0.07–0.42) versus 0.84 (0.33–1.84), p = 0.005) in M+ cases. Overall, CTC positivity by SC was around 80% regardless of clinical setting and time point of analysis, except for a lower occurrence at T1 in M0 cases. At T0, circulating tumour microemboli were more frequently (25% versus 8%) detected and more numerous in M+ compared to M0 patients. The approach used for CTC detection impacts the outcome of CTC studies. Further investigations are required to clarify the clinical validity of AT and SC in specific BC clinical contexts. PMID:28321147

Shallow Water UXO Technology Demonstration Site, Scoring Record No. 4 (CTC, FEREX DLG-GPS), MAG)

DTIC Science & Technology

2008-04-01

Detection and Discrimination Demonstration of a Fluxgate Vertical Gradient Magnetometer at the Aberdeen Shallow Water Test Site. Submitted in...TECHNOLOGY TYPE/PLATFORM: FEREX DLG-GPS MAGNETOMETER SYSTEM PREPARED BY: U.S. ARMY ABERDEEN TEST CENTER ABERDEEN PROVING GROUND, MD 21005...efforts of Concurrent Technologies Corporation (CTC) to detect and discriminate inert unexploded ordnance (UXO) using a FEREX DLG- magnetometer with a

Automated synthesis, insertion and detection of polyps for CT colonography

NASA Astrophysics Data System (ADS)

Sezille, Nicolas; Sadleir, Robert J. T.; Whelan, Paul F.

2003-03-01

CT Colonography (CTC) is a new non-invasive colon imaging technique which has the potential to replace conventional colonoscopy for colorectal cancer screening. A novel system which facilitates automated detection of colorectal polyps at CTC is introduced. As exhaustive testing of such a system using real patient data is not feasible, more complete testing is achieved through synthesis of artificial polyps and insertion into real datasets. The polyp insertion is semi-automatic: candidate points are manually selected using a custom GUI, suitable points are determined automatically from an analysis of the local neighborhood surrounding each of the candidate points. Local density and orientation information are used to generate polyps based on an elliptical model. Anomalies are identified from the modified dataset by analyzing the axial images. Detected anomalies are classified as potential polyps or natural features using 3D morphological techniques. The final results are flagged for review. The system was evaluated using 15 scenarios. The sensitivity of the system was found to be 65% with 34% false positive detections. Automated diagnosis at CTC is possible and thorough testing is facilitated by augmenting real patient data with computer generated polyps. Ultimately, automated diagnosis will enhance standard CTC and increase performance.

Robust coordinated control of a dual-arm space robot

NASA Astrophysics Data System (ADS)

Shi, Lingling; Kayastha, Sharmila; Katupitiya, Jay

2017-09-01

Dual-arm space robots are more capable of implementing complex space tasks compared with single arm space robots. However, the dynamic coupling between the arms and the base will have a serious impact on the spacecraft attitude and the hand motion of each arm. Instead of considering one arm as the mission arm and the other as the balance arm, in this work two arms of the space robot perform as mission arms aimed at accomplishing secure capture of a floating target. The paper investigates coordinated control of the base's attitude and the arms' motion in the task space in the presence of system uncertainties. Two types of controllers, i.e. a Sliding Mode Controller (SMC) and a nonlinear Model Predictive Controller (MPC) are verified and compared with a conventional Computed-Torque Controller (CTC) through numerical simulations in terms of control accuracy and system robustness. Both controllers eliminate the need to linearly parameterize the dynamic equations. The MPC has been shown to achieve performance with higher accuracy than CTC and SMC in the absence of system uncertainties under the condition that they consume comparable energy. When the system uncertainties are included, SMC and CTC present advantageous robustness than MPC. Specifically, in a case where system inertia increases, SMC delivers higher accuracy than CTC and costs the least amount of energy.

Application of optically-induced-dielectrophoresis in microfluidic system for purification of circulating tumour cells for gene expression analysis- Cancer cell line model

NASA Astrophysics Data System (ADS)

Chiu, Tzu-Keng; Chou, Wen-Pin; Huang, Song-Bin; Wang, Hung-Ming; Lin, Yung-Chang; Hsieh, Chia-Hsun; Wu, Min-Hsien

2016-09-01

Circulating tumour cells (CTCs) in a blood circulation system are associated with cancer metastasis. The analysis of the drug-resistance gene expression of cancer patients’ CTCs holds promise for selecting a more effective therapeutic regimen for an individual patient. However, the current CTC isolation schemes might not be able to harvest CTCs with sufficiently high purity for such applications. To address this issue, this study proposed to integrate the techniques of optically induced dielectrophoretic (ODEP) force-based cell manipulation and fluorescent microscopic imaging in a microfluidic system to further purify CTCs after the conventional CTC isolation methods. In this study, the microfluidic system was developed, and its optimal operating conditions and performance for CTC isolation were evaluated. The results revealed that the presented system was able to isolate CTCs with cell purity as high as 100%, beyond what is possible using the previously existing techniques. In the analysis of CTC gene expression, therefore, this method could exclude the interference of leukocytes in a cell sample and accordingly contribute to higher analytical sensitivity, as demonstrated in this study. Overall, this study has presented an ODEP-based microfluidic system capable of simply and effectively isolating a specific cell species from a cell mixture.

Application of optically-induced-dielectrophoresis in microfluidic system for purification of circulating tumour cells for gene expression analysis- Cancer cell line model.

PubMed

Chiu, Tzu-Keng; Chou, Wen-Pin; Huang, Song-Bin; Wang, Hung-Ming; Lin, Yung-Chang; Hsieh, Chia-Hsun; Wu, Min-Hsien

2016-09-09

Circulating tumour cells (CTCs) in a blood circulation system are associated with cancer metastasis. The analysis of the drug-resistance gene expression of cancer patients' CTCs holds promise for selecting a more effective therapeutic regimen for an individual patient. However, the current CTC isolation schemes might not be able to harvest CTCs with sufficiently high purity for such applications. To address this issue, this study proposed to integrate the techniques of optically induced dielectrophoretic (ODEP) force-based cell manipulation and fluorescent microscopic imaging in a microfluidic system to further purify CTCs after the conventional CTC isolation methods. In this study, the microfluidic system was developed, and its optimal operating conditions and performance for CTC isolation were evaluated. The results revealed that the presented system was able to isolate CTCs with cell purity as high as 100%, beyond what is possible using the previously existing techniques. In the analysis of CTC gene expression, therefore, this method could exclude the interference of leukocytes in a cell sample and accordingly contribute to higher analytical sensitivity, as demonstrated in this study. Overall, this study has presented an ODEP-based microfluidic system capable of simply and effectively isolating a specific cell species from a cell mixture.

Application of optically-induced-dielectrophoresis in microfluidic system for purification of circulating tumour cells for gene expression analysis- Cancer cell line model

PubMed Central

Chiu, Tzu-Keng; Chou, Wen-Pin; Huang, Song-Bin; Wang, Hung-Ming; Lin, Yung-Chang; Hsieh, Chia-Hsun; Wu, Min-Hsien

2016-01-01

Circulating tumour cells (CTCs) in a blood circulation system are associated with cancer metastasis. The analysis of the drug-resistance gene expression of cancer patients’ CTCs holds promise for selecting a more effective therapeutic regimen for an individual patient. However, the current CTC isolation schemes might not be able to harvest CTCs with sufficiently high purity for such applications. To address this issue, this study proposed to integrate the techniques of optically induced dielectrophoretic (ODEP) force-based cell manipulation and fluorescent microscopic imaging in a microfluidic system to further purify CTCs after the conventional CTC isolation methods. In this study, the microfluidic system was developed, and its optimal operating conditions and performance for CTC isolation were evaluated. The results revealed that the presented system was able to isolate CTCs with cell purity as high as 100%, beyond what is possible using the previously existing techniques. In the analysis of CTC gene expression, therefore, this method could exclude the interference of leukocytes in a cell sample and accordingly contribute to higher analytical sensitivity, as demonstrated in this study. Overall, this study has presented an ODEP-based microfluidic system capable of simply and effectively isolating a specific cell species from a cell mixture. PMID:27609546

Reprint of: Quantitative proteomic analysis reveals that chemotaxis is involved in chlortetracycline resistance of Aeromonas hydrophila.

PubMed

Li, Wanxin; Ali, Farman; Cai, Qilan; Yao, Zujie; Sun, Lina; Lin, Wenxiong; Lin, Xiangmin

2018-05-30

In recent years, Aeromonas hydrophila, which has been classified as a food borne pathogen, has presented with increased levels of antibiotic resistance, with the mechanisms of this resistance being poorly understood. In this study, iTRAQ coupled mass spectrometry was employed to compare differentially expressed proteins in chlortetracycline (CTC) resistant A. hydrophila relative to a control strain. Result showed that a total of 234 differential proteins including 151 down-regulated and 83 up-regulated were identified in chlortetracycline resistance strain. Bioinformatics analysis showed that chemotaxis related proteins, such as CheA-2, CheR-3, CheW-2, EnvZ, PolA, FliS and FliG were down-regulated in addition to previously reported tricarboxylic acid cycle (TCA) related proteins also being down-regulated. A subset of identified differentially expressed proteins was then further validated via Western blotting. Exogenous metabolite combined with CTC further enhanced the bacterial susceptibilities to CTC in A. hydrophila. Furthermore, a bacterial survival capability assay showed that several chemotaxis related mutants, such as ΔcheR-3 and ΔAHA_0305, may affect the antimicrobial susceptibility of A. hydrophila. Overall, these findings contribute to a further understanding of the mechanism of CTC resistance in A. hydrophila and may contribute to the development of more effective future treatments. A. hydrophila is a well-known fish pathogenic bacterium and has presented with increasing levels of antibiotic resistance, with the mechanisms of this resistance being poorly understood. Our current study compared the differentially expression proteins between chlortetracycline (CTC) resistant and control stains via an iTARQ-based quantitative proteomics method. Chemotaxis related proteins were down-regulated in CTC resistant strain but exogenous metabolite addition increased bacterial susceptibility in A.hydrophila. Significantly, chemotaxis related genes depletion affected antimicrobial susceptibilities of A.hydrophila indicating the role of chemotaxis process in antibiotics resistance. Copyright © 2018 Elsevier B.V. All rights reserved.

Isolation and characterization of circulating tumor cells using a novel workflow combining the CellSearch® system and the CellCelector™.

PubMed

Neumann, Martin Horst Dieter; Schneck, Helen; Decker, Yvonne; Schömer, Susanne; Franken, André; Endris, Volker; Pfarr, Nicole; Weichert, Wilko; Niederacher, Dieter; Fehm, Tanja; Neubauer, Hans

2017-01-01

Circulating tumor cells (CTC) are rare cells which have left the primary tumor to enter the blood stream. Although only a small CTC subgroup is capable of extravasating, the presence of CTCs is associated with an increased risk of metastasis and a shorter overall survival. Understanding the heterogeneous CTC biology will optimize treatment decisions and will thereby improve patient outcome. For this, robust workflows for detection and isolation of CTCs are urgently required. Here, we present a workflow to characterize CTCs by combining the advantages of both the CellSearch ® and the CellCelector™ micromanipulation system. CTCs were isolated from CellSearch ® cartridges using the CellCelector™ system and were deposited into PCR tubes for subsequent molecular analysis (whole genome amplification (WGA) and massive parallel multigene sequencing). By a CellCelector™ screen we reidentified 97% of CellSearch ® SKBR-3 cells. Furthermore, we isolated 97% of CellSearch ® -proven patient CTCs using the CellCelector™ system. Therein, we found an almost perfect correlation of R 2  = 0.98 (Spearman's rho correlation, n = 20, p < 0.00001) between the CellSearch ® CTC count (n = 271) and the CellCelector™ detected CTCs (n = 252). Isolated CTCs were analyzed by WGA and massive parallel multigene sequencing. In total, single nucleotide polymorphisms (SNPs) could be detected in 50 genes in seven CTCs, 12 MCF-7, and 3 T47D cells, respectively. Taken together, CTC quantification via the CellCelector™ system ensures a comprehensive detection of CTCs preidentified by the CellSearch ® system. Moreover, the isolation of CTCs after CellSearch ® using the CellCelector™ system guarantees for CTC enrichment without any contaminants enabling subsequent high throughput genomic analyses on single cell level. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:125-132, 2017. © 2016 American Institute of Chemical Engineers.

RECIST response and variation of circulating tumour cells in phase 1 trials: A prospective multicentric study.

PubMed

Massard, Christophe; Borget, Isabelle; Farace, Françoise; Aspeslagh, Sandrine; Le Deley, Marie-Cécile; Le Tourneau, Christophe; Bidard, François-Clement; Pierga, Jean-Yves; Dieras, Veronique; Hofman, Paul; Spano, Jean-Philippe; Ferte, Charles; Lacroix, Ludovic; Soria, Jean-Charles

2017-09-01

Circulating tumour cell (CTC) counting could be a new biomarker for better evaluation of tumour response to molecules tested in phase I trials. Consenting patients with advanced metastatic cancer referred to various phase I units were enrolled prospectively in this study. CTCs from 7.5 ml of whole blood drawn at baseline and after starting experimental therapy were counted using the CellSearch system, and tumour response was assessed using RECIST 1.1 criteria at baseline and 2 months after treatment initiation. Between March 2010 and May 2013, a total of 326 patients were enrolled, among whom 214 were evaluable (49% male, median age = 56; main cancer types: lung [28], colon [53], ovarian [18], breast [28]). At baseline, we detected ≥1 CTC/7.5 ml in 113/214 patients (53%), and at day 30, we observed ≥1 CTC/7.5 ml in 103/214 patients (48%). Two months after treatment initiation, 11 (5%) of the 214 patients were classified as having a partial response, with no CTCs in 9 of them or a decrease in the CTC count after therapy. In contrast, among the 104 patients (49%) classified as having progressive disease, 38 patients had a higher CTC count. The remaining 99 patients (49%), 33 of whom (33%) had a lower CTC count, were classified as having stable disease. The sensitivity and specificity of CTC variation for predicting progressive disease were 41% (32-51%) and 80% (73-88%) respectively. An early CTC change following therapy does not correlate with RECIST response in patients with advanced cancer enrolled in phase I trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microfluidic devices to enrich and isolate circulating tumor cells

PubMed Central

Myung, J. H.; Hong, S.

2015-01-01

Given the potential clinical impact of circulating tumor cells (CTCs) in blood as a clinical biomarker for diagnosis and prognosis of various cancers, a myriad of detection methods for CTCs have been recently introduced. Among those, a series of microfluidic devices are particularly promising as these uniquely offer micro-scale analytical systems that are highlighted by low consumption of samples and reagents, high flexibility to accommodate other cutting-edge technologies, precise and well-defined flow behaviors, and automation capability, presenting significant advantages over the conventional larger scale systems. In this review, we highlight the advantages of microfluidic devices and their translational potential into CTC detection methods, categorized by miniaturization of bench-top analytical instruments, integration capability with nanotechnologies, and in situ or sequential analysis of captured CTCs. This review provides a comprehensive overview of recent advances in the CTC detection achieved through application of microfluidic devices and their challenges that these promising technologies must overcome to be clinically impactful. PMID:26549749

Cost-effectiveness analysis of 3-D computerized tomography colonography versus optical colonoscopy for imaging symptomatic gastroenterology patients.

PubMed

Gomes, Manuel; Aldridge, Robert W; Wylie, Peter; Bell, James; Epstein, Owen

2013-04-01

When symptomatic gastroenterology patients have an indication for colonic imaging, clinicians have a choice between optical colonoscopy (OC) and computerized tomography colonography with three-dimensional reconstruction (3-D CTC). 3-D CTC provides a minimally invasive and rapid evaluation of the entire colon, and it can be an efficient modality for diagnosing symptoms. It allows for a more targeted use of OC, which is associated with a higher risk of major adverse events and higher procedural costs. A case can be made for 3-D CTC as a primary test for colonic imaging followed if necessary by targeted therapeutic OC; however, the relative long-term costs and benefits of introducing 3-D CTC as a first-line investigation are unknown. The aim of this study was to assess the cost effectiveness of 3-D CTC versus OC for colonic imaging of symptomatic gastroenterology patients in the UK NHS. We used a Markov model to follow a cohort of 100,000 symptomatic gastroenterology patients, aged 50 years or older, and estimate the expected lifetime outcomes, life years (LYs) and quality-adjusted life years (QALYs), and costs (£, 2010-2011) associated with 3-D CTC and OC. Sensitivity analyses were performed to assess the robustness of the base-case cost-effectiveness results to variation in input parameters and methodological assumptions. 3D-CTC provided a similar number of LYs (7.737 vs 7.739) and QALYs (7.013 vs 7.018) per individual compared with OC, and it was associated with substantially lower mean costs per patient (£467 vs £583), leading to a positive incremental net benefit. After accounting for the overall uncertainty, the probability of 3-D CTC being cost effective was around 60 %, at typical willingness-to-pay values of £20,000-£30,000 per QALY gained. 3-D CTC is a cost-saving and cost-effective option for colonic imaging of symptomatic gastroenterology patients compared with OC.

Administration of a co-crystal of tramadol and celecoxib in a 1:1 molecular ratio produces synergistic antinociceptive effects in a postoperative pain model in rats.

PubMed

Merlos, Manuel; Portillo-Salido, Enrique; Brenchat, Alex; Aubel, Bertrand; Buxens, Jordi; Fisas, Angels; Codony, Xavier; Romero, Luz; Zamanillo, Daniel; Vela, José Miguel

2018-06-19

Drug combination for the treatment of pain is common clinical practice. Co-crystal of Tramadol-Celecoxib (CTC) consists of two active pharmaceutical ingredients (APIs), namely the atypical opioid tramadol and the preferential cyclooxygenase-2 inhibitor celecoxib, at a 1:1 molecular ratio. In this study, a non-formulated 'raw' form of CTC administered in suspension (referred to as ctc susp ) was compared with both tramadol and celecoxib alone in a rat plantar incision postoperative pain model. For comparison, the strong opioids morphine and oxycodone, and a tramadol plus acetaminophen combination at a molecular ratio of 1:17 were also tested. Isobolographic analyses showed that ctc susp exerted synergistic mechanical antiallodynic (experimental ED 50 =2.0±0.5mg/kg, i.p.; theoretical ED 50 =3.8±0.4mg/kg, i.p.) and thermal (experimental ED 50 =2.3±0.5mg/kg, i.p.; theoretical ED 50 =9.8±0.8mg/kg, i.p.) antihyperalgesic effects in the postoperative pain model. In contrast, the tramadol and acetaminophen combination showed antagonistic effects on both mechanical allodynia and thermal hyperalgesia. No synergies between tramadol and celecoxib on locomotor activity, motor coordination, ulceration potential and gastrointestinal transit were observed after the administration of ctc susp . Overall, rat efficacy and safety data revealed that ctc susp provided synergistic analgesic effects compared with each API alone, without enhancing adverse effects. Moreover, ctc susp showed similar efficacy but improved safety ratio (80, measured as gastrointestinal transit vs postoperative pain ED 50 ratios) compared with the strong opioids morphine (2.5) and oxycodone (5.8). The overall in vivo profile of ctc susp supports the further investigation of CTC in the clinical management of moderate-to-severe acute pain as an alternative to strong opioids. Copyright © 2018. Published by Elsevier B.V.

The potential of imaging techniques as a screening tool for colorectal cancer: a cost-effectiveness analysis.

PubMed

Greuter, Marjolein J E; Berkhof, Johannes; Fijneman, Remond J A; Demirel, Erhan; Lew, Jie-Bin; Meijer, Gerrit A; Stoker, Jaap; Coupé, Veerle M H

2016-07-01

Imaging may be promising for colorectal cancer (CRC) screening, since it has test characteristics comparable with colonoscopy but is less invasive. We aimed to assess the potential of CT colonography (CTC) and MR colonography (MRC) in terms of (cost-effectiveness) using the Adenoma and Serrated pathway to Colorectal CAncer model. We compared several CTC and MRC strategies with 5- or 10-yearly screening intervals with no screening, 10-yearly colonoscopy screening and biennial faecal immunochemical test (FIT) screening. We assumed trial-based participation rates in the base-case analyses and varied the rates in sensitivity analyses. Incremental lifetime costs and health effects were estimated from a healthcare perspective. The health gain of CTC and MRC was similar and ranged from 0.031 to 0.048 life-year gained compared with no screening, for 2-5 screening rounds. Lifetime costs per person for MRC strategies were €60-110 higher than those for CTC strategies with an equal number of screening rounds. All imaging-based strategies were cost-effective compared with no screening. FIT screening was the dominant screening strategy, leading to most LYG and highest cost-savings. Compared with three rounds of colonoscopy screening, CTC with five rounds was found to be cost-effective in an incremental analysis of imaging strategies. Assumptions on screening participation have a major influence on the ordering of strategies in terms of costs and effects. CTC and MRC have potential for CRC screening, compared with no screening and compared with three rounds of 10-yearly colonoscopy screening. When taking FIT screening as the reference, imaging is not cost-effective. Participation is an important driver of effectiveness and cost estimates. This is the first study to assess the cost-effectiveness of MRC screening for CRC.

High-purity and label-free isolation of circulating tumor cells (CTCs) in a microfluidic platform by using optically-induced-dielectrophoretic (ODEP) force.

PubMed

Huang, Song-Bin; Wu, Min-Hsien; Lin, Yen-Heng; Hsieh, Chia-Hsun; Yang, Chih-Liang; Lin, Hung-Chih; Tseng, Ching-Ping; Lee, Gwo-Bin

2013-04-07

Negative selection-based circulating tumor cell (CTC) isolation is believed valuable to harvest more native, and in particular all possible CTCs without biases relevant to the properties of surface antigens on the CTCs. Under such a cell isolation strategy, however, the CTC purity is normally compromised. To address this issue, this study reports the integration of optically-induced-dielectrophoretic (ODEP) force-based cell manipulation, and a laminar flow regime in a microfluidic platform for the isolation of untreated, and highly pure CTCs after conventional negative selection-based CTC isolation. In the design, six sections of moving light-bar screens were continuously and simultaneously exerted in two parallel laminar flows to concurrently separate the cancer cells from the leukocytes based on their size difference and electric properties. The separated cell populations were further partitioned, delivered, and collected through the two flows. With this approach, the cancer cells can be isolated in a continuous, effective, and efficient manner. In this study, the operating conditions of ODEP for the manipulation of prostate cancer (PC-3) and human oral cancer (OEC-M1) cells, and leukocytes with minor cell aggregation phenomenon were first characterized. Moreover, performances of the proposed method for the isolation of cancer cells were experimentally investigated. The results showed that the presented CTC isolation scheme was able to isolate PC-3 cells or OEC-M1 cells from a leukocyte background with high recovery rate (PC-3 cells: 76-83%, OEC-M1 cells: 61-68%), and high purity (PC-3 cells: 74-82%, OEC-M1 cells: 64-66%) (set flow rate: 0.1 μl min(-1) and sample volume: 1 μl). The latter is beyond what is currently possible in the conventional CTC isolations. Moreover, the viability of isolated cancer cells was evaluated to be as high as 94 ± 2%, and 95 ± 3% for the PC-3, and OEC-M1 cells, respectively. Furthermore, the isolated cancer cells were also shown to preserve their proliferative capability. As a whole, this study has presented an ODEP-based microfluidic platform that is capable of isolating CTCs in a continuous, label-free, cell-friendly, and particularly highly pure manner. All these traits are found particularly meaningful for exploiting the harvested CTCs for the subsequent cell-based, or biochemical assays.

Transparent, biocompatible nanostructured surfaces for cancer cell capture and culture

PubMed Central

Cheng, Boran; He, Zhaobo; Zhao, Libo; Fang, Yuan; Chen, Yuanyuan; He, Rongxiang; Chen, Fangfang; Song, Haibin; Deng, Yuliang; Zhao, Xingzhong; Xiong, Bin

2014-01-01

Circulating tumor cells (CTCs) in the blood which have detached from both the primary tumor and any metastases may be considered as a “liquid biopsy” and are expected to replace tumor biopsies in the monitoring of treatment response and determining patient prognosis. Here, we introduce a facile and efficient CTC detection material made of hydroxyapatite/chitosan (HA/CTS), which is beneficial because of its transparency and excellent biological compatibility. Atomic force microscopy images show that the roughness of the HA/CTS nanofilm (HA/CTSNF) substrates can be controlled by changing the HA:CTS ratio. Enhanced local topographic interactions between nano-components on cancer cell membranes, and the antibody coated nanostructured substrate lead to improved CTC capture and separation. This remarkable nanostructured substrate has the potential for CTC culture in situ and merits further analysis. CTCs captured from artificial blood samples were observed in culture on HA/CTSNF substrates over a period of 14 days by using conventional staining methods (hematoxylin eosin and Wright’s stain). We conclude that these substrates are multifunctional materials capable of isolating and culturing CTCs for subsequent studies. PMID:24904216

Installing the Communities that Care Prevention System: Implementation Progress and Fidelity in a Randomized Controlled Trial

ERIC Educational Resources Information Center

Quinby, Rose K.; Hanson, Koren; Brooke-Weiss, Blair; Arthur, Michael W.; Hawkins, J. David; Fagan, Abigail A.

2008-01-01

This article describes the degree to which high fidelity implementation of the Communities That Care (CTC) prevention operating system was reached during the first 18 months of intervention in 12 communities in the Community Youth Development Study, a 5-year group randomized controlled trial designed to test the efficacy of the CTC system. CTC…

Sensitive detection of viable circulating tumor cells using a novel conditionally telomerase-selective replicating adenovirus in non-small cell lung cancer patients

PubMed Central

Togo, Shinsaku; Katagiri, Nobuyoshi; Namba, Yukiko; Tulafu, Miniwan; Nagahama, Kumi; Kadoya, Kotarou; Takamochi, Kazuya; Oh, Siaki; Suzuki, Kenji; Sakurai, Fuminori; Mizuguchi, Hiroyuki; Urata, Yasuo; Takahashi, Kazuhisa

2017-01-01

Circulating tumor cells (CTCs) have a crucial role in the clinical outcome of cancer patients. Detection of non-small cell lung cancer (NSCLC) using an antibody against epithelial cell adhesion molecule (EpCAM) in captured CTCs has low sensitivity; the loss of epithelial markers leads to underestimation of CTCs with mesenchymal phenotype. We propose a new approach for detection of viable CTCs, including those with epithelial-mesenchymal transition status (EMT-CTCs), using the new telomerase-specific replication-selective adenovirus (OBP-1101), TelomeScan F35. Peripheral venous blood samples and clinicopathological data were collected from 123 NSCLC patients. The sensitivity of CTC detection was 69.1%, and for patients with stage I, II, III and IV, it was 59.6%, 40.0%, 85.7%, and 75.0%, respectively. Among the EMT-CTC samples, 46% were vimentin positive and 39.0% of non-EMT-CTC samples were EpCAM positive. Patients testing positive for EMT-CTCs at baseline had poor response to chemotherapy (P = 0.025) and decreased progression-free survival (EMT-CTC positive vs. negative: 193 ± 47 days vs. 388 ± 47. days, P = 0.040) in comparison to those testing negative. TelomeScan F35 is a highly sensitive CTC detection system and will be a useful screening tool for early diagnosis of NSCLC patients. Mesenchymal-phenotype CTCs are crucial indicators of chemotherapeutic efficacy in NSCLC patients. PMID:28432274

Circulating Tumor Cells: What Is in It for the Patient? A Vision towards the Future

PubMed Central

van de Stolpe, Anja; den Toonder, Jaap M. J.

2014-01-01

Knowledge on cellular signal transduction pathways as drivers of cancer growth and metastasis has fuelled development of “targeted therapy” which “targets” aberrant oncogenic signal transduction pathways. These drugs require nearly invariably companion diagnostic tests to identify the tumor-driving pathway and the cause of the abnormal pathway activity in a tumor sample, both for therapy response prediction as well as for monitoring of therapy response and emerging secondary drug resistance. Obtaining sufficient tumor material for this analysis in the metastatic setting is a challenge, and circulating tumor cells (CTCs) may provide an attractive alternative to biopsy on the premise that they can be captured from blood and the companion diagnostic test results are correctly interpreted. We discuss novel companion diagnostic directions, including the challenges, to identify the tumor driving pathway in CTCs, which in combination with a digital pathology platform and algorithms to quantitatively interpret complex CTC diagnostic results may enable optimized therapy response prediction and monitoring. In contrast to CTC-based companion diagnostics, CTC enumeration is envisioned to be largely replaced by cell free tumor DNA measurements in blood for therapy response and recurrence monitoring. The recent emergence of novel in vitro human model systems in the form of cancer-on-a-chip may enable elucidation of some of the so far elusive characteristics of CTCs, and is expected to contribute to more efficient CTC capture and CTC-based diagnostics. PMID:24879438

Sensitive detection of viable circulating tumor cells using a novel conditionally telomerase-selective replicating adenovirus in non-small cell lung cancer patients.

PubMed

Togo, Shinsaku; Katagiri, Nobuyoshi; Namba, Yukiko; Tulafu, Miniwan; Nagahama, Kumi; Kadoya, Kotarou; Takamochi, Kazuya; Oh, Siaki; Suzuki, Kenji; Sakurai, Fuminori; Mizuguchi, Hiroyuki; Urata, Yasuo; Takahashi, Kazuhisa

2017-05-23

Circulating tumor cells (CTCs) have a crucial role in the clinical outcome of cancer patients. Detection of non-small cell lung cancer (NSCLC) using an antibody against epithelial cell adhesion molecule (EpCAM) in captured CTCs has low sensitivity; the loss of epithelial markers leads to underestimation of CTCs with mesenchymal phenotype. We propose a new approach for detection of viable CTCs, including those with epithelial-mesenchymal transition status (EMT-CTCs), using the new telomerase-specific replication-selective adenovirus (OBP-1101), TelomeScan F35. Peripheral venous blood samples and clinicopathological data were collected from 123 NSCLC patients. The sensitivity of CTC detection was 69.1%, and for patients with stage I, II, III and IV, it was 59.6%, 40.0%, 85.7%, and 75.0%, respectively. Among the EMT-CTC samples, 46% were vimentin positive and 39.0% of non-EMT-CTC samples were EpCAM positive. Patients testing positive for EMT-CTCs at baseline had poor response to chemotherapy (P = 0.025) and decreased progression-free survival (EMT-CTC positive vs. negative: 193 ± 47 days vs. 388 ± 47. days, P = 0.040) in comparison to those testing negative. TelomeScan F35 is a highly sensitive CTC detection system and will be a useful screening tool for early diagnosis of NSCLC patients. Mesenchymal-phenotype CTCs are crucial indicators of chemotherapeutic efficacy in NSCLC patients.

Effects of Communities That Care on Males' and Females' Drug Use and Delinquency 9 Years After Baseline in a Community-Randomized Trial.

PubMed

Oesterle, Sabrina; Hawkins, J David; Kuklinski, Margaret R; Fagan, Abigail A; Fleming, Christopher; Rhew, Isaac C; Brown, Eric C; Abbott, Robert D; Catalano, Richard F

2015-12-01

This study tested sustained effects of the Communities That Care (CTC) prevention system on health-risking behaviors 9 years after baseline in a community-randomized trial involving 24 towns in seven states. Earlier analyses found sustained effects on abstinence from drug use and delinquency through Grade 12 in a panel of fifth graders. At age 19, 91 % (n = 3986) of the living panel completed the survey. Data were analyzed using generalized linear mixed models. The prevalence of lifetime and current substance use and delinquency were the primary outcomes. Secondary outcomes included substance use disorders, major depression, suicidality, educational attainment, and sexual risk behaviors. CTC had a significant overall effect across lifetime measures of the primary outcomes for males, but not for females or the full sample, although lifetime abstinence from delinquency in the full sample was significantly higher in CTC communities (ARR = 1.16). Males in CTC communities also continued to show greater lifetime abstinence from cigarette smoking (ARR = 1.22). CTC did not have a sustained effect on current substance use and delinquency nor did it improve the secondary outcomes at age 19 for either gender. Communities using CTC may need to extend their prevention planning to include the high school years to sustain effects on drug use and delinquency beyond high school for both genders. ClinicalTrials.gov identifier: NCT01088542.

Effects of Communities That Care on Males’ and Females’ Drug Use and Delinquency 9 Years After Baseline in a Community-Randomized Trial

PubMed Central

Hawkins, J. David; Kuklinski, Margaret R.; Fagan, Abigail A.; Fleming, Christopher; Rhew, Isaac C.; Brown, Eric C.; Abbott, Robert D.; Catalano, Richard F.

2016-01-01

This study tested sustained effects of the Communities That Care (CTC) prevention system on health-risking behaviors 9 years after baseline in a community-randomized trial involving 24 towns in seven states. Earlier analyses found sustained effects on abstinence from drug use and delinquency through Grade 12 in a panel of fifth graders. At age 19, 91 % (n = 3986) of the living panel completed the survey. Data were analyzed using generalized linear mixed models. The prevalence of lifetime and current substance use and delinquency were the primary outcomes. Secondary outcomes included substance use disorders, major depression, suicidality, educational attainment, and sexual risk behaviors. CTC had a significant overall effect across lifetime measures of the primary outcomes for males, but not for females or the full sample, although lifetime abstinence from delinquency in the full sample was significantly higher in CTC communities (ARR = 1.16). Males in CTC communities also continued to show greater lifetime abstinence from cigarette smoking (ARR = 1.22). CTC did not have a sustained effect on current substance use and delinquency nor did it improve the secondary outcomes at age 19 for either gender. Communities using CTC may need to extend their prevention planning to include the high school years to sustain effects on drug use and delinquency beyond high school for both genders. PMID:26377418

Prognostic value of Child-Turcotte criteria in medically treated cirrhosis.

PubMed

Christensen, E; Schlichting, P; Fauerholdt, L; Gluud, C; Andersen, P K; Juhl, E; Poulsen, H; Tygstrup, N

1984-01-01

The Child- Turcotte criteria (CTC) (based on serum bilirubin and albumin, ascites, neurological disorder and nutrition) are established prognostic factors in patients with cirrhosis having portacaval shunt surgery. The objective of this study was to evaluate the prognostic value of CTC in conservatively treated cirrhosis. Patients (n = 245) with histologically verified cirrhosis from a control group of a controlled clinical trial were studied. Data at entry into the trial were used to classify patients according to CTC. Survival curves for up to 16 years were made, and survival rates were compared using the log-rank test. Survival decreased significantly with increasing degree of abnormality (A----B----C) of albumin (p less than 0.001), ascites (p less than 0.001), bilirubin (p = 0.02) and nutritional status (p = 0.03). Survival was insignificantly influenced by neurological status (p = 0.11) probably because none of the patients had hepatic coma at entry into the trial. The five variables in CTC were combined to a score. With increasing score, the median survival time decreased from 6.4 years (score 5) to 2 months (scores 12 or more). Furthermore, the mortality from hepatic failure, gastrointestinal bleeding or hepatocellular carcinoma increased significantly with increasing score. CTC provide valuable and easily obtainable prognostic information in cirrhosis. However, CTC are inferior to a prognostic index based on multivariate analysis of prognostic factors.

Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer

PubMed Central

Lim, Tony KH; Tan, Daniel Shao-Weng; Chua, Yong Wei; Ang, Mei Kim; Pang, Brendan; Lim, Chwee Teck; Takano, Angela; Lim, Alvin Soon-Tiong; Leong, Man Chun; Lim, Wan-Teck

2016-01-01

Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) is routinely evaluated by fluorescent in-situ hybridization (FISH) testing on biopsy tissues. Testing can be challenging however, when suitable tissue samples are unavailable. We examined the relevance of circulating tumor cells (CTC) as a surrogate for biopsy-based FISH testing. We assessed paired tumor and CTC samples from patients with ALK rearranged lung cancer (n = 14), ALK-negative lung cancer (n = 12), and healthy controls (n = 5) to derive discriminant CTC counts, and to compare ALK rearrangement patterns. Blood samples were enriched for CTCs to be used for ALK FISH testing. ALK-positive CTCs counts were higher in ALK-positive NSCLC patients (3–15 cells/1.88 mL of blood) compared with ALK-negative NSCLC patients and healthy donors (0–2 cells/1.88 mL of blood). The latter range was validated as the ‘false positive’ cutoff for ALK FISH testing of CTCs. ALK FISH signal patterns observed on tumor biopsies were recapitulated in CTCs in all cases. Sequential CTC counts in an index case of lung cancer with no evaluable tumor tissue treated with crizotinib showed six, three and eleven ALK-positive CTCs per 1.88 mL blood at baseline, partial response and post-progression time points, respectively. Furthermore, ALK FISH rearrangement suggestive of gene copy number increase was observed in CTCs following progression. Recapitulation of ALK rearrangement patterns in the tumor on CTCs, suggested that CTCs might be used to complement tissue-based ALK testing in NSCLC to guide ALK-targeted therapy when suitable tissue biopsy samples are unavailable for testing. PMID:26993609

Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer.

PubMed

Tan, Chye Ling; Lim, Tse Hui; Lim, Tony Kh; Tan, Daniel Shao-Weng; Chua, Yong Wei; Ang, Mei Kim; Pang, Brendan; Lim, Chwee Teck; Takano, Angela; Lim, Alvin Soon-Tiong; Leong, Man Chun; Lim, Wan-Teck

2016-04-26

Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) is routinely evaluated by fluorescent in-situ hybridization (FISH) testing on biopsy tissues. Testing can be challenging however, when suitable tissue samples are unavailable. We examined the relevance of circulating tumor cells (CTC) as a surrogate for biopsy-based FISH testing. We assessed paired tumor and CTC samples from patients with ALK rearranged lung cancer (n = 14), ALK-negative lung cancer (n = 12), and healthy controls (n = 5) to derive discriminant CTC counts, and to compare ALK rearrangement patterns. Blood samples were enriched for CTCs to be used for ALK FISH testing. ALK-positive CTCs counts were higher in ALK-positive NSCLC patients (3-15 cells/1.88 mL of blood) compared with ALK-negative NSCLC patients and healthy donors (0-2 cells/1.88 mL of blood). The latter range was validated as the 'false positive' cutoff for ALK FISH testing of CTCs. ALK FISH signal patterns observed on tumor biopsies were recapitulated in CTCs in all cases. Sequential CTC counts in an index case of lung cancer with no evaluable tumor tissue treated with crizotinib showed six, three and eleven ALK-positive CTCs per 1.88 mL blood at baseline, partial response and post-progression time points, respectively. Furthermore, ALK FISH rearrangement suggestive of gene copy number increase was observed in CTCs following progression. Recapitulation of ALK rearrangement patterns in the tumor on CTCs, suggested that CTCs might be used to complement tissue-based ALK testing in NSCLC to guide ALK-targeted therapy when suitable tissue biopsy samples are unavailable for testing.

Variation in the sustained effects of the communities that care prevention system on adolescent smoking, delinquency, and violence.

PubMed

Oesterle, Sabrina; Hawkins, J David; Fagan, Abigail A; Abbott, Robert D; Catalano, Richard F

2014-04-01

Communities That Care (CTC) is a universal, science-based community prevention system designed to reduce risk, enhance protection, and prevent adolescent health and behavior problems community wide. CTC has been found to have sustained effects on cigarette use and delinquent and violent behaviors in grade 10 in a panel of 4,407 students followed from fifth grade in a community randomized trial. It is important to test variation in the effects of this prevention system designed to be universal to understand for whom it is most effective and whether it fails to produce change or leads to iatrogenic effects for certain categories of individuals. The present study examined variation in the sustained effects of CTC on tenth-grade cigarette use and delinquent and violent behaviors. Interaction analyses suggest that the effect of CTC did not differ between those who had high levels of community-targeted risk factors at baseline or had already engaged in substance use, delinquency, or violence at baseline versus those who had not. Although CTC reduced the prevalence of both girls' and boys' problem behaviors, the effect on delinquency was marginally (p = 0.08) larger for boys than for girls.

Effect of monoclonal antibodies (MoAb) to class I and class II HLA antigens on lectin- and MoAb OKT3-induced lymphocyte proliferation.

PubMed

Akiyama, Y; Zicht, R; Ferrone, S; Bonnard, G D; Herberman, R B

1985-04-01

We have examined the effect of several monoclonal antibodies (MoAb) to monomorphic determinants of class II HLA antigens, and MoAb to monomorphic determinants of class I HLA antigens and to beta-2-microglobulin (beta 2-mu) on lectin- and MoAb OKT3-induced proliferation of human peripheral blood mononuclear cells (PBMNC) and cultured T cells (CTC). Some, but not all, anti-class II HLA MoAb inhibited the proliferative response of PBMNC to MoAb OKT3 and pokeweed mitogen (PWM). The degree of inhibitory effect varied considerably. This effect was not limited to anti-class II HLA MoAb since anti-class I HLA MoAb and anti-beta 2-mu MoAb also inhibited MoAb OKT3- or PWM-induced proliferative responses. In contrast, the response of PBMNC to phytohemagglutinin (PHA) and concanavalin A (Con A) was not blocked by any anti-class II HLA MoAb. However, some anti-class II HLA MoAb also inhibited the proliferative response of CTC plus allogeneic peripheral blood adherent accessory cells (AC) to PHA or Con A as well as to MoAb OKT3 or PWM. This may be attributable to the substantially greater class II HLA antigen expression by CTC than by fresh lymphocytes. Pretreatment of either CTC or AC with anti-class II HLA MoAb inhibited OKT3-induced proliferation. In contrast, pretreatment of CTC, but not AC, with anti-class I HLA MoAb inhibited the proliferative response of CTC to OKT3. Pretreatment of CTC with anti-class I HLA MoAb inhibited PHA-, Con A and PWM-induced proliferation, to a greater degree than the anti-class II HLA MoAb. It appears as if lymphocyte activation by different mitogens exhibits variable requirements for the presence of cells expressing major histocompatibility determinants. Binding of Ab to membrane markers may interfere with lymphocyte-AC cooperation, perhaps by inhibiting binding of mitogens to their receptors or by interfering with lymphocyte and AC function. We also have examined the role of class II HLA antigens on CTC by depleting class II HLA-positive cells. As expected, elimination of class II HLA-positive AC with anti-class II HLA MoAb plus complement caused a decrease in proliferation of CTC in response to all the mitogens tested. In contrast, elimination of class II HLA-positive CTC was shown to clearly increase proliferation of CTC, perhaps because this may deplete class II HLA-positive suppressor cells.

Arrays of High-Aspect Ratio Microchannels for High-Throughput Isolation of Circulating Tumor Cells (CTCs).

PubMed

Hupert, Mateusz L; Jackson, Joshua M; Wang, Hong; Witek, Małgorzata A; Kamande, Joyce; Milowsky, Matthew I; Whang, Young E; Soper, Steven A

2014-10-01

Microsystem-based technologies are providing new opportunities in the area of in vitro diagnostics due to their ability to provide process automation enabling point-of-care operation. As an example, microsystems used for the isolation and analysis of circulating tumor cells (CTCs) from complex, heterogeneous samples in an automated fashion with improved recoveries and selectivity are providing new opportunities for this important biomarker. Unfortunately, many of the existing microfluidic systems lack the throughput capabilities and/or are too expensive to manufacture to warrant their widespread use in clinical testing scenarios. Here, we describe a disposable, all-polymer, microfluidic system for the high-throughput (HT) isolation of CTCs directly from whole blood inputs. The device employs an array of high aspect ratio (HAR), parallel, sinusoidal microchannels (25 µm × 150 µm; W × D; AR = 6.0) with walls covalently decorated with anti-EpCAM antibodies to provide affinity-based isolation of CTCs. Channel width, which is similar to an average CTC diameter (12-25 µm), plays a critical role in maximizing the probability of cell/wall interactions and allows for achieving high CTC recovery. The extended channel depth allows for increased throughput at the optimized flow velocity (2 mm/s in a microchannel); maximizes cell recovery, and prevents clogging of the microfluidic channels during blood processing. Fluidic addressing of the microchannel array with a minimal device footprint is provided by large cross-sectional area feed and exit channels poised orthogonal to the network of the sinusoidal capillary channels (so-called Z-geometry). Computational modeling was used to confirm uniform addressing of the channels in the isolation bed. Devices with various numbers of parallel microchannels ranging from 50 to 320 have been successfully constructed. Cyclic olefin copolymer (COC) was chosen as the substrate material due to its superior properties during UV-activation of the HAR microchannels surfaces prior to antibody attachment. Operation of the HT-CTC device has been validated by isolation of CTCs directly from blood secured from patients with metastatic prostate cancer. High CTC sample purities (low number of contaminating white blood cells, WBCs) allowed for direct lysis and molecular profiling of isolated CTCs.

Unbiased and automated identification of a circulating tumour cell definition that associates with overall survival.

PubMed

Ligthart, Sjoerd T; Coumans, Frank A W; Attard, Gerhardt; Cassidy, Amy Mulick; de Bono, Johann S; Terstappen, Leon W M M

2011-01-01

Circulating tumour cells (CTC) in patients with metastatic carcinomas are associated with poor survival and can be used to guide therapy. Classification of CTC however remains subjective, as they are morphologically heterogeneous. We acquired digital images, using the CellSearch™ system, from blood of 185 castration resistant prostate cancer (CRPC) patients and 68 healthy subjects to define CTC by computer algorithms. Patient survival data was used as the training parameter for the computer to define CTC. The computer-generated CTC definition was validated on a separate CRPC dataset comprising 100 patients. The optimal definition of the computer defined CTC (aCTC) was stricter as compared to the manual CellSearch CTC (mCTC) definition and as a consequence aCTC were less frequent. The computer-generated CTC definition resulted in hazard ratios (HRs) of 2.8 for baseline and 3.9 for follow-up samples, which is comparable to the mCTC definition (baseline HR 2.9, follow-up HR 4.5). Validation resulted in HRs at baseline/follow-up of 3.9/5.4 for computer and 4.8/5.8 for manual definitions. In conclusion, we have defined and validated CTC by clinical outcome using a perfectly reproducing automated algorithm.

Prior Image Constrained Compressed Sensing Metal Artifact Reduction (PICCS-MAR): 2D and 3D Image Quality Improvement with Hip Prostheses at CT Colonography.

PubMed

Bannas, Peter; Li, Yinsheng; Motosugi, Utaroh; Li, Ke; Lubner, Meghan; Chen, Guang-Hong; Pickhardt, Perry J

2016-07-01

To assess the effect of the prior-image-constrained-compressed-sensing-based metal-artefact-reduction (PICCS-MAR) algorithm on streak artefact reduction and 2D and 3D-image quality improvement in patients with total hip arthroplasty (THA) undergoing CT colonography (CTC). PICCS-MAR was applied to filtered-back-projection (FBP)-reconstructed DICOM CTC-images in 52 patients with THA (unilateral, n = 30; bilateral, n = 22). For FBP and PICCS-MAR series, ROI-measurements of CT-numbers were obtained at predefined levels for fat, muscle, air, and the most severe artefact. Two radiologists independently reviewed 2D and 3D CTC-images and graded artefacts and image quality using a five-point-scale (1 = severe streak/no-diagnostic confidence, 5 = no streak/excellent image-quality, high-confidence). Results were compared using paired and unpaired t-tests and Wilcoxon signed-rank and Mann-Whitney-tests. Streak artefacts and image quality scores for FBP versus PICCS-MAR 2D-images (median: 1 vs. 3 and 2 vs. 3, respectively) and 3D images (median: 2 vs. 4 and 3 vs. 4, respectively) showed significant improvement after PICCS-MAR (all P < 0.001). PICCS-MAR significantly improved the accuracy of mean CT numbers for fat, muscle and the area with the most severe artefact (all P < 0.001). PICCS-MAR substantially reduces streak artefacts related to THA on DICOM images, thereby enhancing visualization of anatomy on 2D and 3D CTC images and increasing diagnostic confidence. • PICCS-MAR significantly reduces streak artefacts associated with total hip arthroplasty on 2D and 3D CTC. • PICCS-MAR significantly improves 2D and 3D CTC image quality and diagnostic confidence. • PICCS-MAR can be applied retrospectively to DICOM images from single-kVp CT.

Highly efficient capture and harvest of circulating tumor cells on a microfluidic chip integrated with herringbone and micropost arrays.

PubMed

Xue, Peng; Wu, Yafeng; Guo, Jinhong; Kang, Yuejun

2015-04-01

Circulating tumor cells (CTCs), which are derived from primary tumor site and transported to distant organs, are considered as the major cause of metastasis. So far, various techniques have been applied for CTC isolation and enumeration. However, there exists great demand to improve the sensitivity of CTC capture, and it remains challenging to elute the cells efficiently from device for further biomolecular and cellular analyses. In this study, we fabricate a dual functional chip integrated with herringbone structure and micropost array to achieve CTC capture and elution through EpCAM-based immunoreaction. Hep3B tumor cell line is selected as the model of CTCs for processing using this device. The results demonstrate that the capture limit of Hep3B cells can reach up to 10 cells (per mL of sample volume) with capture efficiency of 80% on average. Moreover, the elution rate of the captured Hep3B cells can reach up to 69.4% on average for cell number ranging from 1 to 100. These results demonstrate that this device exhibits dual functions with considerably high capture rate and elution rate, indicating its promising capability for cancer diagnosis and therapeutics.

Circulating tumour cells, their role in metastasis and their clinical utility in lung cancer.

PubMed

O'Flaherty, John D; Gray, Steven; Richard, Derek; Fennell, Dean; O'Leary, John J; Blackhall, Fiona H; O'Byrne, Kenneth J

2012-04-01

Circulating tumour cells (CTCs) have attracted much recent interest in cancer research as a potential biomarker and as a means of studying the process of metastasis. It has long been understood that metastasis is a hallmark of malignancy, and conceptual theories on the basis of metastasis from the nineteenth century foretold the existence of a tumour "seed" which is capable of establishing discrete tumours in the "soil" of distant organs. This prescient "seed and soil" hypothesis accurately predicted the existence of CTCs; microscopic tumour fragments in the blood, at least some of which are capable of forming metastases. However, it is only in recent years that reliable, reproducible methods of CTC detection and analysis have been developed. To date, the majority of studies have employed the CellSearch™ system (Veridex LLC), which is an immunomagnetic purification method. Other promising techniques include microfluidic filters, isolation of tumour cells by size using microporous polycarbonate filters and flow cytometry-based approaches. While many challenges still exist, the detection of CTCs in blood is becoming increasingly feasible, giving rise to some tantalizing questions about the use of CTCs as a potential biomarker. CTC enumeration has been used to guide prognosis in patients with metastatic disease, and to act as a surrogate marker for disease response during therapy. Other possible uses for CTC detection include prognostication in early stage patients, identifying patients requiring adjuvant therapy, or in surveillance, for the detection of relapsing disease. Another exciting possible use for CTC detection assays is the molecular and genetic characterization of CTCs to act as a "liquid biopsy" representative of the primary tumour. Indeed it has already been demonstrated that it is possible to detect HER2, KRAS and EGFR mutation status in breast, colon and lung cancer CTCs respectively. In the course of this review, we shall discuss the biology of CTCs and their role in metastagenesis, the most commonly used techniques for their detection and the evidence to date of their clinical utility, with particular reference to lung cancer. Copyright © 2012. Published by Elsevier Ireland Ltd.

Registration of prone and supine CT colonography scans using correlation optimized warping and canonical correlation analysis

PubMed Central

Wang, Shijun; Yao, Jianhua; Liu, Jiamin; Petrick, Nicholas; Van Uitert, Robert L.; Periaswamy, Senthil; Summers, Ronald M.

2009-01-01

Purpose: In computed tomographic colonography (CTC), a patient will be scanned twice—Once supine and once prone—to improve the sensitivity for polyp detection. To assist radiologists in CTC reading, in this paper we propose an automated method for colon registration from supine and prone CTC scans. Methods: We propose a new colon centerline registration method for prone and supine CTC scans using correlation optimized warping (COW) and canonical correlation analysis (CCA) based on the anatomical structure of the colon. Four anatomical salient points on the colon are first automatically distinguished. Then correlation optimized warping is applied to the segments defined by the anatomical landmarks to improve the global registration based on local correlation of segments. The COW method was modified by embedding canonical correlation analysis to allow multiple features along the colon centerline to be used in our implementation. Results: We tested the COW algorithm on a CTC data set of 39 patients with 39 polyps (19 training and 20 test cases) to verify the effectiveness of the proposed COW registration method. Experimental results on the test set show that the COW method significantly reduces the average estimation error in a polyp location between supine and prone scans by 67.6%, from 46.27±52.97 to 14.98 mm±11.41 mm, compared to the normalized distance along the colon centerline algorithm (p<0.01). Conclusions: The proposed COW algorithm is more accurate for the colon centerline registration compared to the normalized distance along the colon centerline method and the dynamic time warping method. Comparison results showed that the feature combination of z-coordinate and curvature achieved lowest registration error compared to the other feature combinations used by COW. The proposed method is tolerant to centerline errors because anatomical landmarks help prevent the propagation of errors across the entire colon centerline. PMID:20095272

Registration of prone and supine CT colonography scans using correlation optimized warping and canonical correlation analysis

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

Wang Shijun; Yao Jianhua; Liu Jiamin

Purpose: In computed tomographic colonography (CTC), a patient will be scanned twice--Once supine and once prone--to improve the sensitivity for polyp detection. To assist radiologists in CTC reading, in this paper we propose an automated method for colon registration from supine and prone CTC scans. Methods: We propose a new colon centerline registration method for prone and supine CTC scans using correlation optimized warping (COW) and canonical correlation analysis (CCA) based on the anatomical structure of the colon. Four anatomical salient points on the colon are first automatically distinguished. Then correlation optimized warping is applied to the segments defined bymore » the anatomical landmarks to improve the global registration based on local correlation of segments. The COW method was modified by embedding canonical correlation analysis to allow multiple features along the colon centerline to be used in our implementation. Results: We tested the COW algorithm on a CTC data set of 39 patients with 39 polyps (19 training and 20 test cases) to verify the effectiveness of the proposed COW registration method. Experimental results on the test set show that the COW method significantly reduces the average estimation error in a polyp location between supine and prone scans by 67.6%, from 46.27{+-}52.97 to 14.98 mm{+-}11.41 mm, compared to the normalized distance along the colon centerline algorithm (p<0.01). Conclusions: The proposed COW algorithm is more accurate for the colon centerline registration compared to the normalized distance along the colon centerline method and the dynamic time warping method. Comparison results showed that the feature combination of z-coordinate and curvature achieved lowest registration error compared to the other feature combinations used by COW. The proposed method is tolerant to centerline errors because anatomical landmarks help prevent the propagation of errors across the entire colon centerline.« less

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

PubMed

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

2015-01-01

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

Contribution of native phosphorous-solubilizing bacteria of acid soils on phosphorous acquisition in peanut (Arachis hypogaea L.).

PubMed

Pradhan, Madhusmita; Sahoo, Ranjan Kumar; Pradhan, Chinmay; Tuteja, Narendra; Mohanty, Santanu

2017-11-01

The present investigation analyzes the in vitro P solubilization [Ca-P, Al-P, Fe(II)-P, and Fe(III)-P] efficiency of native PSB strains from acid soils of Odisha and exploitation of the same through biofertilization in peanut (Arachis hypogaea L.) growth and P acquisition. One hundred six numbers of soil samples with pH ≤ 5.50 were collected from five districts of Odisha viz., Balasore, Cuttack, Khordha, Keonjhar, and Mayurbhanj. One bacterial isolate from each district were selected and analyzed for their P solubilization efficiency in National Botanical Research Institute Phosphate broths with Ca, Al, and Fe-complexed phosphates. CTC12 and KHD08 transformed more amount of soluble P from Ca-P (CTC12 393.30 mg/L; KHD08 465.25 mg/L), Al-P (CTC12 40.00 mg/L; KHD08 34.50 mg/L), Fe(III)-P (CTC12 175.50 mg/L; KHD08 168.75 mg/L), and Fe(II)-P (CTC12 47.40 mg/L; KHD08 42.00 mg/L) after 8 days of incubation. The bioconversion of P by all the five strains in the broth medium followed the order Ca-P > Fe(III)-P > Fe(II)-P > Al-P. The identified five strains were Bacillus cereus BLS18 (KT582541), Bacillus amyloliquefaciens CTC12 (KT633845), Burkholderia cepacia KHD08 (KT717633), B. cepacia KJR03 (KT717634), and B. cepacia K1 (KM030037) and further studied for biofertilization effects on peanut. CTC12 and KHD08 enhanced the soil available P around 65 and 58% and reduced the amount of each Al 3+ about 79 and 81%, respectively, over the uninoculated control pots in the peanut rhizosphere. Moreover, all tested PSB strains could be able to successfully mobilize P from inorganic P fractions (non-occluded Al-P and Fe-P). The strains CTC12 and KHD08 increased the pod yield (114 and 113%), shoot P (92 and 94%), and kernel P (100 and 101%), respectively, over the control. However, B. amyloliquefaciens CTC12 and B. cepacia KHD08 proved to be the potent P solubilizers in promoting peanut growth and yield.

Extracolonic findings (ECF) on CT colonography (CTC) in patients presenting with colorectal symptoms.

PubMed

Badiani, Sarit; Tomas-Hernandez, Silvia; Karandikar, Sharad; Roy-Choudhury, Shuvro

2013-10-01

Computed tomographic colonography (CTC) is now an established method for imaging the colon and rectum in the screening and symptomatic setting. Additional benefit of CTC is the ability to assess for extracolonic findings especially in patients presenting with colorectal symptoms. To determine prevalence of extracolonic findings (ECF) in symptomatic patients undergoing CTC and determine accuracy of CTC for exclusion of significant abdominal disease and extracolonic malignancy (ECM). A total of 1359 unenhanced prone and postcontrast supine CTC studies were performed between March 2002 and December 2007. ECF were retrospectively classified according to C-RADS criteria into E1 to E4 findings. For ECM, a gold standard of clinical and/or radiological follow-up supplemented with data from the regional cancer registry with a median follow-up of 42 months was created. Sensitivity and negative predictive values for ECM was calculated. Following exclusions, 1177 CTCs were analyzed. Of 1423 extracolonic findings reported, 328/1423 (23%) E3 and 100/1423 (7%) E4 (including six eventual FP studies) findings were identified. Thirty-two ECMs were confirmed following further investigations. Seven further small ECMs were detected during the entire follow-up, of which two were potentially visible in retrospect (false-negative studies). Additional tests were generated from 55/1177 (4.7%) studies. Sensitivity and negative predictive value for ECM was 94.1% (95% CI 78.9-98.9%) and 99.8% (95% CI 99.3-99.9%), respectively. One in 37 patients were found to have an ECM. Two potentially detectable cancers were missed. Only a small proportion of patients underwent additional work-up.

Detection and Characterization of Circulating Tumor Associated Cells in Metastatic Breast Cancer.

PubMed

Mu, Zhaomei; Benali-Furet, Naoual; Uzan, Georges; Znaty, Anaëlle; Ye, Zhong; Paolillo, Carmela; Wang, Chun; Austin, Laura; Rossi, Giovanna; Fortina, Paolo; Yang, Hushan; Cristofanilli, Massimo

2016-09-30

The availability of blood-based diagnostic testing using a non-invasive technique holds promise for real-time monitoring of disease progression and treatment selection. Circulating tumor cells (CTCs) have been used as a prognostic biomarker for the metastatic breast cancer (MBC). The molecular characterization of CTCs is fundamental to the phenotypic identification of malignant cells and description of the relevant genetic alterations that may change according to disease progression and therapy resistance. However, the molecular characterization of CTCs remains a challenge because of the rarity and heterogeneity of CTCs and technological difficulties in the enrichment, isolation and molecular characterization of CTCs. In this pilot study, we evaluated circulating tumor associated cells in one blood draw by size exclusion technology and cytological analysis. Among 30 prospectively enrolled MBC patients, CTCs, circulating tumor cell clusters (CTC clusters), CTCs of epithelial-mesenchymal transition (EMT) and cancer associated macrophage-like cells (CAMLs) were detected and analyzed. For molecular characterization of CTCs, size-exclusion method for CTC enrichment was tested in combination with DEPArray™ technology, which allows the recovery of single CTCs or pools of CTCs as a pure CTC sample for mutation analysis. Genomic mutations of TP53 and ESR1 were analyzed by targeted sequencing on isolated 7 CTCs from a patient with MBC. The results of genomic analysis showed heterozygous TP53 R248W mutation from one single CTC and pools of three CTCs, and homozygous TP53 R248W mutation from one single CTC and pools of two CTCs. Wild-type ESR1 was detected in the same isolated CTCs. The results of this study reveal that size-exclusion method can be used to enrich and identify circulating tumor associated cells, and enriched CTCs were characterized for genetic alterations in MBC patients, respectively.

Clinical Utility of CLIA-Grade AR-V7 Testing in Patients With Metastatic Castration-Resistant Prostate Cancer.

PubMed

Markowski, Mark C; Silberstein, John L; Eshleman, James R; Eisenberger, Mario A; Luo, Jun; Antonarakis, Emmanuel S

2017-01-01

A splice variant of the androgen receptor, AR-V7, confers resistance to AR-targeted therapies (ATTs) but not taxane chemotherapies in patients with metastatic castration-resistant prostate cancer. Since August 2015, a clinical-grade assay to detect AR-V7 messenger RNA expression in circulating tumors cells (CTCs) has been available to providers through a Clinical Laboratory Improvement Amendments-certified laboratory at Johns Hopkins University. We contacted ordering providers of the first 150 consecutive tests by using a questionnaire-based survey to determine how the results of AR-V7 testing were used to influence clinical practice. In all, 142 (95%) of 150 questionnaires were completed by 38 providers from 29 sites across the United States and Canada. AR-V7 test results were reported either as CTC- (28%), CTC+/AR-V7- (30%), or CTC+/AR-V7+ (42%). Prevalence of AR-V7 detection increased with prior exposure to ATTs (abiraterone and enzalutamide naïve, 22%; after abiraterone or enzalutamide, 35%; after abiraterone and enzalutamide, 43%). Overall, management was affected by AR-V7 testing in 53% of the patients and even more often with CTC+/AR-V7+ results. AR-V7+ patients were commonly switched from ATT to taxane chemotherapy (43%) or were offered a clinical trial (43%); management remained unchanged in only 14% of these patients. Overall, patients who had a change in management on the basis of AR-V7 testing were significantly more likely to achieve a physician-reported 50% decline in prostate-specific antigen response on next-line therapy than those who did not change treatment (54% v 31%; P = .015). Providers used AR-V7 testing to influence clinical decision making more often than not. Physicians reported thatmenwithAR-V7+results had the most treatment changes, and such men were preferentially managed with taxane therapy or offered a clinical trial, which may have improved outcomes.

Effects of substrates and phosphate on INT (2-(4-iodophenyl)-3-(4-nitrophenyl)-5-phenyl tetrazolium chloride) and CTC (5-cyano-2,3-ditolyl tetrazolium chloride) reduction in Escherichia coli

NASA Technical Reports Server (NTRS)

Smith, J. J.; McFeters, G. A.

1996-01-01

The effects of substrates of primary aerobic dehydrogenases, and inorganic phosphate on aerobic INT and CTC reduction in Escherichia coli were examined. In general, INT produced less formazan than CTC, but INT (+) cell counts remained near values of CTC (+) cells. INT and CTC (+) cell numbers were higher than plate counts on R2A medium using succinate, formate, lactate, casamino acids, glucose, glycerol (INT only) and no substrate. Formate resulted in the greatest amount of INT and CTC formazan. Reduction of both INT and CTC was inhibited above 10 mmol l-1 phosphate, and this appeared to be related to decreased rates of O2 consumption. Formation of fluorescent CTC (+), but not INT (+) cells was also inhibited in a concentration dependent manner by phosphate above 10 mmol l-1. From light microscopic observations it appeared CTC formed increasing amounts of poorly or non-fluorescent formazan with increasing phosphate. Therefore, use of phosphate buffer in excess of 10 mmol l-1 may not be appropriate in CTC and INT reduction assays.

KRAS mutations in pancreatic circulating tumor cells: a pilot study.

PubMed

Kulemann, Birte; Liss, Andrew S; Warshaw, Andrew L; Seifert, Sindy; Bronsert, Peter; Glatz, Torben; Pitman, Martha B; Hoeppner, Jens

2016-06-01

Pancreatic ductal adenocarcinoma (PDAC) is most often diagnosed in a metastatic stage. Circulating tumor cells (CTC) in the blood are hypothesized as the means of systemic dissemination. We aimed to isolate and characterize CTC to evaluate their significance as prognostic markers in PDAC. Blood obtained from healthy donors and patients with PDAC before therapy was filtered with ScreenCell® filtration devices for size-based CTC isolation. Captured cells were analyzed by immunofluorescence for an epithelial to mesenchymal transition (EMT) marker (zinc finger E-box binding homebox 1 (ZEB1)) and an epithelial antigen (cytokeratin (CK)). Molecular analysis of parallel specimens evaluated the KRAS mutation status of the CTC. The survival of each patient after study was recorded. As demonstrated by either cytology or finding of a KRAS mutation, CTC were detected in 18 of 21 patients (86 %) with proven PDAC: 8 out of 10 patients (80 %) with early stage (UICC IIA/IIB) and 10 out of 11 (91 %) with late stage (UICC III/IV) disease. CTC were not found in any of the 10 control patients (p < 0.001). The presence of CTC did not adversely affect median survival: 16 months in CTC-positive (n = 18) vs. 10 months in CTC-negative (n = 3) patients. Neither ZEB1 nor cytological characteristics correlated with overall survival, although ZEB1 was found almost exclusively in CTC of patients with established metastases. Patients with a CTC KRAS mutation (CTC-KRAS (mut)) had a substantially better survival, 19.4 vs. 7.4 months than patients with wild type KRAS (p = 0.015). With ScreenCell filtration, CTC are commonly found in PDAC (86 %). Molecular and genetic characterization, including mutations such as KRAS, may prove useful for prognosis.

High performance liquid chromatography time of flight electrospray ionization mass spectrometry for quantification of sesquiterpenes in Chrysanthemi indici Flos active extract

PubMed Central

Fu, Ling; Wang, Pan; Sun, Yiqun; Wang, Yangyang; Zhao, Jing; Ye, Yuting; Zhang, Yanbin; Bi, Yuefeng

2015-01-01

Background: Chrysanthemi indici Flos, a traditional herbal medicine is used to clearing heat–toxicity, removing the liver fire, and improving eyesight. In our preliminary work, an active extract of CTC in C. An indici Flos with anti-hepatitis B virus and liver protective activity was found by HepG2.2.1.5 test and experiment of protein synthesis in mice's injured liver. In this work, we aimed to study the active faction CTC further by qualitative and quantitative analysis method. Materials and Methods: High performance liquid chromatography time of flight electrospray ionization mass spectrometry (HPLC TOF ESI-MS) analysis method of the CTC was established. Cumambrin A and angeloylcumambrin B in CTC were analyzed by high performance liquid chromatography-ultraviolet-evaporative light scattering detector (HPLC-UV-ELSD) analysis methods. A binary gradient elution program was conducted for chromatographic separation with acetonitrile (A) and ultrapure water (B) as follows: 0–10 min, 42–46% A; 10–20 min, 46–55% A; 20–25 min, 55–60% A; and 25–35 min, 60–75% A. The column temperature and UV wavelength were set at 30°C and 205 nm. Result: Ten constituents including (3R, 5R, 6S, 7S, 10R)-7-(2-hydroxy-2-propyl)-10-methyl-4-methyleneperhy, dronaphthal-ene-3, 5, 6-triol acetone solvate; (+)-edusmance-4, (14)-ene-11, 13-diol; linarin; luteolin; apigenin; tricin; 5, 3’,4’- trimethyl-6,7-dimethoxy flavones; cumambrin A; acacetin; and angeloylcumambrin B in CTC were identified by HPLC TOF ESI-MS. The contents of sesquiterpenes in CTC were decreased by storing years. Conclusions: The results showed that both UV and ELSD methods were feasible, accurate, and the determination results were in good consistency. The contents of two sesquiterpenes decreased with storing years. Two sesquiterpenes could be used as quality control for C. indici flos CTC. PMID:26600718

Clinical significance of detecting circulating tumor cells in colorectal cancer using subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH)

PubMed Central

Shen, Zhen; Jing, Yan; Lu, Haibo; Li, Heng; Yang, Xiaoye; Cui, Xiangbin; Li, Yuqing; Lou, Zheng; Liu, Peng; Zhang, Cun; Zhang, Wei

2017-01-01

Circulating tumor cells (CTC) are useful in early detection of colorectal cancer. This study described a newly developed platform, integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH), to assess CTCs in colorectal cancer. CTCs were detected by SE-iFISH in 40 of 44 preoperative colorectal cancer patients, and yielded a sensitivity of 90.9%, which was significantly higher than CellSearch system (90.9% vs. 43.2%, P=0.033). No significant association was found between tumor stage, survival and preoperative CTC number. CTCs were detected in 10 colorectal cancer patients one week after surgery; seven patients with decreased CTC numbers (compared with preoperative CTC number) were free of recurrence; whereas two of the three patients with increased CTC numbers had tumor recurrence. Moreover, CTCs were detected in 34 colorectal cancer patients three months after surgery; patients with CTC<2 at three months after surgery had significantly longer Progression Free Survival than those with CTC>=2 (P=0.019); patients with decreased CTC number (compared with preoperative CTC number) had significantly longer Progression Free Survival than those with increased CTC number (P=0.003). In conclusion, CTCs could be detected in various stages of colorectal cancer using SE-iFISH. Dynamic monitoring of CTC numbers could predict recurrence and prognosis. PMID:28423493

Integrated Device for Circulating Tumor Cell Capture, Characterization and Lens-Free Microscopy

DTIC Science & Technology

2012-08-01

peripheral blood of breast cancer patients indicates high metastatic potential and increased morbidity. Development of a cost - effective CTC detection and...microfilter platform captures CTC from the cancer patients’ blood cost effectively , where the larger CTC are preferentially retained on the membrane...development of a cost - effective and high-throughput CTC analysis system would revolutionize the field of CTC detection, prognosis, and therapeutic

Pencilbeam irradiation technique for whole brain radiotherapy: technical and biological challenges in a small animal model.

PubMed

Schültke, Elisabeth; Trippel, Michael; Bräuer-Krisch, Elke; Renier, Michel; Bartzsch, Stefan; Requardt, Herwig; Döbrössy, Máté D; Nikkhah, Guido

2013-01-01

We have conducted the first in-vivo experiments in pencilbeam irradiation, a new synchrotron radiation technique based on the principle of microbeam irradiation, a concept of spatially fractionated high-dose irradiation. In an animal model of adult C57 BL/6J mice we have determined technical and physiological limitations with the present technical setup of the technique. Fifty-eight animals were distributed in eleven experimental groups, ten groups receiving whole brain radiotherapy with arrays of 50 µm wide beams. We have tested peak doses ranging between 172 Gy and 2,298 Gy at 3 mm depth. Animals in five groups received whole brain radiotherapy with a center-to-center (ctc) distance of 200 µm and a peak-to-valley ratio (PVDR) of ∼ 100, in the other five groups the ctc was 400 µm (PVDR ∼ 400). Motor and memory abilities were assessed during a six months observation period following irradiation. The lower dose limit, determined by the technical equipment, was at 172 Gy. The LD50 was about 1,164 Gy for a ctc of 200 µm and higher than 2,298 Gy for a ctc of 400 µm. Age-dependent loss in motor and memory performance was seen in all groups. Better overall performance (close to that of healthy controls) was seen in the groups irradiated with a ctc of 400 µm.

Effects of chlortetracycline and copper supplementation on antimicrobial resistance of fecal Escherichia coli from weaned pigs.

PubMed

Agga, G E; Scott, H M; Amachawadi, R G; Nagaraja, T G; Vinasco, J; Bai, J; Norby, B; Renter, D G; Dritz, S S; Nelssen, J L; Tokach, M D

2014-06-01

Feed-grade chlortetracycline (CTC) and copper are both widely utilized in U.S. pig production. Cluster randomized experiment was conducted to evaluate the effects of CTC and copper supplementation in weaned pigs on antimicrobial resistance (AMR) among fecal Escherichia coli. Four treatment groups: control, copper, CTC, or copper plus CTC were randomly allocated to 32 pens with five pigs per pen. Fecal samples were collected weekly from three pigs per pen for six weeks. Two E. coli isolates per fecal sample were tested for phenotypic and genotypic resistance against antibiotics and copper. Data were analyzed with multilevel mixed effects logistic regression, multivariate probit analysis and discrete time survival analysis. CTC-supplementation was significantly (99% [95% CI=98-100%]) associated with increased tetracycline resistance compared to the control group (95% [95% CI=94-97%]). Copper supplementation was associated with decreased resistance to most of the antibiotics tested, including cephalosporins, over the treatment period. Overall, 91% of the E. coli isolates were multidrug resistant (MDR) (resistant to ≥3 antimicrobial classes). tetA and blaCMY-2 genes were positively associated (P<0.05) with MDR categorization, while tetB and pcoD were negatively associated with MDR. tetA and blaCMY-2 were positively associated with each other and in turn, these were negatively associated with both tetB and pcoD genes; which were also positively associated with one another. Copper minimum inhibitory concentration was not affected by copper supplementation or by pcoD gene carriage. CTC supplementation was significantly associated with increased susceptibilities of E. coli to copper (HR=7 [95% CI=2.5-19.5]) during treatment period. In conclusion, E. coli isolates from the nursery pigs exhibited high levels of antibiotic resistance, with diverse multi-resistant phenotypic profiles. The roles of copper supplementation in pig production, and pco-mediated copper resistance among E. coli in particular, need to be further explored since a strong negative association of pco with both tetA and blaCMY-2 points to opportunities for selecting a more innocuous resistance profile. Copyright © 2014 Elsevier B.V. All rights reserved.

The Lessons of Modularity in Informing Australian Army Transformation

DTIC Science & Technology

2014-12-12

States) CALL Center for Army Lessons Learned (United States) Cbt Bde Combat Brigade (Australian) CTC Combat Training Center DOTMLPF Doctrine ...Center ix TRADOC Training and Doctrine Command US United States x ILLUSTRATIONS Figure 1. The Australian Cbt Bde Structure...that could be task-organized for deployment and provide a sustained capability over multiple rotations. The changes to organization, doctrine , training

Feasibility of a novel one-stop ISET device to capture CTCs and its clinical application

PubMed Central

Zheng, Liang; Zhi, Xuan; Cheng, Boran; Chen, Yuanyuan; Zhang, Chunxiao; Shi, Dongdong; Song, Haibin; Cai, Congli; Zhou, Pengfei; Xiong, Bin

2017-01-01

Introduction Circulating tumor cells (CTCs) play a crucial role in cancer metastasis. In this study, we introduced a novel isolation method by size of epithelial tumor cells (ISET) device with automatic isolation and staining procedure, named one-stop ISET (osISET) and validated its feasibility to capture CTCs from cancer patients. Moreover, we aim to investigate the correlation between clinicopathologic features and CTCs in colorectal cancer (CRC) in order to explore its clinical application. Results The capture efficiency ranged from 80.3% to 88% with tumor cells spiked into medium while 67% to 78.3% with tumor cells spiked into healthy donors’ blood. In detection blood samples of 72 CRC patients, CTCs and clusters of circulating tumor cells (CTC-clusters) were detected with a positive rate of 52.8% (38/72) and 18.1% (13/72) respectively. Moreover, CTC positive rate was associated with factors of lymphatic or venous invasion, tumor depth, lymph node metastasis and TNM stage in CRC patients (p < 0.01). Lymphocyte count and neutrophil to lymphocyte ratio (NLR) were significantly different between CTC positive and negative groups (p < 0.01). Materials and Methods The capture efficiency of the device was tested by spiking cancer cells (MCF-7, A549, SW480, Hela) into medium or blood samples of healthy donors. Blood samples of 72 CRC patients were detected by osISET device. The clinicopathologic characteristics of 72 CRC patients were collected and the association with CTC positive rate or CTC count were analyzed. Conclusions Our osISET device was feasible to capture and identify CTCs and CTC-clusters from cancer patients. In addition, our device holds a potential for application in cancer management. PMID:27935872

Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis.

PubMed

Bidard, François-Clément; Michiels, Stefan; Riethdorf, Sabine; Mueller, Volkmar; Esserman, Laura J; Lucci, Anthony; Naume, Bjørn; Horiguchi, Jun; Gisbert-Criado, Rafael; Sleijfer, Stefan; Toi, Masakazu; Garcia-Saenz, Jose A; Hartkopf, Andreas; Generali, Daniele; Rothé, Françoise; Smerage, Jeffrey; Muinelo-Romay, Laura; Stebbing, Justin; Viens, Patrice; Magbanua, Mark Jesus M; Hall, Carolyn S; Engebraaten, Olav; Takata, Daisuke; Vidal-Martínez, José; Onstenk, Wendy; Fujisawa, Noriyoshi; Diaz-Rubio, Eduardo; Taran, Florin-Andrei; Cappelletti, Maria Rosa; Ignatiadis, Michail; Proudhon, Charlotte; Wolf, Denise M; Bauldry, Jessica B; Borgen, Elin; Nagaoka, Rin; Carañana, Vicente; Kraan, Jaco; Maestro, Marisa; Brucker, Sara Yvonne; Weber, Karsten; Reyal, Fabien; Amara, Dominic; Karhade, Mandar G; Mathiesen, Randi R; Tokiniwa, Hideaki; Llombart-Cussac, Antonio; Meddis, Alessandra; Blanche, Paul; d'Hollander, Koenraad; Cottu, Paul; Park, John W; Loibl, Sibylle; Latouche, Aurélien; Pierga, Jean-Yves; Pantel, Klaus

2018-04-12

We conducted a meta-analysis in nonmetastatic breast cancer patients treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of circulating tumor cell (CTC) detection as a prognostic marker. We collected individual patient data from 21 studies in which CTC detection by CellSearch was performed in early breast cancer patients treated with NCT. The primary end point was overall survival, analyzed according to CTC detection, using Cox regression models stratified by study. Secondary end points included distant disease-free survival, locoregional relapse-free interval, and pathological complete response. All statistical tests were two-sided. Data from patients were collected before NCT (n = 1574) and before surgery (n = 1200). CTC detection revealed one or more CTCs in 25.2% of patients before NCT; this was associated with tumor size (P < .001). The number of CTCs detected had a detrimental and decremental impact on overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P < .001), but not on pathological complete response. Patients with one, two, three to four, and five or more CTCs before NCT displayed hazard ratios of death of 1.09 (95% confidence interval [CI] = 0.65 to 1.69), 2.63 (95% CI = 1.42 to 4.54), 3.83 (95% CI = 2.08 to 6.66), and 6.25 (95% CI = 4.34 to 9.09), respectively. In 861 patients with full data available, adding CTC detection before NCT increased the prognostic ability of multivariable prognostic models for overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P = .008). CTC count is an independent and quantitative prognostic factor in early breast cancer patients treated by NCT. It complements current prognostic models based on tumor characteristics and response to therapy.

Deep ensemble learning of virtual endoluminal views for polyp detection in CT colonography

NASA Astrophysics Data System (ADS)

Umehara, Kensuke; Näppi, Janne J.; Hironaka, Toru; Regge, Daniele; Ishida, Takayuki; Yoshida, Hiroyuki

2017-03-01

Robust training of a deep convolutional neural network (DCNN) requires a very large number of annotated datasets that are currently not available in CT colonography (CTC). We previously demonstrated that deep transfer learning provides an effective approach for robust application of a DCNN in CTC. However, at high detection accuracy, the differentiation of small polyps from non-polyps was still challenging. In this study, we developed and evaluated a deep ensemble learning (DEL) scheme for reviewing of virtual endoluminal images to improve the performance of computer-aided detection (CADe) of polyps in CTC. Nine different types of image renderings were generated from virtual endoluminal images of polyp candidates detected by a conventional CADe system. Eleven DCNNs that represented three types of publically available pre-trained DCNN models were re-trained by transfer learning to identify polyps from the virtual endoluminal images. A DEL scheme that determines the final detected polyps by a review of the nine types of VE images was developed by combining the DCNNs using a random forest classifier as a meta-classifier. For evaluation, we sampled 154 CTC cases from a large CTC screening trial and divided the cases randomly into a training dataset and a test dataset. At 3.9 falsepositive (FP) detections per patient on average, the detection sensitivities of the conventional CADe system, the highestperforming single DCNN, and the DEL scheme were 81.3%, 90.7%, and 93.5%, respectively, for polyps ≥6 mm in size. For small polyps, the DEL scheme reduced the number of false positives by up to 83% over that of using a single DCNN alone. These preliminary results indicate that the DEL scheme provides an effective approach for improving the polyp detection performance of CADe in CTC, especially for small polyps.

Label-free Rapid Viable Enrichment of Circulating Tumor Cell by Photosensitive Polymer-based Microfilter Device.

PubMed

Kang, Yoon-Tae; Doh, Il; Byun, Jiyoung; Chang, Hee Jin; Cho, Young-Ho

2017-01-01

We present a clinical device for simple, rapid, and viable isolation of circulating tumor cells (CTCs) from cancer patient bloods. In spite of the clinical importance of CTCs, the lack of easy and non-biased isolation methods is a big hurdle for implementing CTC into clinical use. The present device made of photosensitive polymer was designed to attach to conventional syringe to isolate the CTCs at minimal resources. Its unique tapered-slits on the filter are capable not only to isolate the cell based on their size and deformability, but also to increase sample flow rate, thus achieving label-free rapid viable CTC isolation. We verified our device performance using 9 different types of cancer cells at the cell concentration from 5 to 100cells/ml, showing that the device capture 77.7% of the CTCs while maintaining their viability of 80.6%. We extended our study using the 18 blood samples from lung, colorectal, pancreatic and renal cancer patients and captured 1-172 CTCs or clustered CTCs by immunofluorescent or immunohistochemical staining. The captured CTCs were also molecularly assayed by RT-PCR with three cancer-associated genes (CK19, EpCAM, and MUC1). Those comprehensive studies proved to use our device for cancer study, thereby inaugurating further in-depth CTC-based clinical researches.

A microfluidic device for label-free, physical capture of circulating tumor cell-clusters

PubMed Central

Sarioglu, A. Fatih; Aceto, Nicola; Kojic, Nikola; Donaldson, Maria C.; Zeinali, Mahnaz; Hamza, Bashar; Engstrom, Amanda; Zhu, Huili; Sundaresan, Tilak K.; Miyamoto, David T.; Luo, Xi; Bardia, Aditya; Wittner, Ben S.; Ramaswamy, Sridhar; Shioda, Toshi; Ting, David T.; Stott, Shannon L.; Kapur, Ravi; Maheswaran, Shyamala; Haber, Daniel A.; Toner, Mehmet

2015-01-01

Cancer cells metastasize through the bloodstream either as single migratory circulating tumor cells (CTCs) or as multicellular groupings (CTC-clusters). Existing technologies for CTC enrichment are designed primarily to isolate single CTCs, and while CTC-clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here, we developed a microchip technology (Cluster-Chip) specifically designed to capture CTC-clusters independent of tumor-specific markers from unprocessed blood. CTC-clusters are isolated through specialized bifurcating traps under low shear-stress conditions that preserve their integrity and even two-cell clusters are captured efficiently. Using the Cluster-Chip, we identify CTC-clusters in 30–40% of patients with metastatic cancers of the breast, prostate and melanoma. RNA sequencing of CTC-clusters confirms their tumor origin and identifies leukocytes within the clusters as tissue-derived macrophages. Together, the development of a device for efficient capture of CTC-clusters will enable detailed characterization of their biological properties and role in cancer metastasis. PMID:25984697

[Anaerobic digestion of animal manure contaminated by tetracyclines].

PubMed

Tong, Zi-Lin; Liu, Yuan-Lu; Hu, Zhen-Hu; Yuan, Shou-Jun

2012-03-01

Anaerobic digestion of pig manure spiked with tetracycline (TC) and chlortetracycline (CTC) and the degradation of the two antibiotics during the anaerobic digestion at 35 degrees C were investigated. The results indicate that propionate was the main volatile fatty acid produced during the anaerobic digestion followed by acetate. Compared with the CTC addition, TC + CTC addition showed obvious inhibitory effect on the hydrolysis and acidification of easily digestible organic components of pig manure. The cumulative methane production of TC, CTC, TC + CTC and CK2 during anaerobic digestion was 386.4 mL, 406.0 mL, 412.1 mL and 464.6 mL, respectively. Degradation of TC and CTC followed the first-order kinetic equation. The half-life of TC and CTC was 14-18 days and 10 days, respectively. After the treatment of 45-day anaerobic digestion, the degradation efficiency of TC was 88.6%-91.6% with 97.7%-98.2% of CTC. Therefore, anaerobic digestion shows the benefit on the management of animal manures contaminated by tetracyclines.

Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors

NASA Astrophysics Data System (ADS)

Cho, Edward H.; Wendel, Marco; Luttgen, Madelyn; Yoshioka, Craig; Marrinucci, Dena; Lazar, Daniel; Schram, Ethan; Nieva, Jorge; Bazhenova, Lyudmila; Morgan, Alison; Ko, Andrew H.; Korn, W. Michael; Kolatkar, Anand; Bethel, Kelly; Kuhn, Peter

2012-02-01

Circulating tumor cells (CTCs) have been implicated as a population of cells that may seed metastasis and venous thromboembolism (VTE), two major causes of mortality in cancer patients. Thus far, existing CTC detection technologies have been unable to reproducibly detect CTC aggregates in order to address what contribution CTC aggregates may make to metastasis or VTE. We report here an enrichment-free immunofluorescence detection method that can reproducibly detect and enumerate homotypic CTC aggregates in patient samples. We identified CTC aggregates in 43% of 86 patient samples. The fraction of CTC aggregation was investigated in blood draws from 24 breast, 14 non-small cell lung, 18 pancreatic, 15 prostate stage IV cancer patients and 15 normal blood donors. Both single CTCs and CTC aggregates were measured to determine whether differences exist in the physical characteristics of these two populations. Cells contained in CTC aggregates had less area and length, on average, than single CTCs. Nuclear to cytoplasmic ratios between single CTCs and CTC aggregates were similar. This detection method may assist future studies in determining which population of cells is more physically likely to contribute to metastasis and VTE.

Deciphering and engineering of the final step halogenase for improved chlortetracycline biosynthesis in industrial Streptomyces aureofaciens.

PubMed

Zhu, Tao; Cheng, Xueqing; Liu, Yuntian; Deng, Zixin; You, Delin

2013-09-01

Chlortetracycline (CTC) is an important member from antibiotics tetracycline (TC) family, which inhibits protein synthesis in bacteria and is widely involved in clinical therapy, animal feeds and aquaculture. Previous works have reported intricately the biosynthesis of CTC from the intermediates in random mutants of Streptomyces aureofaciens and the crucial chlorination remained unclear. We have developed the genetic manipulation in an industrial producer, in which about 15.0g/l CTC predominated along with 1.2g/l TC, and discovered that chlorination by ctcP (an FADH2-dependent halogenase gene) is the last inefficient step during CTC biosynthesis. Firstly, the ΔctcP strain accumulated about 18.9g/l "clean" TC without KBr addition and abolished the production of CTC. Subsequently, CtcP was identified to exhibit a substrate stereo-specificity to absolute TC (4S) rather than TC (4R), with low kcat of 0.51±0.01min(-1), while it could halogenate several TC analogs. Accordingly, we devised a strategy for overexpression of ctcP in S. aureofaciens and improved CTC production to a final titer of 25.9g/l. We anticipate that our work will provide a biotechnological potential of enzymatic evolution and strain engineering towards new TC derivatives in microorganisms. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

C-terminal, endoplasmic reticulum-lumenal domain of prosurfactant protein C - structural features and membrane interactions.

PubMed

Casals, Cristina; Johansson, Hanna; Saenz, Alejandra; Gustafsson, Magnus; Alfonso, Carlos; Nordling, Kerstin; Johansson, Jan

2008-02-01

Surfactant protein C (SP-C) constitutes the transmembrane part of prosurfactant protein C (proSP-C) and is alpha-helical in its native state. The C-terminal part of proSP-C (CTC) is localized in the endoplasmic reticulum lumen and binds to misfolded (beta-strand) SP-C, thereby preventing its aggregation and amyloid fibril formation. In this study, we investigated the structure of recombinant human CTC and the effects of CTC-membrane interaction on protein structure. CTC forms noncovalent trimers and supratrimeric oligomers. It contains two intrachain disulfide bridges, and its secondary structure is significantly affected by urea or heat only after disulfide reduction. The postulated Brichos domain of CTC, with homologs found in proteins associated with amyloid and proliferative disease, is up to 1000-fold more protected from limited proteolysis than the rest of CTC. The protein exposes hydrophobic surfaces, as determined by CTC binding to the environment-sensitive fluorescent probe 1,1'-bis(4-anilino-5,5'-naphthalenesulfonate). Fluorescence energy transfer experiments further reveal close proximity between bound 1,1'-bis(4-anilino-5,5'-naphthalenesulfonate) and tyrosine residues in CTC, some of which are conserved in all Brichos domains. CTC binds to unilamellar phospholipid vesicles with low micromolar dissociation constants, and differential scanning calorimetry and CD analyses indicate that membrane-bound CTC is less structurally ordered than the unbound protein. The exposed hydrophobic surfaces and the structural disordering that result from interactions with phospholipid membranes suggest a mechanism whereby CTC binds to misfolded SP-C in the endoplasmic reticulum membrane.

Prevalence and risk factors of poor immune recovery among adult HIV patients attending care and treatment centre in northwestern Tanzania following the use of highly active antiretroviral therapy: a retrospective study.

PubMed

Gunda, Daniel W; Kilonzo, Semvua B; Kamugisha, Erasmus; Rauya, Engelbert Z; Mpondo, Bonaventura C

2017-06-08

Highly Active Antiretroviral therapy (HAART) reverses the effect of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) by durably suppressing viral replication. This allows CD4 gain to levels that are adequate enough to restore the body's capability to fight against opportunistic infections (OIs). Patients with poor immune recovery have been shown to have higher risk of developing both AIDS and non AIDS related clinical events. This study aimed at assessing the proportions and risk factors of poor immune recovery in adult HIV-infected patients on 48 months of HAART attending care and treatment center (CTC) in northwestern Tanzania. A retrospective analysis of adult HIV patients' data attending CTC at Sekou Toure hospital and who initiated HAART between February 2004 and January 2008 was done. Poor immune recovery was defined as a CD4 count less than 350 cells/µl on follow up as used in other studies. A total of 734 patients were included in the study. In this study 50.25% of patients attending CTC at Sekou Toure hospital were found to have poor immune recovery. The risk of developing inadequate immune recovery was independently associated with male gender, age older than 50 years, low baseline CD4 counts, and advanced World Health Organization (WHO) clinical stage. Poor immune recovery is prevalent among adult HIV patients attending CTC at Sekou Toure hospital in Northwestern part of Tanzania and opportunistic infections are common in this sub group of patients. Clinicians in resource limited countries need to identify these patients timely and plan them for targeted viral assessment and close clinical follow up to improve their long term clinical outcome.

Improved computer-aided detection of small polyps in CT colonography using interpolation for curvature estimationa

PubMed Central

Liu, Jiamin; Kabadi, Suraj; Van Uitert, Robert; Petrick, Nicholas; Deriche, Rachid; Summers, Ronald M.

2011-01-01

Purpose: Surface curvatures are important geometric features for the computer-aided analysis and detection of polyps in CT colonography (CTC). However, the general kernel approach for curvature computation can yield erroneous results for small polyps and for polyps that lie on haustral folds. Those erroneous curvatures will reduce the performance of polyp detection. This paper presents an analysis of interpolation’s effect on curvature estimation for thin structures and its application on computer-aided detection of small polyps in CTC. Methods: The authors demonstrated that a simple technique, image interpolation, can improve the accuracy of curvature estimation for thin structures and thus significantly improve the sensitivity of small polyp detection in CTC. Results: Our experiments showed that the merits of interpolating included more accurate curvature values for simulated data, and isolation of polyps near folds for clinical data. After testing on a large clinical data set, it was observed that sensitivities with linear, quadratic B-spline and cubic B-spline interpolations significantly improved the sensitivity for small polyp detection. Conclusions: The image interpolation can improve the accuracy of curvature estimation for thin structures and thus improve the computer-aided detection of small polyps in CTC. PMID:21859029

Nanobiotechnology for the capture and manipulation of circulating tumor cells.

PubMed

Hughes, Andrew D; King, Michael R

2012-01-01

A necessary step in metastasis is the dissemination of malignant cells into the bloodstream, where cancer cells travel throughout the body as circulating tumor cells (CTC) in search of an opportunity to seed a secondary tumor. CTC represent a valuable diagnostic tool: evidence indicates that the quantity of CTC in the blood has been shown to relate to the severity of the illness, and samples are readily obtained through routine blood draws. As such, there has been a push toward developing technologies to reliably detect CTC using a variety of molecular and immunocytochemical techniques. In addition to their use in diagnostics, CTC detection systems that isolate CTC in such a way that the cells remain viable will allow for the performance of live-cell assays to facilitate the development of personalized cancer therapies. Moreover, techniques for the direct manipulation of CTC in circulation have been developed, intending to block metastasis in situ. We review a number of current and emerging micro- and nanobiotechnology approaches for the detection, capture, and manipulation of rare CTC aimed at advancing cancer treatment. Copyright © 2011 Wiley Periodicals, Inc.

Diversity of assessing circulating tumor cells (CTCs) emphasizes need for standardization: a CTC Guide to design and report trials.

PubMed

Bünger, S; Zimmermann, M; Habermann, J K

2015-09-01

Hematogenous spreading of tumor cells from primary tumors is a crucial step in the cascade to metastasis, the latter being the most limiting factor for patients' survival prognosis. Therefore, circulating tumor cells (CTCs) have become a field of intensive research. However, the process of isolation and identification of CTCs lacks standardization. This article presents an overview of 71 CTC studies reported in PUBMED since 2000 and focusing on colorectal cancer. These studies are evaluated regarding standardization of CTC isolation and identification, marker proteins used, study population and blood sample quality management, clinical performance, and quality measures. Overall, standardization of CTC assessment seems insufficient. Thus, comparability of CTC studies is hampered and results should be interpreted carefully. We here propose a standardized CTC guideline (CTC Guide) to prospectively design and report studies/trials in a harmonized form. Despite the current interstudy heterogeneity, the data indicate that CTC detection is of clinical relevance and CTCs should be considered as a surrogate prognostic marker. Many studies indicate the high potential for CTCs as prognostic markers, e.g., in colorectal cancer treatment. However, standardized, large-scale multicenter validation studies are still needed to pave the way for clinical implementation of CTC detection that could ameliorate individualized medicine regimes.

Detection of circulating tumor cells in cervical cancer using a conditionally replicative adenovirus targeting telomerase-positive cells.

PubMed

Takakura, Masahiro; Matsumoto, Takeo; Nakamura, Mitsuhiro; Mizumoto, Yasunari; Myojyo, Subaru; Yamazaki, Rena; Iwadare, Jyunpei; Bono, Yukiko; Orisaka, Shunsuke; Obata, Takeshi; Iizuka, Takashi; Kagami, Kyosuke; Nakayama, Kentaro; Hayakawa, Hideki; Sakurai, Fuminori; Mizuguchi, Hiroyuki; Urata, Yasuo; Fujiwara, Toshiyoshi; Kyo, Satoru; Sasagawa, Toshiyuki; Fujiwara, Hiroshi

2018-01-01

Circulating tumor cells (CTC) are newly discovered biomarkers of cancers. Although many systems detect CTC, a gold standard has not yet been established. We analyzed CTC in uterine cervical cancer patients using an advanced version of conditionally replicative adenovirus targeting telomerase-positive cells, which was enabled to infect coxsackievirus-adenovirus receptor-negative cells and to reduce false-positive signals in myeloid cells. Blood samples from cervical cancer patients were hemolyzed and infected with the virus and then labeled with fluorescent anti-CD45 and anti-pan cytokeratin antibodies. GFP (+)/CD45 (-) cells were isolated and subjected to whole-genome amplification followed by polymerase chain reaction analysis of human papillomavirus (HPV) DNA. CTC were detected in 6 of 23 patients with cervical cancers (26.0%). Expression of CTC did not correlate with the stage of cancer or other clinicopathological factors. In 5 of the 6 CTC-positive cases, the same subtype of HPV DNA as that of the corresponding primary lesion was detected, indicating that the CTC originated from HPV-infected cancer cells. These CTC were all negative for cytokeratins. The CTC detected by our system were genetically confirmed. CTC derived from uterine cervical cancers had lost epithelial characteristics, indicating that epithelial marker-dependent systems do not have the capacity to detect these cells in cervical cancer patients. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

AR-V7 in circulating tumor cells cluster as a predictive biomarker of abiraterone acetate and enzalutamide treatment in castration-resistant prostate cancer patients.

PubMed

Okegawa, Takatsugu; Ninomiya, Naoki; Masuda, Kazuki; Nakamura, Yu; Tambo, Mitsuhiro; Nutahara, Kikuo

2018-06-01

We examined whether androgen receptor splice variant 7 (AR-V7) in circulating tumor cell(CTC)clusters can be used to predict survival in patients with bone metastatic castration resistant-prostate cancer (mCRPC) treated with abiraterone or enzalutamide. We retrospectively enrolled 98 patients with CRPC on abiraterone or enzalutamide, and investigated the prognostic value of CTC cluster detection (+ v -) and AR-V7 detection (+ v -) using a CTC cluster detection - based AR-V7 mRNA assay. We examined ≤50% prostate-specific antigen (PSA) responses, PSA progression-free survival (PSA-PFS), clinical and radiological progression-free survival (radiologic PSF), and overall survival (OS). We then assessed whether AR-V7 expression in CTC clusters identified after On-chip multi-imaging flow cytometry was related to disease progression and survival after first-line systemic therapy. All abiraterone-treated or enzalutamide-treated patients received prior docetaxel. The median follow-up was 20.7 (range: 3.0-37.0) months in the abiraterone and enzalutamide cohorts, respectively. Forty-nine of the 98 men (50.0%) were CTC cluster (-), 23 of the 98 men (23.5%) were CTC cluster(+)/AR-V7(-), and 26 of the 98 men (26.5%) were CTC cluster(+)/AR-V7(+). CTC cluster(+)/AR-V7(+) patients were more likely to have EOD ≥3 at diagnosis (P = 0.003), pain (P = 0.023), higher alkaline phosphatase levels (P < 0.001), and visceral metastases (P < 0.001). On multivariable analysis, pretherapy CTC cluster(+), CTC cluster(+)/AR-V7(-), and ALP >UNL were independently associated with a poor PSA-PFS, radiographic PFS, and OS in abiraterone-treated patients and enzalutamide-treated patients. The CTC clusters and AR-V7-positive CTC clusters detected were important for assessing the response to abiraterone or enzalutamide therapy and for predicting disease outcome. © 2018 Wiley Periodicals, Inc.

Circulating Tumor Cells Versus Circulating Tumor DNA in Colorectal Cancer: Pros and Cons

PubMed Central

Tan, Carlyn Rose C.; Zhou, Lanlan

2016-01-01

Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are emerging noninvasive multifunctional biomarkers in liquid biopsy allowing for early diagnosis, accurate prognosis, therapeutic target selection, spatiotemporal monitoring of metastasis, as well as monitoring response and resistance to treatment. CTCs and ctDNA are released from different tumor types at different stages and contribute complementary information for clinical decision. Although big strides have been taken in technology development for detection, isolation and characterization of CTCs and sensitive and specific detection of ctDNA, CTC-, and ctDNA-based liquid biopsies may not be widely adopted for routine cancer patient care until the suitability, accuracy, and reliability of these tests are validated and more standardized protocols are corroborated in large, independent, prospectively designed trials. This review covers CTC- and ctDNA-related technologies and their application in colorectal cancer. The promise of CTC-and ctDNA-based liquid biopsies is envisioned. PMID:27516729

Circulating Tumor Cells Versus Circulating Tumor DNA in Colorectal Cancer: Pros and Cons.

PubMed

Tan, Carlyn Rose C; Zhou, Lanlan; El-Deiry, Wafik S

2016-06-01

Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are emerging noninvasive multifunctional biomarkers in liquid biopsy allowing for early diagnosis, accurate prognosis, therapeutic target selection, spatiotemporal monitoring of metastasis, as well as monitoring response and resistance to treatment. CTCs and ctDNA are released from different tumor types at different stages and contribute complementary information for clinical decision. Although big strides have been taken in technology development for detection, isolation and characterization of CTCs and sensitive and specific detection of ctDNA, CTC-, and ctDNA-based liquid biopsies may not be widely adopted for routine cancer patient care until the suitability, accuracy, and reliability of these tests are validated and more standardized protocols are corroborated in large, independent, prospectively designed trials. This review covers CTC- and ctDNA-related technologies and their application in colorectal cancer. The promise of CTC-and ctDNA-based liquid biopsies is envisioned.

Circulating tumor cells in breast cancer.

PubMed

Bidard, Francois-Clement; Proudhon, Charlotte; Pierga, Jean-Yves

2016-03-01

Over the past decade, technically reliable circulating tumor cell (CTC) detection methods allowed the collection of large datasets of CTC counts in cancer patients. These data can be used either as a dynamic prognostic biomarker or as tumor material for "liquid biopsy". Breast cancer appears to be the cancer type in which CTC have been the most extensively studied so far, with level-of-evidence-1 studies supporting the clinical validity of CTC count in both early and metastatic stage. This review summarizes and discusses the clinical results obtained in breast cancer patients, the issues faced by the molecular characterization of CTC and the biological findings about cancer biology and metastasis that were obtained from CTC. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Characterization of lactic acid bacteria isolated from infant faeces as potential probiotic starter cultures for fermented sausages.

PubMed

Rubio, Raquel; Jofré, Anna; Martín, Belén; Aymerich, Teresa; Garriga, Margarita

2014-04-01

A total of 109 lactic acid bacteria isolated from infant faeces were identified by partial 16S rRNA, cpn60 and/or pheS sequencing. Lactobacillus was the most prevalent genus, representing 48% of the isolates followed by Enterococcus (38%). Lactobacillus gasseri (21%) and Enterococcus faecalis (38%) were the main species detected. A further selection of potential probiotic starter cultures for fermented sausages focused on Lactobacillus as the most technologically relevant genus in this type of product. Lactobacilli strains were evaluated for their ability to grow in vitro in the processing conditions of fermented sausages and for their functional and safety properties, including antagonistic activity against foodborne pathogens, survival from gastrointestinal tract conditions (acidity, bile and pancreatin), tyramine production, antibiotic susceptibility and aggregation capacity. The best strains according to the results obtained were Lactobacillus casei/paracasei CTC1677, L. casei/paracasei CTC1678, Lactobacillus rhamnosus CTC1679, L. gasseri CTC1700, L. gasseri CTC1704, Lactobacillus fermentum CTC1693. Those strains were further assayed as starter cultures in model sausages. L. casei/paracasei CTC1677, L. casei/paracasei CTC1678 and L. rhamnosus CTC1679 were able to lead the fermentation and dominate (levels ca. 10(8) CFU/g) the endogenous lactic acid bacteria, confirming their suitability as probiotic starter cultures. Copyright © 2013 Elsevier Ltd. All rights reserved.

Electronic cleansing for CT colonography using spectral-driven iterative reconstruction

NASA Astrophysics Data System (ADS)

Nasirudin, Radin A.; Näppi, Janne J.; Hironaka, Toru; Tachibana, Rie; Yoshida, Hiroyuki

2017-03-01

Dual-energy computed tomography is used increasingly in CT colonography (CTC). The combination of computer-aided detection (CADe) and dual-energy CTC (DE-CTC) has high clinical value, because it can detect clinically significant colonic lesions automatically at higher accuracy than does conventional single-energy CTC. While CADe has demonstrated its ability to detect small polyps, its performance is highly dependent on several factors, including the quality of CTC images and electronic cleansing (EC) of the images. The presence of artifacts such as beam hardening and image noise in ultra-low-dose CTC can produce incorrectly cleansed colon images that severely degrade the detection performance of CTC for small polyps. Also, CADe methods are very dependent on the quality of input images and the information about different tissues in the colon. In this work, we developed a novel method to calculate EC images using spectral information from DE-CTC data. First, the ultra-low dose dual-energy projection data obtained from a CT scanner are decomposed into two materials, soft tissue and the orally administered fecal-tagging contrast agent, to detect the location and intensity of the contrast agent. Next, the images are iteratively reconstructed while gradually removing the presence of tagged materials from the images. Our preliminary qualitative results show that the method can cleanse the contrast agent and tagged materials correctly from DE-CTC images without affecting the appearance of surrounding tissue.

Performance evaluation and microbial community of a sequencing batch biofilm reactor (SBBR) treating mariculture wastewater at different chlortetracycline concentrations.

PubMed

Zheng, Dong; Chang, Qingbo; Gao, Mengchun; She, Zonglian; Jin, Chunji; Guo, Liang; Zhao, Yangguo; Wang, Sen; Wang, Xuejiao

2016-11-01

The effects of chlortetracycline (CTC) on the performance, microbial activity, extracellular polymeric substances (EPS) and microbial community of a sequencing batch biofilm reactor (SBBR) were investigated in treating mariculture wastewater. Low CTC concentration (less than 6 mg/L) had no obvious effect on the SBBR performance, whereas high CTC concentration could inhibit the chemical oxygen demand (COD) and nitrogen removal of the SBBR. The microbial activity of the biofilm in the SBBR decreased with the increase of CTC concentration from 0 to 35 mg/L. The protein (PN) contents were always higher than the PS contents in both loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) at different CTC concentrations. The chemical compositions of LB-EPS and TB-EPS had obvious variations with the increase of CTC concentration from 0 to 35 mg/L. The high-throughput sequencing revealed the effects of CTC on the microbial communities of the biofilm at phylum, class and genus level. The relative abundances of some genera displayed a decreasing tendency with the increase of CTC concentration from 0 to 35 mg/L, such as Nitrospira, Paracoccus, Hyphomicrobium, Azospirillum. However, the relative abundances of the genera Flavobacterium, Aequorivita, Buchnera, Azonexus and Thioalbus increased with the increase of CTC concentration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Detection and Characterization of Circulating Tumour Cells from Frozen Peripheral Blood Mononuclear Cells

PubMed Central

Lu, David; Graf, Ryon P.; Harvey, Melissa; Madan, Ravi A.; Heery, Christopher; Marte, Jennifer; Beasley, Sharon; Tsang, Kwong Y.; Krupa, Rachel; Louw, Jessica; Wahl, Justin; Bales, Natalee; Landers, Mark; Marrinucci, Dena; Schlom, Jeffrey; Gulley, James L.; Dittamore, Ryan

2015-01-01

Retrospective analysis of patient tumour samples is a cornerstone of clinical research. CTC biomarker characterization offers a non-invasive method to analyse patient samples. However, current CTC technologies require prospective blood collection, thereby reducing the ability to utilize archived clinical cohorts with long-term outcome data. We sought to investigate CTC recovery from frozen, archived patient PBMC pellets. Matched samples from both mCRPC patients and mock samples, which were prepared by spiking healthy donor blood with cultured prostate cancer cell line cells, were processed “fresh” via Epic CTC Platform or from “frozen” PBMC pellets. Samples were analysed for CTC enumeration and biomarker characterization via immunofluorescent (IF) biomarkers, fluorescence in-situ hybridization (FISH) and CTC morphology. In the frozen patient PMBC samples, the median CTC recovery was 18%, compared to the freshly processed blood. However, abundance and localization of cytokeratin (CK) and androgen receptor (AR) protein, as measured by IF, were largely concordant between the fresh and frozen CTCs. Furthermore, a FISH analysis of PTEN loss showed high concordance in fresh vs. frozen. The observed data indicate that CTC biomarker characterization from frozen archival samples is feasible and representative of prospectively collected samples. PMID:28936240

Neighbor effect in complexation of a conjugated polymer.

PubMed

Sosorev, Andrey; Zapunidi, Sergey

2013-09-19

Charge-transfer complex (CTC) formation between a conjugated polymer and low-molecular-weight organic acceptor is proposed to be driven by the neighbor effect. Formation of a CTC on the polymer chain results in an increased probability of new CTC formation near the existing one. We present an analytical model for CTC distribution considering the neighbor effect, based on the principles of statistical mechanics. This model explains the experimentally observed threshold-like dependence of the CTC concentration on the acceptor content in a polymer:acceptor blend. It also allows us to evaluate binding energies of the complexes.

CTC Sentinel. Volume 4, Issue 2, February 2011

DTIC Science & Technology

2011-02-01

Brotherhood differs from jihadist groups in that the Broth- erhood rejects violence as a means to alter society, instead advocating political...appear to be working at cross purposes in combating AQIM in the Sahara and Sahel and this has created an opening for the group’s different factions to...significant sums. The revenue generated by kidnap operations—which could amount to tens of millions—has reportedly augmented the capabilities of different

Fleet Battle Experiment Juliet Final Reconstruction and Analysis Report

DTIC Science & Technology

2003-04-01

8000 tons 145 Selected Vessel Statistics Joint Venture Sea SLICE Ship particulars Wave Piercing Catamaran ( CAT ) Small Waterplane Area Twin Hull (SWATH...and broadcasting capabilities. NSWC Corona used a built-in function within GCCS-M to broadcast all OTH Gold Contact (CTC) messages to a file. These...example would be the prohibition of e-mail from electronically accessing the e- 309 mail address book; thus denying many self-propagating viruses

Circulating tumour cells and pathological complete response: independent prognostic factors in inflammatory breast cancer in a pooled analysis of two multicentre phase II trials (BEVERLY-1 and -2) of neoadjuvant chemotherapy combined with bevacizumab.

PubMed

Pierga, J-Y; Bidard, F-C; Autret, A; Petit, T; Andre, F; Dalenc, F; Levy, C; Ferrero, J-M; Romieu, G; Bonneterre, J; Lerebours, F; Bachelot, T; Kerbrat, P; Campone, M; Eymard, J-C; Mouret-Reynier, M-A; Gligorov, J; Hardy-Bessard, A-C; Lortholary, A; Soulie, P; Boher, J-M; Proudhon, C; Charafe-Jaufret, E; Lemonnier, J; Bertucci, F; Viens, P

2017-01-01

We present a pooled analysis of predictive and prognostic values of circulating tumour cells (CTC) and circulating endothelial cells (CEC) in two prospective trials of patients with inflammatory breast cancer (IBC) treated with neoadjuvant chemotherapy combined with neoadjuvant and adjuvant bevacizumab. Nonmetastatic T4d patients were enrolled in two phase II multicentre trials, evaluating bevacizumab in combination with sequential neoadjuvant chemotherapy of four cycles of FEC followed by four cycles of docetaxel in HER2-negative tumour (BEVERLY-1) or docetaxel and trastuzumab in HER2-positive tumour (BEVERLY-2). CTC and CEC were detected in 7.5 and 4 ml of blood, respectively, with the CellSearch System. From October 2008 to September 2010, 152 patients were included and 137 were evaluable for CTC and CEC. At baseline, 55 patients had detectable CTC (39%). After four cycles of chemotherapy, a dramatic drop in CTC to a rate of 9% was observed (P < 0.01). Pathological complete response (pCR) rate was 40%. No correlation was found between CTC or CEC levels and pCR rate. Median follow-up was 43 months. CTC detection (≥1 CTC/7.5 ml) at baseline was associated with shorter 3-year disease-free survival (39% versus 70% for patients without CTC, P < 0.01, HR 2.80) and shorter 3-year overall survival (OS) (P < 0.01). In multivariate analysis, independent prognostic parameters for shorter survival were absence of hormonal receptors, no pCR and CTC detection at baseline. CEC level at baseline or variations during treatment had no prognostic value. In this pooled analysis of two prospective trials in nonmetastatic IBC, detection rate of CTC was 39% with a strong and independent prognostic value for survival. Combination of pCR after neoadjuvant treatment with no CTC detection at baseline isolated a subgroup of IBC with excellent OS (94% 3-year OS), suggesting that CTC count could be part of IBC stratification in prospective trials. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The clinical value of circulating tumour cells (CTCs) in patients undergoing pulmonary metastasectomy for metastatic colorectal cancer.

PubMed

Hashimoto, Masaki; Tanaka, Fumihiro; Yoneda, Kazue; Takuwa, Teruhisa; Kuroda, Ayumi; Matsumoto, Seiji; Okumura, Yoshitomo; Kondo, Nobuyuki; Tsujimura, Tohru; Nakano, Takashi; Hasegawa, Seiki

2018-03-01

Circulating tumour cells (CTCs) are a potential surrogate for distant metastasis and are considered a useful clinical prognostic marker for metastatic colorectal cancer (mCRC). This prospective study evaluated the preoperative CTC count as a prognostic factor for pulmonary metastasectomy in mCRC patients. Seventy-nine mCRC patients who underwent curative-intent pulmonary metastasectomy were included. Preoperatively, 7.5 mL of peripheral blood from each patient was quantitatively evaluated for CTCs with the CellSearch ® system. The clinical significance of CTC count was evaluated according to Kaplan-Meier analyses and log-rank test. Multivariate analyses of the perioperative variables were performed. The distribution of CTC counts were as follows; 0 in 66 patients (83.5%), 1 in eight patients (10.1%), 2 in three patients (3.8%), and 3 and 6 in one patient (1.3%). The patients with multiple CTCs (CTC count ≥2) had significant shorter disease-free survival (DFS) (P=0.005, median DFS; 19.8 vs . 8.6 months) and overall survival (OS) (P=0.035, median DFS; not reached vs. 37.8 months), respectively. Multivariate analysis showed the patients with multiple CTCs had elevated risk of recurrence [hazard ratio (HR), 3.28; 95% confidence interval (CI), 1.24-8.67; P=0.017]. The detected rate of CTCs was quite low in mCRC patients who underwent pulmonary metastasectomy. The patient with multiple CTCs had shorter DFS in this study. The larger prospective clinical study is needed to establish the meaning of CTC in mCRC candidate for pulmonary metastasectomy.

Seeing is believing: video classification for computed tomographic colonography using multiple-instance learning.

PubMed

Wang, Shijun; McKenna, Matthew T; Nguyen, Tan B; Burns, Joseph E; Petrick, Nicholas; Sahiner, Berkman; Summers, Ronald M

2012-05-01

In this paper, we present development and testing results for a novel colonic polyp classification method for use as part of a computed tomographic colonography (CTC) computer-aided detection (CAD) system. Inspired by the interpretative methodology of radiologists using 3-D fly-through mode in CTC reading, we have developed an algorithm which utilizes sequences of images (referred to here as videos) for classification of CAD marks. For each CAD mark, we created a video composed of a series of intraluminal, volume-rendered images visualizing the detection from multiple viewpoints. We then framed the video classification question as a multiple-instance learning (MIL) problem. Since a positive (negative) bag may contain negative (positive) instances, which in our case depends on the viewing angles and camera distance to the target, we developed a novel MIL paradigm to accommodate this class of problems. We solved the new MIL problem by maximizing a L2-norm soft margin using semidefinite programming, which can optimize relevant parameters automatically. We tested our method by analyzing a CTC data set obtained from 50 patients from three medical centers. Our proposed method showed significantly better performance compared with several traditional MIL methods.

Seeing is Believing: Video Classification for Computed Tomographic Colonography Using Multiple-Instance Learning

PubMed Central

Wang, Shijun; McKenna, Matthew T.; Nguyen, Tan B.; Burns, Joseph E.; Petrick, Nicholas; Sahiner, Berkman

2012-01-01

In this paper we present development and testing results for a novel colonic polyp classification method for use as part of a computed tomographic colonography (CTC) computer-aided detection (CAD) system. Inspired by the interpretative methodology of radiologists using 3D fly-through mode in CTC reading, we have developed an algorithm which utilizes sequences of images (referred to here as videos) for classification of CAD marks. For each CAD mark, we created a video composed of a series of intraluminal, volume-rendered images visualizing the detection from multiple viewpoints. We then framed the video classification question as a multiple-instance learning (MIL) problem. Since a positive (negative) bag may contain negative (positive) instances, which in our case depends on the viewing angles and camera distance to the target, we developed a novel MIL paradigm to accommodate this class of problems. We solved the new MIL problem by maximizing a L2-norm soft margin using semidefinite programming, which can optimize relevant parameters automatically. We tested our method by analyzing a CTC data set obtained from 50 patients from three medical centers. Our proposed method showed significantly better performance compared with several traditional MIL methods. PMID:22552333

A Historical Perspective on Primary and Possible Secondary Sources of Atmospheric Carbon Tetrachloride

NASA Technical Reports Server (NTRS)

Singh, Hanwant B.

2015-01-01

Atmospheric sources of Carbon Tetrachloride (CTC) have been controversial since its detection in the early 1970. Initial proposals were that it is globally uniformly distributed and its lack of current emissions and inferred lifetime indicated that it was likely of natural origin. Historical analysis of CTC use and emissions showed that atmospheric CTC was long-lived and mainly of man-made origin although small natural sources and sinks (e. g. oceans) could not be ruled out. This deduction was hard because a majority of emissions had occurred in early part of the 20th century when CTC was commonly used as a fumigant, a solvent, and a raw material for the manufacture of many chemicals. In the 1940's adverse health effects of exposure to CTC became evident and its emissions were greatly curtailed and substituted with C2Cl4 which was thought to be much safer. There were smog chamber studies that showed that C2Cl4, a widely used solvent during the late 20th century, could produce CTC with up to a 7% yield. Subsequently it was discovered that this chemistry probably required Cl atoms and since Cl atoms were not abundant in the atmosphere actual yields based on OH oxidation were probably closer to 0.1%. CTC was subsequently banned by the Montreal Protocol to prevent stratospheric ozone depletion and its preferred substitute C2Cl4 was also banned by EPA for reasons of potential carcinogenicity and toxicity. CTC since has been measured in many airborne NASA campaigns in which plumes have been sampled from a variety of regions which may still be emitting CTC. I will briefly discuss this historical perspective of CTC and show some recent data that may shed light on its current sources or lack there off.

Liquid biopsy: ready to guide therapy in advanced prostate cancer?

PubMed

Hegemann, Miriam; Stenzl, Arnulf; Bedke, Jens; Chi, Kim N; Black, Peter C; Todenhöfer, Tilman

2016-12-01

The identification of molecular markers associated with response to specific therapy is a key step for the implementation of personalised treatment strategies in patients with metastatic prostate cancer. Only in a low proportion of patients biopsies of metastatic tissue are performed. Circulating tumour cells (CTC), cell-free DNA (cfDNA) and RNA offer the potential for non-invasive characterisation of disease and molecular stratification of patients. Furthermore, a 'liquid biopsy' approach permits longitudinal assessments, allowing sequential monitoring of response and progression and the potential to alter therapy based on observed molecular changes. In prostate cancer, CTC enumeration using the CellSearch© platform correlates with survival. Recent studies on the presence of androgen receptor (AR) variants in CTC have shown that such molecular characterisation of CTC provides a potential for identifying patients with resistance to agents that inhibit the androgen signalling axis, such as abiraterone and enzalutamide. New developments in CTC isolation, as well as in vitro and in vivo analysis of CTC will further promote the use of CTC as a tool for retrieving molecular information from advanced tumours in order to identify mechanisms of therapy resistance. In addition to CTC, nucleic acids such as RNA and cfDNA released by tumour cells into the peripheral blood contain important information on transcriptomic and genomic alterations in the tumours. Initial studies have shown that genomic alterations of the AR and other genes detected in CTC or cfDNA of patients with castration-resistant prostate cancer correlate with treatment outcomes to enzalutamide and abiraterone. Due to recent developments in high-throughput analysis techniques, it is likely that CTC, cfDNA and RNA will be an important component of personalised treatment strategies in the future. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Circulating Tumor Cell Count Is a Prognostic Factor in Metastatic Colorectal Cancer Patients Receiving First-Line Chemotherapy Plus Bevacizumab: A Spanish Cooperative Group for the Treatment of Digestive Tumors Study

PubMed Central

Maestro, M. Luisa; Gómez-España, Auxiliadora; Rivera, Fernando; Valladares, Manuel; Massuti, Bartomeu; Benavides, Manuel; Gallén, Manuel; Marcuello, Eugenio; Abad, Albert; Arrivi, Antonio; Fernández-Martos, Carlos; González, Encarnación; Tabernero, Josep M.; Vidaurreta, Marta; Aranda, Enrique; Díaz-Rubio, Eduardo

2012-01-01

Background. The Maintenance in Colorectal Cancer trial was a phase III study to assess maintenance therapy with single-agent bevacizumab versus bevacizumab plus chemotherapy in patients with metastatic colorectal cancer. An ancillary study was conducted to evaluate the circulating tumor cell (CTC) count as a prognostic and/or predictive marker for efficacy endpoints. Patients and Methods. One hundred eighty patients were included. Blood samples were obtained at baseline and after three cycles. CTC enumeration was carried out using the CellSearch® System (Veridex LLC, Raritan, NJ). Computed tomography scans were performed at cycle 3 and 6 and every 12 weeks thereafter for tumor response assessment. Results. The median progression-free survival (PFS) interval for patients with a CTC count ≥3 at baseline was 7.8 months, versus the 12.0 months achieved by patients with a CTC count <3 (p = .0002). The median overall survival (OS) time was 17.7 months for patients with a CTC count ≥3, compared with 25.1 months for patients with a lower count (p = .0059). After three cycles, the median PFS interval for patients with a low CTC count was 10.8 months, significantly longer than the 7.5 months for patients with a high CTC count (p = .005). The median OS time for patients with a CTC count <3 was significantly longer than for patients with a CTC count ≥3, 25.1 months versus 16.2 months, respectively (p = .0095). Conclusions. The CTC count is a strong prognostic factor for PFS and OS outcomes in metastatic colorectal cancer patients. PMID:22643538

Experimental Observations of Localization Phenomena in Sands: Plane Strain Versus Triaxial Compression Conditions

NASA Technical Reports Server (NTRS)

Alshibli, Khalid A.; Batiste, Susan N.; Sture, Stein; Curreri, Peter A. (Technical Monitor)

2002-01-01

A comprehensive experimental investigation was conducted to investigate the effects of loading condition and confining pressure on strength properties and instability phenomena in sands. A uniform sub-rounded to rounded natural silica sand known as F-75 Ottawa sand was used in the investigation. The results of a series on Conventional Triaxial Compression (CTC) experiments tested under very low confining pressures (0.05 - 1.30) kPa tested in a Microgravity environment abroad the NASA Space Shuttle are presented in addition to the results similar specimens tested in terrestrial laboratory to investigate the effect of confining pressure on the constitutive behavior of sands. The behavior of the CTC experiments is compared with the results of Plane Strain (PS) experiments. Computed tomography and other digital imaging techniques were used to study the development and evolution of shear bands.

Effects of chlortetracycline amended feed on anaerobic sequencing batch reactor performance of swine manure digestion.

PubMed

Dreher, Teal M; Mott, Henry V; Lupo, Christopher D; Oswald, Aaron S; Clay, Sharon A; Stone, James J

2012-12-01

The effects of antimicrobial chlortetracycline (CTC) on the anaerobic digestion (AD) of swine manure slurry using anaerobic sequencing batch reactors (ASBRs) was investigated. Reactors were loaded with manure collected from pigs receiving CTC and no-antimicrobial amended diets at 2.5 g/L/d. The slurry was intermittently fed to four 9.5L lab-scale anaerobic sequencing batch reactors, two with no-antimicrobial manure, and two with CTC-amended manure, and four 28 day ASBR cycles were completed. The CTC concentration within the manure was 2 8 mg/L immediately after collection and 1.02 mg/L after dilution and 250 days of storage. CTC did not inhibit ASBR biogas production extent, however the volumetric composition of methane was significantly less (approximately 13% and 15% for cycles 1 and 2, respectively) than the no-antimicrobial through 56 d. CTC decreased soluble chemical oxygen demand and acetic acid utilization through 56 d, after which acclimation to CTC was apparent for the duration of the experiment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Circulating tumoral cells lack circadian-rhythm in hospitalized metastasic breast cancer patients.

PubMed

García-Sáenz, José Angel; Martín, Miguel; Maestro, Marisa; Vidaurreta, Marta; Veganzones, Silvia; Villalobos, Laura; Rodríguez-Lajusticia, Laura; Rafael, Sara; Sanz-Casla, María Teresa; Casado, Antonio; Sastre, Javier; Arroyo, Manuel; Díaz-Rubio, Eduardo

2006-11-01

The relationship between breast cancer and circadian rhythm variation has been extensively studied. Increased breast tumorigenesis has been reported in melatonin-suppressed experimental models and in observational studies. Circulating Tumor Cells (CTC) circadian- rhythm may optimize the timing of therapies. This is a prospective experimental study to ascertain the day-time and night-time CTC levels in hospitalized metastasic breast cancer (MBC) patients. CTC are isolated and enumerated from a 08:00 AM and 08:00 PM blood collections. 23 MBC and 23 healthy volunteers entered the study. 69 samples were collected (23 samples at 08:00 AM and 23 samples at 08:00 PM from MBC; 23 samples from healthy volunteers). Results from two patients were rejected due to sample processing errors. No CTC were isolated from healthy-volunteers. No-differences between daytime and night-time CTC were observed. Therefore, we could not ascertain CTC circadian-rhythm in hospitalized metastasic breast cancer patients.

The role of circulating tumor cells in evaluation of prognosis and treatment response in advanced non-small-cell lung cancer.

PubMed

Zhou, Jia; Dong, Fei; Cui, Fang; Xu, Rui; Tang, Xiaokui

2017-04-01

Non-small-cell lung cancer (NSCLC) lacks validated biomarkers to predict the prognosis and treatment response. This study investigated whether circulating tumor cells (CTCs) detectable could reminder high risk of distant metastasis, provide prognostic information, and early indicate the response to the conventional therapy in patients with advanced NSCLC. In this single-center prospective study, blood samples for CTC analysis were obtained from 59 patients with previously untreated, stage III or IV NSCLC both before and after administration of two cycles of chemotherapy. CTCs took in peripheral blood were measured by Cell Search detect technique. Carcino-embryonic antigen and count of metastatic sites were positively related to CTC count analyzed by multiple linear regression (P < 0.05). The median overall survival was 11.2 months (95% CI: 10.37-12.03 months) for the baseline CTC ≥ 2 group compared with 8.3 months (95% CI: 7.72-8.88 months) for the CTC < 2 group (log-rank test P < 0.05). Similarly, patients with CTC ≥ 2 at baseline had a significantly shorter median PFS (4.3 months, 95% CI: 3.7-4.9 months) compared with patients with CTC < 2 (6.2 months, 95% CI: 5.59-6.82 months) (log-rank test P < 0.05). For the disease control (stable disease, partial response, or complete response), group CTC value before treatment did not present difference with that after therapy compared by pared-samples T test (t = 1.455, P = 0.154), similar to the result of progressed group (progressive disease) (t = -0.987, P = 0.335). The CTC value of progressed group was higher than that of disease control group either at baseline or post chemotherapy. These data provide an evidence of positive correlation between CTC counts with CEA, as well as count of metastatic sites. Meanwhile, CTCs could be an effective predictor of distant metastasis and poor prognosis. In this study, CTCs are poorly related to treatment response. Whether CTCs could be a predictor of curative effect in advanced NSCLC should be validated by more researches in the future.

Test Review: Beal, A. L. (2011). "Insight Test of Cognitive Abilities." Markham, Ontario, Canadian Test Centre

ERIC Educational Resources Information Center

Colp, S. Mitchell; Nordstokke, David W.

2014-01-01

Published by the Canadian Test Centre (CTC), "Insight" represents a group-administered test of cognitive functioning that has been built entirely upon the Cattell-Horn-Carroll (CHC) theoretical framework. "Insight" is intended to be administered by educators and screen entire classrooms for students who present learning…

At what costs will screening with CT colonography be competitive? A cost-effectiveness approach.

PubMed

Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein; Zauber, Ann G; Boer, Rob; Wilschut, Janneke; Habbema, J Dik F

2009-03-01

The costs of computed tomographic colonography (CTC) are not yet established for screening use. In our study, we estimated the threshold costs for which CTC screening would be a cost-effective alternative to colonoscopy for colorectal cancer (CRC) screening in the general population. We used the MISCAN-colon microsimulation model to estimate the costs and life-years gained of screening persons aged 50-80 years for 4 screening strategies: (i) optical colonoscopy; and CTC with referral to optical colonoscopy of (ii) any suspected polyp; (iii) a suspected polyp >or=6 mm and (iv) a suspected polyp >or=10 mm. For each of the 4 strategies, screen intervals of 5, 10, 15 and 20 years were considered. Subsequently, for each CTC strategy and interval, the threshold costs of CTC were calculated. We performed a sensitivity analysis to assess the effect of uncertain model parameters on the threshold costs. With equal costs ($662), optical colonoscopy dominated CTC screening. For CTC to gain similar life-years as colonoscopy screening every 10 years, it should be offered every 5 years with referral of polyps >or=6 mm. For this strategy to be as cost-effective as colonoscopy screening, the costs must not exceed $285 or 43% of colonoscopy costs (range in sensitivity analysis: 39-47%). With 25% higher adherence than colonoscopy, CTC threshold costs could be 71% of colonoscopy costs. Our estimate of 43% is considerably lower than previous estimates in literature, because previous studies only compared CTC screening to 10-yearly colonoscopy, where we compared to different intervals of colonoscopy screening.

CTC Sentinel. Volume 8, Issue 5

DTIC Science & Technology

2015-05-01

Al-Qahtani was sent by the AQ senior leadership to go from Pakistan to the Nuristan/Kunar area [in north-eastern Afghanistan] to create a...difficult to get to. As you said, this is a guy with charisma, with leadership capability. This guy is incredibly operationally savvy. I can’t go...extremist groups out there, the most important of which are AQAP [al-Qa`ida in the Arabian Peninsula] in Yemen, AQSL [al-Qa`ida Senior Leadership

Counterterrorism and Counterinsurgency in Somalia: Assessing the Campaign Against Al Shabaab

DTIC Science & Technology

2016-01-01

establishment of Islam.”11 Research Design In an effort to better understand al Shabaab and U.S. efforts to degrade it, this study asks three sets of questions...and International Studies , July 2011; Ken Menkhaus, “Al-Shabab’s Capabilities Post -Westgate,” CTC Sentinel, March 24, 2014; United Nations (UN...representation of RAND intellectual property is provided for noncommercial use only. Unauthorized posting of this publication online is prohibited

Importance of cholera and other etiologies of acute diarrhea in post-earthquake Port-au-Prince, Haiti.

PubMed

Charles, Macarthur; Delva, Glavdia G; Boutin, Jethro; Severe, Karine; Peck, Mireille; Mabou, Marie Marcelle; Wright, Peter F; Pape, Jean W

2014-03-01

We estimated the proportion of diarrhea attributable to cholera and other pathogens during the rainy and dry seasons in patients seen in two urban health settings: a cholera treatment center (CTC) and oral rehydration points (ORPs). During April 1, 2011-November 30, 2012, stool samples were collected from 1,206 of 10,845 patients who came to the GHESKIO CTC or to the community ORPs with acute diarrhea, cultured for Vibrio cholerae, and tested by multiplex polymerase reaction. Vibrio cholerae was isolated from 409 (41.8%, 95% confidence interval [CI] = 38.7-44.9%) of the 979 specimens from the CTC and in 45 (19.8%, 95% CI = 14.8-25.6%) of the 227 specimens from the ORPs. Frequencies varied from 21.4% (95% CI = 16.6-26.7%) during the dry season to 46.8% (95% CI = 42.9-50.7%) in the rainy season. Shigella, enterotoxigenic Escherichia coli, rotavirus, and Cryptosporidium were frequent causes of diarrhea in children less than five years of age.

Association of CA27.29 and Circulating Tumor Cells Before and at Different Times After Adjuvant Chemotherapy in Patients with Early-stage Breast Cancer - The SUCCESS Trial.

PubMed

Hepp, Philip; Andergassen, Ulrich; Jäger, Bernadette; Trapp, Elisabeth; Alunni-Fabbroni, Marianna; Friedl, Thomas W P; Hecker, Nadeschda; Lorenz, Ralf; Fasching, Peter; Schneeweiss, Andreas; Fehm, Tanja; Janni, Wolfgang; Rack, Brigitte

2016-09-01

Evidence for the prognostic value of circulating tumor cells (CTCs) in early-stage breast cancer is swiftly increasing. An alternative approach for identifying patients at risk for recurrence is based on the detection of the mucin-1 (MUC1)-based tumor marker CA27.29. Here we report the association of these two prognostic markers before and immediately after chemotherapy (CHT), as well as after 2 and 5 years of follow-up. The SUCCESS trial compared fluorouracil, epirubicin and cyclophosphamide followed by docetaxel vs. FEC followed by docetaxel plus gemcitabine, and 2 vs. 5 years of treatment with zoledronic acid in 3,754 patients with node-positive or high-risk node-negative early-stage breast cancer. CA27.29 was measured with the ST AIA-PACK CA27.29 reagent (Tosoh Bioscience, Belgium). The cutoff for CA27.29 positivity was >31 U/ml. CTCs were assessed with the CellSearch System (Veridex, USA). The cutoff for CTC positivity was ≥1 CTC/15 ml whole blood. The relationship between CTC positivity and CA27.29 positivity was assessed based on Chi-square statistics and Cramer's V, which varies from 0 (no association between the variables) to 1 (complete association). Samples for CA27.29 and CTC determinations during follow-up were only drawn from patients that had no relapse. Both CA27.29 and CTC data were available for 1,981, 1,602, 1,159 and 707 patients before, immediately after and at 2 and 5 years after CHT, respectively. Positivity rates for CTC were 21.3%, 22.8%, 18.6% and 8.5%, respectively. CA27.29 was positive in 7.9%, 21.0%, 2.8%and 7.5%, respectively. Positivity for both CA27.29 and CTC was found in 2.4%, 4.2%, 0.7% and 1.8% of patients, respectively. The association between CA27.29 and CTC was significant but weak before CHT (p=0.0015; Cramer's V=0.063) and 5 years after CHT (p<0.001; Cramer's V=0.164), and not significant immediately after CHT (p=0.162; Cramer's V=0.035) and 2 years after (p=0.349; Cramer's V=0.028). We showed that CTC and CA27.29 positivity were significantly, but only weakly associated before CHT and 5 years after CHT, while no significant association was found immediately or 2 years after CHT during the course of early-stage breast cancer. It, therefore, seems reasonable to further evaluate the prognostic value of CTCs and CA27.29 as a combined prognostic test of two potentially independent markers that might provide complementary prognostic information. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

CTC1-STN1 coordinates G- and C-strand synthesis to regulate telomere length.

PubMed

Gu, Peili; Jia, Shuting; Takasugi, Taylor; Smith, Eric; Nandakumar, Jayakrishnan; Hendrickson, Eric; Chang, Sandy

2018-05-17

Coats plus (CP) is a rare autosomal recessive disorder caused by mutations in CTC1, a component of the CST (CTC1, STN1, and TEN1) complex important for telomere length maintenance. The molecular basis of how CP mutations impact upon telomere length remains unclear. The CP CTC1 L1142H mutation has been previously shown to disrupt telomere maintenance. In this study, we used CRISPR/Cas9 to engineer this mutation into both alleles of HCT116 and RPE cells to demonstrate that CTC1:STN1 interaction is required to repress telomerase activity. CTC1 L1142H interacts poorly with STN1, leading to telomerase-mediated telomere elongation. Impaired interaction between CTC1 L1142H :STN1 and DNA Pol-α results in increased telomerase recruitment to telomeres and further telomere elongation, revealing that C:S binding to DNA Pol-α is required to fully repress telomerase activity. CP CTC1 mutants that fail to interact with DNA Pol-α resulted in loss of C-strand maintenance and catastrophic telomere shortening. Our findings place the CST complex as an important regulator of both G-strand extensions by telomerase and C-strand synthesis by DNA Pol-α. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Effect of oxytocin and PGF2α on chlortetracycline absorption from the uterus of early postpartum camels (Camelus dromedarius).

PubMed

Ghoneim, I M; Abdelghany, A M; Waheed, M M; Elmoslemany, A M; Alhaider, A K; Al-Eknah, M M

2015-09-01

Fifteen parturient camels given chlortetracycline (CTC) as intrauterine pessaries (3 g/head) were divided into the control group (n = 5), which remained untreated, oxytocin-treated group (50 IU, intramuscular; n = 5), and cloprostenol-treated group (Estrumate, 500 μg, intramuscular; n = 5). Serum samples were collected at 0, 1, 2, 4, 8, 24, 48, and 72 hours after treatment and CTC was determined. The CTC appeared in blood within 1 hour. The maximum concentration of CTC was detected in blood after 72 (543.58 ± 117.85 μg/L), 8 (520.48 ± 13.65 μg/L), and 1 hour (831.98 ± 111.01 μg/L) of administration in control, oxytocin-, and PGF2α-treated camels, respectively. There was a high significant effect of time (P < 0.001) and treatment-by-time interaction (P < 0.001) on serum CTC concentration. In the control group, there was a significant (P < 0.05) increase in CTC concentrations at 72 hours compared to the other times. In the oxytocin group, there was a significant (P < 0.05) decrease in CTC concentrations at 24, 48, and 72 hours compared to its level after 1 or 8 hours. In PGF2α, there was a significant (P < 0.001) decrease in CTC concentrations at 2, 4, 8, 24, 48, and 72 hours compared to its level after 1 hour. Treatment contrast at different time points showed a significant (P < 0.001) increase in CTC concentration after 1 hour in the PGF2α-treated group compared to oxytocin and control groups. By 72 hours, CTC concentrations were significantly (P < 0.05) lower in PGF2α and oxytocin groups than in the control group. In conclusion, serum CTC concentration in dromedary camels increases within 1 hour after intrauterine administration and remains elevated for at least 72 hours in control, oxytocin-, and PGF2α-treated animals. Copyright © 2015 Elsevier Inc. All rights reserved.

Rapid Isolation of Viable Circulating Tumor Cells from Patient Blood Samples

PubMed Central

Hughes, Andrew D.; Mattison, Jeff; Powderly, John D.; Greene, Bryan T.; King, Michael R.

2012-01-01

Circulating tumor cells (CTC) are cells that disseminate from a primary tumor throughout the circulatory system and that can ultimately form secondary tumors at distant sites. CTC count can be used to follow disease progression based on the correlation between CTC concentration in blood and disease severity1. As a treatment tool, CTC could be studied in the laboratory to develop personalized therapies. To this end, CTC isolation must cause no cellular damage, and contamination by other cell types, particularly leukocytes, must be avoided as much as possible2. Many of the current techniques, including the sole FDA-approved device for CTC enumeration, destroy CTC as part of the isolation process (for more information see Ref. 2). A microfluidic device to capture viable CTC is described, consisting of a surface functionalized with E-selectin glycoprotein in addition to antibodies against epithelial markers3. To enhance device performance a nanoparticle coating was applied consisting of halloysite nanotubes, an aluminosilicate nanoparticle harvested from clay4. The E-selectin molecules provide a means to capture fast moving CTC that are pumped through the device, lending an advantage over alternative microfluidic devices wherein longer processing times are necessary to provide target cells with sufficient time to interact with a surface. The antibodies to epithelial targets provide CTC-specificity to the device, as well as provide a readily adjustable parameter to tune isolation. Finally, the halloysite nanotube coating allows significantly enhanced isolation compared to other techniques by helping to capture fast moving cells, providing increased surface area for protein adsorption, and repelling contaminating leukocytes3,4. This device is produced by a straightforward technique using off-the-shelf materials, and has been successfully used to capture cancer cells from the blood of metastatic cancer patients. Captured cells are maintained for up to 15 days in culture following isolation, and these samples typically consist of >50% viable primary cancer cells from each patient. This device has been used to capture viable CTC from both diluted whole blood and buffy coat samples. Ultimately, we present a technique with functionality in a clinical setting to develop personalized cancer therapies. PMID:22733259

A New Size-based Platform for Circulating Tumor Cell Detection in Colorectal Cancer Patients.

PubMed

Oh, Bo Young; Kim, Jhingook; Lee, Woo Yong; Kim, Hee Cheol

2017-09-01

Circulating tumor cells (CTCs) might play a significant role in cancer progression and metastasis. However, the ability to detect CTCs is limited, especially in cells undergoing epithelial-mesenchymal transition. In this study, we evaluated a new size-based CTC detection platform and its clinical efficacy in colorectal cancer. Blood samples were obtained from 76 patients with colorectal cancer and 20 healthy control subjects for CTC analysis. CTCs were enriched using a high-density microporous chip filter and were detected using a 4-color staining protocol including 4',6-diamidino-2-phenylindole (DAPI) for nucleated cells, CD45 monoclonal antibody (mAb) as a leukocyte marker, and epithelial cell adhesion molecule (EpCAM) mAb or cytokeratin (CK) mAb as an epithelial cell marker. CTC positivity was defined as DAPI-positive (DAPI + )/CD45 - /EpCAM + or CK + cells and clinical outcomes of patients were analyzed according to CTC counts. CTCs were detected in 50 patients using this size-based filtration platform. CTC + patients were more frequently identified with a high level of carcinoembryonic antigen and advanced stage cancer (P = .038 and P = .017, respectively). CTC counts for patients with stage IV cancer (12.47 ± 24.00) were significantly higher than those for patients with cancers that were stage I to III (2.84 ± 5.29; P = .005) and healthy control subjects (0.25 ± 0.55; P < .001). In addition, progression-free survival tended to be lower in CTC + patients compared with CTC - patients (P = .092). In patients with stage I to III cancer, recurrence occurred only in CTC + patients. CTC positivity was found to correlate with clinical features of colorectal cancer patients. Our results suggest that this new size-based platform has potential for determining prognosis and therapeutic response in colorectal cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Benefits of using vaccines out of the cold chain: delivering meningitis A vaccine in a controlled temperature chain during the mass immunization campaign in Benin.

PubMed

Zipursky, Simona; Djingarey, Mamoudou Harouna; Lodjo, Jean-Claude; Olodo, Laifoya; Tiendrebeogo, Sylvestre; Ronveaux, Olivier

2014-03-14

In October 2012, the Meningococcal A conjugate vaccine MenAfriVac was granted a label variation to allow for its use in a controlled temperature chain (CTC), at temperatures of up to 40°C for not more than four days. This paper describes the first field use of MenAfriVac in a CTC during a campaign in Benin, December 2012, and assesses the feasibility and acceptability of the practice. We implemented CTC in one selected district, Banikoara (target population of 147,207; 1-29 years of age), across 14 health facilities and 150 villages. We monitored the CTC practice using temperature indicators and daily monitoring sheets. At the end of the campaign we conducted a face-to-face survey to assess vaccinators' and supervisors' experience with CTC. A mix of strategies were implemented in the field to maximize the benefits from CTC practice, depending on the distance from health centre to populations and the availability of a functioning refrigerator in the health centre. Coverage across Banikoara was 105.7%. Over the course of the campaign only nine out of approx. 15,000 vials were discarded due to surpassing the 4 day CTC limit and no vial was discarded because of exposure to a temperature higher than 40°C or due to the Vaccine Vial Monitor (VVM) reaching its endpoint. Overall confidence and perceived usefulness of the CTC approach were very high among vaccinators and supervisors. Vaccinators and supervisors see clear benefits from the CTC approach in low income settings, especially in hard-to-reach areas or where cold chain is weak. Taking advantage of the flexibility offered by CTC opens the door for the implementation of new immunization strategies to ensure all those at risk are protected. Copyright © 2014. Published by Elsevier Ltd.

Isolation of breast cancer and gastric cancer circulating tumor cells by use of an anti HER2-based microfluidic device.

PubMed

Galletti, Giuseppe; Sung, Matthew S; Vahdat, Linda T; Shah, Manish A; Santana, Steven M; Altavilla, Giuseppe; Kirby, Brian J; Giannakakou, Paraskevi

2014-01-07

Circulating tumor cells (CTCs) have emerged as a reliable source of tumor cells, and their concentration has prognostic implications. CTC capture offers real-time access to cancer tissue without the need of an invasive biopsy, while their phenotypic and molecular interrogation can provide insight into the biological changes of the tumor that occur during treatment. The majority of the CTC capture methods are based on EpCAM expression as a surface marker of tumor-derived cells. However, EpCAM protein expression levels can be significantly down regulated during cancer progression as a consequence of the process of epithelial to mesenchymal transition. In this paper, we describe a novel HER2 (Human Epidermal Receptor 2)-based microfluidic device for the isolation of CTCs from peripheral blood of patients with HER2-expressing solid tumors. We selected HER2 as an alternative to EpCAM as the receptor is biologically and therapeutically relevant in several solid tumors, like breast cancer (BC), where it is overexpressed in 30% of the patients and expressed in 90%, and gastric cancer (GC), in which HER2 presence is identified in more than 60% of the cases. We tested the performance of various anti HER2 antibodies in a panel of nine different BC cell lines with varying HER2 protein expression levels, using immunoblotting, confocal microscopy, live cells imaging and flow cytometry analyses. The antibody associated with the highest capture efficiency and sensitivity for HER2 expressing cells on the microfluidic device was the one that performed best in live cells imaging and flow cytometry assays as opposed to the fixed cell analyses, suggesting that recognition of the native conformation of the HER2 extracellular epitope on living cells was essential for specificity and sensitivity of CTC capture. Next, we tested the performance of the HER2 microfluidic device using blood from metastatic breast and gastric cancer patients. The HER2 microfluidic device exhibited CTC capture in 9/9 blood samples. Thus, the described HER2-based microfluidic device can be considered as a valid clinically relevant method for CTC capture in HER2 expressing solid cancers.

Use of generalized ordered logistic regression for the analysis of multidrug resistance data.

PubMed

Agga, Getahun E; Scott, H Morgan

2015-10-01

Statistical analysis of antimicrobial resistance data largely focuses on individual antimicrobial's binary outcome (susceptible or resistant). However, bacteria are becoming increasingly multidrug resistant (MDR). Statistical analysis of MDR data is mostly descriptive often with tabular or graphical presentations. Here we report the applicability of generalized ordinal logistic regression model for the analysis of MDR data. A total of 1,152 Escherichia coli, isolated from the feces of weaned pigs experimentally supplemented with chlortetracycline (CTC) and copper, were tested for susceptibilities against 15 antimicrobials and were binary classified into resistant or susceptible. The 15 antimicrobial agents tested were grouped into eight different antimicrobial classes. We defined MDR as the number of antimicrobial classes to which E. coli isolates were resistant ranging from 0 to 8. Proportionality of the odds assumption of the ordinal logistic regression model was violated only for the effect of treatment period (pre-treatment, during-treatment and post-treatment); but not for the effect of CTC or copper supplementation. Subsequently, a partially constrained generalized ordinal logistic model was built that allows for the effect of treatment period to vary while constraining the effects of treatment (CTC and copper supplementation) to be constant across the levels of MDR classes. Copper (Proportional Odds Ratio [Prop OR]=1.03; 95% CI=0.73-1.47) and CTC (Prop OR=1.1; 95% CI=0.78-1.56) supplementation were not significantly associated with the level of MDR adjusted for the effect of treatment period. MDR generally declined over the trial period. In conclusion, generalized ordered logistic regression can be used for the analysis of ordinal data such as MDR data when the proportionality assumptions for ordered logistic regression are violated. Published by Elsevier B.V.

Clinical experience with CT colonography

NASA Astrophysics Data System (ADS)

Reed, Judd E.; Garry, John L.; Wilson, Lynn A.; Johnson, C. Daniel

2000-04-01

Since the introduction of Computed Tomographic Colonography (CTC) in 1995, many advances in computer equipment and software have become available. Despite these advances, the promise of colon cancer prevention has not been realized. A colorectal screening tool that performs at a high level, is acceptable to patients, and can be performed safely and at low cost holds promise of saving lives in the future. Our institution has performed over two hundred seventy five clinical CTC examinations. These scans, which each entail a supine and a prone acquisition, only differ from our research protocol in the necessity of an expeditious interpretation. Patients arrive for their CTC examination early in the morning following a period of fasting and bowel preparation. If a CTC examination has a positive finding, the patient is scheduled for colonoscopic polypectomy that same morning. To facilitate this, the patients are required to continue fasting until the CTC examination has been interpreted. It is therefore necessary to process the CTC examination very quickly to minimize patient discomfort. A positive CTC result occurred in fifteen percent of examinations. Among these positive results, the specificity has been in excess of ninety five percent. Additionally, life threatening extra-colonic lesions were discovered in two percent of the screened population.

Separation of cancer cells from a red blood cell suspension using inertial force.

PubMed

Tanaka, Tatsuya; Ishikawa, Takuji; Numayama-Tsuruta, Keiko; Imai, Yohsuke; Ueno, Hironori; Matsuki, Noriaki; Yamaguchi, Takami

2012-11-07

The circulating tumor cell (CTC) test has recently become popular for evaluating prognosis and treatment efficacy in cancer patients. The accuracy of the test is strongly dependent on the precision of the cancer cell separation. In this study, we developed a multistage microfluidic device to separate cancer cells from a red blood cell (RBC) suspension using inertial migration forces. The device was able to effectively remove RBCs up to the 1% hematocrit (Hct) condition with a throughput of 565 μL min(-1). The collection efficiency of cancer cells from a RBC suspension was about 85%, and the enrichment of cancer cells was about 120-fold. Further improvements can be easily achieved by parallelizing the device. These results illustrate that the separation of cancer cells from RBCs is possible using only inertial migration forces, thus paving the way for the development of a novel microfluidic device for future CTC tests.

Youth problem behaviors 8 years after implementing the communities that care prevention system: a community-randomized trial.

PubMed

Hawkins, J David; Oesterle, Sabrina; Brown, Eric C; Abbott, Robert D; Catalano, Richard F

2014-02-01

Community-based efforts to prevent adolescent problem behaviors are essential to promote public health and achieve collective impact community wide. OBJECTIVE To test whether the Communities That Care (CTC) prevention system reduced levels of risk and adolescent problem behaviors community wide 8 years after implementation of CTC. A community-randomized trial was performed in 24 small towns in 7 states, matched within state, assigned randomly to a control or intervention group in 2003. All fifth-grade students attending public schools in study communities in 2003-2004 who received consent from their parents to participate (76.4% of the eligible population) were included. A panel of 4407 fifth graders was surveyed through 12th grade, with 92.5% of the sample participating at the last follow-up. A coalition of community stakeholders received training and technical assistance to install CTC, used epidemiologic data to identify elevated risk factors and depressed protective factors for adolescent problem behaviors in the community, and implemented tested and effective programs for youths aged 10 to 14 years as well as their families and schools to address their community's elevated risks. MAIN OUTCOMES AND MEASURES Levels of targeted risk; sustained abstinence, and cumulative incidence by grade 12; and current prevalence of tobacco, alcohol, and other drug use, delinquency, and violence in 12th grade. By spring of 12th grade, students in CTC communities were more likely than students in control communities to have abstained from any drug use (adjusted risk ratio [ARR] = 1.32; 95% CI, 1.06-1.63), drinking alcohol (ARR = 1.31; 95% CI, 1.09-1.58), smoking cigarettes (ARR = 1.13; 95% CI, 1.01-1.27), and engaging in delinquency (ARR = 1.18; 95% CI, 1.03-1.36). They were also less likely to ever have committed a violent act (ARR = 0.86; 95% CI, 0.76-0.98). There were no significant differences by intervention group in targeted risks, the prevalence of past-month or past-year substance use, or past-year delinquency or violence. Using the CTC system continued to prevent the initiation of adolescent problem behaviors through 12th grade, 8 years after implementation of CTC and 3 years after study-provided resources ended, but did not produce reductions in current levels of risk or current prevalence of problem behavior in 12th grade. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01088542.

An economic evaluation of the controlled temperature chain approach for vaccine logistics: evidence from a study conducted during a meningitis A vaccine campaign in Togo.

PubMed

Mvundura, Mercy; Lydon, Patrick; Gueye, Abdoulaye; Diaw, Ibnou Khadim; Landoh, Dadja Essoya; Toi, Bafei; Kahn, Anna-Lea; Kristensen, Debra

2017-01-01

A recent innovation in support of the final segment of the immunization supply chain is licensing certain vaccines for use in a controlled temperature chain (CTC), which allows excursions into ambient temperatures up to 40°C for a specific number of days immediately prior to administration. However, limited evidence exists on CTC economics to inform investments for labeling other eligible vaccines for CTC use. Using data collected during a MenAfriVac™ campaign in Togo, we estimated economic costs for vaccine logistics when using the CTC approach compared to full cold chain logistics (CCL) approach. We conducted the study in Togo's Central Region, where two districts were using the CTC approach and two relied on a fullCCL approach during the MenAfriVac™ campaign. Data to estimate vaccine logistics costs were obtained from primary data collected using costing questionnaires and from financial cost data from campaign microplans. Costs are presented in 2014 US dollars. Average logistics costs per dose were estimated at $0.026±0.032 for facilities using a CTC and $0.029±0.054 for facilities using the fullCCL approach, but the two estimates were not statistically different. However, if the facilities without refrigerators had not used a CTC but had received daily deliveries of vaccines, the average cost per dose would have increased to $0.063 (range $0.007 to $0.33), with larger logistics cost increases occurring for facilities that were far from the district. Using the CTC approach can reduce logistics costs for remote facilities without cold chain infrastructure, which is where CTC is designed to reduce logistical challenges of vaccine distribution.

An economic evaluation of the controlled temperature chain approach for vaccine logistics: evidence from a study conducted during a meningitis A vaccine campaign in Togo

PubMed Central

Mvundura, Mercy; Lydon, Patrick; Gueye, Abdoulaye; Diaw, Ibnou Khadim; Landoh, Dadja Essoya; Toi, Bafei; Kahn, Anna-Lea; Kristensen, Debra

2017-01-01

Introduction A recent innovation in support of the final segment of the immunization supply chain is licensing certain vaccines for use in a controlled temperature chain (CTC), which allows excursions into ambient temperatures up to 40°C for a specific number of days immediately prior to administration. However, limited evidence exists on CTC economics to inform investments for labeling other eligible vaccines for CTC use. Using data collected during a MenAfriVac™ campaign in Togo, we estimated economic costs for vaccine logistics when using the CTC approach compared to full cold chain logistics (CCL) approach. Methods We conducted the study in Togo’s Central Region, where two districts were using the CTC approach and two relied on a fullCCL approach during the MenAfriVac™ campaign. Data to estimate vaccine logistics costs were obtained from primary data collected using costing questionnaires and from financial cost data from campaign microplans. Costs are presented in 2014 US dollars. Results Average logistics costs per dose were estimated at $0.026±0.032 for facilities using a CTC and $0.029±0.054 for facilities using the fullCCL approach, but the two estimates were not statistically different. However, if the facilities without refrigerators had not used a CTC but had received daily deliveries of vaccines, the average cost per dose would have increased to $0.063 (range $0.007 to $0.33), with larger logistics cost increases occurring for facilities that were far from the district. Conclusion Using the CTC approach can reduce logistics costs for remote facilities without cold chain infrastructure, which is where CTC is designed to reduce logistical challenges of vaccine distribution. PMID:29296162

Detection of circulating tumor cells using oHSV1-hTERT-GFP in lung cancer.

PubMed

Gao, Hongjun; Liu, Wenjing; Yang, Shaoxing; Zhang, Wen; Li, Xiaoyan; Qin, Haifeng; Wang, Weixia; Zhao, Changyun

2018-01-01

This study was conducted to evaluate the clinical utility of the oHSV1-hTERT-GFP circulating tumor cell (CTC) detection method in the peripheral blood of patients with lung cancer by comparing its sensitivity to the CellSearch CTC detection method. The oHSV1-hTERT-GFP and CellSearch CTC detection methods were compared using peripheral blood samples of patients pathologically diagnosed with lung cancer. A total of 240 patients with lung cancer were recruited, including 89 patients who were newly diagnosed and 151 patients who had previously received treatment. Sixty-six newly diagnosed patients were evaluated using both methods. The CTC detection rates were 71.2% and 33.3% using the oHSV1-hTERT-GFP and CellSearch methods, respectively; this difference was statistically significant (P = 0.000). Among the entire cohort (n = 240), the CTC detection rate using the oHSV1-hTERT-GFP method was 76.3%, with a CTC count of 0-81. The CTC detection rates were 76.7%, 68.9%, and 76.3% in patients with squamous cell carcinoma, adenocarcinoma, and small cell lung cancer, respectively. There was no statistically significant difference in the CTC detection rates between these different pathological subtypes (P = 0.738). The CTC detection rates of 79.8% and 74.4% in patients with stage I-III and IV lung cancer, respectively, were not significantly different (P = 0.427). The oHSV1-hTERT-GFP method is highly effective for detecting CTCs in patients with lung cancer, independent of pathological type and disease stage, and is ideal for large-scale clinical applications. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Chlortetracycline - resistant intestinal bacteria in organically-raised and feral swine

USDA-ARS?s Scientific Manuscript database

Organically-raised swine had high fecal populations of chlortetracycline (CTC)-resistant (growing at 64 micro g CTC/ml) Escherichia coli, Megasphaera elsdenii and anaerobe populations. By comparison, predominant CTC-resistant bacteria in feral swine feces were over 1000-fold fewer and exhibited lo...

NASA Northeast Regional Technology Transfer Center

NASA Technical Reports Server (NTRS)

Dunn, James P.

2001-01-01

This report is a summary of the primary activities and metrics for the NASA Northeast Regional Technology Transfer Center, operated by the Center for Technology Commercialization, Inc. (CTC). This report covers the contract period January 1, 2000 - March 31, 2001. This report includes a summary of the overall CTC Metrics, a summary of the Major Outreach Events, an overview of the NASA Business Outreach Program, a summary of the Activities and Results of the Technology into the Zone program, and a Summary of the Major Activities and Initiatives performed by CTC in supporting this contract. Between January 1, 2000 and March 31, 2001, CTC has facilitated 10 license agreements, established 35 partnerships, provided assistance 517 times to companies, and performed 593 outreach activities including participation in 57 outreach events. CTC also assisted Goddard in executing a successful 'Technology into the Zone' program.' CTC is pleased to have performed this contract, and looks forward to continue providing their specialized services in support of the new 5 year RTTC Contract for the Northeast region.

Clusters of circulating tumor cells traverse capillary-sized vessels

PubMed Central

Au, Sam H.; Storey, Brian D.; Moore, John C.; Tang, Qin; Chen, Yeng-Long; Javaid, Sarah; Sarioglu, A. Fatih; Sullivan, Ryan; Madden, Marissa W.; O’Keefe, Ryan; Haber, Daniel A.; Maheswaran, Shyamala; Langenau, David M.; Stott, Shannon L.; Toner, Mehmet

2016-01-01

Multicellular aggregates of circulating tumor cells (CTC clusters) are potent initiators of distant organ metastasis. However, it is currently assumed that CTC clusters are too large to pass through narrow vessels to reach these organs. Here, we present evidence that challenges this assumption through the use of microfluidic devices designed to mimic human capillary constrictions and CTC clusters obtained from patient and cancer cell origins. Over 90% of clusters containing up to 20 cells successfully traversed 5- to 10-μm constrictions even in whole blood. Clusters rapidly and reversibly reorganized into single-file chain-like geometries that substantially reduced their hydrodynamic resistances. Xenotransplantation of human CTC clusters into zebrafish showed similar reorganization and transit through capillary-sized vessels in vivo. Preliminary experiments demonstrated that clusters could be disrupted during transit using drugs that affected cellular interaction energies. These findings suggest that CTC clusters may contribute a greater role to tumor dissemination than previously believed and may point to strategies for combating CTC cluster-initiated metastasis. PMID:27091969

CTC-mRNA (AR-V7) Analysis from Blood Samples—Impact of Blood Collection Tube and Storage Time

PubMed Central

Luk, Alison W. S.; Ma, Yafeng; Ding, Pei N.; Young, Francis P.; Chua, Wei; Balakrishnar, Bavanthi; Dransfield, Daniel T.; de Souza, Paul; Becker, Therese M.

2017-01-01

Circulating tumour cells (CTCs) are an emerging resource for monitoring cancer biomarkers. New technologies for CTC isolation and biomarker detection are increasingly sensitive, however, the ideal blood storage conditions to preserve CTC-specific mRNA biomarkers remains undetermined. Here we tested the preservation of tumour cells and CTC-mRNA over time in common anticoagulant ethylene-diamine-tetra-acetic acid (EDTA) and acid citrate dextrose solution B (Citrate) blood tubes compared to preservative-containing blood tubes. Blood samples spiked with prostate cancer cells were processed after 0, 24, 30, and 48 h storage at room temperature. The tumour cell isolation efficiency and the mRNA levels of the prostate cancer biomarkers androgen receptor variant 7 (AR-V7) and total AR, as well as epithelial cell adhesion molecule (EpCAM) were measured. Spiked cells were recovered across all storage tube types and times. Surprisingly, tumour mRNA biomarkers were readily detectable after 48 h storage in EDTA and Citrate tubes, but not in preservative-containing tubes. Notably, AR-V7 expression was detected in prostate cancer patient blood samples after 48 h storage in EDTA tubes at room temperature. This important finding presents opportunities for measuring AR-V7 expression from clinical trial patient samples processed within 48 h—a much more feasible timeframe compared to previous recommendations. PMID:28498319

Determine the Dynamic Response to Androgen-Blockade Therapy in Circulating Tumor Cells of CRPC Patients by Transcription-Based Reporter Vectors

DTIC Science & Technology

2016-08-01

green fluorescent reporter gene. Specific Aim 2: To evaluate the functional capability of Ad-mediated CTC detection and the response to AR...6 Specific Aim 3: To evaluate the therapeutic responses to AR antagonists in CTCs of CRPC patients before, during and after AR blockade...A., Mali, A., Khirade, M. & Bapat, S. A tumor deconstruction platform identifies definitive end points in the evaluation of drug responses. Oncogene

A stochastic model of input effectiveness during irregular gamma rhythms.

PubMed

Dumont, Grégory; Northoff, Georg; Longtin, André

2016-02-01

Gamma-band synchronization has been linked to attention and communication between brain regions, yet the underlying dynamical mechanisms are still unclear. How does the timing and amplitude of inputs to cells that generate an endogenously noisy gamma rhythm affect the network activity and rhythm? How does such "communication through coherence" (CTC) survive in the face of rhythm and input variability? We present a stochastic modelling approach to this question that yields a very fast computation of the effectiveness of inputs to cells involved in gamma rhythms. Our work is partly motivated by recent optogenetic experiments (Cardin et al. Nature, 459(7247), 663-667 2009) that tested the gamma phase-dependence of network responses by first stabilizing the rhythm with periodic light pulses to the interneurons (I). Our computationally efficient model E-I network of stochastic two-state neurons exhibits finite-size fluctuations. Using the Hilbert transform and Kuramoto index, we study how the stochastic phase of its gamma rhythm is entrained by external pulses. We then compute how this rhythmic inhibition controls the effectiveness of external input onto pyramidal (E) cells, and how variability shapes the window of firing opportunity. For transferring the time variations of an external input to the E cells, we find a tradeoff between the phase selectivity and depth of rate modulation. We also show that the CTC is sensitive to the jitter in the arrival times of spikes to the E cells, and to the degree of I-cell entrainment. We further find that CTC can occur even if the underlying deterministic system does not oscillate; quasicycle-type rhythms induced by the finite-size noise retain the basic CTC properties. Finally a resonance analysis confirms the relative importance of the I cell pacing for rhythm generation. Analysis of whole network behaviour, including computations of synchrony, phase and shifts in excitatory-inhibitory balance, can be further sped up by orders of magnitude using two coupled stochastic differential equations, one for each population. Our work thus yields a fast tool to numerically and analytically investigate CTC in a noisy context. It shows that CTC can be quite vulnerable to rhythm and input variability, which both decrease phase preference.

Prevention Service System Transformation Using "Communities That Care"

ERIC Educational Resources Information Center

Brown, Eric C.; Hawkins, J. David; Arthur, Michael W.; Briney, John S.; Fagan, Abigail A.

2011-01-01

This study examines prevention system transformation as part of a community-randomized controlled trial of Communities That Care (CTC). Using data from surveys of community leaders, we examine differences between CTC and control communities 4.5 years after CTC implementation. Significantly higher levels of adopting a science-based approach to…

Development of Multifunctional Fluorescent–Magnetic Nanoprobes for Selective Capturing and Multicolor Imaging of Heterogeneous Circulating Tumor Cells

PubMed Central

2016-01-01

Circulating tumor cells (CTC) are highly heterogeneous in nature due to epithelial–mesenchymal transition (EMT), which is the major obstacle for CTC analysis via “liquid biopsy”. This article reports the development of a new class of multifunctional fluorescent–magnetic multicolor nanoprobes for targeted capturing and accurate identification of heterogeneous CTC. A facile design approach for the synthesis and characterization of bioconjugated multifunctonal nanoprobes that exhibit excellent magnetic properties and emit very bright and photostable multicolor fluorescence at red, green, and blue under 380 nm excitation is reported. Experimental data presented show that the multifunctional multicolor nanoprobes can be used for targeted capture and multicolor fluorescence mapping of heterogeneous CTC and can distinguish targeted CTC from nontargeted cells. PMID:27255574

Effects of the Communities That Care Model in Pennsylvania on Change in Adolescent Risk and Problem Behaviors

PubMed Central

Jones, Damon; Greenberg, Mark T.; Osgood, D. Wayne; Bontempo, Daniel

2015-01-01

Despite the public health burden of adolescent substance use, delinquency, and other problem behavior, few comprehensive models of disseminating evidence-based prevention programs to communities have demonstrated positive youth outcomes at a population level, capacity to maintain program fidelity, and sustainability. We examined whether the Communities That Care (CTC; Hawkins and Catalano 1992) model had a positive impact on risk/protective factors and academic and behavioral outcomes among adolescents in a quasi-experimental effectiveness study. We conducted a longitudinal study of CTC in Pennsylvania utilizing biannual surveillance data collected through anonymous in-school student surveys. We utilized multilevel models to examine CTC impact on change in risk/protective factors, grades, delinquency, and substance use over time. Youth in CTC communities demonstrated less growth in delinquency, but not substance use, than youth in non-CTC communities. Levels of risk factors increased more slowly, and protective factors and academic performance decreased more slowly, among CTC community grade-cohorts that were exposed to evidence-based, universal prevention programs than comparison grade cohorts. Community coalitions can affect adolescent risk and protective behaviors at a population level when evidence-based programs are utilized. CTC represents an effective model for disseminating such programs. PMID:20020209

Computed tomographic colonography (CTC): a retrospective analysis of a single site experience and a review of the literature on the status of CTC.

PubMed

Ghuman, Marcus; Bates, Ngaire; Moore, Helen

2012-06-08

To review local CT colonography (CTC) data with regard to demographics, and both colonic and extracolonic findings. To improve performance by identifying any deficiencies that need to be addressed, in relation to a literature review of the current status of CTC. A retrospective observational analysis was conducted of all the patients undergoing CTC for the 3-year period from 9 August 2007 - 12 August 2010 (n=302) conducted at a single site: Greenlane Hospital (ADHB outpatients). In total, 12 of the 302 patients (4%) were found to have cancer, 24 polyps (8%), and 111 diverticular disease (37%). 21 patients (7%) were referred on for optical colonoscopy following their CTC, and 34 patients (11%) had follow-up recommendations resulting from extracolonic findings, including 24 recommendations for further imaging. A trend towards under-representation of both Māori and Pacific Island groups undergoing CTC, and over-representation of Asians was identified. This study has reported on the experience of CT colonography at Greenlane Hospital over a 3-year period. It has provided important local data on rates of detection of colonic pathology. Māori and Pacific Islanders need encouragement from primary health practitioners to present for bowel examination.

Circulating Tumor Cell Increase as a Biomarker of Disease Progression in Metastatic Castration-Resistant Prostate Cancer Patients with Low Baseline CTC Counts.

PubMed

Lorente, D; Olmos, D; Mateo, J; Dolling, D; Bianchini, D; Seed, G; Flohr, P; Crespo, M; Figueiredo, I; Miranda, S; Scher, H I; Terstappen, L W M M; de Bono, J S

2018-05-07

The development of treatment response and surrogate biomarkers for advanced prostate cancer care is an unmet clinical need. Patients with baseline circulating tumor cell counts (BLCTCs)<5/7.5 mL represent a good prognosis subgroup, but are non-evaluable for response assessment (decrease in CTCs). The aim of the study is to determine the value of any increase in CTCs (CTC Progression) as an indicator of progression in prostate cancer patients with low pre-treatment CTCs (<5). We performed a post-hoc analysis of patients with BLCTCs < 5 treated in the COU-AA-301 (abiraterone or placebo + prednisone) and IMMC-38 (chemotherapy) trials. The association of CTC Progression (increase in CTCs at 4, 8 or 12 weeks) with overall survival (OS) was evaluated in multivariable Cox regression models. Performance of survival models with and without CTC Progression was evaluated by calculating ROC curve AUCs and weighted c-indices. Overall, 511 patients with CTCs <5 (421 in COU-AA-301; 90 in IMMC-38) were selected; 212 (41.7%) had CTC Progression at 4, 8 or 12 weeks after treatment initiation. CTC Progression was associated with significantly worse OS (27.1 vs 15.1m; HR: 3.4 [95%CI:2.5-4.5; p < 0.001]); independent of baseline CTCs and established clinical variables. Adding CTC Progression to the OS model significantly improved ROC AUC (0.77 vs 0.66; p < 0.001). Models including CTC Progression had superior ROC AUC (0.77 vs 0.69; p < 0.001) and weighted c-index (0.750 vs 0.705; delta c-index: 0.045 [95%CI: 0.019-0.071]) values than those including CTC conversion (increase to CTCs ≥5). In COU-AA-301, the impact of CTC Progression was independent of treatment arm. Increasing CTCs during the first 12-weeks of treatment are independently associated with worse OS from advanced prostate cancer in patients with baseline CTCs < 5 treated with abiraterone or chemotherapy and improve models with established prognostic variables. These findings must be prospectively validated.

Effects of dietary polysavone (Alfalfa extract) and chlortetracycline supplementation on antioxidation and meat quality in broiler chickens.

PubMed

Dong, X F; Gao, W W; Su, J L; Tong, J M; Zhang, Q

2011-06-01

1. A total of 360 1-d-old male commercial Arbor Acre broiler chickens were randomly assigned to 5 groups (6 replicates of 12 birds each) to evaluate the dietary effects of polysavone (0·5, 1·0 and 1·5 g/kg), a natural extract from alfalfa, and 0·15 g/kg chlortetracycline (CTC) on growth performance, antioxidation and meat quality of broiler chickens. 2. Over the 6-week study, feed intake increased significantly with CTC supplementation and final body weight (BW) was significantly higher for 1·0 g/kg polysavone and 0·15 g/kg CTC treatments. Feed:gain ratio was not significantly affected by the dietary treatments. 3. At 3 weeks of age, serum total superoxide dismutase (T-SOD) activity for all polysavone treatments was significantly higher than controls, liver T-SOD activity in 1·5 g/kg polysavone group was significantly higher than the control and CTC groups, and serum glutathione peroxidase (GSHPx) activity for 1·5 g/kg polysavone and liver GSHPx activity in all polysavone groups were significantly higher than CTC. 4. At 6 weeks of age, serum and liver T-SOD activity in 1·5 g/kg polysavone group and liver GSHPx activity for all polysavone treatments were higher significantly than the control and CTC groups, and serum malondialdehyde (MDA) content for all polysavone treatments was significantly lower than CTC. 5. Breast muscle T-SOD activity and pH value at 6 weeks of age were significantly higher and MDA content was significantly lower in 1·0 and 1·5 g/kg polysavone groups than in the control and CTC groups. Breast muscle shear force was significantly lower in l·5 g/kg polysavone group compared with the control, and drip loss for all polysavone treatments was significantly lower than CTC. 6. It was indicated that polysavone modulates antioxidation and modifies meat quality, but with no adverse effect on performance of broiler chickens, and that CTC can be beneficial to performance but has no beneficial effect on antioxidant function or meat quality.

28 CFR 550.40 - Purpose and scope.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Drug Services (Urine Surveillance and Counseling for Sentenced Inmates in Contract CTCs) § 550.40... community treatment center (CTC) participate in a program of urine testing for drug use. An inmate who is...

28 CFR 550.40 - Purpose and scope.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Drug Services (Urine Surveillance and Counseling for Sentenced Inmates in Contract CTCs) § 550.40... community treatment center (CTC) participate in a program of urine testing for drug use. An inmate who is...

28 CFR 550.40 - Purpose and scope.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Drug Services (Urine Surveillance and Counseling for Sentenced Inmates in Contract CTCs) § 550.40... community treatment center (CTC) participate in a program of urine testing for drug use. An inmate who is...

28 CFR 550.40 - Purpose and scope.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Drug Services (Urine Surveillance and Counseling for Sentenced Inmates in Contract CTCs) § 550.40... community treatment center (CTC) participate in a program of urine testing for drug use. An inmate who is...

Circulating Tumor Cells as an Independent Predictor of Survival in Advanced Gastric Cancer.

PubMed

Okabe, H; Tsunoda, S; Hosogi, H; Hisamori, S; Tanaka, E; Tanaka, S; Sakai, Y

2015-11-01

When the indication for surgery of highly advanced gastric cancer is considered, careful selection of the patients is important. In addition to tumor-node-metastasis factors and peritoneal lavage cytology (CY), which are important predictors of prognosis, detection of circulating tumor cells (CTCs) could be another potential marker. This study prospectively evaluated CTCs using a semi-automated immunomagnetic separation system (CellSearch) for 136 patients with advanced gastric cancer to determine the frequency of CTC positivity. For 123 patients who also had their CY evaluated, the significance of both CTC and CY, was investigated as a potential biomarker to predict progression-free survival (PFS) or to monitor the therapeutic effect. In 25 patients (18.4 %), CTCs were positive. Positive CTC counts were more common for tumors with diffuse histologic type and distant metastasis. The PFS of CTC-positive patients was significantly shorter than that of CTC-negative patients (hazard ratio 2.03; P = 0.016). A multivariate analysis of 123 patients showed that CTC and CY as well as performance status and macroscopic distant metastasis were independent factors for PFS. When both CTC and CY were converted to negative values by therapeutic interventions, long-term PFS was achieved. Detection of CTCs was an independent predictor of a shorter PFS in advanced gastric cancer. For selecting patients who require intensive treatment, CTCs could be a valuable biomarker. The combined status of CTC and CY would be useful in selecting patients for radical surgery. Further investigation with a larger number of patients is necessary to establish the importance of CTCs.

Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver.

PubMed

Kaifi, Jussuf T; Kunkel, Miriam; Dicker, David T; Joude, Jamal; Allen, Joshua E; Das, Avisnata; Zhu, Junjia; Yang, Zhaohai; Sarwani, Nabeel E; Li, Guangfu; Staveley-O'Carroll, Kevin F; El-Deiry, Wafik S

2015-01-01

Metastatic spread is the most common cause of cancer-related death in colorectal cancer (CRC) patients, with the liver being the mostly affected organ. Circulating tumor cells (CTCs) are a prognostic marker in stage IV CRC. We hypothesized that tumor burden in the liver correlates with CTC quantity. Blood (7.5 ml) was prospectively collected from 24 patients with novel stage IV CRC diagnosis. Baseline EpCAM+ CTCs were analyzed with the FDA-approved CellSearch® system. Clinicopathological data were collected, and hepatic tumor burden was determined by radiographic liver volumetry with contrast-enhanced CT scans. CRC primary tumors were immunohistochemically stained for EpCAM expression with BerEP4 monoclonal antibody. Statistical analyses were performed using 2-sample T-test, non-parametric Wilcoxon Rank-Sum test, and Fisher's exact test. CTCs were detected n 17 (71%) of 24 patients. The overall mean CTC number as determined by EpCAM-based CellSearch® detection was 6.3 (SEM 2.9). High baseline CTC numbers (≥3) correlated significantly with a high tumor/liver ratio (≥30%), and with high serum CEA levels, as determined by two-sample T-test on log-transformed data and by Fisher's Exact test on categorical data analysis (P < 0.05). The CRC primary tumors were consistently expressing EpCAM by immunostaining. High tumor burden in the liver and high baseline serum CEA levels are associated with high number of baseline CTCs in stage IV CRC patients. Future studies should further investigate the biological role and expression patterns of single CTCs in cancer patients to further improve personalized treatment strategies.

Chlortetracycline and Oxytetracycline Residues in Poultry Tissues and Eggs

PubMed Central

Meredith, W. E.; Weiser, H. H.; Winter, A. R.

1965-01-01

A pad-plate method of assaying residual amounts of chlortetracycline (CTC) and oxytetracycline (OTC) using Bacillus cereus 213 was used to determine amounts of antibiotic left in tissues and eggs of poultry fed 1,000 and 200 ppm of CTC and OTC in basal feed mixtures. The effects of various methods of cooking the tissues and eggs and the potentiating effect of terephthalic acid (TPA) were studied. It was found that normal methods of roasting, frying, and autoclaving poultry tissue destroyed all residual CTC and OTC, even with the potentiating effect of TPA. The largest amounts of residual antibiotic were found in the liver, then breast, and then thigh tissue when assayed for CTC. Tissue assays for CTC revealed that it was not taken up as extensively as CTC and the largest amounts were found in the liver, then breast. OTC residue was seldom found in the thigh tissue. Terephthalic acid in 0.5% concentration increased the concentration found in all cases. Cooking by poaching and scrambling eggs did not destroy the antibiotic in all cases. PMID:14264853

Effects of chlortetracycline on the fate of multi-antibiotic resistance genes and the microbial community during swine manure composting.

PubMed

Chen, Zhiqiang; Wang, Yao; Wen, Qinxue

2018-06-01

Excessive use of antibiotics in breeding industry leads to accumulation of antibiotic residuals and antibiotic resistance genes (ARGs) in environment from improperly treated livestock excrements. Four commonly used veterinary antibiotics including chlortetracycline (CTC), sulfamerazine (SMZ), enrofloxacin (ENR) and erythromycin (ERY) were monitored in the swine manure composting. Co-resistance and cross-resistance effects among relative ARGs, correlations between ARGs and bacterial community under multiple antibiotics residual during the composting were investigated in this research. With CTC addition up to 20 mg/kg, more than 99% of CTC removal was achieved after composting, and most of the other antibiotics can be thoroughly removed as well. The variations in ARGs during the composting were strongly correlated to the compositions of the microbial community, Bacteroides and Sporosarcina were main ARGs carriers in the thermophlic phase. Clostridium Ⅺ, Clostridium sensu stricto, and Pseudoxanthomonas, might spread ARGs in cooling and maturing stage. Most of the tested ARGs in swine manure can be effectively reduced through composting, thus makes the compost products safe for soil fertilization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Digital-Direct-RT-PCR: a sensitive and specific method for quantification of CTC in patients with cervical carcinoma

PubMed Central

Pfitzner, Claudia; Schröder, Isabel; Scheungraber, Cornelia; Dogan, Askin; Runnebaum, Ingo Bernhard; Dürst, Matthias; Häfner, Norman

2014-01-01

The detection of circulating tumour cells (CTC) in cancer patients may be useful for therapy monitoring and prediction of relapse. A sensitive assay based on HPV-oncogene transcripts which are highly specific for cervical cancer cells was established. The Digital-Direct-RT-PCR (DD-RT-PCR) combines Ficoll-separation, ThinPrep-fixation and one-step RT-PCR in a low-throughput digital-PCR format enabling the direct analysis and detection of individual CTC without RNA isolation. Experimental samples demonstrated a sensitivity of one HPV-positive cell in 500,000 HPV-negative cells. Spike-in experiments with down to 5 HPV-positive cells per millilitre EDTA-blood resulted in concordant positive results by PCR and immunocytochemistry. Blood samples from 3 of 10 CxCa patients each contained a single HPV-oncogene transcript expressing CTC among 5 to 15*105 MNBC. Only 1 of 7 patients with local but 2 of 3 women with systemic disease had CTC. This highly sensitive DD-RT-PCR for the detection of CTC may also be applied to other tumour entities which express tumour-specific transcripts. Abbreviations: CTC – circulating tumour cells, CxCa – cervical cancer, DD-RT-PCR – Digital-Direct Reverse Transcriptase PCR, HPV – Human Papilloma Virus, MNBC – mononuclear blood cells, ICC – immunocytochemistry. PMID:24496006

Effect of antimicrobial compounds tylosin and chlortetracycline during batch anaerobic swine manure digestion.

PubMed

Stone, James J; Clay, Sharon A; Zhu, Zhenwei; Wong, Kwok L; Porath, Laura R; Spellman, Garth M

2009-10-01

Tylosin and chlortetracycline (CTC) are antimicrobial chemicals that are fed to >45% of the US swine herds at therapeutic and sub-therapeutic dosages to enhance growth rates and treat swine health problems. These compounds are poorly absorbed during digestion so that the bioactive compound or metabolites are excreted. This study investigated the degradation and stabilization of swine manure that contained no additives and compared the observed processes with those of manure containing either tylosin or CTC. The batch anaerobic incubation lasted 216 days. The breakdown of insoluble organic matter through anaerobic hydrolysis reactions was faster for manure containing CTC compared with tylosin or no-antimicrobial treatments. Volatile fatty acid (VFA) accumulation, including acetate, butyrate, and propionate, was greater for CTC-containing manure compared to tylosin and no-antimicrobial treatments. The relative abundance of two aceticlastic methanogens, Methanosaetaceae and Methanosarcinaceae spp., were less for CTC manure than manure with no-antimicrobial treatment. In addition, generation of methane and carbon dioxide was inhibited by 27.8% and 28.4%, respectively, due to the presence of CTC. Tylosin effects on manure degradation were limited, however the relative abundance of Methanosarcinaceae spp. was greater than found in the CTC or no-antimicrobial manures. These data suggest that acetate and other C-1 VFA compounds would be effectively utilized during methanogenesis in the presence of tylosin.

The prognostic value of circulating tumor cells in patients with melanoma: a systematic review and meta-analysis.

PubMed

Mocellin, Simone; Hoon, Dave; Ambrosi, Alessandro; Nitti, Donato; Rossi, Carlo Riccardo

2006-08-01

The detection of circulating tumor cells (CTC) in patients with melanoma represents an appealing prognostic tool, but no consensus exists on this topic. We aimed to comprehensively and quantitatively summarize the evidence for the use of CTC to predict patients' clinical outcome. Fifty-three studies enrolling 5,433 patients were reviewed. Correlation of CTC status with tumor-node-metastasis disease stage and patients' overall (OS) and progression-free (PFS) survival was assessed by means of association statistics and meta-analysis, respectively. CTC status correlated with both tumor-node-metastasis stage (stage I, 32%; stage II, 41.7%; stage III, 41.1%; stage IV, 47.4%; P(trend) < 0.0001) and survival (OS: hazard ratio, 2.42; 95% confidence interval, 1.7-3.45, P < 0.0001; PFS: hazard ratio, 2.45; 95% confidence interval, 1.78-3.38; P < 0.0001). However, statistical heterogeneity was significant for both OS and PFS, likely underscoring the wide variability in study design. Furthermore, CTC positivity rates in early stages were higher and in the metastatic setting were lower than expected, which indicates an unsatisfactory accuracy of currently available CTC detection assays. Our findings suggest that CTC might have a clinically valuable prognostic power in patients with melanoma. However, the heterogeneity of the studies thus far published warrants caution not to overestimate the favorable results of pooled data.

Association Between Visceral Adiposity and Colorectal Polyps on CT Colonography

PubMed Central

Summers, Ronald M.; Liu, Jiamin; Sussman, Daniel L.; Dwyer, Andrew J.; Rehani, Bhavya; Pickhardt, Perry J.; Choi, J. Richard; Yao, Jianhua

2012-01-01

OBJECTIVE To determine if there is an association between visceral adiposity measured on CT colonography (CTC) and colorectal polyps. MATERIALS AND METHODS The study was HIPAA-compliant and approved by our Institutional Review Board and Office of Human Subjects Research. 1186 patients who underwent CTC and same day optical colonoscopy were analyzed. Visceral adipose tissue volumes (VAV) and volume percents relative to total internal body volume (VAV%) were measured on slices in the L2–L3 regions on supine CTC scan with validated fully-automated software. Student t-test, odds ratio (OR), logistic regression and receiver operating characteristic analyses were performed. RESULTS For subjects with and without adenomatous polyps, means and s. d. of VAV% were 31.2 ± 10.8% (n=345) and 28.2% ± 11.3% (n=841) (p<0.0001), respectively. For subjects with and without hyperplastic polyps they were 31.8% ± 10.7% (n=244) and 28.3% ± 11.2% (n=942) (p<0.0001), respectively. Comparing the lowest and highest quintiles of VAV%, the ORs for having at least one adenomatous polyp or hyperplastic polyp versus no polyp were 2.06 (95% CI: 1.36–3.13) and 1.71 [1.08, 2.71] and the prevalence of having adenomatous polyps or hyperplastic polyps increased 14% and 8%, respectively. CONCLUSION Subjects with higher visceral adiposity measurements on CTC have a greater risk for the presence of colonic polyps. PMID:22733893

Cryopreservation for delayed circulating tumor cell isolation is a valid strategy for prognostic association of circulating tumor cells in gastroesophageal cancer.

PubMed

Brungs, Daniel; Lynch, David; Luk, Alison Ws; Minaei, Elahe; Ranson, Marie; Aghmesheh, Morteza; Vine, Kara L; Carolan, Martin; Jaber, Mouhannad; de Souza, Paul; Becker, Therese M

2018-02-21

To demonstrate the feasibility of cryopreservation of peripheral blood mononuclear cells (PBMCs) for prognostic circulating tumor cell (CTC) detection in gastroesophageal cancer. Using 7.5 mL blood samples collected in EDTA tubes from patients with gastroesopheagal adenocarcinoma, CTCs were isolated by epithelial cell adhesion molecule based immunomagnetic capture using the IsoFlux platform. Paired specimens taken during the same blood draw ( n = 15) were used to compare number of CTCs isolated from fresh and cryopreserved PBMCs. Blood samples were processed within 24 h to recover the PBMC fraction, with PBMCs used for fresh analysis immediately processed for CTC isolation. Cryopreservation of PBMCs lasted from 2 wk to 25.2 mo (median 14.6 mo). CTCs isolated from pre-treatment cryopreserved PBMCs ( n = 43) were examined for associations with clinicopathological variables and survival outcomes. While there was a significant trend to a decrease in CTC numbers associated with cryopreserved specimens (mean number of CTCs 34.4 vs 51.5, P = 0.04), this was predominately in samples with a total CTC count of > 50, with low CTC count samples less affected ( P = 0.06). There was no significant association between the duration of cryopreservation and number of CTCs. In cryopreserved PBMCs from patient samples prior to treatment, a high CTC count (> 17) was associated with poorer overall survival (OS) ( n = 43, HR = 4.4, 95%CI: 1.7-11.7, P = 0.0013). In multivariate analysis, after controlling for sex, age, stage, ECOG performance status, and primary tumor location, a high CTC count remained significantly associated with a poorer OS (HR = 3.7, 95%CI: 1.2-12.4, P = 0.03). PBMC cryopreservation for delayed CTC isolation is a valid strategy to assist with sample collection, transporting and processing.

Quantum Fluctuations and Thermodynamic Processes in the Presence of Closed Timelike Curves

NASA Astrophysics Data System (ADS)

Tanaka, Tsunefumi

1997-10-01

A closed timelike curve (CTC) is a closed loop in spacetime whose tangent vector is everywhere timelike. A spacetime which contains CTC's will allow time travel. One of these spacetimes is Grant space. It can be constructed from Minkowski space by imposing periodic boundary conditions in spatial directions and making the boundaries move toward each other. If Hawking's chronology protection conjecture is correct, there must be a physical mechanism preventing the formation of CTC's. Currently the most promising candidate for the chronology protection mechanism is the back reaction of the metric to quantum vacuum fluctuations. In this thesis the quantum fluctuations for a massive scalar field, a self-interacting field, and for a field at nonzero temperature are calculated in Grant space. The stress-energy tensor is found to remain finite everywhere in Grant space for the massive scalar field with sufficiently large field mass. Otherwise it diverges on chronology horizons like the stress-energy tensor for a massless scalar field. If CTC's exist they will have profound effects on physical processes. Causality can be protected even in the presence of CTC's if the self-consistency condition is imposed on all processes. Simple classical thermodynamic processes of a box filled with ideal gas in the presence of CTC's are studied. If a system of boxes is closed, its state does not change as it travels through a region of spacetime with CTC's. But if the system is open, the final state will depend on the interaction with the environment. The second law of thermodynamics is shown to hold for both closed and open systems. A similar problem is investigated at a statistical level for a gas consisting of multiple selves of a single particle in a spacetime with CTC's.

Membrane microfilter device for selective capture, electrolysis and genomic analysis of human circulating tumor cells.

PubMed

Zheng, Siyang; Lin, Henry; Liu, Jing-Quan; Balic, Marija; Datar, Ram; Cote, Richard J; Tai, Yu-Chong

2007-08-31

This paper presents development of a parylene membrane microfilter device for single stage capture and electrolysis of circulating tumor cells (CTCs) in human blood, and the potential of this device to allow genomic analysis. The presence and number of CTCs in blood has recently been demonstrated to provide significant prognostic information for patients with metastatic breast cancer. While finding as few as five CTCs in about 7.5mL of blood (i.e., 10(10) blood cells in) is clinically significant, detection of CTCs is currently difficult and time consuming. CTC enrichment is performed by either gradient centrifugation of CTC based on their buoyant density or magnetic separation of epithelial CTC, both of which are laborious procedures with variable efficiency, and CTC identification is typically done by trained pathologists through visual observation of stained cytokeratin-positive epithelial CTC. These processes may take hours, if not days. Work presented here provides a micro-electro-mechanical system (MEMS)-based option to make this process simpler, faster, better and cheaper. We exploited the size difference between CTCs and human blood cells to achieve the CTC capture on filter with approximately 90% recovery within 10 min, which is superior to current approaches. Following capture, we facilitated polymerase chain reaction (PCR)-based genomic analysis by performing on-membrane electrolysis with embedded electrodes reaching each of the individual 16,000 filtering pores. The biggest advantage for this on-membrane in situ cell lysis is the high efficiency since cells are immobilized, allowing their direct contact with electrodes. As a proof-of-principle, we show beta actin gene PCR, the same technology can be easily extended to real time PCR for CTC-specific transcript to allow molecular identification of CTC and their further characterization.

Computed tomography-based virtual colonoscopy in the assessment of bowel endometriosis: The surgeon's point of view.

PubMed

Roman, H; Carilho, J; Da Costa, C; De Vecchi, C; Suaud, O; Monroc, M; Hochain, P; Vassilieff, M; Savoye-Collet, C; Saint-Ghislain, M

2016-01-01

To discuss the role of computed tomography-based virtual colonoscopy (CTC) in preoperative assessment of bowel endometriosis. Retrospective study using data prospectively recorded, including 127 patients with colorectal endometriosis, having undergone CTC for bowel endometriosis. The study was conducted in a tertiary referral center during 38 consecutive months. Preoperative assessment included CTC, magnetic resonance imaging (MRI), endorectal ultrasound (ERUS) and clinical examination. Information concerning identification of deep infiltrating endometriosis (DIE) of the bowel, the length and height of colorectal involvement, stenosis of digestive lumen and associated digestive localizations were compared with intraoperative findings. Sensitivity and specificity of CTC for DIE of the rectum, the sigmoid colon, associated digestive localizations, and stenosis of the digestive lumen were respectively 97% and 84%, 93% and 88%, 84% and 97%, 96% and 96%. Intraoperative estimation of the length of digestive tract involved by DIE was closer to that provided by CTC than those provided by MRI and ERUS. When CTC revealed stenosis of digestive lumen, higher rates of colorectal resection (63% vs. 9.6%, < 0.001) and disc excision (25.9% vs. 11%, 0.03) were recorded. For those surgeons using various procedures for management of bowel endometriosis, accurate information on the length and height of bowel involvement, as well as the existence of bowel stenosis enables informed decision regarding the feasibility of conservative techniques versus bowel resection. Preoperative identification of associated localizations above the sigmoid colon is another major advantage related to CTC. CTC provides accurate data on the length and height of colorectal involvement by DIE, stenosis of digestive lumen and associated lesions of digestive tract, which impact on the choice of surgical procedure. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

NAVEL BASE VENTURA COUNTY, PORT HUENEME, CALIFORNIA EPA CHARACTERIZATION TEST CELL REPORT ON ELECTROMAGNETIC SURVEYS IN THE TEST CELL AREA

EPA Science Inventory

The objective of the geophysical surveys at the EPA Characterization Test Cell (CTC) area (Site) at Naval Base Ventura County, Port Hueneme, California is to locate geophysical anomalies indicative of metallic objects within the area of the cell. The goal was to provide backgroun...

Circulating Tumor Cells: Moving Biological Insights into Detection

PubMed Central

Chen, Lichan; Bode, Ann M; Dong, Zigang

2017-01-01

Circulating tumor cells (CTCs) have shown promising potential as liquid biopsies that facilitate early detection, prognosis, therapeutic target selection and monitoring treatment response. CTCs in most cancer patients are low in abundance and heterogeneous in morphological and phenotypic profiles, which complicate their enrichment and subsequent characterization. Several methodologies for CTC enrichment and characterization have been developed over the past few years. However, integrating recent advances in CTC biology into these methodologies and the selection of appropriate enrichment and characterization methods for specific applications are needed to improve the reliability of CTC biopsies. In this review, we summarize recent advances in the studies of CTC biology, including the mechanisms of their generation and their potential forms of existence in blood, as well as the current CTC enrichment technologies. We then critically examine the selection of methods for appropriately enriching CTCs for further investigation of their clinical applications. PMID:28819450

Nutritionally enhanced fermented sausages as a vehicle for potential probiotic lactobacilli delivery.

PubMed

Rubio, Raquel; Jofré, Anna; Aymerich, Teresa; Guàrdia, Maria Dolors; Garriga, Margarita

2014-02-01

The suitability of three potential probiotic lactobacilli strains (Lactobacillus casei CTC1677, L. casei CTC1678 and Lactobacillus rhamnosus CTC1679), previously isolated from infants' faeces and characterized, and three commercial probiotic strains (Lactobacillus plantarum 299v, L. rhamnosus GG and L. casei Shirota) was assessed during the manufacture of low-acid fermented sausages (fuets) with reduced Na(+) and fat content. The inoculated strains were successfully monitored by RAPD-PCR during the process. L. rhamnosus CTC1679 was the only strain able to grow and dominate (levels ca. 10(8)CFU/g) the endogenous lactic acid bacteria population in two independent trials, throughout the ripening process. Thus, fuet containing L. rhamnosus CTC1679 as a starter culture could be a suitable vehicle for putative probiotic bacteria delivery. All the final products recorded a satisfactory overall sensory quality without any noticeable off-flavour, and with the characteristic sensory properties of low-acid fermented sausages. © 2013.

Circulating tumor cells: clinical validity and utility.

PubMed

Cabel, Luc; Proudhon, Charlotte; Gortais, Hugo; Loirat, Delphine; Coussy, Florence; Pierga, Jean-Yves; Bidard, François-Clément

2017-06-01

Circulating tumor cells (CTCs) are rare tumor cells and have been investigated as diagnostic, prognostic and predictive biomarkers in many types of cancer. Although CTCs are not currently used in clinical practice, CTC studies have accumulated a high level of clinical validity, especially in breast, lung, prostate and colorectal cancers. In this review, we present an overview of the current clinical validity of CTCs in metastatic and non-metastatic disease, and the main concepts and studies investigating the clinical utility of CTCs. In particular, this review will focus on breast, lung, colorectal and prostate cancer. Three major topics concerning the clinical utility of CTC are discussed-(1) treatment based on CTCs used as liquid biopsy, (2) treatment based on CTC count or CTC variations, and (3) treatment based on CTC biomarker expression. A summary of published or ongoing phase II and III trials is also presented.

Objective and Subjective Intra-patient Comparison of Iohexol versus Diatrizoate for Bowel Preparation Quality at CT Colonography

PubMed Central

Johnson, Brandon; Hinshaw, J. Louis; Robbins, Jessica B.; Pickhardt, Perry J.

2017-01-01

Objective To objectively and subjectively compare nonionic iohexol and ionic diatrizoate iodinated oral contrast as part of a cathartic bowel regimen within the same CT colonography (CTC) cohort, with otherwise identical preparations. Materials and Methods In our IRB-approved retrospective study, 46 asymptomatic adults (mean age, 59.4 years; 26M/20F) returning for follow-up CTC over a 9-month interval underwent the same bowel preparation with the exception of 75 ml iohexol 350 (Omnipaque) in place of 60 ml diatrizoate (Gastrografin). All other preparation components (bisacodyl, magnesium citrate, and 2% barium) remained constant. Objective volumetric analysis of residual colonic fluid volume and fluid attenuation was performed. Additionally, two radiologists experienced with CTC, blinded to the specific bowel preparation, scored each of 6 colonic segments for adherent residual solid stool using a previously validated 4-point scale (0 for no stool; 1–3 for increasing residual stool). Paired t-test was used for comparison of the cohorts. Results No clear clinically-meaningful difference was found between the two preparations on overall objective or subjective evaluation. Mean (±SD) residual fluid volume was 173±126 ml with the iohexol preparation and 130±79 ml with the diatrizoate prep (p=0.02). Mean total colonic stool score was 2.5 (0.42/segment) with iohexol and 2.3 (0.38/segment) with diatrizoate (p=0.69). Mean (±SD) fluid attenuation was higher with iohexol (849±270HU) compared with diatrizoate (732±168HU) (p=0.03). Conclusions Based on this direct intra-patient comparison, we found that oral iohexol is a suitable alternative to diatrizoate for fluid tagging as part of a cathartic bowel preparation at CTC. Because this nonionic tagging agent is more palatable, less expensive, and likely safer than ionic diatrizoate, our CTC program now utilizes iohexol as the standard recommended regimen. PMID:27010251

Digital-Direct-RT-PCR: a sensitive and specific method for quantification of CTC in patients with cervical carcinoma.

PubMed

Pfitzner, Claudia; Schröder, Isabel; Scheungraber, Cornelia; Dogan, Askin; Runnebaum, Ingo Bernhard; Dürst, Matthias; Häfner, Norman

2014-02-05

The detection of circulating tumour cells (CTC) in cancer patients may be useful for therapy monitoring and prediction of relapse. A sensitive assay based on HPV-oncogene transcripts which are highly specific for cervical cancer cells was established. The Digital-Direct-RT-PCR (DD-RT-PCR) combines Ficoll-separation, ThinPrep-fixation and one-step RT-PCR in a low-throughput digital-PCR format enabling the direct analysis and detection of individual CTC without RNA isolation. Experimental samples demonstrated a sensitivity of one HPV-positive cell in 500,000 HPV-negative cells. Spike-in experiments with down to 5 HPV-positive cells per millilitre EDTA-blood resulted in concordant positive results by PCR and immunocytochemistry. Blood samples from 3 of 10 CxCa patients each contained a single HPV-oncogene transcript expressing CTC among 5 to 15*10(5) MNBC. Only 1 of 7 patients with local but 2 of 3 women with systemic disease had CTC. This highly sensitive DD-RT-PCR for the detection of CTC may also be applied to other tumour entities which express tumour-specific transcripts.

Benefit-Cost Analysis of a Randomized Evaluation of Communities That Care: Monetizing Intervention Effects on the Initiation of Delinquency and Substance Use Through Grade 12.

PubMed

Kuklinski, Margaret R; Fagan, Abigail A; Hawkins, J David; Briney, John S; Catalano, Richard F

2015-06-01

To determine whether the Communities That Care (CTC) prevention system is a cost-beneficial intervention. Data were from a longitudinal panel of 4,407 youth participating in a randomized controlled trial including 24 towns in 7 states, matched in pairs within state and randomly assigned to condition. Significant differences favoring intervention youth in sustained abstinence from delinquency, alcohol use, and tobacco use through Grade 12 were monetized and compared to economic investment in CTC. CTC was estimated to produce $4,477 in benefits per youth (discounted 2011 dollars). It cost $556 per youth to implement CTC for 5 years. The net present benefit was $3,920. The benefit-cost ratio was $8.22 per dollar invested. The internal rate of return was 21%. Risk that investment would exceed benefits was minimal. Investment was expected to be recouped within 9 years. Sensitivity analyses in which effects were halved yielded positive cost-beneficial results. CTC is a cost-beneficial, community-based approach to preventing initiation of delinquency, alcohol use, and tobacco use. CTC is estimated to generate economic benefits that exceed implementation costs when disseminated with fidelity in communities.

Determination analaysis of the power losses of transformers with continuously transpored conductors (CTC) based fuzzy logic

NASA Astrophysics Data System (ADS)

Kaloko, Bambang Sri; Atsari, Erinna Dyah

2017-03-01

Electric motive force which flows into the iron core continuously on a plate - plate iron isolated may cause heat posed by current eddy (eddy current). No water loss occurs due to detainees on the circuit at the the flow of current load because this loss happened on the entanglement of the transformer is made of copper. Continuously Transposed Conductors (CTC) consist of a number of enameled rectangular wires (5-84 strands) made into an assembly. Each strand is transposed in turn to each position in the cable and is then covered with layers of insulation paper. Continuously Transposed Conductors are used in winding wires for medium and ultra high power transformers. CTC is manufactured by OFHC copper and indeed, is able to supply polyester roped. CTC which has been designed to reduce production cost, oil pocket and improve cooling efficiency. Hardened type CTC (CPR1, CPR2, and CPR3: BS1432) and Self-bonding CTC which can be used to improve mechanical and electrical strength are also available. This analysis is performed using the methods of fuzzy logic in taking account of the resources.

Northeast Florida rural transit intelligent transportation system (ITS) : evaluation plan

DOT National Transportation Integrated Search

2001-05-01

The Northeast Florida Rural Transportation Intelligent Transportation System (ITS) project is a demonstration of ITS deployment in five rural Community Transportation Coordinator (CTC) agencies. The objective of the project is to test and evaluate th...

Quantum Physics, Fields and Closed Timelike Curves: The D-CTC Condition in Quantum Field Theory

NASA Astrophysics Data System (ADS)

Tolksdorf, Jürgen; Verch, Rainer

2018-01-01

The D-CTC condition has originally been proposed by David Deutsch as a condition on states of a quantum communication network that contains "backward time-steps" in some of its branches. It has been argued that this is an analogue for quantum processes in the presence of closed timelike curves (CTCs). The unusual properties of states of quantum communication networks that fulfill the D-CTC condition have been discussed extensively in recent literature. In this work, the D-CTC condition is investigated in the framework of quantum field theory in the local, operator-algebraic approach due to Haag and Kastler. It is shown that the D-CTC condition cannot be fulfilled in states that are analytic in the energy, or satisfy the Reeh-Schlieder property, for a certain class of processes and initial conditions. On the other hand, if a quantum field theory admits sufficiently many uncorrelated states across acausally related spacetime regions (as implied by the split property), then the D-CTC condition can always be fulfilled approximately to arbitrary precision. As this result pertains to quantum field theory on globally hyperbolic spacetimes where CTCs are absent, one may conclude that interpreting the D-CTC condition as characteristic for quantum processes in the presence of CTCs could be misleading, and should be regarded with caution. Furthermore, a construction of the quantized massless Klein-Gordon field on the Politzer spacetime, often viewed as spacetime analogue for quantum communication networks with backward time-steps, is proposed in this work.

From illite/smectite clay to mesoporous silicate adsorbent for efficient removal of chlortetracycline from water.

PubMed

Wang, Wenbo; Tian, Guangyan; Zong, Li; Zhou, Yanmin; Kang, Yuru; Wang, Qin; Wang, Aiqin

2017-01-01

A series of mesoporous silicate adsorbents with superior adsorption performance for hazardous chlortetracycline (CTC) were sucessfully prepared via a facile one-pot hydrothermal reaction using low-cost illite/smectite (IS) clay, sodium silicate and magnesium sulfate as the starting materials. In this process, IS clay was "teared up" and then "rebuilt" as new porous silicate adsorbent with high specific surface area of 363.52m 2 /g (about 8.7 folds higher than that of IS clay) and very negative Zeta potential (-34.5mV). The inert SiOSi (Mg, Al) bonds in crystal framework of IS were broken to form Si(Al) O - groups with good adsorption activity, which greatly increased the adsorption sites served for holding much CTC molecules. Systematic evaluation on adsorption properties reveals the optimal silicate adsorbent can adsorb 408.81mg/g of CTC (only 159.7mg/g for raw IS clay) and remove 99.3% (only 46.5% for raw IS clay) of CTC from 100mg/L initial solution (pH3.51; adsorption temperature 30°C; adsorbent dosage, 3g/L). The adsorption behaviors of CTC onto the adsorbent follows the Langmuir isotherm model, Temkin equation and pseudo second-order kinetic model. The mesopore adsorption, electrostatic attraction and chemical association mainly contribute to the enhanced adsorption properties. As a whole, the high-efficient silicate adsorbent could be candidates to remove CTC from the wastewater with high amounts of CTC. Copyright © 2016. Published by Elsevier B.V.

Degradation and metabolization of chlortetracycline during the anaerobic digestion of manure from medicated calves.

PubMed

Arikan, Osman A

2008-10-30

The fate of antibiotic residues in the manure of treated animals is of considerable concern because of the potential development of antibiotic-resistant bacteria in the environment. The objective of this study was to determine the fate of chlortetracycline (CTC) during the anaerobic digestion of manure from medicated calves. Five beef calves were medicated for 5 days with 22 mg/kg/day of CTC. Manure samples collected from calves after medication were diluted 5-fold with water, loaded into triplicate 1L anaerobic digesters and incubated at 35 degrees C. The CTC concentration decreased approximately 75% (from 5.9 to 1.4 ppm) during the 33 days digestion period, yielding a half-life of about 18 days. The concentration of the CTC epimer, 4-epi-chlortetracycline (ECTC), declined roughly 33% (from 4.1 to 2.5mg/L) during anaerobic digestion. However, the concentration of the CTC metabolite, iso-chlortetracycline (ICTC), increased 2-fold (from 2.3 to 4.6 mg/L) during the digestion period. Although the water-soluble concentration of CTC decreased 84% (from 0.3 to 0.04 mg/L), the water-soluble concentrations of ECTC and ICTC increased roughly 2-fold during digestion (from 0.5 to 0.93, and 1.0 to 2.7 mg/L, respectively). Since ECTC and ICTC are more water-soluble than the parent tetracycline CTC, it is more likely that these compounds present in digested manure slurry will be detected in water monitoring samples.

Patient Preferences Regarding Colorectal Cancer Screening: Test Features and Cost Willing to Pay Out of Pocket.

PubMed

Moreno, Courtney C; Weiss, Paul S; Jarrett, Thomas L; Roberts, David L; Mittal, Pardeep K; Votaw, John R

2016-01-01

The purpose of this investigation was to evaluate whether test features would make an individual more or less likely to undergo colorectal cancer screening and how much an individual would be willing to pay out of pocket for a screening test. The methods include an administration of a survey to consecutive adult patients of a general medicine clinic. The survey consisted of Likert-scale questions assessing the patients' likelihood of choosing a screening test based on various test characteristics. Additional questions measured the patients' age, race, gender, and maximum out-of-pocket cost they would be willing to pay. Chi-square tests were used to assess the associations between the likelihood questions and the various demographic characteristics. In results, survey response rate was 88.8% (213 of 240). Respondents were 48.4% female (103 of 213), 51.6% male (110 of 213), 82.6% White (176 of 213), 11.3% African-American (24 of 213), and 6.1% other (13 of 213). Risk of internal injury and light exposure to radiation were the least desirable test features. Light sedation was the only test feature that most respondents (54.8%) indicated would make them likely or very likely to undergo a colorectal cancer screening test. The vast majority of respondents (86.8%) were willing to pay less than $200 out of pocket for a colorectal cancer screening test. There was no statistically significant difference in the responses of males and females, or in the responses of individuals of different races or different ages regarding test features, or the amount individuals were willing to pay for a screening test. To conclude, survey results suggest that patient education emphasizing the low complication rate of computed tomographic colonography (CTC), the minimal risks associated with the low-level radiation exposure resulting from CTC, and the benefits of a sedation-free test (eg, no risk of sedation-related complication and no need for a driver) may increase patient acceptance of CTC. Additionally, an out-of-pocket cost of <$200 would be preferable from the patient perspective. Copyright © 2015 Mosby, Inc. All rights reserved.

Incidental physiological sliding hiatal hernia: a single center comparison study between CT with water enema and CT colonography.

PubMed

Revelli, Matteo; Furnari, Manuele; Bacigalupo, Lorenzo; Paparo, Francesco; Astengo, Davide; Savarino, Edoardo; Rollandi, Gian Andrea

2015-08-01

Hiatal hernia is a well-known factor impacting on most mechanisms underlying gastroesophageal reflux, related with the risk of developing complications such as erosive esophagitis, Barrett's esophagus and ultimately, esophageal adenocarcinoma. It is our firm opinion that an erroneous reporting of hiatal hernia in CT exams performed with colonic distention may trigger a consecutive diagnostic process that is not only unnecessary, inducing a unmotivated anxiety in the patient, but also expensive and time-consuming for both the patient and the healthcare system. The purposes of our study were to determine whether colonic distention at CT with water enema and CT colonography can induce small sliding hiatal hernias and to detect whether hiatal hernias size modifications could be considered significant for both water and gas distention techniques. We retrospectively evaluated 400 consecutive patients, 200 undergoing CT-WE and 200 undergoing CTC, including 59 subjects who also underwent a routine abdominal CT evaluation on a different time, used as internal control, while a separate group of 200 consecutive patients who underwent abdominal CT evaluation was used as external control. Two abdominal radiologists assessed the CT exams for the presence of a sliding hiatal hernia, grading the size as small, moderate, or large; the internal control groups were directly compared with the corresponding CT-WE or CTC study looking for a change in hernia size. We used the Student's t test applying a size-specific correction factor, in order to account for the effect of colonic distention: these "corrected" values were then individually compared with the external control group. A sliding hiatal hernia was present in 51 % (102/200) of the CT-WE patients and in 48.5 % (97/200) of the CTC patients. Internal control CT of the 31 patients with a hernia at CT-WE showed resolution of the hernia in 58.1 % (18/31) of patients, including 76.5 % (13/17) and 45.5 % (5/11) of small and moderate hernias. Comparison CT of the 28 patients with a hiatal hernia at CTC showed the absence of the hernia in 57.1 % (16/28) patients, including 68.8 % (11/16) and 50 % (5/10) of small and moderate hernias. The prevalence of sliding hiatal hernias in the external control group was 22 % (44/200), significantly lower than the CT-WE and CTC cohorts' prevalence of 51 % (p < 0.0001) and 48.5 % (p < 0.0001). After applying the correction factors for the CT-WE and the CTC groups, the estimated residual prevalences (16 and 18.5 %, respectively) were much closer to that of the external control patients (p = 0.160 for CT-WE and p = 0.455 for CTC). We believe that incidental findings at CT-WE and CTC should be considered according to the clinical background, and that small sliding hiatal hernias should not be reported in patients with symptoms not related to reflux disease undergoing CT-WE or CTC: When encountering these findings, accurate anamnesis and review of medical history looking for GERD-related symptoms are essential, in order to address these patients to a correct diagnostic iter, taking advantage from more appropriate techniques such as endoscopy or functional techniques.

Detection of BRAF-V600E and V600K in melanoma circulating tumour cells by droplet digital PCR.

PubMed

Reid, Anna L; Freeman, James B; Millward, Michael; Ziman, Melanie; Gray, Elin S

2015-10-01

Defining the BRAF mutation status in metastatic melanoma patients is critical to selecting patients for therapeutic treatment with targeted therapies. Circulating tumour cells (CTCs) can provide an alternative source of contemporaneous tumour genetic material. However methodologies to analyse the presence of rare mutations in a background of wild-type DNA requires a detailed assessment. Here we evaluate the sensitivity of two technologies for cancer mutation detection and the suitability of whole genome amplified DNA as a template for the detection of BRAF-V600 mutations. Serial dilutions of mutant BRAF-V600E DNA in wild-type DNA were tested using both competitive allele-specific PCR (castPCR) and droplet digital PCR (ddPCR), with and without previous whole genome amplification (WGA). Using immunomagnetic beads, we partially enriched CTCs from blood obtained from metastatic melanoma patients with confirmed BRAF mutation positive tumours and extracted RNA and DNA from the CTCs. We used RT-PCR of RNA to confirm the presence of melanoma cells in the CTC fraction then the DNAs of CTC positive fractions were WGA and tested for BRAF V600E or V600K mutations by ddPCRs. WGA DNA produced lower than expected fractional abundances by castPCR analysis but not by ddPCR. Moreover, ddPCR was found to be 200 times more sensitive than castPCR and in combination with WGA produced the most concordant results, with a limit of detection of 0.0005%. BRAF-V600E or V600K mutated DNA was detected in 77% and 44%, respectively, of enriched CTC fractions from metastatic melanoma patients carrying the corresponding mutations. Our results demonstrate that using ddPCR in combination with WGA DNA allows the detection with high sensitivity of cancer mutations in partially enriched CTC fractions. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Detection of colorectal masses in CT colonography: application of deep residual networks for differentiating masses from normal colon anatomy

NASA Astrophysics Data System (ADS)

Näppi, Janne J.; Hironaka, Toru; Yoshida, Hiroyuki

2018-02-01

Even though the clinical consequences of a missed colorectal cancer far outweigh those of a missed polyp, there has been little work on computer-aided detection (CADe) for colorectal masses in CT colonography (CTC). One of the problems is that it is not clear how to manually design mathematical image-based features that could be used to differentiate effectively between masses and certain types of normal colon anatomy such as ileocecal valves (ICVs). Deep learning has demonstrated ability to automatically determine effective discriminating features in many image-based problems. Recently, residual networks (ResNets) were developed to address the practical problems of constructing deep network architectures for optimizing the performance of deep learning. In this pilot study, we compared the classification performance of a conventional 2D-convolutional ResNet (2D-ResNet) with that of a volumetric 3D-convolutional ResNet (3D-ResNet) in differentiating masses from normal colon anatomy in CTC. For the development and evaluation of the ResNets, 695 volumetric images of biopsy-proven colorectal masses, ICVs, haustral folds, and rectal tubes were sampled from 196 clinical CTC cases and divided randomly into independent training, validation, and test datasets. The training set was expanded by use of volumetric data augmentation. Our preliminary results on the 140 test samples indicate that it is feasible to train a deep volumetric 3D-ResNet for performing effective image-based discriminations in CTC. The 3D-ResNet slightly outperformed the 2D-ResNet in the discrimination of masses and normal colon anatomy, but the statistical difference between their very high classification accuracies was not significant. The highest classification accuracy was obtained by combining the mass-likelihood estimates of the 2D- and 3D-ResNets, which enabled correct classification of all of the masses.

Accuracy of CT Colonography for Detection of Polypoid and Nonpolypoid Neoplasia by Gastroenterologists and Radiologists: A Nationwide Multicenter Study in Japan.

PubMed

Nagata, Koichi; Endo, Shungo; Honda, Tetsuro; Yasuda, Takaaki; Hirayama, Michiaki; Takahashi, Sho; Kato, Takashi; Horita, Shoichi; Furuya, Ken; Kasai, Kenji; Matsumoto, Hiroshi; Kimura, Yoshiki; Utano, Kenichi; Sugimoto, Hideharu; Kato, Hiroyuki; Yamada, Rieko; Yamamichi, Junta; Shimamoto, Takeshi; Ryu, Yasuji; Matsui, Osamu; Kondo, Hitoshi; Doi, Ayako; Abe, Taro; Yamano, Hiro-O; Takeuchi, Ken; Hanai, Hiroyuki; Saida, Yukihisa; Fukuda, Katsuyuki; Näppi, Janne; Yoshida, Hiroyuki

2017-01-01

The objective of this study was to assess prospectively the diagnostic accuracy of computer-assisted computed tomographic colonography (CTC) in the detection of polypoid (pedunculated or sessile) and nonpolypoid neoplasms and compare the accuracy between gastroenterologists and radiologists. This nationwide multicenter prospective controlled trial recruited 1,257 participants with average or high risk of colorectal cancer at 14 Japanese institutions. Participants had CTC and colonoscopy on the same day. CTC images were interpreted independently by trained gastroenterologists and radiologists. The main outcome was the accuracy of CTC in the detection of neoplasms ≥6 mm in diameter, with colonoscopy results as the reference standard. Detection sensitivities of polypoid vs. nonpolypoid lesions were also evaluated. Of the 1,257 participants, 1,177 were included in the final analysis: 42 (3.6%) were at average risk of colorectal cancer, 456 (38.7%) were at elevated risk, and 679 (57.7%) had recent positive immunochemical fecal occult blood tests. The overall per-participant sensitivity, specificity, and positive and negative predictive values for neoplasms ≥6 mm in diameter were 0.90, 0.93, 0.83, and 0.96, respectively, among gastroenterologists and 0.86, 0.90, 0.76, and 0.95 among radiologists (P<0.05 for gastroenterologists vs. radiologists). The sensitivity and specificity for neoplasms ≥10 mm in diameter were 0.93 and 0.99 among gastroenterologists and 0.91 and 0.98 among radiologists (not significant for gastroenterologists vs. radiologists). The CTC interpretation time by radiologists was shorter than that by gastroenterologists (9.97 vs. 15.8 min, P<0.05). Sensitivities for pedunculated and sessile lesions exceeded those for flat elevated lesions ≥10 mm in diameter in both groups (gastroenterologists 0.95, 0.92, and 0.68; radiologists: 0.94, 0.87, and 0.61; P<0.05 for polypoid vs. nonpolypoid), although not significant (P>0.05) for gastroenterologists vs. radiologists. CTC interpretation by gastroenterologists and radiologists was accurate for detection of polypoid neoplasms, but less so for nonpolypoid neoplasms. Gastroenterologists had a higher accuracy in the detection of neoplasms ≥6 mm than did radiologists, although their interpretation time was longer than that of radiologists.

Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

NASA Astrophysics Data System (ADS)

Wendel, Marco; Bazhenova, Lyudmila; Boshuizen, Rogier; Kolatkar, Anand; Honnatti, Meghana; Cho, Edward H.; Marrinucci, Dena; Sandhu, Ajay; Perricone, Anthony; Thistlethwaite, Patricia; Bethel, Kelly; Nieva, Jorge; van den Heuvel, Michel; Kuhn, Peter

2012-02-01

Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL-1 (range 0-515.6) and a mean of 44.7 (±95.2) HD-CTCs mL-1. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in lung cancer patients.

CT colonography with rectal iodine tagging: Feasibility and comparison with oral tagging in a colorectal cancer screening population.

PubMed

Neri, Emanuele; Mantarro, Annalisa; Faggioni, Lorenzo; Scalise, Paola; Bemi, Pietro; Pancrazi, Francesca; D'Ippolito, Giuseppe; Bartolozzi, Carlo

2015-09-01

To evaluate feasibility, diagnostic performance, patient acceptance, and overall examination time of CT colonography (CTC) performed through rectal administration of iodinated contrast material. Six-hundred asymptomatic subjects (male:female=270:330; mean 63 years) undergoing CTC for colorectal cancer screening on an individual basis were consecutively enrolled in the study. Out of them, 503 patients (group 1) underwent CTC with rectal tagging, of which 55 had a total of 77 colonic lesions. The remaining 97 patients (group 2) were randomly selected to receive CTC with oral tagging of which 15 had a total of 20 colonic lesions. CTC findings were compared with optical colonoscopy, and per-segment image quality was visually assessed using a semi-quantitative score (1=poor, 2=adequate, 3=excellent). In 70/600 patients (11.7%), CTC was performed twice with both types of tagging over a 5-year follow-up cancer screening program. In this subgroup, patient acceptance was rated via phone interview two weeks after CTC using a semi-quantitative scale (1=poor, 2=fair, 3=average, 4=good, 5=excellent). Mean per-polyp sensitivity, specificity, positive and negative predictive values of CTC with rectal vs oral tagging were 96.1% (CI95% 85.4÷99.3%) vs 89.4% (CI95% 65.4÷98.1%), 95.3% (CI95% 90.7÷97.8%) vs 95.8% (CI95% 87.6÷98.9%), 86.0% (CI95% 73.6÷93.3) vs 85.0% (CI95% 61.1÷96.0%), and 98.8% (CI95% 95.3÷99.8%) vs 97.2% (CI95% 89.4÷99.5%), respectively (p>0.05). Polyp detection rates were not statistically different between groups 1 and 2 (p>0.05). Overall examination time was significantly shorter with rectal than with oral tagging (18.3±3.5 vs 215.6±10.3 minutes, respectively; p<0.0001). Rectal iodine tagging can be an effective alternative to oral tagging for CTC with the advantages of greater patient acceptance and lower overall examination time. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Identification of Circulating Tumor Cell（CTC）in Breast Cancer Patients Using a Newly Established CTC Detecting System].

PubMed

Nagata, Takuya; Ohnaga, Takashi; Lu, Xiao Long; Watanabe, Toru; Hirano, Katsuhisa; Okumura, Tomoyuki; Tsukada, Kazuhiro

2015-10-01

We developed a new circulating tumor cell (CTC) chip in order to identify CTCs in the peripheral blood of cancer patients. In this study, we aimed to identify CTCs in the blood of breast cancer patients by using this CTC detecting system. In addition, we used this system to evaluate the response to anticancer agents. We were able to identify CTCs in 5 of 6 patients. In addition, the system showed that the number of CTCs had decreased after chemotherapy. Thus, the CTC detecting system was useful in the identification of CTCs in the breast cancer patients and in the early prediction of response to anticancer agents.

Controversies in colorectal cancer screening.

PubMed

Pox, Christian P

2014-01-01

Colorectal cancer (CRC) is one of the most common cancers worldwide and a good candidate for screening programmes. However, there is controversy concerning which of the available screening tests should be used. There is general agreement that screening for CRC in the asymptomatic population should begin at the age of 50. Several different screening methods are available which can be separated into those that mainly detect cancers: faecal occult blood tests [guaiac (FOBT) and immunochemical (FIT)], genetic stool tests, blood tests and the M2-pyruvate kinase (M2-PK) test. Methods that detect cancers and polyps are colonoscopy, sigmoidoscopy, CT-colonography (CT-C) and colon capsule endoscopy. The only tests for which a reduction in CRC mortality compared to no screening have been proven in randomized trials are FOBT and sigmoidoscopy. Several trials suggest that FIT are superior to FOBT in terms of detection rates of cancers and advanced adenomas and possibly compliance. There is indirect evidence suggesting efficacy of colonoscopy as a screening test. The role of CT-C is controversial. There is data suggesting a good sensitivity for neoplasia >9 mm with a lower sensitivity for smaller neoplasia. However, radiation exposure is considered a major limitation in some countries. Unresolved questions include the lesion cut-off for referral to colonoscopy and work-up of extracolonic findings. For other methods, like genetic stool testing using newer markers, blood tests, capsule endoscopy and M2-PK, there is currently insufficient data on screening of the asymptomatic population. Key Messages: Colorectal screening is recommended and should be performed in the form of an organized programme. If detection of early-stage cancers is the aim of a screening programme, FIT seem to be superior to FOBT. If detection and removal of adenomas is the aim of a screening programme, endoscopic methods seem to be good alternatives. Sigmoidoscopy is easier to perform but will likely only have an effect on distal cancers. Colonoscopy is more invasive but enables inspection of the whole colon. The role of CT-C, capsule endoscopy, genetic stool tests, blood tests and M2-PK is currently unknown. © 2014 S. Karger AG, Basel.

Residue analysis of tetracyclines in poultry muscle: shortcomings revealed by a proficiency test.

PubMed

Berendsen, B J A; Van Rhijn, J A

2006-11-01

A proficiency test for tetracycline drug residues in poultry muscle was organized according to the guidelines of International Laboratory Accreditation Cooperation (ILAC) ILAC-G13:2000 (2000). For the proficiency test, three test materials were prepared. The homogeneity and stability of the materials during the study were demonstrated. Sixteen laboratories accepted the invitation to participate in the proficiency test; 11 laboratories reported results within the time frame of the study. Most notably, only four of the participating laboratories complied with the definition of the maximum residue limit (MRL) concerning the inclusion of 4-epimers as stated in European Commission Regulation 281/96 (1996). Most participants reported values for the decision limit (CCalpha) and detection capability (CCbeta) and hence were already in compliance with European Commission 2002/657/EC (2002) for this aspect of method validation. However, some CCalpha and CCbeta values were not in agreement with the actual within-laboratory reproducibility calculated from the results reported in this proficiency test. Although most laboratories obtained satisfactory results, it is clear that an effort is needed to include 4-epiOTC, 4-epiTC and 4-epiCTC in the analytical methods. Moreover, reconsideration of values determined for CCalpha and CCbeta with respect to their accuracy may be necessary in some cases.

Expression of Epithelial Mesenchymal Transition and Cancer Stem Cell Markers in Circulating Tumor Cells.

PubMed

Werner, Stefan; Stenzl, Arnulf; Pantel, Klaus; Todenhöfer, Tilman

2017-01-01

The characterization of circulating tumor cells (CTC) has the potential not only to provide important insights into molecular alterations of advanced tumor disease but also to facilitate risk prediction. Epithelial mesenchymal transition (EMT) has been discovered as important process for the development of metastases and the dissemination of tumor cells into the blood stream. In different tumor types, CTC with a mesenchymal phenotype have been reported that have presumably underwent EMT. Moreover, CTC with stem-cell like characteristics have been postulated as important drivers of tumor progression. Different platforms have been introduced to allow CTC enrichment independent of expression of epithelial antigens, as these may be downregulated in EMT- or stem-cell-like CTC. Both for CTCs with EMT- or stem-cell features different markers have been proposed. However, there is still a lack of evidence on the association of these markers with functional features and characteristics for stem cells and cells undergoing EMT.

N-type molecular electrical doping in organic semiconductors: formation and dissociation efficiencies of charge transfer complex

NASA Astrophysics Data System (ADS)

Kim, Jae-Min; Yoo, Seung-Jun; Moon, Chang-Ki; Sim, Bomi; Lee, Jae-Hyun; Lim, Heeseon; Kim, Jeong Won; Kim, Jang-Joo

2016-09-01

Electrical doping is an important method in organic electronics to enhance device efficiency by controlling Fermi level, increasing conductivity, and reducing injection barrier from electrode. To understand the charge generation process of dopant in doped organic semiconductors, it is important to analyze the charge transfer complex (CTC) formation and dissociation into free charge carrier. In this paper, we correlate charge generation efficiency with the CTC formation and dissociation efficiency of n-dopant in organic semiconductors (OSs). The CTC formation efficiency of Rb2CO3 linearly decreases from 82.8% to 47.0% as the doping concentration increases from 2.5 mol% to 20 mol%. The CTC formation efficiency and its linear decrease with doping concentration are analytically correlated with the concentration-dependent size and number of dopant agglomerates by introducing the degree of reduced CTC formation. Lastly, the behavior of dissociation efficiency is discussed based on the picture of the statistical semiconductor theory and the frontier orbital hybridization model.

Role of Setbp1 in Myeloid Leukemia Development

DTIC Science & Technology

2014-09-05

CTC ACT GTG GAG ACG ATT C 3’ 5’ TTC TTA TCC AGC ACA CCA AGC TT 3’ Hoxa9 5’ TGT CTC CTC TCC CCC AAA CC 3’ 5’ GAG ATG AGG CCT GGG ATTTAG A 3’ Hoxa10...highlighted in yellow and noncoding exons in gray . Arrows indicate transcription start sites. The location and orientation of viral integrations are

Benefit-Cost Analysis of a Randomized Evaluation of Communities That Care: Monetizing Intervention Effects on the Initiation of Delinquency and Substance Use Through Grade 12

PubMed Central

Kuklinski, Margaret R.; Fagan, Abigail A.; Hawkins, J. David; Briney, John S.; Catalano, Richard F.

2015-01-01

Objective To determine whether the Communities That Care (CTC) prevention system is a cost-beneficial intervention. Methods Data were from a longitudinal panel of 4,407 youth participating in a randomized controlled trial including 24 towns in 7 states, matched in pairs within state and randomly assigned to condition. Significant differences favoring intervention youth in sustained abstinence from delinquency, alcohol use, and tobacco use through Grade 12 were monetized and compared to economic investment in CTC. Results CTC was estimated to produce $4,477 in benefits per youth (discounted 2011 dollars). It cost $556 per youth to implement CTC for 5 years. The net present benefit was $3,920. The benefit-cost ratio was $8.22 per dollar invested. The internal rate of return was 21%. Risk that investment would exceed benefits was minimal. Investment was expected to be recouped within 9 years. Sensitivity analyses in which effects were halved yielded positive cost-beneficial results. Conclusions CTC is a cost-beneficial, community-based approach to preventing initiation of delinquency, alcohol use, and tobacco use. CTC is estimated to generate economic benefits that exceed implementation costs when disseminated with fidelity in communities. PMID:26213527

Circulating tumor cells in metastatic breast cancer: timing of blood extraction for analysis.

PubMed

Martín, Miguel; García-Sáenz, José Angel; Maestro De las Casas, Maria Luisa; Vidaurreta, Marta; Puente, Javier; Veganzones, Silvia; Rodríguez-Lajusticia, Laura; De la Orden, Virginia; Oliva, Belén; De la Torre, Julio-César; López-Tarruella, Sara; Casado, Antonio; Sastre, Javier; Díaz-Rubio, Eduardo

2009-10-01

Circulating tumor cells (CTCs) can be detected in the peripheral blood of around 50% of patients with metastatic breast cancer. Their numbers are an independent predictor of the patient's progression-free survival (PFS) and of overall survival (OS). However, to date, none of the studies carried out with the most commonly used system of CTC determination (the CellSearch System, approved by the US Food and Drug Administration) has examined the intra-patient variation in CTC numbers, a variation that could impact on prognosis assessment. To evaluate possible circadian variations in the number of CTCs in patients with breast cancer a pilot study was conducted in which these cells were quantified 12 h apart (at 8:00 a.m. and 8:00 p.m. of the same day) in a cohort of hospitalized patients with metastatic breast cancer. Out of the 58 patients included in the study, 51 were evaluable. No statistically significant differences between day-time and night-time CTC numbers were observed (p=0.8427, Wilcoxon matched pair test). Only two of the patients were classified in different prognostic categories in the morning and night determinations (5 or more CTCs=poor prognosis group; <5 CTCs=good prognosis group). The prognostic classification of the remaining 49 patients was the same at 8:00 a.m. and 8:00 p.m. The number of peripheral blood CTCs in metastatic breast cancer patients is not significantly different at 8:00 a.m. from that at 8:00 p.m. and, as such, indicates a lack of circadian rhythm with respect to CTC numbers in these patients.

Intimate partner violence and challenges facing women living with HIV/AIDS in accessing antiretroviral treatment at Singida Regional Hospital, central Tanzania

PubMed Central

Kosia, Agnes; Kakoko, Deodatus; Semakafu, Ave Maria Emilius; Nyamhanga, Tumaini; Frumence, Gasto

2016-01-01

Background Human immunodeficiency virus (HIV) remains a global public health problem. Sub-Saharan Africa is the region most affected by HIV/AIDS in the world. Globally, and in Tanzania in particular, women are more affected by HIV/AIDS than men. Tanzania has been reported to be among the countries with the highest burden of intimate partner violence (IPV). This study explored the challenges facing women living with HIV/AIDS (LWHA) attending the care and treatment clinic (CTC) in Singida Regional Hospital in Tanzania. Design A qualitative study was performed in which data were collected through in-depth interviews with 35 women LWHA who also experienced IPV. Content analysis was used to analyse the data. Results The study findings showed that women LWHA experienced challenges from their male partners in the form of lack of fare to attend CTC, delayed attendance to CTC, verbal threats and intimidation, mistrust partner resulting in changed antiretroviral (ARV) dosing time. Also, systemic challenges such as malfunction of CD4 count testing apparatus contributed to mistrust from their male partners which led to IPV. Conclusion In this study, women LWHA experienced IPV challenges that resulted in poor adherence to ARV medication and CTC attendance, as well as insufficient time to collect ARV medication. It is recommended that the government address systemic challenges faced by women LWHA, introduce multiple approaches to address the needs of women LWHA experiencing IPV, and develop strong policies to prevent IPV against women in Tanzania, regardless of their HIV status. PMID:27987296

Cost-effectiveness of colorectal cancer screening with computed tomography colonography according to a polyp size threshold for polypectomy.

PubMed

Heresbach, Denis; Chauvin, Pauline; Hess-Migliorretti, Aurélie; Riou, Françoise; Grolier, Jacques; Josselin, Jean-Michel

2010-06-01

Computed tomography colonography (CTC) has an acceptable accuracy in detecting colonic lesions, especially for polyps at least 6 mm. The aim of this analysis is to determine the cost-effectiveness of population-based screening for colorectal cancer (CRC) using CTC with a polyp size threshold. The cost-effectiveness ratios of CTC performed at 50, 60 and 70 years old, without (PL strategy) or with (TS strategy) polyp size threshold were compared using a Markov process. Incremental cost-effectiveness ratios (ICER) were calculated per life-years gained (LYG) for a time horizon of 30 years. The ICER of PL and TS strategies were 12 042 and 2765 euro/LYG associated to CRC prevention rates of 37.9 and 36.5%. The ICER of PL and TS strategies dropped to 9687 and 1857 euro/LYG when advanced adenoma (AA) prevalence increased from 6.9 to 8.6% for male participants and 3.8-4.9% for female participants or to 9482 and 2067 euro/LYG when adenoma and AA annual recurrence rates dropped to 3.2 and 0.25%. The ICER for PL and TS strategies decreased to 7947 and 954 euro/LYG or when only two CTC were performed at 50 and 60-years-old. Conversely, the ICER did not significantly change when varying population participation rate or accuracy of CTC. CTC with a 6 mm threshold for polypectomy is associated to a substantial cost reduction without significant loss of efficacy. Cost-effectiveness depends more on the AA prevalence or transition rate to CRC than on CTC accuracy or screening compliance.

Effects of chlortetracycline and copper supplementation on the prevalence, distribution, and quantity of antimicrobial resistance genes in the fecal metagenome of weaned pigs.

PubMed

Agga, Getahun E; Scott, H Morgan; Vinasco, Javier; Nagaraja, T G; Amachawadi, Raghavendra G; Bai, Jianfa; Norby, Bo; Renter, David G; Dritz, Steve S; Nelssen, Jim L; Tokach, Mike D

2015-05-01

Use of in-feed antibiotics such as chlortetracycline (CTC) in food animals is fiercely debated as a cause of antimicrobial resistance in human pathogens; as a result, alternatives to antibiotics such as heavy metals have been proposed. We used a total community DNA approach to experimentally investigate the effects of CTC and copper supplementation on the presence and quantity of antimicrobial resistance elements in the gut microbial ecology of pigs. Total community DNA was extracted from 569 fecal samples collected weekly over a 6-week period from groups of 5 pigs housed in 32 pens that were randomized to receive either control, CTC, copper, or copper plus CTC regimens. Qualitative and quantitative PCR were used to detect the presence of 14 tetracycline resistance (tet) genes and to quantify gene copies of tetA, tetB, blaCMY-2 (a 3rd generation cephalosporin resistance gene), and pcoD (a copper resistance gene), respectively. The detection of tetA and tetB decreased over the subsequent sampling periods, whereas the prevalence of tetC and tetP increased. CTC and copper plus CTC supplementation increased both the prevalence and gene copy numbers of tetA, while decreasing both the prevalence and gene copies of tetB. In summary, tet gene presence was initially very diverse in the gut bacterial community of weaned pigs; thereafter, copper and CTC supplementation differentially impacted the prevalence and quantity of the various tetracycline, ceftiofur and copper resistance genes resulting in a less diverse gene population. Published by Elsevier B.V.

Performance evaluation of multi-material electronic cleansing for ultra-low-dose dual-energy CT colonography

NASA Astrophysics Data System (ADS)

Tachibana, Rie; Kohlhase, Naja; Näppi, Janne J.; Hironaka, Toru; Ota, Junko; Ishida, Takayuki; Regge, Daniele; Yoshida, Hiroyuki

2016-03-01

Accurate electronic cleansing (EC) for CT colonography (CTC) enables the visualization of the entire colonic surface without residual materials. In this study, we evaluated the accuracy of a novel multi-material electronic cleansing (MUMA-EC) scheme for non-cathartic ultra-low-dose dual-energy CTC (DE-CTC). The MUMA-EC performs a wateriodine material decomposition of the DE-CTC images and calculates virtual monochromatic images at multiple energies, after which a random forest classifier is used to label the images into the regions of lumen air, soft tissue, fecal tagging, and two types of partial-volume boundaries based on image-based features. After the labeling, materials other than soft tissue are subtracted from the CTC images. For pilot evaluation, 384 volumes of interest (VOIs), which represented sources of subtraction artifacts observed in current EC schemes, were sampled from 32 ultra-low-dose DE-CTC scans. The voxels in the VOIs were labeled manually to serve as a reference standard. The metric for EC accuracy was the mean overlap ratio between the labels of the reference standard and the labels generated by the MUMA-EC, a dualenergy EC (DE-EC), and a single-energy EC (SE-EC) scheme. Statistically significant differences were observed between the performance of the MUMA/DE-EC and the SE-EC methods (p<0.001). Visual assessment confirmed that the MUMA-EC generated less subtraction artifacts than did DE-EC and SE-EC. Our MUMA-EC scheme yielded superior performance over conventional SE-EC scheme in identifying and minimizing subtraction artifacts on noncathartic ultra-low-dose DE-CTC images.

Highly efficient removal of chlorotetracycline from aqueous solution using graphene oxide/TiO2 composite: Properties and mechanism

NASA Astrophysics Data System (ADS)

Li, Zhaoqian; Qi, Mengyu; Tu, Chunyan; Wang, Weiping; Chen, Jianrong; Wang, Ai-Jun

2017-12-01

The extensive usage of chlorotetracycline (CTC) has caused the persistence of antibiotic residues in aquatic environments, resulting in serious threat to human health and ecosystems. In this study, graphene oxide/titanium dioxide (GO/TiO2) nanocomposite was successfully synthesized via in situ hydrolysis of tetra-n-butyl titanate (Ti(BuO)4) to TiO2 particles on GO sheets and used as adsorbent for efficient adsorptive removal of CTC from aqueous solution. The prepared GO/TiO2 was characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transformed infrared (FT-IR), Raman spectroscopy and X-ray photoelectron (XPS). Adsorption kinetics, isotherms and thermodynamics were systematically investigated to evaluate the adsorption properties of GO/TiO2. Adsorption mechanism was further analyzed by FT-IR, UV-vis and XPS. The results indicated that adsorption kinetics closely followed the pseudo-second order model; the maximum adsorption capacity determined by Langmuir model was 261.10 mg g-1 at 298 K and the thermodynamic studies revealed that the adsorption of CTC onto the GO/TiO2 was a spontaneous and endothermic process. Moreover, the interactions between CTC and GO/TiO2 were presumed to be ligand exchange between CTC and TiO2, while the π-π electron donor-acceptor interaction, hydrogen bond and cation-π bonding were constructed between CTC and GO. Finally, the prepared GO/TiO2 was successfully applied for the efficient removal of CTC from Wu River water.

CT colonography without cathartic preparation: positive predictive value and patient experience in clinical practice.

PubMed

Zueco Zueco, Carmen; Sobrido Sampedro, Carolina; Corroto, Juan D; Rodriguez Fernández, Paula; Fontanillo Fontanillo, Manuela

2012-06-01

To determine the positive predictive value (PPV) for polyps ≥ 6 mm detected at CT colonography (CTC) performed without cathartic preparation, with low-dose iodine faecal tagging regimen and to evaluate patient experience. 1920 average-risk patients underwent CTC without cathartic preparation. Faecal tagging was performed by diatrizoate meglumine and diatrizoate sodium at a total dose of 60 ml (22.2 g of iodine).The standard interpretation method was primary 3D with 2D problem solving. We calculated per-patient and per-polyp PPV in relation to size and morphology. All colonic segments were evaluated for image quality (faecal tagging, amount of liquid and solid residual faeces and luminal distension). Patients completed a questionnaire before and after CTC to assess preparation and examination experience. Per-polyp PPV for detected lesions of ≥ 6 mm, 6-9 mm, ≥ 10 mm and ≥ 30 mm were 94.3%, 93.1%, 94.7% and 98%, respectively. Per-polyp PPV, according to lesion morphology, was 94.6%, 97.3% and 85.1% for sessile, pedunculated and flat polyps, respectively. Per-patient PPV was 92.8%. Preparation without frank cathartics was reported to cause minimal discomfort by 78.9% of patients. CTC without cathartic preparation and low-dose iodine faecal tagging may yield high PPVs for lesions ≥ 6 mm and is well accepted by patients. • Computed tomographic colonography (CTC) without cathartic preparation is well accepted by patients • Cathartic-free faecal tagging CTC yields high positive predictive values • CTC without cathartic preparation could improve uptake of colorectal cancer screening.

Computer-assisted polyp matching between optical colonoscopy and CT colonography: a phantom study

NASA Astrophysics Data System (ADS)

Roth, Holger R.; Hampshire, Thomas E.; Helbren, Emma; Hu, Mingxing; Vega, Roser; Halligan, Steve; Hawkes, David J.

2014-03-01

Potentially precancerous polyps detected with CT colonography (CTC) need to be removed subsequently, using an optical colonoscope (OC). Due to large colonic deformations induced by the colonoscope, even very experienced colonoscopists find it difficult to pinpoint the exact location of the colonoscope tip in relation to polyps reported on CTC. This can cause unduly prolonged OC examinations that are stressful for the patient, colonoscopist and supporting staff. We developed a method, based on monocular 3D reconstruction from OC images, that automatically matches polyps observed in OC with polyps reported on prior CTC. A matching cost is computed, using rigid point-based registration between surface point clouds extracted from both modalities. A 3D printed and painted phantom of a 25 cm long transverse colon segment was used to validate the method on two medium sized polyps. Results indicate that the matching cost is smaller at the correct corresponding polyp between OC and CTC: the value is 3.9 times higher at the incorrect polyp, comparing the correct match between polyps to the incorrect match. Furthermore, we evaluate the matching of the reconstructed polyp from OC with other colonic endoluminal surface structures such as haustral folds and show that there is a minimum at the correct polyp from CTC. Automated matching between polyps observed at OC and prior CTC would facilitate the biopsy or removal of true-positive pathology or exclusion of false-positive CTC findings, and would reduce colonoscopy false-negative (missed) polyps. Ultimately, such a method might reduce healthcare costs, patient inconvenience and discomfort.

Cryopreservation for delayed circulating tumor cell isolation is a valid strategy for prognostic association of circulating tumor cells in gastroesophageal cancer

PubMed Central

Brungs, Daniel; Lynch, David; Luk, Alison WS; Minaei, Elahe; Ranson, Marie; Aghmesheh, Morteza; Vine, Kara L; Carolan, Martin; Jaber, Mouhannad; de Souza, Paul; Becker, Therese M

2018-01-01

AIM To demonstrate the feasibility of cryopreservation of peripheral blood mononuclear cells (PBMCs) for prognostic circulating tumor cell (CTC) detection in gastroesophageal cancer. METHODS Using 7.5 mL blood samples collected in EDTA tubes from patients with gastroesopheagal adenocarcinoma, CTCs were isolated by epithelial cell adhesion molecule based immunomagnetic capture using the IsoFlux platform. Paired specimens taken during the same blood draw (n = 15) were used to compare number of CTCs isolated from fresh and cryopreserved PBMCs. Blood samples were processed within 24 h to recover the PBMC fraction, with PBMCs used for fresh analysis immediately processed for CTC isolation. Cryopreservation of PBMCs lasted from 2 wk to 25.2 mo (median 14.6 mo). CTCs isolated from pre-treatment cryopreserved PBMCs (n = 43) were examined for associations with clinicopathological variables and survival outcomes. RESULTS While there was a significant trend to a decrease in CTC numbers associated with cryopreserved specimens (mean number of CTCs 34.4 vs 51.5, P = 0.04), this was predominately in samples with a total CTC count of > 50, with low CTC count samples less affected (P = 0.06). There was no significant association between the duration of cryopreservation and number of CTCs. In cryopreserved PBMCs from patient samples prior to treatment, a high CTC count (> 17) was associated with poorer overall survival (OS) (n = 43, HR = 4.4, 95%CI: 1.7-11.7, P = 0.0013). In multivariate analysis, after controlling for sex, age, stage, ECOG performance status, and primary tumor location, a high CTC count remained significantly associated with a poorer OS (HR = 3.7, 95%CI: 1.2-12.4, P = 0.03). CONCLUSION PBMC cryopreservation for delayed CTC isolation is a valid strategy to assist with sample collection, transporting and processing. PMID:29467551

How do gender relations affect the working lives of close to community health service providers? Empirical research, a review and conceptual framework.

PubMed

Steege, Rosalind; Taegtmeyer, Miriam; McCollum, Rosalind; Hawkins, Kate; Ormel, Hermen; Kok, Maryse; Rashid, Sabina; Otiso, Lilian; Sidat, Mohsin; Chikaphupha, Kingsley; Datiko, Daniel Gemechu; Ahmed, Rukhsana; Tolhurst, Rachel; Gomez, Woedem; Theobald, Sally

2018-05-05

Close-to-community (CTC) providers have been identified as a key cadre to progress universal health coverage and address inequities in health service provision due to their embedded position within communities. CTC providers both work within, and are subject to, the gender norms at community level but may also have the potential to alter them. This paper synthesises current evidence on gender and CTC providers and the services they deliver. This study uses a two-stage exploratory approach drawing upon qualitative research from the six countries (Bangladesh, Indonesia, Ethiopia, Kenya, Malawi, Mozambique) that were part of the REACHOUT consortium. This research took place from 2013 to 2014. This was followed by systematic review that took place from January-September 2017, using critical interpretive synthesis methodology. This review included 58 papers from the literature. The resulting findings from both stages informed the development of a conceptual framework. We present the holistic conceptual framework to show how gender roles and relations shape CTC provider experience at the individual, community, and health system levels. The evidence presented highlights the importance of safety and mobility at the community level. At the individual level, influence of family and intra-household dynamics are of importance. Important at the health systems level, are career progression and remuneration. We present suggestions for how the role of a CTC provider can, with the right support, be an empowering experience. Key priorities for policymakers to promote gender equity in this cadre include: safety and well-being, remuneration, and career progression opportunities. Gender roles and relations shape CTC provider experiences across multiple levels of the health system. To strengthen the equity and efficiency of CTC programmes gender dynamics should be considered by policymakers and implementers during both the conceptualisation and implementation of CTC programmes. Copyright © 2018. Published by Elsevier Ltd.

Computed Tomography Colonography vs Colonoscopy for Colorectal Cancer Surveillance After Surgery.

PubMed

Weinberg, David S; Pickhardt, Perry J; Bruining, David H; Edwards, Kristin; Fletcher, Joel G; Gollub, Marc J; Keenan, Eileen M; Kupfer, Sonia S; Li, Tianyu; Lubner, Sam J; Markowitz, Arnold J; Ross, Eric A

2018-03-01

Recommendations for surveillance after curative surgery for colorectal cancer (CRC) include a 1-year post-resection abdominal-pelvic computed tomography (CT) scan and optical colonoscopy (OC). CT colonography (CTC), when used in CRC screening, effectively identifies colorectal polyps ≥10 mm and cancers. We performed a prospective study to determine whether CTC, concurrent with CT, could substitute for OC in CRC surveillance. Our study enrolled 231 patients with resected stage 0-III CRC, identified at 5 tertiary care academic centers. Approximately 1 year after surgery, participants underwent outpatient CTC plus CT, followed by same-day OC. CTC results were revealed after endoscopic visualization of sequential colonic segments, which were re-examined for discordant findings. The primary outcome was performance of CTC in the detection of colorectal adenomas and cancers using endoscopy as the reference standard. Of the 231 participants, 116 (50.2%) had polyps of any size or histology identified by OC, and 15.6% had conventional adenomas and/or serrated polyps ≥6 mm. No intra-luminal cancers were detected. CTC detected patients with polyps of ≥6 mm with 44.0% sensitivity (95% CI, 30.2-57.8) and 93.4% specificity (95% CI, 89.7-97.0). CTC detected polyps ≥10 mm with 76.9% sensitivity (95% CI, 54.0-99.8) and 89.0% specificity (95% CI, 84.8-93.1). Similar values were found when only adenomatous polyps were considered. The negative predictive value of CTC for adenomas ≥6 mm was 90.7% (95% CI, 86.7-94.5) and for adenomas ≥10 mm the negative predictive value was 98.6% (95% CI, 97.0-100). In a CRC surveillance population 1 year following resection, CTC was inferior to OC for detecting patients with polyps ≥6 mm. Clinical Trials.gov Registration Number: NCT02143115. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Circulating tumor cells in patients with breast cancer: monitoring chemotherapy success.

PubMed

Ušiaková, Zuzana; Mikulová, Veronika; Pintérová, Daniela; Brychta, Milan; Valchář, Josef; Kubecová, Martina; Tesařová, Petra; Bobek, Vladimír; Kološtová, Katarína

2014-01-01

Circulating tumor cells (CTCs) are an independent prognostic factor for patients with metastatic breast cancer (MBC). However, the role of CTCs in early breast cancer management is not yet clearly defined. The aim of this study was to assess the CTC-positivity rate in patients undergoing chemotherapy depending on breast cancer stage in the adjuvant and neoadjuvant setting. We evaluated the ability to confirm therapy response by CTC analysis. CTCs isolated from blood by means of immunomagnetic separation were further characterized by means of reverse transcriptase - polymerase chain reaction (RT-PCR) for epithelial cell adhesion molecule (EPCAM), mucin 1 (MUC1) and v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (HER2) transcripts with the AdnaTest™. This prospective study included 179 patients; altogether 419 blood samples were evaluated. Patients with primary tumors were divided into neoadjuvant (n=38), and adjuvant (n=100) groups. Forty-one patients with MBC were evaluated under palliative treatment. CTC positivity was described in 35% of patients with early breast cancer without detected metastases before neoadjuvant chemotherapy; similarly, a 26% positivity rate was found in the adjuvant group. In patients with MBC, we detected CTCs in 43% of them. After completing the therapy, the CTC positivity rate decreased to 5% in the neoadjuvant group, to 13% in the adjuvant group and to 12% in the MBC group. CTC positivity after the therapy may classify a subgroup of patients at high risk of developing metastatic disease. This was even true when a patient was evaluated as being CTC-negative before chemotherapy. The multivariate analysis evaluating the correlation of CTC positivity with clinicopathological characteristics such as tumor size, nodal involvement, hormone receptor status, HER2 expression and number of metastatic sites revealed no statistically significant relationships. CTC status may have a significant impact on early BC management. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Radiographic clearance of blunt cervical spine injury: plain radiograph or computed tomography scan?

PubMed

Griffen, Margaret M; Frykberg, Eric R; Kerwin, Andrew J; Schinco, Miren A; Tepas, Joseph J; Rowe, Kathleen; Abboud, Jennifer

2003-08-01

The purpose of this study was to evaluate the roles of cervical spine radiographs (CSR) and computed tomography of the cervical spine (CTC) in the exclusion of cervical spine injury for adult blunt trauma patients. At the authors' institution, all adult blunt trauma patients with physical findings of posterior midline neck tenderness, altered mental status, or neurologic deficit are considered at risk of cervical spine injury and undergo both CSR and CTC for evaluation of the cervical spine. The TRACS database at level 1 of the trauma center at this institution was queried for all blunt trauma patients from November 2000 to October 2001. Patient injury severity score (ISS), Glascow Coma Score (GCS), age, gender, CSR results, CTC results, and treatment data were analyzed. The review included 3,018 blunt trauma patients with appropriate data. For 1,199 of these patients (779 men and 420 women) (40%) at risk for cervical spine injury, both CSR and CTC were performed for cervical spine evaluation. The average age of these patients was 39.4 years (range, 18-89 years). The average GCS was 13 and the average ISS was 8.4 in this study population. In 116 (9.5%) of these patients, a cervical spine injury (fracture or subluxation) was detected. The injury was identified on both CSR and CTC in 75 of these patients. In the remaining 41 patients (3.2%), the CSR results were negative, but injury was detected by CTC. All these injuries missed by CSR required treatment. For this group with false-negative CSR, the average GCS was 12 and the average ISS was 14.6. There were no missed cervical spine injuries among the patients with negative CTC results. No identifiable factors predicted false-negative CSR. There does not appear to be any role for CSR screening in this setting. The data from this study add to the growing body of evidence that CTC should replace CSR for the evaluation of the cervical spine in blunt trauma.

Building Local Infrastructure for Community Adoption of Science-Based Prevention: The Role of Coalition Functioning.

PubMed

Shapiro, Valerie B; Hawkins, J David; Oesterle, Sabrina

2015-11-01

The widespread adoption of science-based prevention requires local infrastructures for prevention service delivery. Communities That Care (CTC) is a tested prevention service delivery system that enables a local coalition of community stakeholders to use a science-based approach to prevention and improve the behavioral health of young people. This paper uses data from the Community Youth Development Study (CYDS), a community-randomized trial of CTC, to examine the extent to which better internal team functioning of CTC coalitions increases the community-wide adoption of science-based prevention within 12 communities, relative to 12 matched comparison communities. Specifically, this paper examines the potential of both a direct relationship between coalition functioning and the community-wide adoption of science-based prevention and a direct relationship between functioning and the coalition capacities that ultimately enable the adoption of science-based prevention. Findings indicate no evidence of a direct relationship between four dimensions of coalition functioning and the community-wide adoption of a science-based approach to prevention, but suggest a relationship between coalition functioning and coalition capacities (building new member skills and establishing external linkages with existing community organizations) that enable science-based prevention.

Probing Androgen Receptor Signaling in Circulating Tumor Cells in Prostate Cancer

DTIC Science & Technology

2013-07-01

validation of the CTC AR activity assay in additional patients, and on transcriptional profiling analysis of single CTCs to provide insights into the...protocol. A clinical research protocol for the collection of blood from patients with solid tumors for CTC analysis (DF/HCC 05-300) was initially...on 30 May 2014. Task 2. (Aim 1) Recruitment of patients with castration-resistant prostate cancer for CTC AR activity analysis . Thus far, 17

Rapidly moving cosmic strings and chronology protection

NASA Astrophysics Data System (ADS)

Ori, Amos

1991-10-01

Recently, Gott has provided a family of solutions of the Einstein equations describing pairs of parallel cosmic strings in motion. He has shown that if the strings' relative velocity is sufficiently high, there exist closed timelike curves (CTC's) in the spacetime. Here we show that if there are CTC's in such a solution, then every t=const hypersurface in the spacetime intersects CTC's. Therefore, these solutions do not contradict the chronology protection conjecture of Hawking.

CTC Sentinel. Volume 1, Issue, July 2008

DTIC Science & Technology

2008-07-01

1 I n recent months, there has been a spate of seemingly good news in the counter- terrorism arena, as former terrorist leaders and clerics have...28 CTC Sentinel Staff & Contacts JULy 2008 . VoL 1 . IssUE 8 About the CTC Sentinel The Combating Terrorism Center is an independent educational... the Center’s global network of scholars and practitioners in order to understand and confront contemporary threats posed by terrorism and other

Circulating Tumor Cells: From Theory to Nanotechnology-Based Detection.

PubMed

Ming, Yue; Li, Yuanyuan; Xing, Haiyan; Luo, Minghe; Li, Ziwei; Chen, Jianhong; Mo, Jingxin; Shi, Sanjun

2017-01-01

Cancer stem cells with stem-cell properties are regarded as tumor initiating cells. Sharing stem-cell properties, circulating tumor cells (CTCs) are responsible for the development of metastasis, which significant affects CTC analysis in clinical practice. Due to their extremely low occurrence in blood, however, it is challenging to enumerate and analyze CTCs. Nanotechnology is able to address the problems of insufficient capture efficiency and low purity of CTCs owing to the unique structural and functional properties of nanomaterials, showing strong promise for CTC isolation and detection. In this review, we discuss the role of stem-like CTCs in metastases, provide insight into recent progress in CTC isolation and detection approaches using various nanoplatforms, and highlight the role of nanotechnology in the advancement of CTC research.

Missed Lesions at CT Colonography: Lessons Learned

PubMed Central

Pickhardt, Perry J.

2017-01-01

Misinterpretation at CT colonography (CTC) can result in either a colorectal lesion being missed (false negative) or a false-positive diagnosis. This review will largely focus on potential missed lesions – and ways to avoid such misses. The general causes of false-negative interpretation at CTC can be broadly characterized and grouped into discrete categories related to suboptimal study technique, specific lesion characteristics, anatomic location, and imaging artifacts. Overlapping causes further increase the likelihood of missing a clinically relevant lesion. In the end, if the technical factors of bowel preparation, colonic distention, and robust CTC software are adequately addressed on a consistent basis, and the reader is aware of all the potential pitfalls at CTC, important lesions will seldom be missed. PMID:22539045

Biochemical Characterisation of TSC1 and TSC2 Variants Identified in Patients with Tuberous Sclerosis Complex

DTIC Science & Technology

2010-07-01

G-3¶) and TSC1 reverse (5¶-GCG GGT ACC TTA GCT GTG TTC ATG AGT CTC-3¶). Subsequently, an mCherry tag was inserted N-terminally in pcDNA3.1-TSC1 to...primer pair mCherry forward (5¶-GCG TCT AGA ACC ATG GTG AGC AAG GGC GA-3¶) and mCherry reverse (5¶-GCG GCT AGC CTT GTA CAG CTC GTC CAT GCC-3¶). The...5¶-GAT GAG ATC CGC ACC CTC TGA GAC CAG CTG CTT TTA CTG CAC AAC-3¶; TSC1R692X reverse: 5¶-GTT GTG CAG TAA AAG CAG CTG GTC TCA GAG GGT GCG GAT CTC ATC

Standard Procedures for Air Force Operational Test and Evaluation. Volume I. Appendices

DTIC Science & Technology

1974-10-01

Participates in selected tests data for assessment of suitability Participates in the intepretation of and effectiveness, as practicable tet results...selected tests Interprels test results Inteprets test resultst ReplRorts to CNO the results of the "eports independent operational TI’ECIIEVAL assessment" v... films , lists, tapes, drawings, specifications. parts breakdowns, ctc. RAW DATA; ’The original form of data at the time it was recorded. DATA

Business plan to establish a CT colonography service.

PubMed

Fajardo, Laurie L; Hurley, James P; Brown, Bruce P; Summers, Robert W; McDaniel, R Donald

2006-03-01

The authors describe the University of Iowa Department of Radiology's business planning process to initiate a new service in computed tomographic colonography (CTC). Also known as virtual colonoscopy, CTC is a noninvasive technology that offers less risk, and potentially similar sensitivity and specificity, than conventional optical colonoscopy (OC). Although not currently covered by all insurance payers, about a year ago, the Centers for Medicare and Medicaid Services instituted temporary Current Procedural Terminology codes (Category III) for CTC. In locales where the procedure is not covered by insurers, it is likely to be sought by patients willing to pay out of pocket to undergo noninvasive cancer screening as an alternative to OC. Thus, CTC could become the preferred method of colon cancer surveillance by insurance providers in the near future. In developing the business plan, the authors reviewed pertinent scientific and clinical data to evaluate the need for and efficacy of CTC. Local market data were used to estimate patient and procedure volumes and utilization. The authors modeled financial expectations with respect to return on investment on the basis of recently reported models specific to CTC, resource requirements, and the operational impact of the new service on existing hospital and departmental clinical functions. Because there are few local providers of CTC in the authors' region, the business plan also included a publicity campaign and plan to market the new service, stimulate general public interest early, and differentiate the program as a leader in applying this unique new technology to promote cancer screening. Finally, the planning committee acknowledged and accommodated needs specific to the missions of an academic medical center with respect to research and education in designing the new service.

The Prognostic Role of Circulating Tumor Cells (CTC) in High-risk Non-muscle-invasive Bladder Cancer.

PubMed

Busetto, Gian Maria; Ferro, Matteo; Del Giudice, Francesco; Antonini, Gabriele; Chung, Benjamin I; Sperduti, Isabella; Giannarelli, Diana; Lucarelli, Giuseppe; Borghesi, Marco; Musi, Gennaro; de Cobelli, Ottavio; De Berardinis, Ettore

2017-08-01

The purpose of this study was to evaluate the impact of circulating tumor cells (CTCs) as a prognostic marker in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) and assess the efficacy and reliability of 2 different CTC isolation methods. Globally, 155 patients with a pathologically confirmed diagnosis of high-risk NMIBC were included (pT1G3 with or without carcinoma in situ) and underwent transurethral resection of bladder tumor (TURB) after a blood withdrawal for CTC evaluation. A total of 101 patients (Group A) had their samples analyzed with the CellSearch automated system, and 54 (Group B) had their samples analyzed with the CELLection Dynabeads manual system. Patients were followed for 28 months, and during this interval, there were a total of 65 (41.9%) recurrences, 27 (17.4%) disease progressions, and 9 (5.8%) lymph node and/or bone metastasis. In our CTC analysis, there were 20 (19.8%) positive patients in Group A and 24 in Group B (44.4%). In our analysis, we found a strong correlation between CTC presence and time to first recurrence; in Group A, we observed an incidence of recurrence in 75% of CTC-positive patients and in Group B of 83% of CTC-positive patients. The time to progression was also strongly correlated with CTCs: 65% and 29%, respectively, of those patients who progressed in those with CTCs in Group A and B. The study demonstrates the potential role of CTCs as a prognostic marker for risk stratification in patients with NMIBC, to predict both recurrence and progression. Copyright © 2017 Elsevier Inc. All rights reserved.

Nanosphere-based one-step strategy for efficient and nondestructive detection of circulating tumor cells.

PubMed

Wu, Ling-Ling; Wen, Cong-Ying; Hu, Jiao; Tang, Man; Qi, Chu-Bo; Li, Na; Liu, Cui; Chen, Lan; Pang, Dai-Wen; Zhang, Zhi-Ling

2017-08-15

Detecting viable circulating tumor cells (CTCs) without disruption to their functions for in vitro culture and functional study could unravel the biology of metastasis and promote the development of personalized anti-tumor therapies. However, existing CTC detection approaches commonly include CTC isolation and subsequent destructive identification, which damages CTC viability and functions and generates substantial CTC loss. To address the challenge of efficiently detecting viable CTCs for functional study, we develop a nanosphere-based cell-friendly one-step strategy. Immunonanospheres with prominent magnetic/fluorescence properties and extraordinary stability in complex matrices enable simultaneous efficient magnetic capture and specific fluorescence labeling of tumor cells directly in whole blood. The collected cells with fluorescent tags can be reliably identified, free of the tedious and destructive manipulations from conventional CTC identification. Hence, as few as 5 tumor cells in ca. 1mL of whole blood can be efficiently detected via only 20min incubation, and this strategy also shows good reproducibility with the relative standard deviation (RSD) of 8.7%. Moreover, due to the time-saving and gentle processing and the minimum disruption of immunonanospheres to cells, 93.8±0.1% of detected tumor cells retain cell viability and proliferation ability with negligible changes of cell functions, capacitating functional study on cell migration, invasion and glucose uptake. Additionally, this strategy exhibits successful CTC detection in 10/10 peripheral blood samples of cancer patients. Therefore, this nanosphere-based cell-friendly one-step strategy enables viable CTC detection and further functional analyses, which will help to unravel tumor metastasis and guide treatment selection. Copyright © 2017 Elsevier B.V. All rights reserved.

Low-dose dual-energy electronic cleansing for fecal-tagging CT Colonography

NASA Astrophysics Data System (ADS)

Cai, Wenli; Zhang, Da; Lee, June-Goo; Yoshida, Hiroyuki

2013-03-01

Dual-energy electronic cleansing (DE-EC) provides a promising means for cleansing the tagged fecal materials in fecaltagging CT colonography (CTC). However, the increased radiation dose due to the double exposures in dual-energy CTC (DE-CTC) scanning is a major limitation for the use of DE-EC in clinical practice. The purpose of this study was to develop and evaluate a low-dose DE-EC scheme in fecal-tagging DE-CTC. In this study, a custom-made anthropomorphic colon phantom, which was filled with simulated tagged materials by non-ionic iodinated contrast agent (Omnipaque iohexol, GE Healthcare), was scanned by a dual-source CT scanner (SOMATON Definition Flash, Siemens Healthcare) at two photon energies: 80 kVp and 140 kVp with nine different tube current settings ranging from 12 to 74 mAs for 140 kVp, and then reconstructed by soft-tissue reconstruction kernel (B30f). The DE-CTC images were subjected to a low-dose DE-EC scheme. First, our image-space DE-CTC denoising filter was applied for reduction of image noise. Then, the noise-reduced images were processed by a virtual lumen tagging method for reduction of partial volume effect and tagging inhomogeneity. The results were compared with the registered CTC images of native phantom without fillings. Preliminary results showed that our low-dose DE-EC scheme achieved the cleansing ratios, defined by the proportion of the cleansed voxels in the tagging mask, between 93.18% (12 mAs) and 96.62% (74 mAs). Also, the soft-tissue preservation ratios, defined by the proportion of the persevered voxels in the soft-tissue mask, were maintained in the range between 94.67% and 96.41%.

Monitoring of Circulating Tumor Cells and Their Expression of EGFR/Phospho-EGFR During Combined Radiotherapy Regimens in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

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

Tinhofer, Ingeborg, E-mail: ingeborg.tinhofer@charite.de; Hristozova, Tsvetana; Stromberger, Carmen

2012-08-01

Purpose: The numbers of circulating tumor cells (CTCs) and their expression/activation of epidermal growth factor receptor (EGFR) during the course of combined chemo- or bioradiotherapy regimens as potential biomarkers of treatment efficacy in squamous cell carcinoma of the head and neck (SCCHN) were determined. Methods and Materials: Peripheral blood samples from SCCHN patients with locally advanced stage IVA/B disease who were treated with concurrent radiochemotherapy or induction chemotherapy followed by bioradiation with cetuximab were included in this study. Using flow cytometry, the absolute number of CTCs per defined blood volume as well as their expression of EGFR and its phosphorylatedmore » form (pEGFR) during the course of treatment were assessed. Results: Before treatment, we detected {>=}1 CTC per 3.75 mL blood in 9 of 31 patients (29%). Basal expression of EGFR was detected in 100% and pEGFR in 55% of the CTC+ cases. The frequency of CTC detection was not influenced by induction chemotherapy. However, the number of CTC+ samples significantly increased after radiotherapy. This radiation-induced increase in CTC numbers was less pronounced when radiotherapy was combined with cetuximab compared to its combination with cisplatin/5-fluorouracil. The former treatment regimen was also more effective in reducing pEGFR expression in CTCs. Conclusions: Definitive radiotherapy regimens of locally advanced SCCHN can increase the number of CTCs and might thus contribute to a systemic spread of tumor cells. Further studies are needed to evaluate the predictive value of the radiation-induced increase in CTC numbers and the persistent activation of the EGFR signalling pathway in individual CTC+ cases.« less

Multivalent Binding and Biomimetic Cell Rolling Improves the Sensitivity and Specificity of Circulating Tumor Cell Capture.

PubMed

Myung, Ja Hye; Eblan, Michael J; Caster, Joseph M; Park, Sin-Jung; Poellmann, Michael J; Wang, Kyle; Tam, Kevin A; Miller, Seth M; Shen, Colette; Chen, Ronald C; Zhang, Tian; Tepper, Joel E; Chera, Bhishamjit S; Wang, Andrew Z; Hong, Seungpyo

2018-06-01

Purpose: We aimed to examine the effects of multivalent binding and biomimetic cell rolling on the sensitivity and specificity of circulating tumor cell (CTC) capture. We also investigated the clinical significance of CTCs and their kinetic profiles in patients with cancer undergoing radiotherapy treatment. Experimental Design: Patients with histologically confirmed primary carcinoma undergoing radiotherapy, with or without chemotherapy, were eligible for enrollment. Peripheral blood was collected prospectively at up to five time points, including before radiotherapy, at the first week, mid-point and final week of treatment, as well as 4 to 12 weeks after completion of radiotherapy. CTC capture was accomplished using a nanotechnology-based assay (CapioCyte) functionalized with aEpCAM, aHER-2, and aEGFR. Results: CapioCyte was able to detect CTCs in all 24 cancer patients enrolled. Multivalent binding via poly(amidoamine) dendrimers further improved capture sensitivity. We also showed that cell rolling effect can improve CTC capture specificity (% of captured cells that are CK + /CD45 - /DAPI + ) up to 38%. Among the 18 patients with sequential CTC measurements, the median CTC decreased from 113 CTCs/mL before radiotherapy to 32 CTCs/mL at completion of radiotherapy ( P = 0.001). CTCs declined throughout radiotherapy in patients with complete clinical and/or radiographic response, in contrast with an elevation in CTCs at mid or post-radiotherapy in the two patients with known pathologic residual disease. Conclusions: Our study demonstrated that multivalent binding and cell rolling can improve the sensitivity and specificity of CTC capture compared with multivalent binding alone, allowing reliable monitoring of CTC changes during and after treatment. Clin Cancer Res; 24(11); 2539-47. ©2018 AACR . ©2018 American Association for Cancer Research.

Evaluation of two minimal-preparation regimes for CT colonography: optimising image quality and patient acceptability.

PubMed

Pollentine, A; Mortimer, A; McCoubrie, P; Archer, L

2012-08-01

To compare a 2 day bowel preparation regime of barium, iodine and a mild stimulant laxative with a 1 day iodine-only regime for CT colonography (CTC). 100 consecutive patients underwent CTC. The first 50 patients (Regime 1) ingested 1 bisacodyl tablet twice a day 3 days before CTC and 1 dose each of 50 ml of barium and 20 ml of iodinated contrast per day starting 2 days before CTC. The second 50 patients (Regime 2) ingested 3 doses of iodinated contrast over 24 h prior to CTC. Volumes of residual stool and fluid, and the effectiveness of stool and fluid tagging, were graded according to methods established by Taylor et al (Taylor S, Slaker A, Burling D, Tam E, Greenhalgh R, Gartner L, et al. CT colonography: optimisation, diagnostic performance and patient acceptability of reduced-laxative regimens using barium-based faecal tagging. Eur Radiol 2008; 18: 32-42). A 3 day low-residue diet was taken by both cohorts. Questionnaires rating the side-effects and burden of the bowel preparation were compared to a control cohort of patients undergoing barium enema. The proportion of colons producing none/scattered stool (score 1) was 90.3% with Regime 1 and 65.0% with Regime 2 (p<0.005). Any residual stool was significantly better tagged with Regime 1 (score 5), with 91.7% of Regime 1 exhibiting optimum tagging vs 71.3% of Regime 2 (p<0.05). No significant differences in side-effects between the bowel preparation regimes for CTC were elicited. Bowel preparation for barium enema was tolerated significantly worse than both of the CTC bowel preparation regimes. Regime 1, containing a 3 day preparation of a mild laxative, barium and iodine, produced a significantly better prepared colon, with no difference in patient acceptability.

Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis

DTIC Science & Technology

2015-10-01

3. ACCOMPLISHMENTS What were the major goals of the project? Dr. David Hong at MD Anderson was the partnering PI of this protocol . The major...blood (CTC analyses). Peripheral blood samples and tumor tissues will be collected and provided by Dr. David Hong under a MDACC IRB- protocol which has...per IRB-approved protocol ) will be drawn and immediately undergo CTC analyses. Blood may be drawn from the same individual on more than one occasion

Efficient Purification and Release of Circulating Tumor Cells by Synergistic Effect of Biomarker and SiO2 @Gel-Microbead-Based Size Difference Amplification.

PubMed

Huang, Qinqin; Cai, Bo; Chen, Bolei; Rao, Lang; He, Zhaobo; He, Rongxiang; Guo, Feng; Zhao, Libo; Kondamareddy, Kiran Kumar; Liu, Wei; Guo, Shishang; Zhao, Xing-Zhong

2016-07-01

Microfluidics-based circulating tumor cell (CTC) isolation is achieved by using gelatin-coated silica microbeads conjugated to CTC-specific antibodies. Bead-binding selectively enlarges target cell size, providing efficient high-purity capture. CTCs captured can be further released non-invasively. This stratagem enables high-performance CTC isolation for subsequent studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Potential Efficacy of Citicoline as Adjunct Therapy in Treatment of Cerebral Malaria

PubMed Central

El-Assaad, Fatima; Combes, Valery; Grau, Georges Emile Raymond

2014-01-01

Cerebral malaria (CM) is characterized by a dysregulated immune response that results in endothelial membrane destabilization and increased microparticle (MP) production. Citicoline (CTC) is a membrane stabilizer used for the treatment of neurological disorders. We evaluated the efficacy of CTC as adjunct therapy to aid recovery from experimental CM. We show that CTC reduces MP production in vitro; in combination with artesunate in vivo, confers partial protection against CM; and prolongs survival. PMID:24165175

Probing Androgen Receptor Signaling in Circulating Tumor Cells in Prostate Cancer

DTIC Science & Technology

2014-07-01

androgen driven) and PSMA (androgen suppressed). Application of this CTC-based assay in a small cohort of men with prostate cancer revealed that the AR...activity in CTCs as measured by PSA and PSMA expression levels could be used to monitor the treatment of patients undergoing AR targeting therapies...transitioned the laboratory to the 3rd generation CTC iChip technology (4), and have adapted the PSA/ PSMA assay for use with this new CTC isolation

Folic acid functionalized surface highlights 5-methylcytosine-genomic content within circulating tumor cells.

PubMed

Malara, Natalia; Coluccio, Maria Laura; Limongi, Tania; Asande, Monica; Trunzo, Valentina; Cojoc, Gheorghe; Raso, Cinzia; Candeloro, Patrizio; Perozziello, Gerardo; Raimondo, Raffaella; De Vitis, Stefania; Roveda, Laura; Renne, Maria; Prati, Ubaldo; Mollace, Vincenzo; Di Fabrizio, Enzo

2014-11-12

Although the detection of methylated cell free DNA represents one of the most promising approaches for relapse risk assessment in cancer patients, the low concentration of cell-free circulating DNA constitutes the biggest obstacle in the development of DNA methylation-based biomarkers from blood. This paper describes a method for the measurement of genomic methylation content directly on circulating tumor cells (CTC), which could be used to deceive the aforementioned problem. Since CTC are disease related blood-based biomarkers, they result essential to monitor tumor's stadiation, therapy, and early relapsing lesions. Within surface's bio-functionalization and cell's isolation procedure standardization, the presented approach reveals a singular ability to detect high 5-methylcytosine CTC-subset content in the whole CTC compound, by choosing folic acid (FA) as transducer molecule. Sensitivity and specificity, calculated for FA functionalized surface (FA-surface), result respectively on about 83% and 60%. FA-surface, allowing the detection and characterization of early metastatic dissemination, provides a unique advance in the comprehension of tumors progression and dissemination confirming the presence of CTC and its association with high risk of relapse. This functionalized surface identifying and quantifying high 5-methylcytosine CTC-subset content into the patient's blood lead significant progress in cancer risk assessment, also providing a novel therapeutic strategy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of chlortetracycline, Cu and their combination on the performance and microbial community dynamics in swine manure anaerobic digestion.

PubMed

Wang, Rui; Zhang, Junya; Liu, Jibao; Yu, Dawei; Zhong, Hui; Wang, Yawei; Chen, Meixue; Tong, Juan; Wei, Yuansong

2018-05-01

Swine manure was typical for the combined pollution of heavy metals and antibiotics. The effects of widely used veterinary antibiotic chlortetracycline (CTC), Cu and their combination on swine manure anaerobic digestion performance and microbial community have never been investigated. Thus, four 2L anaerobic digestion reactors were established including reactor A (control), B (CTC spiked by 0.5g/kg dry weight, dw), C (Cu spiked by 5g/kg dw) and D (combination of CTC, 0.5g/kg dw, and Cu, 5g/kg dw), and dynamics of bacterial and archaeal community structure was investigated using high throughput sequencing method. Results showed that addition of CTC and Cu separately could increase the total biogas production by 21.6% and 15.8%, respectively, while combination of CTC and Cu severely inhibited anaerobic digestion (by 30.3%). Furthermore, corresponding to different stages and reactors, four kinds of microbes including bacteria and archaea were described in detail, and the effects of CTC, Cu and their combination mainly occurred at hydrolysis and acidification phases. The addition of Cu alone changed the dynamics of archaeal community significantly. It was genus Methanomassiliicoccus that dominated at the active methane production for A, B and D, while it was genus Methanobrevibacter and Methanoculleus for C. Copyright © 2017. Published by Elsevier B.V.

Assessment of bacterial endospore viability with fluorescent dyes.

PubMed

Laflamme, C; Lavigne, S; Ho, J; Duchaine, C

2004-01-01

To validate three fluorescence viability assays designed primarily for vegetative cells on pure Bacillus endospores. Purified fresh and gamma-irradiated Bacillus endospores (Bacillus cereus, B. coagulans and two strains of B. subtilis) were used. The viability assays were: 5-cyano-2,3-diotolyl tetrazolium chloride (CTC) to test respiratory activity and early germination, DiBAC4(3) and Live/Dead BacLight to measure membrane energization and permeabilization, respectively. Gamma irradiation treatment completely eliminated spore culturability and was used as negative control. The untreated spores showed respiratory activity after 1 h of incubation and this was characteristic of almost 100% of spores after 24 h. The membrane potential assessment gave no answer about spore viability. A lower proportion of untreated spores had permeabilized membrane compared with gamma-irradiated spores using Live/Dead BacLight (P < 0.02). It is possible to use CTC and Live/Dead BacLight to rapidly test endospore viability and evaluate the proportion of spores in a preparation that could not be recovered with plate count. This study shows that fluorescence tests could be applied to assess viability in potentially pathogenic Bacillus spore preparations within 1 h.

Circulating Tumor Cells: From Theory to Nanotechnology-Based Detection

PubMed Central

Ming, Yue; Li, Yuanyuan; Xing, Haiyan; Luo, Minghe; Li, Ziwei; Chen, Jianhong; Mo, Jingxin; Shi, Sanjun

2017-01-01

Cancer stem cells with stem-cell properties are regarded as tumor initiating cells. Sharing stem-cell properties, circulating tumor cells (CTCs) are responsible for the development of metastasis, which significant affects CTC analysis in clinical practice. Due to their extremely low occurrence in blood, however, it is challenging to enumerate and analyze CTCs. Nanotechnology is able to address the problems of insufficient capture efficiency and low purity of CTCs owing to the unique structural and functional properties of nanomaterials, showing strong promise for CTC isolation and detection. In this review, we discuss the role of stem-like CTCs in metastases, provide insight into recent progress in CTC isolation and detection approaches using various nanoplatforms, and highlight the role of nanotechnology in the advancement of CTC research. PMID:28203204

Simultaneous enzymatic and SERS properties of bifunctional chitosan-modified popcorn-like Au-Ag nanoparticles for high sensitive detection of melamine in milk powder.

PubMed

Li, Junrong; Zhang, Guannan; Wang, Lihua; Shen, Aiguo; Hu, Jiming

2015-08-01

In this work, we suggest a chitosan-modified popcorn-like Au-Ag nanoparticles (CSPNPs) based assay for high sensitive detection of melamine, in which CSPNPs not only provide with an intrinsic peroxidase-like activity but also act as surface enhanced Raman scattering (SERS) substrates. CSPNPs can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to the charge transfer complex (CTC), which contributes to a tremendous surface-enhanced resonant Raman scattering (SERRS) signals with 632.8 nm laser excitation. The target molecule melamine can generate an additional compound with H2O2, which means the available amount of H2O2 for the oxidation of TMB reduced. Correspondingly, the SERRS intensity of CTC is decreased. The decreased Raman intensity is proportional to the concentration of melamine over a wide range from 10 nM to 50 μM (R(2)=0.989), with a limit of detection (LOD) of 8.51 nM. Moreover, the proposed highly selective method is fully capable of rapid, separation-free detection of melamine in milk powder. Copyright © 2015 Elsevier B.V. All rights reserved.

Reciprocal Relations between Coalition Functioning and the Provision of Implementation Support

PubMed Central

Brown, Louis D.; Feinberg, Mark E.; Shapiro, Valerie B.; Greenberg, Mark T.

2014-01-01

Community coalitions have been promoted as a strategy to help overcome challenges to the dissemination and implementation of evidence-based prevention programs. This paper explores the characteristics of coalitions that enable the provision of implementation support for prevention programs in general, and for the implementation of evidence-based prevention programs with fidelity. Longitudinal cross-lagged panel models were used to study 74 Communities That Care (CTC) coalitions in Pennsylvania. These analyses provide evidence of a unidirectional influence of coalition functioning on the provision of implementation support. Coalition member knowledge of the CTC model best predicted the coalition’s provision of support for evidence-based program implementation with fidelity. Implications for developing and testing innovative methods for delivering training and technical assistance to enhance coalition member knowledge are discussed. PMID:24323363

28 CFR 550.40 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Services (Urine Surveillance and Counseling for Sentenced Inmates in Contract CTCs) § 550.40... community treatment center (CTC) participate in a program of urine testing for drug use. An inmate who is...

Clinical evaluation of a novel microfluidic device for epitope-independent enrichment of circulating tumour cells in patients with small cell lung cancer.

PubMed

Chudziak, Jakub; Burt, Deborah J; Mohan, Sumitra; Rothwell, Dominic G; Mesquita, Bárbara; Antonello, Jenny; Dalby, Suzanne; Ayub, Mahmood; Priest, Lynsey; Carter, Louise; Krebs, Matthew G; Blackhall, Fiona; Dive, Caroline; Brady, Ged

2016-01-21

Circulating tumour cells (CTCs) have potential utility as minimally-invasive biomarkers to aid cancer treatment decision making. However, many current CTC technologies enrich CTCs using specific surface epitopes that do not necessarily reflect CTC heterogeneity. Here we evaluated the epitope-independent Parsortix system which enriches CTCs based on size and rigidity using both healthy normal volunteer blood samples spiked with tumour cells and blood samples from patients with small cell lung cancer (SCLC). Blood samples were maintained unfractionated at room temperature for up to 4 days followed by plasma removal for circulating free DNA (cfDNA) isolation and direct application of the remaining cell component to the Parsortix system. For tumour cells expressing the EpCAM cell surface marker the numbers of spiked cells retained using the Parsortix system and by EpCAM-positive selection using CellSearch® were not significantly different, whereas only the Parsortix system showed strong enrichment of cells with undetectable EpCAM expression. In a pilot clinical study we banked both enriched CTCs as well as plasma from SCLC patient blood samples. Upon retrieval of the banked Parsortix cellular samples we could detect cytokeratin positive CTCs in all 12 SCLC patients tested. Interestingly, processing parallel samples from the same patients by EpCAM enrichment using CellSearch® revealed only 83% (10/12) with cytokeratin positive CTCs indicating the Parsortix system is enriching for EpCAM negative SCLC CTCs. Our combined results indicate the Parsortix system is a valuable tool for combined cfDNA isolation and CTC enrichment that enables CTC analysis to be extended beyond dependence on surface epitopes.

Application of gray level mapping in computed tomographic colonography: a pilot study to compare with traditional surface rendering method for identification and differentiation of endoluminal lesions

PubMed Central

Chen, Lih-Shyang; Hsu, Ta-Wen; Chang, Shu-Han; Lin, Chih-Wen; Chen, Yu-Ruei; Hsieh, Chin-Chiang; Han, Shu-Chen; Chang, Ku-Yaw; Hou, Chun-Ju

2017-01-01

Objective: In traditional surface rendering (SR) computed tomographic endoscopy, only the shape of endoluminal lesion is depicted without gray-level information unless the volume rendering technique is used. However, volume rendering technique is relatively slow and complex in terms of computation time and parameter setting. We use computed tomographic colonography (CTC) images as examples and report a new visualization technique by three-dimensional gray level mapping (GM) to better identify and differentiate endoluminal lesions. Methods: There are 33 various endoluminal cases from 30 patients evaluated in this clinical study. These cases were segmented using gray-level threshold. The marching cube algorithm was used to detect isosurfaces in volumetric data sets. GM is applied using the surface gray level of CTC. Radiologists conducted the clinical evaluation of the SR and GM images. The Wilcoxon signed-rank test was used for data analysis. Results: Clinical evaluation confirms GM is significantly superior to SR in terms of gray-level pattern and spatial shape presentation of endoluminal cases (p < 0.01) and improves the confidence of identification and clinical classification of endoluminal lesions significantly (p < 0.01). The specificity and diagnostic accuracy of GM is significantly better than those of SR in diagnostic performance evaluation (p < 0.01). Conclusion: GM can reduce confusion in three-dimensional CTC and well correlate CTC with sectional images by the location as well as gray-level value. Hence, GM increases identification and differentiation of endoluminal lesions, and facilitates diagnostic process. Advances in knowledge: GM significantly improves the traditional SR method by providing reliable gray-level information for the surface points and is helpful in identification and differentiation of endoluminal lesions according to their shape and density. PMID:27925483

Combining heterogeneous features for colonic polyp detection in CTC based on semi-definite programming

NASA Astrophysics Data System (ADS)

Wang, Shijun; Yao, Jianhua; Petrick, Nicholas A.; Summers, Ronald M.

2009-02-01

Colon cancer is the second leading cause of cancer-related deaths in the United States. Computed tomographic colonography (CTC) combined with a computer aided detection system provides a feasible combination for improving colonic polyps detection and increasing the use of CTC for colon cancer screening. To distinguish true polyps from false positives, various features extracted from polyp candidates have been proposed. Most of these features try to capture the shape information of polyp candidates or neighborhood knowledge about the surrounding structures (fold, colon wall, etc.). In this paper, we propose a new set of shape descriptors for polyp candidates based on statistical curvature information. These features, called histogram of curvature features, are rotation, translation and scale invariant and can be treated as complementing our existing feature set. Then in order to make full use of the traditional features (defined as group A) and the new features (group B) which are highly heterogeneous, we employed a multiple kernel learning method based on semi-definite programming to identify an optimized classification kernel based on the combined set of features. We did leave-one-patient-out test on a CTC dataset which contained scans from 50 patients (with 90 6-9mm polyp detections). Experimental results show that a support vector machine (SVM) based on the combined feature set and the semi-definite optimization kernel achieved higher FROC performance compared to SVMs using the two groups of features separately. At a false positive per patient rate of 7, the sensitivity on 6-9mm polyps using the combined features improved from 0.78 (Group A) and 0.73 (Group B) to 0.82 (p<=0.01).

Combining Statistical and Geometric Features for Colonic Polyp Detection in CTC Based on Multiple Kernel Learning

PubMed Central

Wang, Shijun; Yao, Jianhua; Petrick, Nicholas; Summers, Ronald M.

2010-01-01

Colon cancer is the second leading cause of cancer-related deaths in the United States. Computed tomographic colonography (CTC) combined with a computer aided detection system provides a feasible approach for improving colonic polyps detection and increasing the use of CTC for colon cancer screening. To distinguish true polyps from false positives, various features extracted from polyp candidates have been proposed. Most of these traditional features try to capture the shape information of polyp candidates or neighborhood knowledge about the surrounding structures (fold, colon wall, etc.). In this paper, we propose a new set of shape descriptors for polyp candidates based on statistical curvature information. These features called histograms of curvature features are rotation, translation and scale invariant and can be treated as complementing existing feature set. Then in order to make full use of the traditional geometric features (defined as group A) and the new statistical features (group B) which are highly heterogeneous, we employed a multiple kernel learning method based on semi-definite programming to learn an optimized classification kernel from the two groups of features. We conducted leave-one-patient-out test on a CTC dataset which contained scans from 66 patients. Experimental results show that a support vector machine (SVM) based on the combined feature set and the semi-definite optimization kernel achieved higher FROC performance compared to SVMs using the two groups of features separately. At a false positive per scan rate of 5, the sensitivity of the SVM using the combined features improved from 0.77 (Group A) and 0.73 (Group B) to 0.83 (p ≤ 0.01). PMID:20953299

Countries' interest in a hepatitis B vaccine licensed for the controlled temperature chain; survey results from African and Western Pacific regions.

PubMed

Petit, Dörte; Tevi-Benissan, Carole; Woodring, Joseph; Hennessey, Karen; Kahn, Anna-Lea

2017-12-14

Chronic hepatitis B infection can be prevented by hepatitis B vaccine birth dose (hepB-BD) given within 24 h after birth, followed by two hepatitis B vaccinations within the first year of life. Yet nearly half of World Health Organization (WHO) Member States do not provide a hepB-BD. Barriers are primarily attributed to vaccine storage and transportation, as well as high rates of home births. Delivering the vaccine outside the cold chain could potentially increase coverage. To do this, WHO recommends vaccines be licensed for use in a "controlled temperature chain" (CTC), which requires a given product to tolerate temperature excursions up to at least 40 °C for a minimum of three days. To date, no hepB vaccine is labelled for CTC. To inform dialogue with manufacturers, WHO conducted a survey among countries in the African and Western Pacific Regions (AFR and WPR) to assess demand for a hepatitis B product licensed for use in a CTC. Twenty-five (44%) countries responded, with 8 of 11 (73%) from the WPR and 17 of 46 (37%) from the AFR. Of these responding countries, 5 in AFR and all 8 in WPR have introduced universal hepB-BD. Seventy-two percent indicated that CTC would facilitate the provision of hepB-BD. While no overall difference in responses was detected between countries either providing or not providing hepB-BD, countries that already introduced hepB-BD but had low hepB-BD coverage were particularly interested in CTC. Irrespective of hepB-BD policy, responding countries suggested that a CTC-licenced product would be beneficial, though the price of such a vaccine would influence procurement decisions. This survey was beneficial to inform the CTC agenda. However, countries' lack of experience with HepB-BD as well as with CTC and the fact that countries were commenting on a product that is not yet on the market should be acknowledged. Copyright © 2017. Published by Elsevier Ltd.

Genetics Home Reference: Coats plus syndrome

MedlinePlus

... of telomeres. However, it is unclear how CTC1 gene mutations impact telomere structure and function. Some studies have found that people with CTC1 gene mutations have abnormally short telomeres, while other studies have ...

Novel silver nanoparticle-enhanced fluorometric determination of trace tetracyclines in aqueous solutions.

PubMed

Wang, Ping; Wu, Tun-Hua; Zhang, Yong

2016-01-01

Metal-enhanced fluorescence (MEF) has exhibited promise for applications in fluorometric assays. The effects of silver nanoparticles (AgNP) on the fluorescence behaviours of tetracycline hydrochloride (TCH) and chlortetracycline hydrochloride (CTC) in aqueous solutions were investigated. The experimental results demonstrated that the fluorescence intensities of each tetracycline in water solutions were greatly enhanced by AgNP through the MEF effect. In addition, a novel silver nanoparticle-enhanced fluorometric method was established for the direct determination of TCH and CTC in aqueous solutions. Under optimum experimental conditions, the linear dynamic ranges for the determination of TCH and CTC in aqueous solutions varied from 0.10 to 6.0 mg L(-1) and 0.050 to 3.0 mg L(-1) with detection limits of 0.63 µg L(-1) and 0.19 µg L(-1), respectively, and with the relative standard deviation of less than 1.9% (n=9). The experimental recovery results for the determination of TCH and CTC in aqueous solutions ranged from 93-106% and 95-104%, respectively. Compared with the established method without the addition of AgNP, the limits of quantitation of the silver nanoparticle-enhanced fluorometric method were approximately 5-fold lower for TCH and 3-fold lower for CTC. Moreover, the newly established silver nanoparticle-enhanced fluorometric method was successfully applied to the direct determination of TCH and CTC in pharmaceutical preparations. Copyright © 2015 Elsevier B.V. All rights reserved.

Bone disease in patients awaiting liver transplantation. Has the situation improved in the last two decades?

PubMed

Monegal, Ana; Navasa, Miquel; Peris, Pilar; Colmenero, Jordi; Cuervo, Andrea; Muxí, Africa; Gifre, Laia; Guañabens, Núria

2013-12-01

In recent years, there has been speculation about the possibility of a reduction in the incidence of fractures after liver transplantation (LT) because of changes in the characteristics of candidates and the use of different immunosuppressive therapies. We analyzed the characteristics of LT candidates (CTC) and compared them with historical data from a group of LT candidate patients (HTC). Data from 60 CTC patients consecutively included in a screening program of metabolic bone disease were compared with data from 60 HTC patients prospectively evaluated between 1992 and 1993. In all patients, we analyzed the clinical and laboratory characteristics, bone mineral density (BMD) dual-energy X-ray absorptiometry, and skeletal fractures. Patients in the CTC group were older than patients in the HTC group. The CTC group had lower femoral neck T scores. No differences were observed between groups in the proportion of patients with osteoporosis (22 vs. 30 %, p = ns) or fractures (36 vs. 33 %, p = ns). The percentage of patients with normal BMD decreased from 38 to 20 %. 25(OH)D values were low in both groups. Only 7.5 % of the CTC patients received calcium and/or vitamin D supplementation. The prevalence of fractures among CTC patients was similar to that seen two decades ago. At present, candidates for LT are older and have lower femoral bone mass. Vitamin D deficiency remains frequent; however, calcium and/or vitamin D supplementation is uncommon.

Pinocytosis and locomotion of amoebae. XV. Visualization of Ca++-dynamics by chlorotetracycline (CTC) fluorescence during induced pinocytosis in living Amoeba proteus.

PubMed

Gawlitta, W; Stockem, W; Wehland, J; Weber, K

1980-01-01

The dynamics of Ca++ during induced pinocytosis were studied in Amoeba proteus using chlorotetracycline (CTC). The fluorescence of the Ca++ - CTC-complex was monitored by an image intensification system, which has certain advantages over standard equipment: (1) Living cells are not subjected to the damaging influence of intensive microscopic illumination, (2) fluorescent probes are not bleached during observation, and (3) the rapid dynamics of the Ca++ -fluxes can be recorded using short exposure times. The results demonstrate the existence of Ca++ bound to intracellular and extracellular sites of the cell membrane complex in normal locomoting and pinocytotic Amoeba proteus. The application of cations inducing pinocytosis causes a rapid decrease in the external CTC-fluorescence probably due to a release of Ca++ from the mucous layer. The degree of fluorescence intensity is correlated with the capacity of pinocytotic channel formation, i.e., the fluorescence decreases as the number of channels increases. During the phase of vesiculation a distinct fluorescence mainly restricted to the basal region of the channels is observed. Intracellular Ca++ was detected in close vicinity to the plasma membrane after both microinjection and external application of CTC. The internal CTC-fluorescence is slightly decreased during the induction phase of pinocytosis. The observations are in good agreement with previous results on the localization of Ca++ -binding sites at the plasma membrane of Amoeba proteus and demonstrate the important role of Ca++ -fluxes for the process of pinocytosis.

The joint action of destruxins and botanical insecticides (rotenone, azadirachtin and paeonolum) against the cotton aphid, Aphis gossypii Glover.

PubMed

Yi, Fei; Zou, Chunhua; Hu, Qiongbo; Hu, Meiying

2012-06-18

The joint action of destruxins and three botanical insecticides, rotenone (Rot), azadirachtin (Aza) and paeonolum (Pae) against the cotton aphid, Aphis gossypii, was bioassayed. In laboratory experiment, several synergistic groups of destruxins with botanical insecticides were found by means of Sun's Co-toxicity Coefficients (CTC) and Finney's Synergistic Coefficient (SC). The best synergistic effect was discovered in the ratio group Des/Rot 1/9 with the CTC or SC and LC₅₀ values of 479.93 or 4.8 and 0.06 μg/mL, respectively. The second and third synergistic effects were recorded in the ratio groups Des/Rot 7/3 and 9/1. Although the ratio groups Des/Aza 6/4, Des/Pae 4/6, 3/7 and 2/8 indicated synergism by Sun's CTC, they were determined as additive actions by Finney's SC. Additive actions were also found in most of the ratio groups, but antagonism were recorded only in three ratio groups: Des/Pae 9/1, 7/3 and 6/4. In greenhouse tests, the highest mortality was 98.9% with the treatment Des/Rot 1/9 at 0.60 μg/mL, meanwhile, the treatments Des/Pae 4/6 and Des/Aza 6/4 had approximately 88% mortality.

Cadmium Alternatives for High-Strength Steel JTP - Phase 2

DTIC Science & Technology

2008-02-27

Project Overview Objective • Assess DoD- selected Cadmium alternatives in accordance with the DoD-approved Joint Test Protocol (JTP) for both...HE and adhesion testing): NAVAIR (complete) – Phase II (JTP test matrix): AFRL/CTC – Phase III (Testing for Threaded Fasteners): ARL • Selection of...Curry • Hill AFB – Mr. Nate Hughes • Alumiplate – Mr. Gus Vallejo • Marshall Labs – Mr. John Marshall U.S. AIR FORCE Phase I Overview and Selection

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

PubMed

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

2018-05-25

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

Self-Sterilizing and Regeneratable Microchip for the Precise Capture and Recovery of Viable Circulating Tumor Cells from Patients with Cancer.

PubMed

Hui, Lanlan; Su, Yi; Ye, Tingting; Liu, Zhao; Tian, Qingchang; He, Chuanjiang; Zhao, Yueqi; Chen, Pu; Wang, Xiaojia; Han, Weidong; Luo, Yan; Wang, Ben

2018-01-10

Cancer cells metastasize and are transported in the bloodstream, easily reaching any site in the body through the blood circulation. A method designed to assess the number of circulating tumor cells (CTCs) should be validated as a clinical tool for predicting the response to therapy and monitoring the disease progression in patients with cancer. Although CTCs are detectable in many cases, they remain unavailable for clinic usage because of their high testing cost, tedious operation, and poor clinical relevance. Herein, we developed a regeneratable microchip for isolating CTCs, which is available for robust cell heterogeneity assays on-site without the need for a sterile environment. The ivy-like hierarchical roughened zinc oxide (ZnO) nanograss interface was synthesized and directly integrated into the microfluidic devices and enables effective CTC capture and flexible, nontoxic CTC release during incubation in a mildly acidic solution, thus enabling cellular and molecular analyses. The microchip can be regenerated and recycled to capture CTCs with the remaining ZnO without affecting the efficiency, even after countless cycles of cell release. Moreover, microbial infection is avoided during its storage, distribution, and even in the open space usage, which ideally appeals to the demands of point-of-care (POC) and home testing and meets to the requirements for blood examinations in undeveloped or resource-limited settings. Furthermore, the findings generated using this platform based on the cocktail of antiepithelial cell adhesion molecule and antivimentin antibodies indicate that CTC capture was more precise and reasonable for patients with advanced cancer.

Developing and Validating Genetic Catabolic Probes for Monitored Natural Attenuation of 1,4-Dioxane with a One-Year Timeframe

DTIC Science & Technology

2014-04-01

Psed_0815_F TTC CCG CCG TAG GAC AGG GA Psed_0815_R GTT GCC GTG GTT GTG CAG CA tmo3A Psed_1155_F CTC TCC GAG TAC GCC GCC TG Psed_1155_R GCC ATG TCG...GAG CTC GTC GA tmo2A Psed_1436_F CTC TGC AGC CTG TGC CAC CT Psed_1436_R CCC GTT GTG GGT GAG CGA GT tmo4A Psed_6062_F GCT CCA TGA ACT GCT TGA

Nanostructure embedded microchips for detection, isolation, and characterization of circulating tumor cells.

PubMed

Lin, Millicent; Chen, Jie-Fu; Lu, Yi-Tsung; Zhang, Yang; Song, Jinzhao; Hou, Shuang; Ke, Zunfu; Tseng, Hsian-Rong

2014-10-21

Circulating tumor cells (CTCs) are cancer cells that break away from either a primary tumor or a metastatic site and circulate in the peripheral blood as the cellular origin of metastasis. With their role as a "tumor liquid biopsy", CTCs provide convenient access to all disease sites, including that of the primary tumor and the site of fatal metastases. It is conceivable that detecting and analyzing CTCs will provide insightful information in assessing the disease status without the flaws and limitations encountered in performing conventional tumor biopsies. However, identifying CTCs in patient blood samples is technically challenging due to the extremely low abundance of CTCs among a large number of hematologic cells. To address this unmet need, there have been significant research endeavors, especially in the fields of chemistry, materials science, and bioengineering, devoted to developing CTC detection, isolation, and characterization technologies. Inspired by the nanoscale interactions observed in the tissue microenvironment, our research team at UCLA pioneered a unique concept of "NanoVelcro" cell-affinity substrates, in which CTC capture agent-coated nanostructured substrates were utilized to immobilize CTCs with high efficiency. The working mechanism of NanoVelcro cell-affinity substrates mimics that of Velcro: when the two fabric strips of a Velcro fastener are pressed together, tangling between the hairy surfaces on two strips leads to strong binding. Through continuous evolution, three generations (gens) of NanoVelcro CTC chips have been established to achieve different clinical utilities. The first-gen NanoVelcro chip, composed of a silicon nanowire substrate (SiNS) and an overlaid microfluidic chaotic mixer, was created for CTC enumeration. Side-by-side analytical validation studies using clinical blood samples suggested that the sensitivity of first-gen NanoVelcro chip outperforms that of FDA-approved CellSearch. In conjunction with the use of the laser microdissection (LMD) technique, second-gen NanoVelcro chips (i.e., NanoVelcro-LMD), based on polymer nanosubstrates, were developed for single-CTC isolation. The individually isolated CTCs can be subjected to single-CTC genotyping (e.g., Sanger sequencing and next-generation sequencing, NGS) to verify the CTC's role as tumor liquid biopsy. Created by grafting of thermoresponsive polymer brushes onto SiNS, third-gen NanoVelcro chips (i.e., Thermoresponsive NanoVelcro) have demonstrated the capture and release of CTCs at 37 and 4 °C, respectively. The temperature-dependent conformational changes of polymer brushes can effectively alter the accessibility of the capture agent on SiNS, allowing for rapid CTC purification with desired viability and molecular integrity. This Account summarizes the continuous evolution of NanoVelcro CTC assays from the emergence of the original idea all the way to their applications in cancer research. We envision that NanoVelcro CTC assays will lead the way for powerful and cost-efficient diagnostic platforms for researchers to better understand underlying disease mechanisms and for physicians to monitor real-time disease progression.

Is the Cognitive Complexity of Commitment-to-Change Statements Associated With Change in Clinical Practice? An Application of Bloom's Taxonomy.

PubMed

Armson, Heather; Elmslie, Tom; Roder, Stefanie; Wakefield, Jacqueline

2015-01-01

This study categorizes 4 practice change options, including commitment-to-change (CTC) statements using Bloom's taxonomy to explore the relationship between a hierarchy of CTC statements and implementation of changes in practice. Our hypothesis was that deeper learning would be positively associated with implementation of planned practice changes. Thirty-five family physicians were recruited from existing practice-based small learning groups. They were asked to use their usual small-group process while exploring an educational module on peripheral neuropathy. Part of this process included the completion of a practice reflection tool (PRT) that incorporates CTC statements containing a broader set of practice change options-considering change, confirmation of practice, and not convinced a change is needed ("enhanced" CTC). The statements were categorized using Bloom's taxonomy and then compared to reported practice implementation after 3 months. Nearly all participants made a CTC statement and successful practice implementation at 3 months. By using the "enhanced" CTC options, additional components that contribute to practice change were captured. Unanticipated changes accounted for one-third of all successful changes. Categorizing statements on the PRT using Bloom's taxonomy highlighted the progression from knowledge/comprehension to application/analysis to synthesis/evaluation. All PRT statements were classified in the upper 2 levels of the taxonomy, and these higher-level (deep learning) statements were related to higher levels of practice implementation. The "enhanced" CTC options captured changes that would not otherwise be identified and may be worthy of further exploration in other CME activities. Using Bloom's taxonomy to code the PRT statements proved useful in highlighting the progression through increasing levels of cognitive complexity-reflecting deep learning. © 2015 The Alliance for Continuing Education in the Health Professions, the Society for Academic Continuing Medical Education, and the Council on Continuing Medical Education, Association for Hospital Medical Education.

Evaluation of two minimal-preparation regimes for CT colonography: optimising image quality and patient acceptability

PubMed Central

Pollentine, A; Mortimer, A; Mccoubrie, P; Archer, L

2012-01-01

Objective To compare a 2 day bowel preparation regime of barium, iodine and a mild stimulant laxative with a 1 day iodine-only regime for CT colonography (CTC). Methods 100 consecutive patients underwent CTC. The first 50 patients (Regime 1) ingested 1 bisacodyl tablet twice a day 3 days before CTC and 1 dose each of 50 ml of barium and 20 ml of iodinated contrast per day starting 2 days before CTC. The second 50 patients (Regime 2) ingested 3 doses of iodinated contrast over 24 h prior to CTC. Volumes of residual stool and fluid, and the effectiveness of stool and fluid tagging, were graded according to methods established by Taylor et al (Taylor S, Slaker A, Burling D, Tam E, Greenhalgh R, Gartner L, et al. CT colonography: optimisation, diagnostic performance and patient acceptability of reduced-laxative regimens using barium-based faecal tagging. Eur Radiol 2008; 18: 32–42). A 3 day low-residue diet was taken by both cohorts. Questionnaires rating the side-effects and burden of the bowel preparation were compared to a control cohort of patients undergoing barium enema. Results The proportion of colons producing none/scattered stool (score 1) was 90.3% with Regime 1 and 65.0% with Regime 2 (p<0.005). Any residual stool was significantly better tagged with Regime 1 (score 5), with 91.7% of Regime 1 exhibiting optimum tagging vs 71.3% of Regime 2 (p<0.05). No significant differences in side-effects between the bowel preparation regimes for CTC were elicited. Bowel preparation for barium enema was tolerated significantly worse than both of the CTC bowel preparation regimes. Conclusion Regime 1, containing a 3 day preparation of a mild laxative, barium and iodine, produced a significantly better prepared colon, with no difference in patient acceptability. PMID:22422379

Cirugía de los trastornos del comportamiento: el estado del arte

PubMed Central

Yampolsky, Claudio; Bendersky, Damián

2014-01-01

Introducción: La cirugía de los trastornos del comportamiento (CTC) se está convirtiendo en un tratamiento más común desde el desarrollo de la neuromodulación. Métodos: Este artículo es una revisión no sistemática de la historia, indicaciones actuales, técnicas y blancos quirúrgicos de la CTC. Dividimos su historia en 3 eras: la primera comienza en los inicios de la psicocirugía y termina con el desarrollo de las tícnicas estereotácticas, cuando comienza la segunda era. Ésta se caracteriza por la realización de lesiones estereotácticas. Nos encontramos transitando la tercera era, que comienza cuando la estimulación cerebral profunda (ECP) comienza a ser usada en CTC. Resultados: A pesar de los errores graves cometidos en el pasado, hoy en día, la CTC está renaciendo. Los trastornos psiquiátricos que se más frecuentemente se tratan con cirugía son: depresión refractaria, trastorno obsesivo-compulsivo y síndrome de Tourette. Además, algunos pacientes con agresividad fueron tratados quirúrgicamente. Hay varios blancos estereotácticos descriptos para estos trastornos. La estimulación vagal puede ser usada también para depresión. Conclusión: Los resultados de la ECP en estos trastornos parecen alentadores. Sin embargo, se necesitan más estudios randomizados para establecer la efectividad de la CTC. Debe tenerse en cuenta que una apropiada selección de pacientes nos ayudará a realizar un procedimiento más seguro así como también a lograr mejores resultados quirúrgicos, conduciendo a la CTC a ser más aceptada por psiquiatras, pacientes y sus familias. Se necesita mayor investigación en varios temas como: fisiopatología de los trastornos del comportamiento, indicaciones de CTC y nuevos blancos quirúrgicos. PMID:25165612

Results of the National CT Colonography Trial: Questions and Answers

Cancer.gov

Learn the results of the National Computerized Tomographic Colonography (CTC) clinical trial, which evaluated how well CTC identifies participants with at least one significantly large polyp using colonoscopy as the gold (or reference) standard.

(2+1)-dimensional spacetimes containing closed timelike curves

NASA Astrophysics Data System (ADS)

Headrick, Matthew P.; Gott, J. Richard, III

1994-12-01

We investigate the global geometries of (2+1)-dimensional spacetimes as characterized by the transformations undergone by tangent spaces upon parallel transport around closed curves. We critically discuss the use of the term ``total energy-momentum'' as a label for such parallel-transport transformations, pointing out several problems with it. We then investigate parallel-transport transformations in the known (2+1)-dimensional spacetimes containing closed timelike curves (CTC's), and introduce a few new such spacetimes. Using the more specific concept of the holonomy of a closed curve, applicable in simply connected spacetimes, we emphasize that Gott's two-particle CTC-containing spacetime does not have a tachyonic geometry. Finally, we prove the following modified version of Kabat's conjecture: if a CTC is deformable to spacelike or null infinity while remaining a CTC, then its parallel-transport transformation cannot be a rotation; therefore its holonomy, if defined, cannot be a rotation other than through a multiple of 2π.

Circulating Tumor Cell Analysis in Preclinical Mouse Models of Metastasis.

PubMed

Kitz, Jenna; Lowes, Lori E; Goodale, David; Allan, Alison L

2018-04-28

The majority of cancer deaths occur because of metastasis since current therapies are largely non-curative in the metastatic setting. The use of in vivo preclinical mouse models for assessing metastasis is, therefore, critical for developing effective new cancer biomarkers and therapies. Although a number of quantitative tools have been previously developed to study in vivo metastasis, the detection and quantification of rare metastatic events has remained challenging. This review will discuss the use of circulating tumor cell (CTC) analysis as an effective means of tracking and characterizing metastatic disease progression in preclinical mouse models of breast and prostate cancer and the resulting lessons learned about CTC and metastasis biology. We will also discuss how the use of clinically-relevant CTC technologies such as the CellSearch ® and Parsortix™ platforms for preclinical CTC studies can serve to enhance the study of cancer biology, new biomarkers, and novel therapies from the bench to the bedside.

Fiber-Optic Array Scanning Technology (FAST) for Detection and Molecular Characterization of Circulating Tumor Cells.

PubMed

Ao, Zheng; Liu, Xiaohe

2017-01-01

Circulating tumor cell (CTC) as an important component in "liquid biopsy" holds crucial clinical relevance in cancer prognosis, treatment efficiency evaluation, prediction and potentially early detection. Here, we present a Fiber-optic Array Scanning Technology (FAST) that enables antigen-agnostic, size-agnostic detection of CTC. By immunofluorescence staining detection of a combination of a panel of markers, FAST technology can be applied to detect rare CTC in non-small cell lung cancer (NSCLC) setting with high sensitivity and specificity. In combination with Automated Digital Microscopy (ADM) platform, companion markers on CTC such as Vimentin and Programmed death-ligand 1 (PD-L1) can also be analyzed to further characterize these CTCs. FAST data output is also compatible with downstream single cell picking platforms. Single cell can be isolated post ADM confirmation and used for "actionable" genetic mutations analysis.

A hybrid joint based controller for an upper extremity exoskeleton

NASA Astrophysics Data System (ADS)

Mohd Khairuddin, Ismail; Taha, Zahari; Majeed, Anwar P. P. Abdul; Hakeem Deboucha, Abdel; Azraai Mohd Razman, Mohd; Aziz Jaafar, Abdul; Mohamed, Zulkifli

2016-02-01

This paper presents the modelling and control of a two degree of freedom upper extremity exoskeleton. The Euler-Lagrange formulation was used in deriving the dynamic modelling of both the human upper limb as well as the exoskeleton that consists of the upper arm and the forearm. The human model is based on anthropometrical measurements of the upper limb. The proportional-derivative (PD) computed torque control (CTC) architecture is employed in this study to investigate its efficacy performing joint-space control objectives specifically in rehabilitating the elbow and shoulder joints along the sagittal plane. An active force control (AFC) algorithm is also incorporated into the PD-CTC to investigate the effectiveness of this hybrid system in compensating disturbances. It was found that the AFC- PD-CTC performs well against the disturbances introduced into the system whilst achieving acceptable trajectory tracking as compared to the conventional PD-CTC control architecture.

Acute oral mucositis in nasopharyngeal carcinoma patients treated with radiotherapy: association with genetic polymorphism in DNA DSB repair genes.

PubMed

Ren, Jing-Hua; Dai, Xiao-Fang; Yan, Guo-Li; Jin, Min; Liu, Cui-Wei; Yang, Kun-Yu; Wu, Gang; Ma, C-M Charlie

2014-03-01

The aim of this study was to investigate the association between polymorphic variants of DNA repair genes with the susceptibility of acute oral mucositis (OM) in nasopharyngeal carcinoma (NPC) patients treated with radiotherapy. The study population consisted of 120 NPC patients treated with intensity-modulated radiation therapy (IMRT). Among them 70 patients also received concurrent chemotherapy. Genotypes in DNA repair genes Ku70 c.-1310C>G (rs2267437), Ku70 c.1781G> T (rs132788), Ku80 c.2099-2408G> A (rs3835), Ku80 c.*841G> A (rs2440) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) c.2888 + 713C> T (rs2213178) were determined by polymerase chain reaction combined with the restriction fragment length polymorphism (PCR-RFLP) technique. Mucositis was scored using the Common Terminology Criteria (CTC) for Adverse Events v.3.0 scale. The population was divided into the CTC0-2 group (CTC toxicity grade 0, 1 and 2) and the CTC3 + group (CTC toxicity grade 3 and above). Odd ratios (OR) and 95% confidence intervals (CI) were calculated using the multivariate logistic regression analysis. A significant difference in Ku70 c.1781G> T genotype distribution was observed between the CTC0-2 and CTC3 + groups for the 120 patients analyzed. The GG carriers were at higher risks for severe OM (CTC3+) compared with the TT homozygotes (OR = 3.000, 95% CI = 1.287-6.994, p = 0.011). No association was found between Ku70 (c.-1310C> G), Ku80 (c.2099-2408G> A, c.*841G> A), DNA-PKcs (c.2888 + 713 C > T) and the development of severe oral mucositis. Stratification analyses for the 50 patients treated with radiation alone further confirmed the association between the variant genotype of GG and severe OM (OR = 5.128, 95% CI = 1.183-22.238, p = 0.029). Concurrent radiochemotherapy increased the risk of severe OM for both the TT homozygotes and GG genotypes. Our study suggests that the Ku70 c.1781G> T polymorphism may be a susceptibility factor for radiation-induced oral mucositis in Chinese nasopharyngeal carcinoma patients.

Co-crystal of Tramadol-Celecoxib in Patients with Moderate to Severe Acute Post-surgical Oral Pain: A Dose-Finding, Randomised, Double-Blind, Placebo- and Active-Controlled, Multicentre, Phase II Trial.

PubMed

López-Cedrún, José; Videla, Sebastián; Burgueño, Miguel; Juárez, Inma; Aboul-Hosn, Samir; Martín-Granizo, Rafael; Grau, Joan; Puche, Miguel; Gil-Diez, José-Luis; Hueto, José-Antonio; Vaqué, Anna; Sust, Mariano; Plata-Salamán, Carlos; Monner, Antoni

2018-06-01

Co-crystal of tramadol-celecoxib (CTC), containing equimolar quantities of the active pharmaceutical ingredients (APIs) tramadol and celecoxib (100 mg CTC = 44 mg rac-tramadol hydrochloride and 56 mg celecoxib), is a novel API-API co-crystal for the treatment of pain. We aimed to establish the effective dose of CTC for treating acute pain following oral surgery. A dose-finding, double-blind, randomised, placebo- and active-controlled, multicentre (nine Spanish hospitals), phase II study (EudraCT number: 2011-002778-21) was performed in male and female patients aged ≥ 18 years experiencing moderate to severe pain following extraction of two or more impacted third molars requiring bone removal. Eligible patients were randomised via a computer-generated list to receive one of six single-dose treatments (CTC 50, 100, 150, 200 mg; tramadol 100 mg; and placebo). The primary efficacy endpoint was the sum of pain intensity difference (SPID) over 8 h assessed in the per-protocol population. Between 10 February 2012 and 13 February 2013, 334 patients were randomised and received study treatment: 50 mg (n = 55), 100 mg (n = 53), 150 mg (n = 57), or 200 mg (n = 57) of CTC, 100 mg tramadol (n = 58), or placebo (n = 54). CTC 100, 150, and 200 mg showed significantly higher efficacy compared with placebo and/or tramadol in all measures: SPID (0-8 h) (mean [standard deviation]): - 90 (234), - 139 (227), - 173 (224), 71 (213), and 22 (228), respectively. The proportion of patients experiencing treatment-emergent adverse events was lower in the 50 (12.7% [n = 7]), 100 (11.3% [n = 6]), and 150 (15.8% [n = 9]) mg CTC groups, and similar in the 200 mg (29.8% [n = 17]) CTC group, compared with the tramadol group (29.3% [n = 17]), with nausea, dizziness, and vomiting the most frequent events. Significant improvement in the benefit-risk ratio was observed for CTC (doses ≥ 100 mg) over tramadol and placebo in the treatment of acute pain following oral surgery. Laboratorios del Dr. Esteve, S.A.U.

A novel biochar derived from cauliflower (Brassica oleracea L.) roots could remove norfloxacin and chlortetracycline efficiently.

PubMed

Qin, Tingting; Wang, Zhaowei; Xie, Xiaoyun; Xie, Chaoran; Zhu, Junmin; Li, Yan

2017-12-01

The biochar was prepared by pyrolyzing the roots of cauliflowers, at a temperature of 500 °C under oxygen-limited conditions. The structure and characteristics of the biochar were examined using scanning electron microscopy, an energy dispersive spectrometer, a zeta potential analyzer, and Fourier transform infrared spectroscopy. The effects of the temperature, the initial pH, antibiotic concentration, and contact time on the adsorption of norfloxacin (NOR) and chlortetracycline (CTC) onto the biochar were investigated. The adsorption kinetics of NOR and CTC onto the biochar followed the pseudo-second-order kinetic and intra-particle diffusion models. The adsorption isotherm experimental data were well fitted to the Langmuir and Freundlich isotherm models. The maximum adsorption capacities of NOR and CTC were 31.15 and 81.30 mg/g, respectively. There was little difference between the effects of initial solution pH (4.0-10.0) on the adsorption of NOR or CTC onto the biochar because of the buffering effect. The biochar could remove NOR and CTC efficiently in aqueous solutions because of its large specific surface area, abundant surface functional groups, and particular porous structure. Therefore, it could be used as an excellent adsorbent material because of its low cost and high efficiency and the extensive availability of the raw materials.

Fourier Ptychographic Microscopy for Rapid, High-Resolution Imaging of Circulating Tumor Cells Enriched by Microfiltration.

PubMed

Williams, Anthony; Chung, Jaebum; Yang, Changhuei; Cote, Richard J

2017-01-01

Examining the hematogenous compartment for evidence of metastasis has increased significantly within the oncology research community in recent years, due to the development of technologies aimed at the enrichment of circulating tumor cells (CTCs), the subpopulation of primary tumor cells that gain access to the circulatory system and are responsible for colonization at distant sites. In contrast to other technologies, filtration-based CTC enrichment, which exploits differences in size between larger tumor cells and surrounding smaller, non-tumor blood cells, has the potential to improve CTC characterization through isolation of tumor cell populations with greater molecular heterogeneity. However, microscopic analysis of uneven filtration surfaces containing CTCs is laborious, time-consuming, and inconsistent, preventing widespread use of filtration-based enrichment technologies. Here, integrated with a microfiltration-based CTC and rare cell enrichment device we have previously described, we present a protocol for Fourier Ptychographic Microscopy (FPM), a method that, unlike many automated imaging platforms, produces high-speed, high-resolution images that can be digitally refocused, allowing users to observe objects of interest present on multiple focal planes within the same image frame. The development of a cost-effective and high-throughput CTC analysis system for filtration-based enrichment technologies could have profound clinical implications for improved CTC detection and analysis.

Chlortetracycline detoxification in maize via induction of glutathione S-transferases after antibiotic exposure.

PubMed

Farkas, Michael H; Berry, James O; Aga, Diana S

2007-02-15

Soil contamination with nonmetabolized antibiotics is an emerging environmental concern, especially on agricultural croplands that receive animal manure as fertilizer. In this study, phytotoxicity of chlortetracycline (CTC) antibiotics on pinto beans (Phaseolus vulgaris) and maize (Zea mays) was investigated under controlled conditions. When grown in CTC-treated soil, a significant increase in the activities of the plant stress proteins glutathione S-transferases (GST) and peroxidases (POX) were observed in maize plants, but not in pinto beans. In vitro conjugation reactions demonstrated that the induced GST in maize catalyzed the conjugation of glutathione (GSH) with CTC, producing stable conjugates that were structurally characterized using liquid chromatography/mass spectrometry. The antibiotic-induced GST produced CTC-glutathione conjugate at relative concentrations 2-fold higher than that produced by constitutively expressed GST extracted from untreated maize. On the other hand, GST extracted from pinto beans (both treated and untreated) did not efficiently catalyze glutathione conjugation with CTC. These results suggest that maize is able to detoxify chlortetracycline via the glutathione pathway, whereas pinto beans cannot. This may explain the observed stunted growth of pinto beans after antibiotic treatment. This study demonstrates the importance of plant uptake in determining the fate of antibiotics in soil and their potential phytotoxicity to susceptible plants.

An integrated microfluidic chip system for single-cell secretion profiling of rare circulating tumor cells.

PubMed

Deng, Yuliang; Zhang, Yu; Sun, Shuai; Wang, Zhihua; Wang, Minjiao; Yu, Beiqin; Czajkowsky, Daniel M; Liu, Bingya; Li, Yan; Wei, Wei; Shi, Qihui

2014-12-16

Genetic and transcriptional profiling, as well as surface marker identification of single circulating tumor cells (CTCs) have been demonstrated. However, quantitatively profiling of functional proteins at single CTC resolution has not yet been achieved, owing to the limited purity of the isolated CTC populations and a lack of single-cell proteomic approaches to handle and analyze rare CTCs. Here, we develop an integrated microfluidic system specifically designed for streamlining isolation, purification and single-cell secretomic profiling of CTCs from whole blood. Key to this platform is the use of photocleavable ssDNA-encoded antibody conjugates to enable a highly purified CTC population with <75 'contaminated' blood cells. An enhanced poly-L-lysine barcode pattern is created on the single-cell barcode chip for efficient capture rare CTC cells in microchambers for subsequent secreted protein profiling. This system was extensively evaluated and optimized with EpCAM-positive HCT116 cells seeded into whole blood. Patient blood samples were employed to assess the utility of the system for isolation, purification and single-cell secretion profiling of CTCs. The CTCs present in patient blood samples exhibit highly heterogeneous secretion profile of IL-8 and VEGF. The numbers of secreting CTCs are found not in accordance with CTC enumeration based on immunostaining in the parallel experiments.

Long-Term Effects of the Communities That Care Trial on Substance Use, Antisocial Behavior, and Violence Through Age 21 Years.

PubMed

Oesterle, Sabrina; Kuklinski, Margaret R; Hawkins, J David; Skinner, Martie L; Guttmannova, Katarina; Rhew, Isaac C

2018-05-01

To evaluate whether the effects of the Communities That Care (CTC) prevention system, implemented in early adolescence to promote positive youth development and reduce health-risking behavior, endured through age 21 years. We analyzed 9 waves of prospective data collected between 2004 and 2014 from a panel of 4407 participants (grade 5 through age 21 years) in the community-randomized trial of the CTC system in Colorado, Illinois, Kansas, Maine, Oregon, Utah, and Washington State. We used multilevel models to evaluate intervention effects on sustained abstinence, lifetime incidence, and prevalence of past-year substance use, antisocial behavior, and violence. The CTC system increased the likelihood of sustained abstinence from gateway drug use by 49% and antisocial behavior by 18%, and reduced lifetime incidence of violence by 11% through age 21 years. In male participants, the CTC system also increased the likelihood of sustained abstinence from tobacco use by 30% and marijuana use by 24%, and reduced lifetime incidence of inhalant use by 18%. No intervention effects were found on past-year prevalence of these behaviors. Implementation of the CTC prevention system in adolescence reduced lifetime incidence of health-risking behaviors into young adulthood. Clinicaltrials.gov identifier: NCT01088542.

An Integrated Microfluidic Chip System for Single-Cell Secretion Profiling of Rare Circulating Tumor Cells

PubMed Central

Deng, Yuliang; Zhang, Yu; Sun, Shuai; Wang, Zhihua; Wang, Minjiao; Yu, Beiqin; Czajkowsky, Daniel M.; Liu, Bingya; Li, Yan; Wei, Wei; Shi, Qihui

2014-01-01

Genetic and transcriptional profiling, as well as surface marker identification of single circulating tumor cells (CTCs) have been demonstrated. However, quantitatively profiling of functional proteins at single CTC resolution has not yet been achieved, owing to the limited purity of the isolated CTC populations and a lack of single-cell proteomic approaches to handle and analyze rare CTCs. Here, we develop an integrated microfluidic system specifically designed for streamlining isolation, purification and single-cell secretomic profiling of CTCs from whole blood. Key to this platform is the use of photocleavable ssDNA-encoded antibody conjugates to enable a highly purified CTC population with <75 ‘contaminated' blood cells. An enhanced poly-L-lysine barcode pattern is created on the single-cell barcode chip for efficient capture rare CTC cells in microchambers for subsequent secreted protein profiling. This system was extensively evaluated and optimized with EpCAM-positive HCT116 cells seeded into whole blood. Patient blood samples were employed to assess the utility of the system for isolation, purification and single-cell secretion profiling of CTCs. The CTCs present in patient blood samples exhibit highly heterogeneous secretion profile of IL-8 and VEGF. The numbers of secreting CTCs are found not in accordance with CTC enumeration based on immunostaining in the parallel experiments. PMID:25511131

A new fractional order derivative based active contour model for colon wall segmentation

NASA Astrophysics Data System (ADS)

Chen, Bo; Li, Lihong C.; Wang, Huafeng; Wei, Xinzhou; Huang, Shan; Chen, Wensheng; Liang, Zhengrong

2018-02-01

Segmentation of colon wall plays an important role in advancing computed tomographic colonography (CTC) toward a screening modality. Due to the low contrast of CT attenuation around colon wall, accurate segmentation of the boundary of both inner and outer wall is very challenging. In this paper, based on the geodesic active contour model, we develop a new model for colon wall segmentation. First, tagged materials in CTC images were automatically removed via a partial volume (PV) based electronic colon cleansing (ECC) strategy. We then present a new fractional order derivative based active contour model to segment the volumetric colon wall from the cleansed CTC images. In this model, the regionbased Chan-Vese model is incorporated as an energy term to the whole model so that not only edge/gradient information but also region/volume information is taken into account in the segmentation process. Furthermore, a fractional order differentiation derivative energy term is also developed in the new model to preserve the low frequency information and improve the noise immunity of the new segmentation model. The proposed colon wall segmentation approach was validated on 16 patient CTC scans. Experimental results indicate that the present scheme is very promising towards automatically segmenting colon wall, thus facilitating computer aided detection of initial colonic polyp candidates via CTC.

An integrated microfluidic platform for negative selection and enrichment of cancer cells

NASA Astrophysics Data System (ADS)

Luo, Wen-Yi; Tsai, Sung-Chi; Hsieh, Kuangwen; Lee, Gwo-Bin

2015-08-01

Circulating tumor cells (CTCs), tumor cells that disseminate from primary tumors to the bloodstream, have recently emerged as promising indicators for cancer diagnosis and prognosis. However, the technical difficulties in isolating and detecting rare CTCs have limited the widespread applicability of this method to date. In this work, a new integrated microfluidic system integrating micromixers and micropumps capable of performing ‘negative selection and enrichment’ of CTCs was developed. By using anti-human CD45 antibodies-coated magnetic beads, leukocytes were effectively removed by applying an external magnetic force, leaving behind an enriched target cell population. The on-chip CTC recovery rate was experimentally found to be 70   ±   5% after a single round of negative selection and enrichment. Meanwhile, CD45 depletion efficiency was 83.99   ±   1.00% and could be improved to 99.84   ±   0.04% after three consecutive rounds of depletion. Notably, on-chip negative selection and enrichment was 58% faster and the repeated depletion could be processed automatically. These promising results suggested the developed microfluidic chip is potentiated for a standardized CTC isolation platform. Preliminary results of the current paper were presented at Micro TAS 2014, San Antonio, Texas, USA, October 26-30, 2014.

COMPARISON OF RAPID METHODS TO EVALUATE CHLORINE INACTIVATION OF THE BIOLOGICAL AGENT E. COLI 0157:H7

EPA Science Inventory

Rapid viability tests of the Catagory B agent Escherichia coli O157:H7 were evaluated after disinfection with chlorine. The metabolic activity dyes ChemChrome V6, a modified fluorescein diacetate (FDA) and 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) were compared to standard ...

Mutations in CTC1, Encoding the CTS Telomere Maintenance Complex Component 1, Cause Cerebroretinal Microangiopathy with Calcifications and Cysts

PubMed Central

Polvi, Anne; Linnankivi, Tarja; Kivelä, Tero; Herva, Riitta; Keating, James P.; Mäkitie, Outi; Pareyson, Davide; Vainionpää, Leena; Lahtinen, Jenni; Hovatta, Iiris; Pihko, Helena; Lehesjoki, Anna-Elina

2012-01-01

Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) is a rare multisystem disorder characterized by extensive intracranial calcifications and cysts, leukoencephalopathy, and retinal vascular abnormalities. Additional features include poor growth, skeletal and hematological abnormalities, and recurrent gastrointestinal bleedings. Autosomal-recessive inheritance has been postulated. The pathogenesis of CRMCC is unknown, but its phenotype has key similarities with Revesz syndrome, which is caused by mutations in TINF2, a gene encoding a member of the telomere protecting shelterin complex. After a whole-exome sequencing approach in four unrelated individuals with CRMCC, we observed four recessively inherited compound heterozygous mutations in CTC1, which encodes the CTS telomere maintenance complex component 1. Sanger sequencing revealed seven more compound heterozygous mutations in eight more unrelated affected individuals. Two individuals who displayed late-onset cerebral findings, a normal fundus appearance, and no systemic findings did not have CTC1 mutations, implying that systemic findings are an important indication for CTC1 sequencing. Of the 11 mutations identified, four were missense, one was nonsense, two resulted in in-frame amino acid deletions, and four were short frameshift-creating deletions. All but two affected individuals were compound heterozygous for a missense mutation and a frameshift or nonsense mutation. No individuals with two frameshift or nonsense mutations were identified, which implies that severe disturbance of CTC1 function from both alleles might not be compatible with survival. Our preliminary functional experiments did not show evidence of severely affected telomere integrity in the affected individuals. Therefore, determining the underlying pathomechanisms associated with deficient CTC1 function will require further studies. PMID:22387016

Land application of tylosin and chlortetracycline swine manure: Impacts to soil nutrients and soil microbial community structure.

PubMed

Stone, James J; Dreis, Erin K; Lupo, Christopher D; Clay, Sharon A

2011-01-01

The land application of aged chortetracycle (CTC) and tylosin-containing swine manure was investigated to determine associated impacts to soil microbial respiration, nutrient (phosphorus, ammonium, nitrate) cycling, and soil microbial community structure under laboratory conditions. Two silty clay loam soils common to southeastern South Dakota were used. Aerobic soil respiration results using batch reactors containing a soil-manure mixture showed that interactions between soil, native soil microbial populations, and antimicrobials influenced CO(2) generation. The aged tylosin treatment resulted in the greatest degree of CO(2) inhibition, while the aged CTC treatment was similar to the no-antimicrobial treatment. For soil columns in which manure was applied at a one-time agronomic loading rate, there was no significant difference in soil-P behavior between either aged CTC or tylosin and the no-antimicrobial treatment. For soil-nitrogen (ammonium and nitrate), the aged CTC treatment resulted in rapid ammonium accumulation at the deeper 40cm soil column depth, while nitrate production was minimal. The aged CTC treatment microbial community structure was different than the no-antimicrobial treatment, where amines/amide and carbohydrate chemical guilds utilization profile were low. The aged tylosin treatment also resulted in ammonium accumulation at 40 cm column depth, however nitrate accumulation also occurred concurrently at 10 cm. The microbial community structure for the aged tylosin was also significantly different than the no-antimicrobial treatment, with a higher degree of amines/amides and carbohydrate chemical guild utilization compared to the no-antimicrobial treatment. Study results suggest that land application of CTC and tylosin-containing manure appears to fundamentally change microbial-mediated nitrogen behavior within soil A horizons.

Oxidation of tetracycline antibiotics induced by Fe(III) ions without light irradiation.

PubMed

Wang, Hui; Yao, Hong; Sun, Peizhe; Pei, Jin; Li, Desheng; Huang, Ching-Hua

2015-01-01

The presence of Fe(III) ions was found to induce degradation of three tetracycline antibiotics (TCs), tetracycline (TTC), oxytetracycline (OTC) and chlorotetracycline (CTC), in aqueous solutions without light. The presence of Fe(III) promoted the degradation of TCs in most experimental pH (5.0, 7.0 and 9.0) except at pH 9.0 for CTC. Degradation rate constants of TTC, OTC and CTC reached maximum ((6.2±0.5)×10(-3) h(-1), (10.6±0.1)×10(-3) h(-1) and (15.9±0.5)×10(-3) h(-1) at pH 7.0, 20 °C) when Fe(III):TC molar ratio was 1:1, 1:1 and 2:1, respectively. Such metal-to-ligand ratios agreed well with the most favorable complexation between Fe(III) and each TC. Compared to without metals, Fe(III) enhanced the degradation rate of TTC, OTC and CTC by up to 20.67, 7.07 and 2.30 times, respectively, in clean water matrix, and also promoted degradation of TCs in real surface water and wastewater matrices. The promoted degradation likely occurred via complexation of TCs and subsequent oxidation by Fe(III). Degradation results of CTC versus 4-epi-CTC suggested Fe(III) likely binds to TCs' C4 dimethylamino group. Toxicity of the complexes evaluated using Photobacterium phosphoreum T3 was increased after several hours of reaction, suggesting the transformation products may exert a stronger toxicity than parent TCs. This study identifies new oxidative transformation of TCs induced by Fe(III) ions without light irradiation, further supporting the important role of iron species in the environmental fate of TCs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cultural, Transcriptomic, and Proteomic Analyses of Water-Stressed Cells of Actinobacterial Strains Isolated from Compost: Ecological Implications in the Fed-Batch Composting Process.

PubMed

Narihiro, Takashi; Kanosue, Yuji; Hiraishi, Akira

2016-06-25

This study was undertaken to examine the effects of water activity (aw) on the viability of actinobacterial isolates from a fed-batch composting (FBC) process by comparing culturability and stainability with 5-cyano-2,3-ditoryl tetrazolium chloride (CTC). The FBC reactor as the source of these bacteria was operated with the daily loading of household biowaste for 70 d. During this period of composting, aw in the reactor decreased linearly with time and reached approximately 0.95 at the end of operation. The plate counts of aerobic chemoorganotrophic bacteria were 3.2-fold higher than CTC-positive (CTC+) counts on average at the fully acclimated stage (after 7 weeks of operation), in which Actinobacteria predominated, as shown by lipoquinone profiling and cultivation methods. When the actinobacterial isolates from the FBC process were grown under aw stress, no significant differences were observed in culturability among the cultures, whereas CTC stainability decreased with reductions in aw levels. A cDNA microarray-based transcriptomic analysis of a representative isolate showed that many of the genes involved in cellular metabolism and genetic information processing were down-regulated by aw stress. This result was fully supported by a proteomic analysis. The results of the present study suggest that, in low aw mature compost, the metabolic activity of the community with Actinobacteria predominating is temporarily reduced to a level that hardly reacts with CTC; however, these bacteria are easily recoverable by exposure to a high aw culture medium. This may be a plausible reason why acclimated FBC reactors in which Actinobacteria predominate yields higher plate counts than CTC+ counts.

Quantum interactions with closed timelike curves and superluminal signaling

NASA Astrophysics Data System (ADS)

Bub, Jeffrey; Stairs, Allen

2014-02-01

There is now a significant body of results on quantum interactions with closed timelike curves (CTCs) in the quantum information literature, for both the Deutsch model of CTC interactions (D-CTCs) and the projective model (P-CTCs). As a consequence, there is a prima facie argument exploiting entanglement that CTC interactions would enable superluminal and, indeed, effectively instantaneous signaling. In cases of spacelike separation between the sender of a signal and the receiver, whether a receiver measures the local part of an entangled state or a disentangled state to access the signal can depend on the reference frame. We propose a consistency condition that gives priority to either an entangled perspective or a disentangled perspective in spacelike-separated scenarios. For D-CTC interactions, the consistency condition gives priority to frames of reference in which the state is disentangled, while for P-CTC interactions the condition selects the entangled state. Using the consistency condition, we show that there is a procedure that allows Alice to signal to Bob in the past via relayed superluminal communications between spacelike-separated Alice and Clio, and spacelike-separated Clio and Bob. This opens the door to time travel paradoxes in the classical domain. Ralph [T. C. Ralph, arXiv:1107.4675 [quant-ph].] first pointed this out for P-CTCs, but we show that Ralph's procedure for a "radio to the past" is flawed. Since both D-CTCs and P-CTCs allow classical information to be sent around a spacetime loop, it follows from a result by Aaronson and Watrous [S. Aaronson and J. Watrous, Proc. R. Soc. A 465, 631 (2009), 10.1098/rspa.2008.0350] for CTC-enhanced classical computation that a quantum computer with access to P-CTCs would have the power of PSPACE, equivalent to a D-CTC-enhanced quantum computer.

Activity and Phylogenetic Diversity of Bacterial Cells with High and Low Nucleic Acid Content and Electron Transport System Activity in an Upwelling Ecosystem

PubMed Central

Longnecker, K.; Sherr, B. F.; Sherr, E. B.

2005-01-01

We evaluated whether bacteria with higher cell-specific nucleic acid content (HNA) or an active electron transport system, i.e., positive for reduction of 5-cyano-2,3-ditolyl tetrazolium chloride (CTC), were responsible for the bulk of bacterioplankton metabolic activity. We also examined whether the phylogenetic diversity of HNA and CTC-positive cells differed from the diversity of Bacteria with low nucleic acid content (LNA). Bacterial assemblages were sampled both in eutrophic shelf waters and in mesotrophic offshore waters in the Oregon coastal upwelling region. Cytometrically sorted HNA, LNA, and CTC-positive cells were assayed for their cell-specific [3H]leucine incorporation rates. Phylogenetic diversity in sorted non-radioactively labeled samples was assayed using denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA genes. Cell-specific rates of leucine incorporation of HNA and CTC-positive cells were on average only slightly greater than the cell-specific rates of LNA cells. HNA cells accounted for most bacterioplankton substrate incorporation due to high abundances, while the low abundances of CTC-positive cells resulted in only a small contribution by these cells to total bacterial activity. The proportion of the total bacterial leucine incorporation attributable to LNA cells was higher in offshore regions than in shelf waters. Sequence data obtained from DGGE bands showed broadly similar phylogenetic diversity across HNA, LNA, and CTC-positive cells, with between-sample and between-region variability in the distribution of phylotypes. Our results suggest that LNA bacteria are not substantially different from HNA bacteria in either cell-specific rates of substrate incorporation or phylogenetic composition and that they can be significant contributors to bacterial metabolism in the sea. PMID:16332746

Activity and phylogenetic diversity of bacterial cells with high and low nucleic acid content and electron transport system activity in an upwelling ecosystem.

PubMed

Longnecker, K; Sherr, B F; Sherr, E B

2005-12-01

We evaluated whether bacteria with higher cell-specific nucleic acid content (HNA) or an active electron transport system, i.e., positive for reduction of 5-cyano-2,3-ditolyl tetrazolium chloride (CTC), were responsible for the bulk of bacterioplankton metabolic activity. We also examined whether the phylogenetic diversity of HNA and CTC-positive cells differed from the diversity of Bacteria with low nucleic acid content (LNA). Bacterial assemblages were sampled both in eutrophic shelf waters and in mesotrophic offshore waters in the Oregon coastal upwelling region. Cytometrically sorted HNA, LNA, and CTC-positive cells were assayed for their cell-specific [3H]leucine incorporation rates. Phylogenetic diversity in sorted non-radioactively labeled samples was assayed using denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA genes. Cell-specific rates of leucine incorporation of HNA and CTC-positive cells were on average only slightly greater than the cell-specific rates of LNA cells. HNA cells accounted for most bacterioplankton substrate incorporation due to high abundances, while the low abundances of CTC-positive cells resulted in only a small contribution by these cells to total bacterial activity. The proportion of the total bacterial leucine incorporation attributable to LNA cells was higher in offshore regions than in shelf waters. Sequence data obtained from DGGE bands showed broadly similar phylogenetic diversity across HNA, LNA, and CTC-positive cells, with between-sample and between-region variability in the distribution of phylotypes. Our results suggest that LNA bacteria are not substantially different from HNA bacteria in either cell-specific rates of substrate incorporation or phylogenetic composition and that they can be significant contributors to bacterial metabolism in the sea.

Alteration of the ileal microbiota of weanling piglets by the growth-promoting antibiotic chlortetracycline.

PubMed

Rettedal, Elizabeth; Vilain, Sébastien; Lindblom, Stacy; Lehnert, Kelly; Scofield, Clay; George, Sajan; Clay, Sharon; Kaushik, Radhey S; Rosa, Artur J M; Francis, David; Brözel, Volker S

2009-09-01

Antibiotics such as chlortetracycline (CTC) have been used to promote growth of pigs for decades, but concerns over increased antibiotic-resistant infections in humans have prompted the development of alternative strategies. Developing alternatives to antibiotic growth promoters (AGPs) could be informed by information on the mechanisms of growth promotion, notably, how AGPs affect the microbial populations of the gastrointestinal tract. Pigs from three sows were aseptically delivered by cesarean section. Six piglets were distributed to each of two foster mothers until weaning, when piglets were fed a diet with or without 50 mg/kg CTC for 2 weeks. The ileal bacterial microbiota was characterized by using a cultivation-independent approach based on DNA extraction, PCR amplification, cloning, and sequencing of the 16S rRNA gene pool. The ileal and mucosal communities of these growing pigs were dominated by Lactobacillus bacteria, various members of the family Clostridiaceae, and members of the poorly known genus Turicibacter. Overall, CTC treatment resulted in three shifts: a decrease in Lactobacillus johnsonii, an increase in L. amylovorus, and a decrease in Turicibacter phylotypes. The composition of the microbiota varied considerably between individual pigs, as revealed by shared operational taxonomic units (OTUs) and similarity (SONS) analysis (theta(YC) values). While the observed variation between untreated pigs obscured the possible effect of CTC, integral-LIBSHUFF and SONS analyses of pooled libraries indicated a significant shift due to CTC in both the lumen and the mucosa, with some OTUs unique to either treated or control ileum. DOTUR analysis revealed little overlap between control and treated communities at the 3% difference level, indicating unique ileal communities in the presence of CTC.

Detection of circulating tumour cells may add value in endometrial cancer management.

PubMed

Ni, T; Sun, X; Shan, B; Wang, J; Liu, Y; Gu, S-L; Wang, Y-D

2016-12-01

To evaluate the role of circulating tumour cells (CTCs) in patients with endometrial cancer (EC). This study included 40 patients with a pre-operative diagnosis of high-risk EC between April 2015 and May 2016. Patients were further divided into high-risk (grade 3, non-endometrioid, myometrial invasion ≥1/2 and stage III-IV) and high-intermediate-risk (grade 2-3, endometrioid, myometrial invasion <1/2 and stage I-II) groups according to postoperative pathological results. CTCs were detected using the CellSearch system, and CTC results were correlated with standard clinicopathological characteristics and serum tumour marker CA125/HE4 status using Chi-squared test, continuity correction or Fisher's exact test. The pharmacodynamic effect was detected after the first cycle of adjuvant therapy. Patients were followed up for 13 months to assess outcomes. Fifteen percent of patients had one or more CTCs. The presence of CTCs was found to be significantly associated with cervical involvement (83.33% vs 11.76%, p=0.00). No significant difference in CTC-positive rates was detected between the high-risk and high-intermediate-risk groups, and no significant correlation was found between CTCs and serum CA125/HE4, either by positive rates or exact serum levels of the conventional tumour markers. No more CTCs were detected after the first cycle of standard chemotherapy in this study, and no distant metastases or recurrence were found in the CTC-positive patients during the follow-up period. The presence of CTCs was correlated with cervical involvement. Early-stage EC patients with CTCs may benefit from additional adjuvant therapies. Assessment of CTCs may be useful in the management of high-risk EC patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

Liu, Jianfei; Wang, Shijun; Turkbey, Evrim B.

Purpose: Renal calculi are common extracolonic incidental findings on computed tomographic colonography (CTC). This work aims to develop a fully automated computer-aided diagnosis system to accurately detect renal calculi on CTC images. Methods: The authors developed a total variation (TV) flow method to reduce image noise within the kidneys while maintaining the characteristic appearance of renal calculi. Maximally stable extremal region (MSER) features were then calculated to robustly identify calculi candidates. Finally, the authors computed texture and shape features that were imported to support vector machines for calculus classification. The method was validated on a dataset of 192 patients andmore » compared to a baseline approach that detects calculi by thresholding. The authors also compared their method with the detection approaches using anisotropic diffusion and nonsmoothing. Results: At a false positive rate of 8 per patient, the sensitivities of the new method and the baseline thresholding approach were 69% and 35% (p < 1e − 3) on all calculi from 1 to 433 mm{sup 3} in the testing dataset. The sensitivities of the detection methods using anisotropic diffusion and nonsmoothing were 36% and 0%, respectively. The sensitivity of the new method increased to 90% if only larger and more clinically relevant calculi were considered. Conclusions: Experimental results demonstrated that TV-flow and MSER features are efficient means to robustly and accurately detect renal calculi on low-dose, high noise CTC images. Thus, the proposed method can potentially improve diagnosis.« less

Circulating tumor cells: silent predictors of metastasis

PubMed Central

Zhou, LanLan; Dicker, David T.; Matthew, Elizabeth; El-Deiry, Wafik S.; Alpaugh, R. Katherine

2017-01-01

Circulating tumor cells (CTCs) were added to the arsenal of clinical testing in 2004 for three cancer types: metastatic breast, prostate, and colorectal cancer. CTCs were found to be an independent prognostic indicator of survival for these three diseases. Multiple enrichment/isolation strategies have been developed and numerous assay applications have been performed using both single and pooled captured/enriched CTCs. We have reviewed the isolation techniques and touched on many analyses. The true utility of a CTC is that it acts as a “silent” predictor of metastatic disease. The mere presence of a single CTC is an indication that disease has spread from the primary site. Comments and suggestions have been set forth for CTCs and cell-free DNA to be used as a screening panel for the early detection of disease recurrence and metastatic spread, providing the opportunity for early intervention with curative intent to treat metastatic disease. PMID:28868131

Defining NADH-Driven Allostery Regulating Apoptosis-Inducing Factor

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

Brosey, Chris A.; Ho, Chris; Long, Winnie Z.

Apoptosis-inducing factor (AIF) is critical for mitochondrial respiratory complex biogenesis and for mediating necroptotic parthanatos; these functions are seemingly regulated by enigmatic allosteric switching driven by NADH charge-transfer complex (CTC) formation. In this paper, we define molecular pathways linking AIF's active site to allosteric switching regions by characterizing dimer-permissive mutants using small-angle X-ray scattering (SAXS) and crystallography and by probing AIF-CTC communication networks using molecular dynamics simulations. Collective results identify two pathways propagating allostery from the CTC active site: (1) active-site H454 links to S480 of AIF's central β-strand to modulate a hydrophobic border at the dimerization interface, and (2)more » an interaction network links AIF's FAD cofactor, central β-strand, and Cβ-clasp whereby R529 reorientation initiates C-loop release during CTC formation. Finally, this knowledge of AIF allostery and its flavoswitch mechanism provides a foundation for biologically understanding and biomedically controlling its participation in mitochondrial homeostasis and cell death.« less

Microfluidic, marker-free isolation of circulating tumor cells from blood samples

PubMed Central

Karabacak, Nezihi Murat; Spuhler, Philipp S; Fachin, Fabio; Lim, Eugene J; Pai, Vincent; Ozkumur, Emre; Martel, Joseph M; Kojic, Nikola; Smith, Kyle; Chen, Pin-i; Yang, Jennifer; Hwang, Henry; Morgan, Bailey; Trautwein, Julie; Barber, Thomas A; Stott, Shannon L; Maheswaran, Shyamala; Kapur, Ravi; Haber, Daniel A; Toner, Mehmet

2014-01-01

The ability to isolate and analyze rare circulating tumor cells (CTCs) has the potential to further our understanding of cancer metastasis and enhance the care of cancer patients. In this protocol, we describe the procedure for isolating rare CTCs from blood samples by using tumor antigen–independent microfluidic CTC-iChip technology. The CTC-iChip uses deterministic lateral displacement, inertial focusing and magnetophoresis to sort up to 107 cells/s. By using two-stage magnetophoresis and depletion antibodies against leukocytes, we achieve 3.8-log depletion of white blood cells and a 97% yield of rare cells with a sample processing rate of 8 ml of whole blood/h. The CTC-iChip is compatible with standard cytopathological and RNA-based characterization methods. This protocol describes device production, assembly, blood sample preparation, system setup and the CTC isolation process. Sorting 8 ml of blood sample requires 2 h including setup time, and chip production requires 2–5 d. PMID:24577360

Defining NADH-Driven Allostery Regulating Apoptosis-Inducing Factor

DOE PAGES

Brosey, Chris A.; Ho, Chris; Long, Winnie Z.; ...

2016-11-03

Apoptosis-inducing factor (AIF) is critical for mitochondrial respiratory complex biogenesis and for mediating necroptotic parthanatos; these functions are seemingly regulated by enigmatic allosteric switching driven by NADH charge-transfer complex (CTC) formation. In this paper, we define molecular pathways linking AIF's active site to allosteric switching regions by characterizing dimer-permissive mutants using small-angle X-ray scattering (SAXS) and crystallography and by probing AIF-CTC communication networks using molecular dynamics simulations. Collective results identify two pathways propagating allostery from the CTC active site: (1) active-site H454 links to S480 of AIF's central β-strand to modulate a hydrophobic border at the dimerization interface, and (2)more » an interaction network links AIF's FAD cofactor, central β-strand, and Cβ-clasp whereby R529 reorientation initiates C-loop release during CTC formation. Finally, this knowledge of AIF allostery and its flavoswitch mechanism provides a foundation for biologically understanding and biomedically controlling its participation in mitochondrial homeostasis and cell death.« less

Rescreening of persons with a negative colonoscopy result: results from a microsimulation model.

PubMed

Knudsen, Amy B; Hur, Chin; Gazelle, G Scott; Schrag, Deborah; McFarland, Elizabeth G; Kuntz, Karen M

2012-11-06

Persons with a negative result on screening colonoscopy are recommended to repeat the procedure in 10 years. To assess the effectiveness and costs of colonoscopy versus other rescreening strategies after an initial negative colonoscopy result. Microsimulation model. Literature and data from the Surveillance, Epidemiology, and End Results program. Persons aged 50 years who had no adenomas or cancer detected on screening colonoscopy. Lifetime. Societal. No further screening or rescreening starting at age 60 years with colonoscopy every 10 years, annual highly sensitive guaiac fecal occult blood testing (HSFOBT), annual fecal immunochemical testing (FIT), or computed tomographic colonography (CTC) every 5 years. Lifetime cases of colorectal cancer, life expectancy, and lifetime costs per 1000 persons, assuming either perfect or imperfect adherence. Rescreening with any method substantially reduced the risk for colorectal cancer compared with no further screening (range, 7.7 to 12.6 lifetime cases per 1000 persons [perfect adherence] and 17.7 to 20.9 lifetime cases per 1000 persons [imperfect adherence] vs. 31.3 lifetime cases per 1000 persons with no further screening). In both adherence scenarios, the differences in life-years across rescreening strategies were small (range, 30 893 to 30 902 life-years per 1000 persons [perfect adherence] vs. 30 865 to 30 869 life-years per 1000 persons [imperfect adherence]). Rescreening with HSFOBT, FIT, or CTC had fewer complications and was less costly than continuing colonoscopy. Results were sensitive to test-specific adherence rates. Data on adherence to rescreening were limited. Compared with the currently recommended strategy of continuing colonoscopy every 10 years after an initial negative examination, rescreening at age 60 years with annual HSFOBT, annual FIT, or CTC every 5 years provides approximately the same benefit in life-years with fewer complications at a lower cost. Therefore, it is reasonable to use other methods to rescreen persons with negative colonoscopy results. National Cancer Institute.

Assessing Clinical Outcomes in Colorectal Cancer with Assays for Invasive Circulating Tumor Cells.

PubMed

Zhang, Yue; Zarrabi, Kevin; Hou, Wei; Madajewicz, Stefan; Choi, Minsig; Zucker, Stanley; Chen, Wen-Tien

2018-06-06

Colorectal carcinoma (CRC) is the second leading cause of cancer-related mortality. The goals of this study are to evaluate the association between levels of invasive circulating tumor cells (iCTCs) with CRC outcomes and to explore the molecular characteristics of iCTCs. Peripheral blood from 93 patients with Stage I⁻IV CRC was obtained and assessed for the detection and characterization of iCTCs using a functional collagen-based adhesion matrix (CAM) invasion assay. Patients were followed and assessed for overall survival. Tumor cells isolated by CAM were characterized using cell culture and microarray analyses. Of 93 patients, 88 (95%) had detectable iCTCs, ranging over 0⁻470 iCTCs/mL. Patients with Stage I⁻IV disease exhibited median counts of 0.0 iCTCs/mL ( n = 6), 13.0 iCTCs/mL ( n = 12), 41.0 iCTCs/mL ( n = 12), and 133.0 iCTCs/mL ( n = 58), respectively ( p < 0.001). Kaplan⁻Meier curve analysis demonstrated a significant survival benefit in patients with low iCTC counts compared with in patients with high iCTC counts (log-rank p < 0.001). Multivariable Cox model analysis revealed that iCTC count was an independent prognostic factor of overall survival ( p = 0.009). Disease stage ( p = 0.01, hazard ratio 1.66; 95% confidence interval: 1.12⁻2.47) and surgical intervention ( p = 0.03, HR 0.37; 95% CI: 0.15⁻0.92) were also independent prognostic factors. Gene expression analysis demonstrated the expression of both endothelial and tumor progenitor cell biomarkers in iCTCs. CAM-based invasion assay shows a high detection sensitivity of iCTCs that inversely correlated with overall survival in CRC patients. Functional and gene expression analyses showed the phenotypic mosaics of iCTCs, mimicking the survival capability of circulating endothelial cells in the blood stream.

[Impact of Controlled Temperature Chain (CTC) approach on immunization coverage achieved during the preventive vaccination campaign against meningitis A using MenAfriVac in Togo in 2014].

PubMed

Landoh, Dadja Essoya; Kahn, Anna-Léa; Lacle, Anani; Adjeoda, Kodjovi; Saka, Bayaki; Yaya, Issifou; Nassoury, Danladi Ibrahim; Kalao, Assima; Makawa, Makawa-Sy; Biey, Nsiari-Mueyi Joseph; Bita, Andre; Toke, Yaovi Temfa; Dörte, Petit; Imboua, Lucile; Ronveaux, Olivier

2017-01-01

We conducted a survey from 9 to 14 March 2015 (for approximately 3 months) after the end of the vaccination campaign in these four regions. Interviewees were selected using two stages cluster sampling stratified according to the regions. MenAfriVac vaccine in Controlled Temperature Chain (CTC) was used in 10 districts, in Togo. A total of 2707 households were surveyed and 9082 people aged 1-29 years were interviewed. The average age of the individuals surveyed was 11.8±7.7 years and sex-ratio (H/F) was 1.01. The average number of individuals per household was 5.7 and that of persons aged 1-29 years targeted in the campaign was 3.4. Out of 9082 people surveyed 8889 (98%) were vaccinated. Multivariate analysis showed that the factors associated with immunization coverage using MenAfrivac vaccine were: habitual residence in the area at the time of the campaign (AOR = 4.52; 95%CI = [4.07 - 4.97]) and level of information about the campaign before it starts (AOR=2.42; 95%CI = [2.05 - 2.80]). By contrast, there were no differences in vaccination coverage between the areas based on whether the CTC approach was used or not (AOR=0.09; 95%CI = [-0.27 - 0.45]). Two hundred and seven respondents (2.3%) reported that they had Adverse Event Following Immunisation (AEFI) after the administration of the vaccine. These were usually minor AEFI involving fever, abscesses and swelling at the injection site. Survey results show that the use of CTC in a country with limited resources such as Togo doesn't have a negative impact on immunization coverage. Indeed, there was no difference between immunization coverage in CTC and non-CTC areas. It is important to capitalize on the experience gained in order to use vaccines by Expanded Program of Immunization in CTC approach especially in countries with limited resources in terms of cold chain availability.

CT Colonographic Screening of Patients With a Family History of Colorectal Cancer: Comparison With Adults at Average Risk and Implications for Guidelines.

PubMed

Pickhardt, Perry J; Mbah, Ifeanyi; Pooler, B Dustin; Chen, Oliver T; Hinshaw, J Louis; Weiss, Jennifer M; Kim, David H

2017-04-01

The purposes of this study were to compare rates of lesion detection at CT colonographic (CTC) screening of adults without symptoms who had and who did not have a family history of colorectal cancer according to American Cancer Society guidelines and to consider the clinical implications. Over 134 months, consecutively registered CTC cohorts of adults without symptoms who had (n = 156; 88 [56.4%] women; 68 [43.6%] men; mean age, 56.3 years) and who did not have (n = 8857; 4757 [53.7%] women; 4100 [46.3%] men; mean age, 56.6 years) an American Cancer Society-defined family history of colorectal cancer (first-degree relative with diagnosis before age 60 years or two first-degree relatives with diagnosis at any age) were compared for relevant colorectal findings. For the family history versus no family history cohorts, the frequency of all nondiminutive polyps (≥ 6 mm) reported at CTC was 23.7% versus 15.5% (p = 0.007); small polyps (6-9 mm), 13.5% versus 9.1% (p = 0.068); and large polyps (≥ 10 mm), 10.2% versus 6.5% (p = 0.068). The rate of referral for colonoscopy was greater for the family history cohort (16.0% vs 10.5%; p = 0.035). However, the frequencies of proven advanced adenoma (4.5% vs 3.2%; p = 0.357), nonadvanced adenoma (5.1% vs 2.6%; p = 0.070), and cancer (0.0% vs 0.4%; p = 0.999) were not significantly increased. The difference in positive rates between the two cohorts (11.5% vs 4.3%; p < 0.001) was primarily due to nonneoplastic findings of no colorectal cancer relevance, such as small hyperplastic polyps, diverticular disease, and false-positive CTC findings. Although the overall CTC-positive and colonoscopy referral rates were higher in the family history cohort, the clinically relevant frequencies of advanced neoplasia and cancer were not sufficiently increased to preclude CTC screening. These findings support the use of CTC as a front-line screening option in adults with a family history of colorectal cancer.

Equivalence of ELISpot Assays Demonstrated between Major HIV Network Laboratories

PubMed Central

Levine, Gail L.; Sambor, Anna; Carter, Donald K.; Sato, Alicia; Kopycinski, Jakub; Hayes, Peter; Hahn, Bridget; Birungi, Josephine; Tarragona-Fiol, Tony; Wan, Hong; Randles, Mark; Cooper, Andrew Raxworthy; Ssemaganda, Aloysius; Clark, Lorna; Kaleebu, Pontiano; Self, Steven G.; Koup, Richard; Wood, Blake; McElrath, M. Juliana; Cox, Josephine H.; Hural, John; Gilmour, Jill

2010-01-01

Background The Comprehensive T Cell Vaccine Immune Monitoring Consortium (CTC-VIMC) was created to provide standardized immunogenicity monitoring services for HIV vaccine trials. The ex vivo interferon-gamma (IFN-γ) ELISpot is used extensively as a primary immunogenicity assay to assess T cell-based vaccine candidates in trials for infectious diseases and cancer. Two independent, GCLP-accredited central laboratories of CTC-VIMC routinely use their own standard operating procedures (SOPs) for ELISpot within two major networks of HIV vaccine trials. Studies are imperatively needed to assess the comparability of ELISpot measurements across laboratories to benefit optimal advancement of vaccine candidates. Methods We describe an equivalence study of the two independently qualified IFN-g ELISpot SOPs. The study design, data collection and subsequent analysis were managed by independent statisticians to avoid subjectivity. The equivalence of both response rates and positivity calls to a given stimulus was assessed based on pre-specified acceptance criteria derived from a separate pilot study. Findings Detection of positive responses was found to be equivalent between both laboratories. The 95% C.I. on the difference in response rates, for CMV (−1.5%, 1.5%) and CEF (−0.4%, 7.8%) responses, were both contained in the pre-specified equivalence margin of interval [−15%, 15%]. The lower bound of the 95% C.I. on the proportion of concordant positivity calls for CMV (97.2%) and CEF (89.5%) were both greater than the pre-specified margin of 70%. A third CTC-VIMC central laboratory already using one of the two SOPs also showed comparability when tested in a smaller sub-study. Interpretation The described study procedure provides a prototypical example for the comparison of bioanalytical methods in HIV vaccine and other disease fields. This study also provides valuable and unprecedented information for future vaccine candidate evaluations on the comparison and pooling of ELISpot results generated by the CTC-VIMC central core laboratories. PMID:21179404

Circulating Tumor Cells with Aberrant ALK Copy Number Predict Progression-Free Survival during Crizotinib Treatment in ALK-Rearranged Non-Small Cell Lung Cancer Patients.

PubMed

Pailler, Emma; Oulhen, Marianne; Borget, Isabelle; Remon, Jordi; Ross, Kirsty; Auger, Nathalie; Billiot, Fanny; Ngo Camus, Maud; Commo, Frédéric; Lindsay, Colin R; Planchard, David; Soria, Jean-Charles; Besse, Benjamin; Farace, Françoise

2017-05-01

The duration and magnitude of clinical response are unpredictable in ALK -rearranged non-small cell lung cancer (NSCLC) patients treated with crizotinib, although all patients invariably develop resistance. Here, we evaluated whether circulating tumor cells (CTC) with aberrant ALK -FISH patterns [ ALK -rearrangement, ALK -copy number gain ( ALK -CNG)] monitored on crizotinib could predict progression-free survival (PFS) in a cohort of ALK -rearranged patients. Thirty-nine ALK -rearranged NSCLC patients treated with crizotinib as first ALK inhibitor were recruited prospectively. Blood samples were collected at baseline and at an early time-point (2 months) on crizotinib. Aberrant ALK -FISH patterns were examined in CTCs using immunofluorescence staining combined with filter-adapted FISH after filtration enrichment. CTCs were classified into distinct subsets according to the presence of ALK -rearrangement and/or ALK -CNG signals. No significant association between baseline numbers of ALK -rearranged or ALK -CNG CTCs and PFS was observed. However, we observed a significant association between the decrease in CTC number with ALK -CNG on crizotinib and a longer PFS (likelihood ratio test, P = 0.025). In multivariate analysis, the dynamic change of CTC with ALK -CNG was the strongest factor associated with PFS (HR, 4.485; 95% confidence interval, 1.543-13.030, P = 0.006). Although not dominant, ALK -CNG has been reported to be one of the mechanisms of acquired resistance to crizotinib in tumor biopsies. Our results suggest that the dynamic change in the numbers of CTCs with ALK -CNG may be a predictive biomarker for crizotinib efficacy in ALK -rearranged NSCLC patients. Serial molecular analysis of CTC shows promise for real-time patient monitoring and clinical outcome prediction in this population. Cancer Res; 77(9); 2222-30. ©2017 AACR . ©2017 American Association for Cancer Research.

Folic Acid Targeting for Efficient Isolation and Detection of Ovarian Cancer CTCs from Human Whole Blood Based on Two-Step Binding Strategy.

PubMed

Nie, Liju; Li, Fulai; Huang, Xiaolin; Aguilar, Zoraida P; Wang, Yongqiang Andrew; Xiong, Yonghua; Fu, Fen; Xu, Hengyi

2018-04-25

Studies regarding circulating tumor cells (CTCs) have great significance for cancer prognosis, treatment monitoring, and metastasis diagnosis. However, due to their extremely low concentration in peripheral blood, isolation and enrichment of CTCs are the key steps for early detection. To this end, targeting the folic acid receptors (FRs) on the CTC surface for capture with folic acid (FA) using bovine serum albumin (BSA)-tether for multibiotin enhancement in combination with streptavidin-coated magnetic nanoparticles (MNPs-SA) was developed for ovarian cancer CTC isolation. The streptavidin-biotin-system-mediated two-step binding strategy was shown to capture CTCs from whole blood efficiently without the need for a pretreatment process. The optimized parameters for this system exhibited an average capture efficiency of 80%, which was 25% higher than that of FA-decorated magnetic nanoparticles based on the one-step CTC separation method. Moreover, the isolated cells remained highly viable and were cultured directly without detachment from the MNPs-SA-biotin-CTC complex. Furthermore, when the system was applied for the isolation and detection of CTCs in ovarian cancer patients' peripheral blood samples, it exhibited an 80% correlation with clinical diagnostic criteria. The results indicated that FA targeting, in combination with BSA-based multibiotin enhancement magnetic nanoparticle separation, is a promising tool for CTC enrichment and detection of early-stage ovarian cancer.

Development of a rapid biolistic assay to determine changes in relative levels of intracellular calcium in leaves following tetracycline uptake by pinto bean plants.

PubMed

Farkas, Michael H; Mojica, Elmer-Rico E; Patel, Minesh; Aga, Diana S; Berry, James O

2009-08-01

Tetracycline antibiotics, such as chlortetracycline (CTC) and tetracycline (TC), are introduced into agricultural lands through the application of manure as fertilizer. These compounds are phytotoxic to certain crop plants, including pinto beans (Phaseolus vulgaris), the species used for this investigation. While the mechanism of this toxicity is not yet understood, CTC is known to be a calcium chelator. We describe here a novel method to show that CTC is taken up by pinto bean plants and chelates calcium in leaves. Cameleon fusion proteins can provide qualitative and quantitative imaging of intracellular calcium levels, but current methodology requires stable transformation. Many plant species, including pinto beans, are not yet transformable using standard Agrobacterium-based protocols. To determine the role of calcium chelation in this plant, a rapid, biolistic method was developed to transiently express the cameleon protein. This method can easily be adapted to other plant systems. Our findings provide evidence that chelation of intracellular calcium by CTC is related to phytotoxic effects caused by this antibiotic in pinto beans. Root uptake of CTC and TC by pinto beans and their translocation to leaves were further verified by fluorescence spectroscopy and liquid chromatography/mass spectrometry, confirming results of the biolistic method that showed calcium chelation by tetracyclines in leaves.

Nanostructure Embedded Microchips for Detection, Isolation, and Characterization of Circulating Tumor Cells

PubMed Central

2015-01-01

Conspectus Circulating tumor cells (CTCs) are cancer cells that break away from either a primary tumor or a metastatic site and circulate in the peripheral blood as the cellular origin of metastasis. With their role as a “tumor liquid biopsy”, CTCs provide convenient access to all disease sites, including that of the primary tumor and the site of fatal metastases. It is conceivable that detecting and analyzing CTCs will provide insightful information in assessing the disease status without the flaws and limitations encountered in performing conventional tumor biopsies. However, identifying CTCs in patient blood samples is technically challenging due to the extremely low abundance of CTCs among a large number of hematologic cells. To address this unmet need, there have been significant research endeavors, especially in the fields of chemistry, materials science, and bioengineering, devoted to developing CTC detection, isolation, and characterization technologies. Inspired by the nanoscale interactions observed in the tissue microenvironment, our research team at UCLA pioneered a unique concept of “NanoVelcro” cell-affinity substrates, in which CTC capture agent-coated nanostructured substrates were utilized to immobilize CTCs with high efficiency. The working mechanism of NanoVelcro cell-affinity substrates mimics that of Velcro: when the two fabric strips of a Velcro fastener are pressed together, tangling between the hairy surfaces on two strips leads to strong binding. Through continuous evolution, three generations (gens) of NanoVelcro CTC chips have been established to achieve different clinical utilities. The first-gen NanoVelcro chip, composed of a silicon nanowire substrate (SiNS) and an overlaid microfluidic chaotic mixer, was created for CTC enumeration. Side-by-side analytical validation studies using clinical blood samples suggested that the sensitivity of first-gen NanoVelcro chip outperforms that of FDA-approved CellSearch. In conjunction with the use of the laser microdissection (LMD) technique, second-gen NanoVelcro chips (i.e., NanoVelcro-LMD), based on polymer nanosubstrates, were developed for single-CTC isolation. The individually isolated CTCs can be subjected to single-CTC genotyping (e.g., Sanger sequencing and next-generation sequencing, NGS) to verify the CTC’s role as tumor liquid biopsy. Created by grafting of thermoresponsive polymer brushes onto SiNS, third-gen NanoVelcro chips (i.e., Thermoresponsive NanoVelcro) have demonstrated the capture and release of CTCs at 37 and 4 °C, respectively. The temperature-dependent conformational changes of polymer brushes can effectively alter the accessibility of the capture agent on SiNS, allowing for rapid CTC purification with desired viability and molecular integrity. This Account summarizes the continuous evolution of NanoVelcro CTC assays from the emergence of the original idea all the way to their applications in cancer research. We envision that NanoVelcro CTC assays will lead the way for powerful and cost-efficient diagnostic platforms for researchers to better understand underlying disease mechanisms and for physicians to monitor real-time disease progression. PMID:25111636

The Chaos Theory of Careers

ERIC Educational Resources Information Center

Bright, Jim E. H.; Pryor, Robert G. L.

2011-01-01

The Chaos Theory of Careers (CTC; Pryor & Bright, 2011) construes both individuals and the contexts in which they develop their careers in terms of complex dynamical systems. Such systems perpetually operate under influences of stability and change both internally and in relation to each other. The CTC introduces new concepts to account for…

CTC-Endothelial Cell Interactions during Metastasis

DTIC Science & Technology

2014-06-01

antibody. For these experiments, we first tested the Bioflux Microfluidics system. In our hands, the Bioflux microfluidic system was suboptimal for...indicated in the results, a subset of rolling assay experiments were also performed using Bioflux Microfluidics technologies (Fluxion Biosciences...behavior of MDA cells in the presence of neutralizing anti-E-selectin antibody. We performed these experiments using Bioflux Microfluidics technology

Laser Raman spectroscopy of the effect of solvent on the low-frequency oscillations of organic molecules

NASA Astrophysics Data System (ADS)

Brandt, N. N.; Chikishev, A. Yu.; Dolgovskii, V. I.; Lebedenko, S. I.

2007-09-01

The effect of solvent on low-frequency oscillations is studied using an example of the 1,1,2,2-tetrachloroethane (TCE) and 1,1,2,2-tetrabromoethane (TBE) molecules, which exhibit torsional oscillations in the terahertz range. Dimethylsulfoxide (DMSO) and carbon tetrachloride (CTC) are used as solvents. It is demonstrated that a decrease in the concentration of the substance under study in the TBE/CTC, TCE/DMSO, and TCE/CTC mixtures leads to a frequency shift of the low-frequency oscillation. The shift is not observed in the TBE/DMSO mixture but a decrease in the TBE concentration causes significant broadening of the low-frequency line.

Commitment to Practice Change: An Evaluator's Perspective

PubMed Central

Shershneva, Marianna B.; Wang, Min-fen; Lindeman, Gary C.; Savoy, Julia N.; Olson, Curtis A.

2010-01-01

A commitment to practice change (CTC) approach may be used in educational program evaluation to document practice changes, examine the educational impact relative to the instructional focus, and improve understanding of the learning-to-change continuum. The authors reviewed various components and procedures of this approach and discussed some practical aspects of its application using as an example of a study evaluating a presentation on menopausal care for primary care physicians. The CTC approach is a valuable evaluation tool, but it requires supplementation with other data to have a complete picture of the impact of education on practice. From the evaluation perspective, the self-reported nature of the CTC data is a major limitation of this method. PMID:20457715

Clearance Analysis of CTC2 (on ELC4) to S-TRRJ HRS Radiator Rotation Envelope

NASA Technical Reports Server (NTRS)

Liddle, Donn

2014-01-01

In response to the planned retirement of the Space Shuttle Program, International Space Station (ISS) management began stockpiling spare parts on the ISS. Many of the larger orbital replacement units were stored on the Expedite the Processing of Experiments to Space Station (EXPRESS) Logistics Carriers (ELCs) mounted on the end of the S3 and P3 truss segments, immediately outboard of the Thermal Radiator Rotary Joints (TRRJs) and their attached radiators. In an August 2009 computer-aided design (CAD) assessment, it was determined that mounting the Cargo Transport Container (CTC) 2 on the inboard face of ELC4 as planned would create insufficient clearance between the CTC2 and the rotational envelope of the radiators when the TRRJs were rotated to a gamma angle of 35.0 degrees. The true clearance would depend on how the Unpressurized Cargo Carrier Attachment System (UCCAS) was mounted to the S3 truss and how the ELC4 was attached to it. If the plane of the UCCAS attachment points were tilted even slightly inboard, it would significantly change the clearance between CTC2 and the Starboard TRRJ (S-TRRJ) radiators. Additionally, since CTC2 would be covered in multilayer insulation (MLI), the true outer profile of CTC2 was not captured in the CAD models used for the clearance assessment. It was possible that, even if the S-TRRJ radiators cleared CTC2, they could snag the MLI covering. In the fall of 2010, the Image Science and Analysis Group (ISAG) was asked to perform an on-orbit clearance analysis to determine the location of CTC2 on ELC4 and the S-TRRJ radiators at the angle of closest approach so that a positive clearance could be assured. To provide the measurements as quickly as possible to aid in the assessment, it was decided that the clearance analysis would be broken into two phases. Phase I: The location and orientation of the UCCAS fittings, which support and hold the ELC4 in place, would be measured relative to the ISS Analytical Coordinate System (ISSACS) as defined by nine preexisting Space Vision System (SVS) targets affixed to the forward/zenith side of the S1 and S3 truss segments. The location of the outboard edge of the S-TRRJ radiator would also be measured when positioned at the angle of closest approach to CTC2 (gamma = 35.0 degrees). This data would allow the Digital Pre-Assembly Group to predict how the ELC4 would sit on the UCCAS and how that would translate into the clearance between CTC2 and the S-TRRJ radiators. Phase II: After the ELC4 was delivered and installed into the UCCAS, the position of the CTC2 mounting plate on the inboard face of ELC4, would be measured in the ISSACS coordinate system relative to the SVS control points used in Phase I. Although CTC2 would not yet be mounted on ELC4, the working envelope of CTC2 could be mathematically added to the measured position of ELC4 to produce a best estimate for CTC2's mounted location. Comparing CTC2's best estimated location to the S-TRRJ radiator (measured in Phase I); relative to the ISSACS coordinate system, would provide a direct measurement of the expected clearance. Due to the impending delivery of ELC4 (scheduled for January 2011), planning for the Phase I clearance analysis began immediately. Using the Dynamic Onboard Ubiquitous Graphics (DOUG) program, ISAG designed a way to acquire images of the SVS control points on truss segments S1 and S3, the aft facing edge of the S-TRRJ Heat Rejection Subsystem (HRS) radiator, and the three UCCAS latch mechanisms mounted on the zenith face of the S3 truss using the Space Station Remote Manipulator System (SSRMS). To minimize the number of SSRMS movements, the Special Purpose Dexterous Manipulator (SPDM) would be attached to the SSRMS. This would make it possible to park the SPDM in one position and acquire multiple images by changing the viewing orientation of the SPDM body cameras using the pan/tilt units on which they are mounted. Using this implementation concept, ISAG identified four SSRMS/SPDM positions from which the majority of the needed imagery could be acquired. Five additional images would be acquired using the CP-3 external ISS camera mounted on the S1 truss immediately inboard of ELC4. Based on a photogrammetric simulation, it was estimated that the measured location of the HRS radiator and UCCAS latch points would be accurate to about 0.3 in. in each of the three axes relative to ISSACS. Working with ROBO, ISAG collected 78 images of the ISS December 29, 2010. From this imagery, the best 40 were selected for use in the analysis process. The images were radiometrically enhanced to improve color and contrast and loaded into the FotoG analysis software along with the camera parameters and control data, which consisted of the coordinates for the nine SVS targets on the S1 and S3 trusses in the ISSACS coordinate system.

Commission on Teacher Credentialing Approves 8 ELL-Related Credential Options

ERIC Educational Resources Information Center

Frost, Jeff; Cadiero-Kaplan, Karen; Kuhlman, Natalie

2011-01-01

On September 30, 2010, the California Commission on Teacher Credentialing (CTC) voted unanimously to approve a set of eight recommendations for authorization to teach English language learners. These recommendations approved by the CTC had been in development for almost two years and they focused on several issues, including: (1) a specific focus…

Effects of in-feed chlortetracycline prophylaxis of beef cattle on animal health and antimicrobial-resistant Escherichia coli

USDA-ARS?s Scientific Manuscript database

Concerns have been raised that in-feed chlortetracycline (CTC) may increase antimicrobial resistance (AMR), specifically tetracycline-resistant (TETr) Escherichia coli, and third-generation cephalosporin-resistant (3GCr) E. coli. We evaluated the impact of a 5-day in-feed CTC prophylaxis on animal h...

Nanotechnology for the detection and kill of circulating tumor cells

NASA Astrophysics Data System (ADS)

Gao, Yang; Yuan, Zhou

2014-09-01

Circulating tumor cells (CTCs) represent a surrogate biomarker of hematogenous metastases and thus could be considered as a `liquid biopsy' which reveals metastasis in action. But it is absolutely a challenge to detect CTCs due to their extreme rarity. At present, the most common principle is to take advantage of the epithelial surface markers of CTCs which attach to a specific antibody. Antibody-magnetic nanobeads combine with the epithelial surface markers, and then the compound is processed by washing, separation, and detection. However, a proportion of CTC antigen expressions are down-regulated or lost in the process of epithelial-mesenchymal transition (EMT), and thus, this part of CTCs cannot be detected by classical detection methods such as CellSearch. To resolve this problem, some multiple-marker CTC detections have been developed rapidly. Additionally, nanotechnology is a promising approach to kill CTCs with high efficiency. Implantable nanotubes coated with apoptosis-promoting molecules improve the disease-free survival and overall survival. The review introduces some novel CTC detection techniques and therapeutic methods by virtue of nanotechnology to provide a better knowledge of the progress about CTC study.

Two groups of S-layer proteins, SLP1s and SLP2s, in Bacillus thuringiensis co-exist in the S-layer and in parasporal inclusions.

PubMed

Zhou, Zhou; Peng, Donghai; Zheng, Jinshui; Guo, Gang; Tian, Longjun; Yu, Ziniu; Sun, Ming

2011-05-01

We screened four B. thuringiensis strains whose parasporal inclusions contained the S-layer protein (SLP), and cloned two slp genes from each strain. Phylogenetic analysis indicated these SLPs could be divided into two groups, SLP1s and SLP2s. To confirm whether SLPs were present in the S-layer or as a parasporal inclusion, strains CTC and BMB1152 were chosen for further study. Western blots with whole-cell associated proteins from strains CTC and BMB1152 in the vegetative phase showed that SLP1s and SLP2s were constituents of the S-layer. Immunofluorescence utilizing spore-inclusion mixtures of strains CTC and BMB1152 in the sporulation phase showed that SLP1s and SLP2s were also constituents of parasporal inclusions. When heterogeneously expressed in the crystal negative strain BMB171, four SLPs from strains CTC and BMB1152 could also form parasporal inclusions. This temporal and spatial expression is not an occasional phenomenon but ubiquitous in B. thuringiensis strains.

Clinical Applications of NanoVelcro Rare-Cell Assays for Detection and Characterization of Circulating Tumor Cells

PubMed Central

Chen, Jie-Fu; Zhu, Yazhen; Lu, Yi-Tsung; Hodara, Elisabeth; Hou, Shuang; Agopian, Vatche G.; Tomlinson, James S.; Posadas, Edwin M.; Tseng, Hsian-Rong

2016-01-01

Liquid biopsy of tumor through isolation of circulating tumor cells (CTCs) allows non-invasive, repetitive, and systemic sampling of disease. Although detecting and enumerating CTCs is of prognostic significance in metastatic cancer, it is conceivable that performing molecular and functional characterization on CTCs will reveal unprecedented insight into the pathogenic mechanisms driving lethal disease. Nanomaterial-embedded cancer diagnostic platforms, i.e., NanoVelcro CTC Assays represent a unique rare-cell sorting method that enables detection isolation, and characterization of CTCs in peripheral blood, providing an opportunity to noninvasively monitor disease progression in individual cancer patients. Over the past decade, a series of NanoVelcro CTC Assays has been demonstrated for exploring the full potential of CTCs as a clinical biomarker, including CTC enumeration, phenotyping, genotyping and expression profiling. In this review article, the authors will briefly introduce the development of three generations of NanoVelcro CTC Assays, and highlight the clinical applications of each generation for various types of solid cancers, including prostate cancer, pancreatic cancer, lung cancer, and melanoma. PMID:27375790

Multifunctional Lattices with Low Thermal Expansion and Low Thermal Conductivity

NASA Astrophysics Data System (ADS)

Xu, Hang; Liu, Lu; Pasini, Damiano

Systems in space are vulnerable to large temperature changes when travelling into and out of the Earth's shadow. Variations in temperature can lead to undesired geometric changes in susceptible applications requiring very fine precision. In addition, temperature-sensitive electronic equipment hosted in a satellite needs adequate thermal-control to guarantee a moderate ambient temperature. To address these specifications, materials with low coefficient of thermal expansion (CTE) and low coefficient of thermal conductivity (CTC) over a wide range of temperatures are often sought, especially for bearing components in satellites. Besides low CTE and low CTC, these materials should also provide desirable stiffness, strength and extraordinarily low mass. This work presents ultralightweight bi-material lattices with tunable CTE and CTC, besides high stiffness and strength. We show that the compensation of the thermal expansion and joint rotation at the lattice joints can be used as an effective strategy to tailor thermomechanical performance. Proof-of-concept lattices are fabricated from Al and Ti alloy sheets via a simple snap-fit technique and vacuum brazing, and their CTE and CTC are assessed via a combination of experiments and theory. Corresponding Author.

Biochemical effects of veterinary antibiotics on proliferation and cell cycle arrest of human HEK293 cells.

PubMed

Kim, Hyeon Young; Kim, Ki-Tae; Kim, Sang Don

2012-08-01

The purpose of this study was to examine the effects of veterinary antibiotics, including amoxicillin (AMX), chlortetracycline (CTC) and tylosin (TYL), on the biochemical mechanism of human embryonic kidney cells (HEK293). CTC and TYL inhibited HEK293 cell proliferation, in both time- and dose-dependent manners, and changed the cell morphology; whereas, AMX showed no cytotoxic effects. The cell cycle analysis of CTC and TYL revealed G1-arrest in HEK293 cells. Western blot analysis also showed that CTC and TYL affected the activation of DNA damage responsive proteins, as well as cell cycle regulatory proteins, such as p53, p21(Waf1/Cip1) and Rb protein, which are crucial in the G1-S transition. The activation of p21(Waf1/Cip1) was significantly up-regulated over time, but there was no change in the level of CDK2 expression. The results of this study suggest that veterinary antibiotics, even at low level concentrations on continuous exposure, can potentially risk the development of human cells.

Antibiotic degradation and microbial community structures during acidification and methanogenesis of swine manure containing chlortetracycline or oxytetracycline.

PubMed

Yin, Fubin; Dong, Hongmin; Zhang, Wanqin; Zhu, Zhiping; Shang, Bin

2018-02-01

Anaerobic digestion (AD) has been applied to animal manure stabilization, and antibiotics is frequently found in animal manure. However, antibiotic degradation and microbial community structures during two-stage AD (acidification and methanogenesis) remain poorly understood. This experiments on two-stage anaerobic swine manure digesters were performed to investigate the degradation mechanisms and effects of chlortetracycline (CTC) and oxytetracycline (OTC) on microbial community structures. Results showed that acidification and methanogenesis showed good degradation performance for manure containing CTC and OTC at 60 and 40 mg/kg·TS, respectively. CTC and OTC were degraded by 59.8% and 41.3% in the acidogenic stage and by 76.3% and 78.3% in the methanogenic stage, respectively. CTC and OTC negatively affected bacterial community in methanogenic and acidogenic stages, respectively. They also adversely influenced the archaeal species in the methanogenic stage. Two-stage AD was proposed to treat manure containing antibiotics and to reduce the negative effects of antibiotics on AD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of anaerobic digestion on chlortetracycline and oxytetracycline degradation efficiency for swine manure.

PubMed

Yin, Fubin; Dong, Hongmin; Ji, Chao; Tao, Xiuping; Chen, Yongxing

2016-10-01

Manure containing antibiotics is considered a hazardous substance that poses a serious health risk to the environment and to human health. Anaerobic digestion (AD) could not only treatment animal waste but also generate valuable biogas. However, the interaction between antibiotics in manure and the AD process has not been clearly understood. In this study, experiments on biochemical methane potential (BMP) were conducted to determine the inhibition of the AD process from antibiotics and the threshold of complete antibiotic removal. The thresholds of the complete antibiotic removal were 60 and 40mg/kg·TS for CTC and OTC, respectively. CTC and OTC with concentrations below thresholds could increase the BMP of manure. When the CTC and OTC concentrations exceeded the thresholds, they inhibited manure fermentation, and the CTC removal rate declined exponentially with concentration (60-500mg/kg·TS). The relationship between OTC antibiotic concentration and its removal rate in AD treatment was described with exponential (40-100mg/kg·TS) and linear equations (100-500mg/kg·TS). Copyright © 2016 Elsevier Ltd. All rights reserved.

Cerebroretinal microangiopathy with calcifications and cysts associated with CTC1 and NDP mutations.

PubMed

Romaniello, Romina; Arrigoni, Filippo; Citterio, Andrea; Tonelli, Alessandra; Sforzini, Cinzia; Rizzari, Carmelo; Pessina, Marco; Triulzi, Fabio; Bassi, Maria Teresa; Borgatti, Renato

2013-12-01

Mutations in the conserved telomere maintenance component 1 (CTC1) gene were recently described in Coats plus syndrome and in cerebroretinal microangiopathy with calcifications and cysts. Norrie disease protein (NDP) gene was found mutated in Norrie disease, in Familial Exudative Vitreoretinopathy, and in Coats syndrome. Here we describe a boy affected by Norrie disease who developed typical features of cerebroretinal microangiopathy with calcifications and cysts. Direct sequencing of the CTC1 and NDP genes in this patient shows the presence of compound heterozygosity for 2 mutations in CTC1 (c.775G>A, pV259M and a novel microdeletion c.1213delG) and a missense mutation in the NDP gene (c.182T>C, p.L61P). Based on these genetic findings and on the expression of both genes in endothelial cells, we postulate that microangiopathy might be a primary underlying pathologic abnormality in cerebroretinal microangiopathy with calcifications and cysts. This hypothesis is further supported by magnetic resonance imaging (MRI) data showing multiple minute calcifications in the deep gray nuclei and in terminal arteriolar zones.

CTC1-mediated C-strand fill-in is an essential step in telomere length maintenance

PubMed Central

Feng, Xuyang; Hsu, Shih-Jui; Kasbek, Christopher; Chaiken, Mary

2017-01-01

Abstract To prevent progressive telomere shortening as a result of conventional DNA replication, new telomeric DNA must be added onto the chromosome end. The de novo DNA synthesis involves elongation of the G-rich strand of the telomere by telomerase. In human cells, the CST complex (CTC1-STN1-TEN1) also functions in telomere replication. CST first aids in duplication of the telomeric dsDNA. Then after telomerase has extended the G-rich strand, CST facilitates fill-in synthesis of the complementary C-strand. Here, we analyze telomere structure after disruption of human CTC1 and demonstrate that functional CST is essential for telomere length maintenance due to its role in mediating C-strand fill-in. Removal of CTC1 results in elongation of the 3΄ overhang on the G-rich strand. This leads to accumulation of RPA and telomeric DNA damage signaling. G-overhang length increases with time after CTC1 disruption and at early times net G-strand growth is apparent, indicating telomerase-mediated G-strand extension. In contrast, C-strand length decreases continuously, indicating a deficiency in C-strand fill-in synthesis. The lack of C-strand maintenance leads to gradual shortening of the telomeric dsDNA, similar to that observed in cells lacking telomerase. Thus, telomerase-mediated G-strand extension and CST-mediated C-strand fill-in are equally important for telomere length maintenance. PMID:28334750

Computed tomographic colonography to screen for colorectal cancer, extracolonic cancer, and aortic aneurysm: model simulation with cost-effectiveness analysis.

PubMed

Hassan, Cesare; Pickhardt, Perry J; Pickhardt, Perry; Laghi, Andrea; Kim, Daniel H; Kim, Daniel; Zullo, Angelo; Iafrate, Franco; Di Giulio, Lorenzo; Morini, Sergio

2008-04-14

In addition to detecting colorectal neoplasia, abdominal computed tomography (CT) with colonography technique (CTC) can also detect unsuspected extracolonic cancers and abdominal aortic aneurysms (AAA).The efficacy and cost-effectiveness of this combined abdominal CT screening strategy are unknown. A computerized Markov model was constructed to simulate the occurrence of colorectal neoplasia, extracolonic malignant neoplasm, and AAA in a hypothetical cohort of 100,000 subjects from the United States who were 50 years of age. Simulated screening with CTC, using a 6-mm polyp size threshold for reporting, was compared with a competing model of optical colonoscopy (OC), both without and with abdominal ultrasonography for AAA detection (OC-US strategy). In the simulated population, CTC was the dominant screening strategy, gaining an additional 1458 and 462 life-years compared with the OC and OC-US strategies and being less costly, with a savings of $266 and $449 per person, respectively. The additional gains for CTC were largely due to a decrease in AAA-related deaths, whereas the modeled benefit from extracolonic cancer downstaging was a relatively minor factor. At sensitivity analysis, OC-US became more cost-effective only when the CTC sensitivity for large polyps dropped to 61% or when broad variations of costs were simulated, such as an increase in CTC cost from $814 to $1300 or a decrease in OC cost from $1100 to $500. With the OC-US approach, suboptimal compliance had a strong negative influence on efficacy and cost-effectiveness. The estimated mortality from CT-induced cancer was less than estimated colonoscopy-related mortality (8 vs 22 deaths), both of which were minor compared with the positive benefit from screening. When detection of extracolonic findings such as AAA and extracolonic cancer are considered in addition to colorectal neoplasia in our model simulation, CT colonography is a dominant screening strategy (ie, more clinically effective and more cost-effective) over both colonoscopy and colonoscopy with 1-time ultrasonography.

Quality-of-life outcomes from a randomized phase III trial of dose-dense weekly paclitaxel and carboplatin compared with conventional paclitaxel and carboplatin as a first-line treatment for stage II-IV ovarian cancer: Japanese Gynecologic Oncology Group Trial (JGOG3016).

PubMed

Harano, K; Terauchi, F; Katsumata, N; Takahashi, F; Yasuda, M; Takakura, S; Takano, M; Yamamoto, Y; Sugiyama, T

2014-01-01

Dose-dense weekly paclitaxel (Taxol) and carboplatin (dd-TC) improved survival compared with conventional tri-weekly paclitaxel and carboplatin (c-TC) as a first-line chemotherapy for newly diagnosed stage II-IV ovarian cancer in the Japanese Gynecologic Oncology Group 3016 trial. We report the quality-of-life (QoL) results from this trial. A total of 637 patients were randomly assigned to receive c-TC or dd-TC (c-TC, n = 319; dd-TC, n = 312) and were asked to complete a QoL assessment at baseline, just after the third and sixth chemotherapy cycles, and at 12 months after randomization. QoL was assessed using Functional Assessment of Cancer Therapy (FACT)-general (FACT-G), FACT-taxane subscale (FACT-T), and FACT-ovary subscale (FACT-Ov). The overall QoL and that according to each subscale were analyzed using mixed-effects models adjusted for treatment and time. Baseline QoL assessment was completed by 204 out of 319 (63.9%) and 200 out of 312 (64.1%) patients in the c-TC and dd-TC groups, respectively. In these groups, the compliance rates with regard to QoL assessment were 74.5% and 73.0%, respectively, after three chemotherapy cycles; 86.8% and 86.9%, respectively, after six chemotherapy cycles; and 74.2% and 71.6%, respectively, at 12 months after randomization. The overall QoL did not differ significantly between the two treatment groups up to 12 months after randomization (P = 0.46). However, QoL according to the FACT-T subscale was significantly lower in the dd-TC group than in the c-TC group (P = 0.02). dd-TC does not decrease overall QoL compared with c-TC.

Circulating tumor cells in patients with testicular germ cell tumors.

PubMed

Nastały, Paulina; Ruf, Christian; Becker, Pascal; Bednarz-Knoll, Natalia; Stoupiec, Małgorzata; Kavsur, Refik; Isbarn, Hendrik; Matthies, Cord; Wagner, Walter; Höppner, Dirk; Fisch, Margit; Bokemeyer, Carsten; Ahyai, Sascha; Honecker, Friedemann; Riethdorf, Sabine; Pantel, Klaus

2014-07-15

Germ cell tumors (GCTs) represent the most frequent malignancies among young men, but little is known about circulating tumor cells (CTCs) in these tumors. Considering their heterogeneity, CTCs were investigated using two independent assays targeting germ cell tumor and epithelial cell-specific markers, and results were correlated with disease stage, histology, and serum tumor markers. CTCs were enriched from peripheral blood (n = 143 patients) and testicular vein blood (TVB, n = 19 patients) using Ficoll density gradient centrifugation. For CTC detection, a combination of germ cell tumor (anti-SALL4, anti-OCT3/4) and epithelial cell-specific (anti-keratin, anti-EpCAM) antibodies was used. In parallel, 122 corresponding peripheral blood samples were analyzed using the CellSearch system. In total, CTCs were detected in 25 of 143 (17.5%) peripheral blood samples, whereas only 11.5% of patients were CTC-positive when considering exclusively the CellSearch assay. The presence of CTCs in peripheral blood correlated with clinical stage (P < 0.001) with 41% of CTC positivity in patients with metastasized tumors and 100% in patients with relapsed and chemotherapy-refractory disease. Histologically, CTC-positive patients suffered more frequently from nonseminomatous primary tumors (P < 0.001), with higher percentage of yolk sac (P < 0.001) and teratoma (P = 0.004) components. Furthermore, CTC detection was associated with elevated serum levels of α-fetoprotein (AFP; P = 0.025), β-human chorionic gonadotropin (βHCG; P = 0.002), and lactate dehydrogenase (LDH; P = 0.002). Incidence and numbers of CTCs in TVB were much higher than in peripheral blood. The inclusion of germ cell tumor-specific markers improves CTC detection in GCTs. CTCs occur frequently in patients with more aggressive disease, and there is a gradient of CTCs with decreasing numbers from the tumor-draining vein to the periphery. ©2014 American Association for Cancer Research.

In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells.

PubMed

El-Heliebi, Amin; Hille, Claudia; Laxman, Navya; Svedlund, Jessica; Haudum, Christoph; Ercan, Erkan; Kroneis, Thomas; Chen, Shukun; Smolle, Maria; Rossmann, Christopher; Krzywkowski, Tomasz; Ahlford, Annika; Darai, Evangelia; von Amsberg, Gunhild; Alsdorf, Winfried; König, Frank; Löhr, Matthias; de Kruijff, Inge; Riethdorf, Sabine; Gorges, Tobias M; Pantel, Klaus; Bauernhofer, Thomas; Nilsson, Mats; Sedlmayr, Peter

2018-03-01

Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs. Here, we report an approach that adds AR-V7 or KRAS status to CTC enumeration, compatible with multiple CTC-isolation platforms. We studied 3 independent CTC-isolation devices (CellCollector, Parsortix, CellSearch) for the evaluation of AR-V7 or KRAS status of CTCs with in situ padlock probe technology. Padlock probes allow highly specific detection and visualization of transcripts on a cellular level. We applied padlock probes for detecting AR-V7, androgen receptor full length (AR-FL), and prostate-specific antigen (PSA) in CRPC and KRAS wild-type (wt) and mutant (mut) transcripts in PaCa in CTCs from 46 patients. In situ analysis showed that 71% (22 of 31) of CRPC patients had detectable AR-V7 expression ranging from low to high expression [1-76 rolling circle products (RCPs)/CTC]. In PaCa patients, 40% (6 of 15) had KRAS mut expressing CTCs with 1 to 8 RCPs/CTC. In situ padlock probe analysis revealed CTCs with no detectable cytokeratin expression but positivity for AR-V7 or KRAS mut transcripts. Padlock probe technology enables quantification of AR-V7, AR-FL, PSA, and KRAS mut/wt transcripts in CTCs. The technology is easily applicable in routine laboratories and compatible with multiple CTC-isolation devices. © 2017 American Association for Clinical Chemistry.

DTI fiber tractography of cerebro-cerebellar pathways and clinical evaluation of ataxia in childhood posterior fossa tumor survivors.

PubMed

Oh, Myung Eun; Driever, Pablo Hernáiz; Khajuria, Rajiv K; Rueckriegel, Stefan Mark; Koustenis, Elisabeth; Bruhn, Harald; Thomale, Ulrich-Wilhelm

2017-01-01

Pediatric posterior fossa (PF) tumor survivors experience long-term motor deficits. Specific cerebrocerebellar connections may be involved in incidence and severity of motor dysfunction. We examined the relationship between long-term ataxia as well as fine motor function and alteration of differential cerebellar efferent and afferent pathways using diffusion tensor imaging (DTI) and tractography. DTI-based tractography was performed in 19 patients (10 pilocytic astrocytoma (PA) and 9 medulloblastoma patients (MB)) and 20 healthy peers. Efferent Cerebello-Thalamo-Cerebral (CTC) and afferent Cerebro-Ponto-Cerebellar (CPC) tracts were reconstructed and analyzed concerning fractional anisotropy (FA) and volumetric measurements. Clinical outcome was assessed with the International Cooperative Ataxia Rating Scale (ICARS). Kinematic parameters of fine motor function (speed, automation, variability, and pressure) were obtained by employing a digitizing graphic tablet. ICARS scores were significantly higher in MB patients than in PA patients. Poorer ICARS scores and impaired fine motor function correlated significantly with volume loss of CTC pathway in MB patients, but not in PA patients. Patients with pediatric post-operative cerebellar mutism syndrome showed higher loss of CTC pathway volume and were more atactic. CPC pathway volume was significantly reduced in PA patients, but not in MB patients. Neither relationship was observed between the CPC pathway and ICARS or fine motor function. There was no group difference of FA values between the patients and healthy peers. Reduced CTC pathway volumes in our cohorts were associated with severity of long-term ataxia and impaired fine motor function in survivors of MBs. We suggest that the CTC pathway seems to play a role in extent of ataxia and fine motor dysfunction after childhood cerebellar tumor treatment. DTI may be a useful tool to identify relevant structures of the CTC pathway and possibly avoid surgically induced long-term neurological sequelae.

Computer-aided detection of renal calculi from noncontrast CT images using TV-flow and MSER features.

PubMed

Liu, Jianfei; Wang, Shijun; Turkbey, Evrim B; Linguraru, Marius George; Yao, Jianhua; Summers, Ronald M

2015-01-01

Renal calculi are common extracolonic incidental findings on computed tomographic colonography (CTC). This work aims to develop a fully automated computer-aided diagnosis system to accurately detect renal calculi on CTC images. The authors developed a total variation (TV) flow method to reduce image noise within the kidneys while maintaining the characteristic appearance of renal calculi. Maximally stable extremal region (MSER) features were then calculated to robustly identify calculi candidates. Finally, the authors computed texture and shape features that were imported to support vector machines for calculus classification. The method was validated on a dataset of 192 patients and compared to a baseline approach that detects calculi by thresholding. The authors also compared their method with the detection approaches using anisotropic diffusion and nonsmoothing. At a false positive rate of 8 per patient, the sensitivities of the new method and the baseline thresholding approach were 69% and 35% (p < 1e - 3) on all calculi from 1 to 433 mm(3) in the testing dataset. The sensitivities of the detection methods using anisotropic diffusion and nonsmoothing were 36% and 0%, respectively. The sensitivity of the new method increased to 90% if only larger and more clinically relevant calculi were considered. Experimental results demonstrated that TV-flow and MSER features are efficient means to robustly and accurately detect renal calculi on low-dose, high noise CTC images. Thus, the proposed method can potentially improve diagnosis.

Associations among Pericolonic Fat, Visceral Fat, and Colorectal Polyps on CT Colonography

PubMed Central

Liu, Jiamin; Pattanaik, Sanket; Yao, Jianhua; Dwyer, Andrew J.; Pickhardt, Perry J.; Choi, J. Richard; Summers, Ronald M.

2014-01-01

OBJECTIVE To determine the association between pericolonic fat and colorectal polyps using CT colonography (CTC). METHODS 1169 patients who underwent CTC and same day optical colonoscopy were assessed. Pericolonic fat was measured on CTC in a band surrounding the colon. Visceral adipose tissue volume was measured at the L2-L3 levels. Student t-tests, odds ratio, logistic regression, binomial statistics and weighted-kappa were performed to ascertain associations with the incidence of colorectal polyps. RESULTS Pericolonic fat volume fractions (PFVF) were 61.5±11.0% versus 58.1±11.5%, 61.6 ±11.1% versus 58.7±11.5%, and 62.4±10.6% versus 58.8±11.5% for patients with and without any polyps, adenomatous polyps, and hyperplastic polyps, respectively (p<0.0001). Similar trends were observed when examining visceral fat volume fractions (VFVF). When patients were ordered by quintiles of PFVF or VFVF, there were 2.49, 2.19 and 2.39-fold increases in odds ratio for the presence of any polyp, adenomatous polyps, or hyperplastic polyps from the first to the fifth quintile for PFVF, and 1.92, 2.00 and 1.71-fold increases in odds ratio for VFVF. Polyps tended to occur more commonly in parts of the colon that had more PFVF than the spatially-adjusted average for patients in the highest quintile of VFVF. CONCLUSION Pericolonic fat accumulations, like visceral fat, are correlated with an increased risk of adenomatous and hyperplastic polyps. PMID:25558027

EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality.

PubMed

Bailey, Julia N; Patterson, Christopher; de Nijs, Laurence; Durón, Reyna M; Nguyen, Viet-Huong; Tanaka, Miyabi; Medina, Marco T; Jara-Prado, Aurelio; Martínez-Juárez, Iris E; Ochoa, Adriana; Molina, Yolli; Suzuki, Toshimitsu; Alonso, María E; Wight, Jenny E; Lin, Yu-Chen; Guilhoto, Laura; Targas Yacubian, Elza Marcia; Machado-Salas, Jesús; Daga, Andrea; Yamakawa, Kazuhiro; Grisar, Thierry M; Lakaye, Bernard; Delgado-Escueta, Antonio V

2017-02-01

EFHC1 variants are the most common mutations in inherited myoclonic and grand mal clonic-tonic-clonic (CTC) convulsions of juvenile myoclonic epilepsy (JME). We reanalyzed 54 EFHC1 variants associated with epilepsy from 17 cohorts based on National Human Genome Research Institute (NHGRI) and American College of Medical Genetics and Genomics (ACMG) guidelines for interpretation of sequence variants. We calculated Bayesian LOD scores for variants in coinheritance, unconditional exact tests and odds ratios (OR) in case-control associations, allele frequencies in genome databases, and predictions for conservation/pathogenicity. We reviewed whether variants damage EFHC1 functions, whether efhc1 -/- KO mice recapitulate CTC convulsions and "microdysgenesis" neuropathology, and whether supernumerary synaptic and dendritic phenotypes can be rescued in the fly model when EFHC1 is overexpressed. We rated strengths of evidence and applied ACMG combinatorial criteria for classifying variants. Nine variants were classified as "pathogenic," 14 as "likely pathogenic," 9 as "benign," and 2 as "likely benign." Twenty variants of unknown significance had an insufficient number of ancestry-matched controls, but ORs exceeded 5 when compared with racial/ethnic-matched Exome Aggregation Consortium (ExAC) controls. NHGRI gene-level evidence and variant-level evidence establish EFHC1 as the first non-ion channel microtubule-associated protein whose mutations disturb R-type VDCC and TRPM2 calcium currents in overgrown synapses and dendrites within abnormally migrated dislocated neurons, thus explaining CTC convulsions and "microdysgenesis" neuropathology of JME.Genet Med 19 2, 144-156.

Computer-aided detection of renal calculi from noncontrast CT images using TV-flow and MSER features

PubMed Central

Liu, Jianfei; Wang, Shijun; Turkbey, Evrim B.; Linguraru, Marius George; Yao, Jianhua; Summers, Ronald M.

2015-01-01

Purpose: Renal calculi are common extracolonic incidental findings on computed tomographic colonography (CTC). This work aims to develop a fully automated computer-aided diagnosis system to accurately detect renal calculi on CTC images. Methods: The authors developed a total variation (TV) flow method to reduce image noise within the kidneys while maintaining the characteristic appearance of renal calculi. Maximally stable extremal region (MSER) features were then calculated to robustly identify calculi candidates. Finally, the authors computed texture and shape features that were imported to support vector machines for calculus classification. The method was validated on a dataset of 192 patients and compared to a baseline approach that detects calculi by thresholding. The authors also compared their method with the detection approaches using anisotropic diffusion and nonsmoothing. Results: At a false positive rate of 8 per patient, the sensitivities of the new method and the baseline thresholding approach were 69% and 35% (p < 1e − 3) on all calculi from 1 to 433 mm3 in the testing dataset. The sensitivities of the detection methods using anisotropic diffusion and nonsmoothing were 36% and 0%, respectively. The sensitivity of the new method increased to 90% if only larger and more clinically relevant calculi were considered. Conclusions: Experimental results demonstrated that TV-flow and MSER features are efficient means to robustly and accurately detect renal calculi on low-dose, high noise CTC images. Thus, the proposed method can potentially improve diagnosis. PMID:25563255

CT volumetric measurement of colorectal cancer helps predict tumor staging and prognosis

PubMed Central

Park, Jin Young; Lee, Sang Min; Lee, Jeong Sub; Han, Joon Koo

2017-01-01

Purpose To evaluate feasibility of CT colonography (CTC) volumetry of colorectal cancer (CRC) and its correlation with disease stage and patients’ survival. Materials and methods CTC volumetry was performed for 126 patients who underwent preoperative CTC. Reproducibility of tumor volume (Tvol) between two readers was assessed. One-way ANOVA and ROC analysis evaluated correlation between Tvol and pTNM staging. ROC analysis compared diagnostic performance to predict pTNM staging between Tvol and radiologist. Kaplan-Meier test compared overall survival. Results Reproducibility among readers was excellent (interclass correlation = 0.9829). Mean Tvol showed an incremental trend with T stage and Tvol of pT4b stage was significantly larger than other stages (P<0.0001). Az value (0.780) of Tvol to predict pT4b stage was significantly larger than that (0.591) of radiologist (P = 0.004). However, Tvol was not significantly different according to pN stage. Az values (0.723~0.857) of Tvol to predict M1 or M1b were comparable to those (0.772~0.690) of radiologist (P>0.05). Smaller tumor burden (≤12.85cm3), ≤T3, N0, M0 stages, and curative surgery were significantly associated with patients’ longer survival (P<0.05). Conclusion CT volumetry has a limited value to predict N stage; however, it may outperform the radiologist’s performance when predicting pT4b and M1b stage and can be a useful prognostic marker. PMID:28570580

The effects of increasing levels of dietary garlic bulb on growth performance, systolic blood pressure, hematology, and ascites syndrome in broiler chickens.

PubMed

Varmaghany, Saifali; Karimi Torshizi, Mohammad Amir; Rahimi, Shaban; Lotfollahian, Houshang; Hassanzadeh, Mohammad

2015-08-01

The effects of dietary garlic bulb were studied separately on hematological parameters, ascites incidence, and growth performance of an ascites susceptible broiler hybrid under both standard temperature conditions ( STC: ) and cold temperature conditions ( CTC: ). A total of 336 one-day-old male broiler chickens were allocated to 4 experimental groups with 4 replicates of 21 birds each under STC. In addition, the same grouping with another 336 birds was used for CTC. Under CTC, the birds were exposed to cold temperatures for induction of ascites. Experimental groups were defined by the inclusion of 0 (control), 5, 10 or 15 g/kg garlic bulbs in the diets under both STC and CTC. Growth performance, systolic blood pressure (as a measure of systemic arterial blood pressure), physiological and biochemical parameters, as well as ascites indices (right ventricle [ RV: ], total ventricle [ TV: ] weights, and RV/TV: ) were evaluated. Systolic blood pressure was determined using an indirect method with a sphygmomanometer, a pediatric cuff, and a Doppler device. The final body weight decreased quadratically (P = 0.003), with increasing garlic bulb levels in the diets under STC. The feed conversion ratio showed no significant differences among all groups under both STC and CTC. No significant differences were observed in total mortality and ascites-related mortality in all groups under STC, although total mortality (L: P = 0.01; Q: P = 0.001) and ascites-related mortality (L: P = 0.007; Q: P = 0.001) were significantly different among the diets under CTC. Under STC, the systolic blood pressure, packed cell volume, hemoglobin, RV, TV, and RV/TV did not vary significantly among the diets. However, red blood cell count and erythrocyte osmotic fragility decreased linearly (P < 0.005) with increasing garlic bulb levels in the diets under STC. Under CTC, the systolic blood pressure, packed cell volume, red blood cell count, and erythrocyte osmotic fragility decreased (P < 0.05) with increasing garlic levels. It is concluded that the inclusion of 5 g/kg garlic bulb in susceptible broiler chicken diets has a systemic anti-hypertensive effect and could decrease ascites incidence without impairing broiler chicken performance. © 2015 Poultry Science Association Inc.

Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

PubMed

Sasportas, Laura Sarah; Gambhir, Sanjiv Sam

2014-01-01

Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs) into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM) strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

Imaging Circulating Tumor Cells in Freely Moving Awake Small Animals Using a Miniaturized Intravital Microscope

PubMed Central

Sasportas, Laura Sarah; Gambhir, Sanjiv Sam

2014-01-01

Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs) into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM) strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals. PMID:24497977

Simultaneous isolation and detection of circulating tumor cells with a microfluidic silicon-nanowire-array integrated with magnetic upconversion nanoprobes.

PubMed

Wang, Chao; Ye, Min; Cheng, Liang; Li, Rui; Zhu, Wenwen; Shi, Zhen; Fan, Chunhai; He, Jinkang; Liu, Jian; Liu, Zhuang

2015-06-01

The development of sensitive and convenient methods for detection, enrichment, and analysis of circulating tumor cells (CTCs), which serve as an importance diagnostic indicator for metastatic progression of cancer, has received tremendous attention in recent years. In this work, a new approach characteristic of simultaneous CTC capture and detection is developed by integrating a microfluidic silicon nanowire (SiNW) array with multifunctional magnetic upconversion nanoparticles (MUNPs). The MUNPs were conjugated with anti-EpCAM antibody, thus capable to specifically recognize tumor cells in the blood samples and pull them down under an external magnetic field. The capture efficiency of CTCs was further improved by the integration with a microfluidic SiNW array. Due to the autofluorescence free nature in upconversion luminescence (UCL) imaging, our approach allows for highly sensitive detection of small numbers of tumor cells, which afterward could be collected for further analysis and re-culturing. We have further demonstrated that this approach can be applied to detect CTCs in clinical blood samples from lung cancer patients, and obtained consistent results by analyzing the UCL signals and the clinical outcomes of lung cancer metastasis. Therefore our approach represents a promising platform in CTC capture and detection with potential clinical utilization in cancer diagnosis and prognosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modeling Bacteriocin Resistance and Inactivation of Listeria innocua LMG 13568 by Lactobacillus sakei CTC 494 under Sausage Fermentation Conditions

PubMed Central

Leroy, Frédéric; Lievens, Kristoff; De Vuyst, Luc

2005-01-01

In mixed cultures, bacteriocin production by the sausage isolate Lactobacillus sakei CTC 494 rapidly inactivated sensitive Listeria innocua LMG 13568 cells, even at low bacteriocin activity levels. A small fraction of the listerial population was bacteriocin resistant. However, sausage fermentation conditions inhibited regrowth of resistant cells. PMID:16269805

Career and Technology Center Guides Students in Real-Life Careers | Poster

Cancer.gov

By Carolynne Keenan, Contributing Writer Frederick County Public School students have a unique opportunity—a chance to get a real-world, hands-on experience in biomedical science and biotechnology before they even graduate from high school, thanks to the Frederick County Career and Technology Center (CTC). Several years ago, the CTC established its biomedical sciences program

Gott time machines in anti-de Sitter space

NASA Astrophysics Data System (ADS)

Holst, Sören

1996-04-01

In 1991 Gott presented a solution of Einstein's field equations in 2+1 dimensions with λ=0 that contained closed timelike curves ( ctc's). This solution was remarkable because at first it did not seem to be unphysical in any other respect. Later, however, it was shown that Gott's solution is tachyonic in a certain sense. Here the case λ<0 is discussed. We show that it is also possible to construct ctc's in this case, in a way analogous to that used by Gott. We also show a special case of this construction to be tachyonic. λ<0 means that we are dealing with anti-de Sitter space, and since the CTC-construction necessitates some understanding of its structure, a few pages are devoted to this subject.

Role of TAF12 in the Increased VDR Activity in Paget’s Disease of Bone

DTIC Science & Technology

2013-10-01

and 5’‐GCC AAA TGC AGT TTA AGC TCT GCT‐3’ (antisense). The gene‐specific primers for mouse b‐actin were 5’‐GGC CGT ACC ACT GGC ATC GTG ATG‐ 3...cycles. The gene‐specific primers for CYP24A1 mRNA were 5’‐CGG GTG GAC CAT TTA CAA CTC GG‐3’ (sense) and 5’‐CTC AAC AGG CTC ATT GTC TGT GG‐3’ (antisense...The gene specific designing primers for b‐actinwere 5’‐ GTG CGT GAC ATC AAA GAG‐3’ (sense) and 5’‐GCC ACA GGA TTC CAT ACC‐3’ (antisense). The

Massive-training support vector regression and Gaussian process for false-positive reduction in computer-aided detection of polyps in CT colonography

PubMed Central

Xu, Jian-Wu; Suzuki, Kenji

2011-01-01

Purpose: A massive-training artificial neural network (MTANN) has been developed for the reduction of false positives (FPs) in computer-aided detection (CADe) of polyps in CT colonography (CTC). A major limitation of the MTANN is the long training time. To address this issue, the authors investigated the feasibility of two state-of-the-art regression models, namely, support vector regression (SVR) and Gaussian process regression (GPR) models, in the massive-training framework and developed massive-training SVR (MTSVR) and massive-training GPR (MTGPR) for the reduction of FPs in CADe of polyps. Methods: The authors applied SVR and GPR as volume-processing techniques in the distinction of polyps from FP detections in a CTC CADe scheme. Unlike artificial neural networks (ANNs), both SVR and GPR are memory-based methods that store a part of or the entire training data for testing. Therefore, their training is generally fast and they are able to improve the efficiency of the massive-training methodology. Rooted in a maximum margin property, SVR offers excellent generalization ability and robustness to outliers. On the other hand, GPR approaches nonlinear regression from a Bayesian perspective, which produces both the optimal estimated function and the covariance associated with the estimation. Therefore, both SVR and GPR, as the state-of-the-art nonlinear regression models, are able to offer a performance comparable or potentially superior to that of ANN, with highly efficient training. Both MTSVR and MTGPR were trained directly with voxel values from CTC images. A 3D scoring method based on a 3D Gaussian weighting function was applied to the outputs of MTSVR and MTGPR for distinction between polyps and nonpolyps. To test the performance of the proposed models, the authors compared them to the original MTANN in the distinction between actual polyps and various types of FPs in terms of training time reduction and FP reduction performance. The authors’ CTC database consisted of 240 CTC data sets obtained from 120 patients in the supine and prone positions. The training set consisted of 27 patients, 10 of which had 10 polyps. The authors selected 10 nonpolyps (i.e., FP sources) from the training set. These ten polyps and ten nonpolyps were used for training the proposed models. The testing set consisted of 93 patients, including 19 polyps in 7 patients and 86 negative patients with 474 FPs produced by an original CADe scheme. Results: With the MTSVR, the training time was reduced by a factor of 190, while a FP reduction performance [by-polyp sensitivity of 94.7% (18∕19) with 2.5 (230∕93) FPs∕patient] comparable to that of the original MTANN [the same sensitivity with 2.6 (244∕93) FPs∕patient] was achieved. The classification performance in terms of the area under the receiver-operating-characteristic curve value of the MTGPR (0.82) was statistically significantly higher than that of the original MTANN (0.77), with a two-sided p-value of 0.03. The MTGPR yielded a 94.7% (18∕19) by-polyp sensitivity at a FP rate of 2.5 (235∕93) per patient and reduced the training time by a factor of 1.3. Conclusions: Both MTSVR and MTGPR improve the efficiency of the training in the massive-training framework while maintaining a comparable performance. PMID:21626922

Electrochemical Performance of Glucose/Oxygen Biofuel Cells Based on Carbon Nanostructures.

PubMed

Koo, Min-Hye; Das, Gautam; Yoon, Hyon Hee

2016-03-01

The electrochemical performance of glucose/oxygen biofuel cells based on carbon nanostructures was investigated in the present study. Different types of carbon nanomaterials, including multi-walled carbon nanotubes (MWCNT), functionalized MWCNT (f-MWCNT), carbon nanofibers (CNF), and functionalized CNF (f-CNF) were examined for electrode fabrications. The anode for glucose/oxygen biofuel cells were prepared by sequential coating of carbon nanomaterials, charge transfer complex (CTC), glucose oxidase (GOx) and nafion membrane. The anode was then integrated with a bilirubin oxidase-immobilized cathode for the biofuel cell test. It was found that the electrochemical performance of the enzyme electrodes was remarkably enhanced by the amalgamation of carbon nanomaterials with the CTC. The biofuel cell with anode comprising of f-CNF and the cathode with MWCNT exhibited the best electrochemical performance with a maximum power density of 210 μW/cm2 at a cell voltage of 0.44 V for 20 mM glucose concentration, which is comparable with the best power density value reported earlier.

Trends in CT colonography: bibliometric analysis of the 100 most-cited articles.

PubMed

Mohammed, Mohammed Fahim; Chahal, Tejbir; Gong, Bo; Bhulani, Nizar; O'Keefe, Michael; O'Connell, Timothy; Nicolaou, Savvas; Khosa, Faisal

2017-12-01

Our purpose was to identify the top 100 cited articles, which focused on CT colonography (CTC). This list could then be analysed to establish trends in CTC research while also identifying common characteristics of highly cited works. Web of Science search was used to create a database of scientific journals using our search terms. A total of 10,597 articles were returned from this search. Articles were included if they focused on diagnostic imaging, imaging technique, cost-effectiveness analysis, clinical use, patient preference or trends in CTC. Articles were ranked by citation count and screened by two attending radiologists. The following information was collected from each article: database citations, citations per year, year published, journal, authors, department affiliation, study type and design, statistical analysis, sample size, modality and topic. Citations for the top 100 articles ranged from 73 to 1179, and citations per year ranged from 4.5 to 84.21. Articles were published across 22 journals, most commonly Radiology (n = 37) and American Journal of Roentgenology (n = 19). Authors contributed from 1 to 20 articles. 19% of first authors were affiliated with a department other than radiology. Of the 100 articles, the most common topics were imaging technique (n = 40), diagnostic utility of imaging (n = 28) and clinical uses (n = 18). Our study provides intellectual milestones in CTC research, reflecting on the characteristics and quality of published literature. This work also provides the most influential references related to CTC and serves as a guide to the features of a citable paper in this field.

Limited-preparation CT colonography in frail elderly patients: a feasibility study.

PubMed

Keeling, Aoife N; Slattery, Michael M; Leong, Sum; McCarthy, Eoghan; Susanto, Maja; Lee, Michael J; Morrin, Martina M

2010-05-01

Full colonic preparation can be onerous and may be poorly tolerated in frail elderly patients. The purpose of this study was to prospectively assess the image quality and diagnostic yield of limited-preparation CT colonography (CTC) in elderly patients with suspected colorectal cancer who were deemed medically unfit or unsuitable for colonoscopy. A prospective study was performed of 67 elderly patients with reduced functional status referred for CTC. Participants were prescribed a limited bowel preparation consisting of a low-residue diet for 3 days, 1 L of 2% oral diatrizoate meglumine (Gastrografin) 24 hours before CTC, and 1 L of 2% oral Gastrografin over the 2 hours immediately before CTC. No cathartic preparation was administered. All colonic segments were graded from 1 to 5 for image quality (1, unreadable; 2, poor; 3, equivocal; 4, good; 5, excellent) and reader confidence. Clinical and conventional colonoscopy follow-up findings were documented, and all colonic and extracolonic pathologic findings were documented. Overall image quality and reader confidence in the evaluation of the colon was rated good or excellent in 84% of the colonic segments. Colonic abnormalities were identified in 12 patients (18%), including four colonic tumors, two polyps, and seven colonic strictures. Incidental extraintestinal findings were detected in 43 patients (64%), including nine patients with lesions radiologically consistent with malignancy. Limited-preparation low-dose CTC is a feasible and useful minimally invasive technique with which to evaluate the colon and exclude gross pathology (mass lesions and polyps > 1 cm) in elderly patients with diminished performance status, yielding good to excellent image quality.

Game as a Career Metaphor: A Chaos Theory Career Counselling Application

ERIC Educational Resources Information Center

Pryor, Robert George Leslie; Bright, Jim E. H.

2009-01-01

The potential of game as a career metaphor for use in counselling is explored and it is argued that it has been largely overlooked in the literature to date. This metaphor is then explicitly linked with the Chaos Theory of Careers (CTC), by showing how the notion of attractors within the CTC can be illustrated effectively using games metaphors.…

Participatory Appropriation of Health Science by Primary School Students in Rural Zambia.

ERIC Educational Resources Information Center

Mwape, Gertrude; Serpell, Robert

The Child-to-Child (CtC) project involved school-age African children in monitoring younger children's weight and health (since much of the daily infant care in Africa is performed by preadolescents). CtC emphasizes local autonomy and is based on respect for children as morally responsible community members with a basic right to health and…

Consultants' Report to West Virginia State College and Community and Technical College Study Commission: Observations and Recommendations.

ERIC Educational Resources Information Center

Boone, Edgar J.; Vaughan, George B.

West Virginia State College entered into a contract with two professors from North Carolina State University to provide consultation and guidance to the West Virginia State College-Community and Technical College (WVSC-CTC) Study Commission. Findings and recommendations include: (1) the strengths of the CTC, as seen by its community, are the…

Exploiting the Immunological Effects of Standard Treatments in Prostate Cancer

DTIC Science & Technology

2009-03-01

GTG CCT 1114 In progress PTMA F: CAC CAT GTC AGA CGC AGC CGT A R: GTC ATC CTC GTC GGT CTT CT 331 Cloned successfully CEP78 F: CAC CAT GAT CGA CTC CGT...Mde L, Gray A, Hubby B, Kast WM. In vivo effects of vaccination with six-transmembrane epithelial antigen of the prostate: a candidate antigen for

Rapid in situ assessment of physiological activities in bacterial biofilms using fluorescent probes

NASA Technical Reports Server (NTRS)

Yu, F. P.; McFeters, G. A.

1994-01-01

Two rapid in situ enumeration methods using fluorescent probes were used to assess the physiological activities of Klebsiella pneumoniae biofilms on stainless steel. Fluorescent dyes, 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and rhodamine 123 (Rh 123), were chosen to perform this study. CTC is a soluble redox indicator which can be reduced by respiring bacteria to fluorescent CTC-formazan crystals. Rh 123 is incorporated into bacteria with respect to cellular proton motive force. The intracellular accumulation of these fluorescent dyes can be determined using epifluorescence microscopy. The results obtained with these two fluorescent probes in situ were compared to the plate count (PC) and in situ direct viable count (DVC) methods. Viable cell densities within biofilms determined by the three in situ methods were comparable and always showed approximately 2-fold higher values than those obtained with the PC method. As an additional advantage, the results were observed after 2 h, which was shorter than the 4 h incubation time required for the DVC method and 24 h for colony formation. The results indicate that staining with CTC and Rh 123 provides rapid information regarding cell numbers and physiological activities of bacteria within biofilms.

Effects of chlortetracycline and copper on tetracyclines and copper resistance genes and microbial community during swine manure anaerobic digestion.

PubMed

Wang, Rui; Chen, Meixue; Feng, Feng; Zhang, Junya; Sui, Qianwen; Tong, Juan; Wei, Yuansong; Wei, Dongbin

2017-08-01

As antibiotic and heavy metals are over used in the livestock industry, animal manure is a reservoir of antibiotic resistance genes (ARGs). Anaerobic digestion has been reported to have the potential to reduce ARGs. However, few studies investigated whether reduction of ARGs would be affected by different external pressures including antibiotics and heavy metals during anaerobic digestion. The purpose of this study was thus to investigate effects of both chlortetracycline (CTC) and Cu on reduction of ARGs, heavy metal resistance genes (HMRGs) and mobile genetic elements (MGEs) during the swine manure anaerobic digestion. The results showed that the predominant ARGs (tetO, tetW, tetX, tetL) could be effectively reduced (approximately 1.00 log copies/g TS) through mesophilic anaerobic digestion. Microbial community evolution was the main driver. It was interesting that Treponema might indicate the termination of anaerobic digestion and compete with ARGs host bacteria. Addition of CTC, Cu and CTC+Cu affected microbial community change and hindered removal of ARGs, especially, CTC+Cu seriously affected Treponema and ARGs during anaerobic digestion. Copyright © 2017 Elsevier Ltd. All rights reserved.

Data-Driven Discovery of Extravasation Pathway in Circulating Tumor Cells

PubMed Central

Yadavalli, S.; Jayaram, S.; Manda, S. S.; Madugundu, A. K.; Nayakanti, D. S.; Tan, T. Z.; Bhat, R.; Rangarajan, A.; Chatterjee, A.; Gowda, H.; Thiery, J. P.; Kumar, P.

2017-01-01

Circulating tumor cells (CTCs) play a crucial role in cancer dissemination and provide a promising source of blood-based markers. Understanding the spectrum of transcriptional profiles of CTCs and their corresponding regulatory mechanisms will allow for a more robust analysis of CTC phenotypes. The current challenge in CTC research is the acquisition of useful clinical information from the multitude of high-throughput studies. To gain a deeper understanding of CTC heterogeneity and identify genes, pathways and processes that are consistently affected across tumors, we mined the literature for gene expression profiles in CTCs. Through in silico analysis and the integration of CTC-specific genes, we found highly significant biological mechanisms and regulatory processes acting in CTCs across various cancers, with a particular enrichment of the leukocyte extravasation pathway. This pathway appears to play a pivotal role in the migration of CTCs to distant metastatic sites. We find that CTCs from multiple cancers express both epithelial and mesenchymal markers in varying amounts, which is suggestive of dynamic and hybrid states along the epithelial-mesenchymal transition (EMT) spectrum. Targeting the specific molecular nodes to monitor disease and therapeutic control of CTCs in real time will likely improve the clinical management of cancer progression and metastases. PMID:28262832

A direct comparison of CellSearch and ISET for circulating tumour-cell detection in patients with metastatic carcinomas

PubMed Central

Farace, F; Massard, C; Vimond, N; Drusch, F; Jacques, N; Billiot, F; Laplanche, A; Chauchereau, A; Lacroix, L; Planchard, D; Le Moulec, S; André, F; Fizazi, K; Soria, J C; Vielh, P

2011-01-01

Background: Circulating tumour cells (CTCs) can provide information on patient prognosis and treatment efficacy. However, there is no universal method to detect CTC currently available. Here, we compared the performance of two CTC detection systems based on the expression of the EpCAM antigen (CellSearch assay) or on cell size (ISET assay). Methods: Circulating tumour cells were enumerated in 60 patients with metastatic carcinomas of breast, prostate and lung origins using CellSearch according to the manufacturer's protocol and ISET by studying cytomorphology and immunolabelling with anti-cytokeratin or lineage-specific antibodies. Results: Concordant results were obtained in 55% (11 out of 20) of the patients with breast cancer, in 60% (12 out of 20) of the patients with prostate cancer and in only 20% (4 out of 20) of lung cancer patients. Conclusion: Our results highlight important discrepancies between the numbers of CTC enumerated by both techniques. These differences depend mostly on the tumour type. These results suggest that technologies limiting CTC capture to EpCAM-positive cells, may present important limitations, especially in patients with metastatic lung carcinoma. PMID:21829190

Probing charge transfer complex states in organic solar cells using photocurrent spectroscopy

NASA Astrophysics Data System (ADS)

Moghe, Dhanashree; Adil, Danish; Kanimozhi, Catherine; Dutta, Gitesh; Patil, Satish; Guha, Suchismita

2013-03-01

Diketopyrrolopyrrole (DPP) containing copolymers-fullerene blends have gained a lot of interest in organic optoelectronics with a great potential in organic photovoltaics (OPVs). The interfacial charge transfer complex (CTC) states formed in donor-acceptor blended OPVs play a major role in the overall efficiency of the device. We investigate the spectral photocurrent characteristics of five DPP based copolymers; two of them being benzothiadiazole and carbazole -based statistical copolymers of DPP. These systems provide a wide range of bandgap energies ranging from ~ 1.4 to 1.7 eV. We use Fourier transform photocurrent spectroscopy (FTPS) and monochromatic photocurrent (PC) to identify the CTC states in these DPP copolymer -fullerene blends. The stability of the CTC state is found to be dependent on the band gap energy difference between the donor copolymer and the acceptor. We support our inferences from theoretical results obtained using density-functional theory (DFT) and time-dependent DFT for two DPP based copolymers The theoretical calculations reveal a higher contribution of the CTC states to the lowest excited state in the phenyl-based DPP monomer, which has a larger bandgap energy compared to the thiophene-based DPP system, in the presence of a fullerene molecule.

Performance Evaluation of Hap-Free Paint Strippers vs. Methylene-Chloride-Based Strippers for Removing Army Chemical Agent Resistant Coatings (CARC)

DTIC Science & Technology

2006-06-01

Preparation..........................................................................................................3 2.2 Alternatives Selection ...water-borne panels were green. 2.2 Alternatives Selection The Gap Assessment Report generated by CTC/NDCEE identified many HAP-free alternatives to...strip times (as reported by the vendor) of many of the products. ARL used this information to select the alternatives to be included in its test

Microscale Laminar Vortices for High-Purity Extraction and Release of Circulating Tumor Cells.

PubMed

Hur, Soojung Claire; Che, James; Di Carlo, Dino

2017-01-01

Circulating tumor cells (CTCs) are disseminated tumor cells that reflect the tumors of origin and can provide a liquid biopsy that would potentially enable noninvasive tumor profiling, treatment monitoring, and identification of targeted treatments. Accurate and rapid purification of CTCs holds great potential to improve cancer care but the task remains technically challenging. Microfluidic isolation of CTCs within microscale vortices enables high-throughput and size-based purification of rare CTCs from bodily fluids. Collected cells are highly pure, viable, and easily accessible, allowing seamless integration with various downstream applications. Here, we describe how to fabricate the High-Throughput Vortex Chip (Vortex-HT) and to process diluted whole blood for CTC collection. Lastly, immunostaining and imaging protocols for CTC classification and corresponding CTC image galleries are reported.

Pathogenetic Influences of Human Herpesvirus 8 (HHV-8) in Prostate Cancer Progression

DTIC Science & Technology

2012-05-25

expression of each GOI were calculated by raising 2 to the negative value ΔΔCt for each sample. Primer sequences used were: AR-F: 5’ ATG GTG AGC AGA... GTG CCC TAT C 3’ AR- R: 5’ ATG GTC CCT GGC AGT CTC CAA A 3’ PSA-F: CGC AAG TTC ACC CTC AGA AGG T 3’ PSA-R: 5’ GAC GTG ATA CCT TGA AGC ACA CC 3’ MSMB-F...TGG CGT TCC AGG GAC TCA T 3’ Zeb1-F: 5’ GGC ATA CAC CTA CTC AAC TAC GG 3’ Zeb1-R: 5’ TGG GCG GTG TAG AAT CAG AGT C 3’ Snail-F: 5’ TGC CCT CAA GAT

Applicability of tetrazolium salts for the measurement of respiratory activity and viability of groundwater bacteria

USGS Publications Warehouse

Hatzinger, P.B.; Palmer, P.; Smith, R.L.; Penarrieta, C.T.; Yoshinari, T.

2003-01-01

A study was undertaken to measure aerobic respiration by indigenous bacteria in a sand and gravel aquifer on western Cape Cod, MA using tetrazolium salts and by direct oxygen consumption using gas chromatography (GC). In groundwater and aquifer slurries, the rate of aerobic respiration calculated from the direct GC assay was more than 600 times greater than that using the tetrazolium salt 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-phenyl tetrazolium chloride (INT). To explain this discrepancy, the toxicity of INT and two additional tetrazolium salts, sodium 3???-[1-(phenylamino)-carbonyl]-3,4-tetrazolium]-bis(4-methoxy-6-nitro) benzenesulfonic acid hydrate (XTT) and 5-cyano-2,3-ditolyl tetrazolium chloride (CTC), to bacterial isolates from the aquifer was investigated. Each of the three tetrazolium salts was observed to be toxic to some of the groundwater isolates at concentrations normally used in electron transport system (ETS) and viability assays. For example, incubation of cells with XTT (3 mM) caused the density of four of the five groundwater strains tested to decline by more than four orders of magnitude. A reasonable percentage (>57%) of cells killed by CTC and INT contained visible formazan crystals (the insoluble, reduced form of the salts) after 4 h of incubation. Thus, many of the cells reduced enough CTC or INT prior to dying to be considered viable by microscopic evaluation. However, one bacterium (Pseudomonas fluorescens) that remained viable and culturable in the presence of INT and CTC, did not incorporate formazan crystals into more than a few percent of cells, even after 24 h of incubation. This strain would be considered nonviable based on traditional tetrazolium salt reduction assays. The data show that tetrazolium salt assays are likely to dramatically underestimate total ETS activity in groundwater and, although they may provide a reasonable overall estimate of viable cell numbers in a community of groundwater bacteria, some specific strains may be falsely considered nonviable by this assay due to poor uptake or reduction of the salts. ?? 2003 Elsevier Science B.V. All rights reserved.

High-performance computer aided detection system for polyp detection in CT colonography with fluid and fecal tagging

NASA Astrophysics Data System (ADS)

Liu, Jiamin; Wang, Shijun; Kabadi, Suraj; Summers, Ronald M.

2009-02-01

CT colonography (CTC) is a feasible and minimally invasive method for the detection of colorectal polyps and cancer screening. Computer-aided detection (CAD) of polyps has improved consistency and sensitivity of virtual colonoscopy interpretation and reduced interpretation burden. A CAD system typically consists of four stages: (1) image preprocessing including colon segmentation; (2) initial detection generation; (3) feature selection; and (4) detection classification. In our experience, three existing problems limit the performance of our current CAD system. First, highdensity orally administered contrast agents in fecal-tagging CTC have scatter effects on neighboring tissues. The scattering manifests itself as an artificial elevation in the observed CT attenuation values of the neighboring tissues. This pseudo-enhancement phenomenon presents a problem for the application of computer-aided polyp detection, especially when polyps are submerged in the contrast agents. Second, general kernel approach for surface curvature computation in the second stage of our CAD system could yield erroneous results for thin structures such as small (6-9 mm) polyps and for touching structures such as polyps that lie on haustral folds. Those erroneous curvatures will reduce the sensitivity of polyp detection. The third problem is that more than 150 features are selected from each polyp candidate in the third stage of our CAD system. These high dimensional features make it difficult to learn a good decision boundary for detection classification and reduce the accuracy of predictions. Therefore, an improved CAD system for polyp detection in CTC data is proposed by introducing three new techniques. First, a scale-based scatter correction algorithm is applied to reduce pseudo-enhancement effects in the image pre-processing stage. Second, a cubic spline interpolation method is utilized to accurately estimate curvatures for initial detection generation. Third, a new dimensionality reduction classifier, diffusion map and local linear embedding (DMLLE), is developed for classification and false positives (FP) reduction. Performance of the improved CAD system is evaluated and compared with our existing CAD system (without applying those techniques) using CT scans of 1186 patients. These scans are divided into a training set and a test set. The sensitivity of the improved CAD system increased 18% on training data at a rate of 5 FPs per patient and 15% on test data at a rate of 5 FPs per patient. Our results indicated that the improved CAD system achieved significantly better performance on medium-sized colonic adenomas with higher sensitivity and lower FP rate in CTC.

Clinical significance of peripheral circulating tumor cell counts in colorectal polyps and non-metastatic colorectal cancer.

PubMed

Yang, Chengguang; Zhuang, Wenfang; Hu, Yuemei; Zhu, Leiming

2018-01-22

The presence of peripheral circulating tumor cells indicates the possible existence of a tumor in vivo; however, low numbers of circulating tumor cells (CTCs) can be detected in peripheral blood of healthy individuals as well as patients with benign tumors. It is not known whether peripheral CTC counts differ between patients with benign colorectal disease and those with colorectal cancer. Comparative analysis of preoperative peripheral circulating tumor cells counts was completed in patients with benign colorectal disease (colorectal polyps) and non-metastatic cancer of the colon and rectum. The results of this analysis showed that patients with colorectal cancer had higher CTC counts than patients with colorectal polyps (3.47 ± 0.32/3.2 ml vs 1.49 ± 0.2/3.2 ml, P < 0.001). Colorectal cancer patients with tumors of the sigmoid colon displayed the highest CTC counts (4.87 ± 0.95/3.2 ml), followed by those with tumors of the rectum (3.73 ± 0.54/3.2 ml), ascending colon (3.5 ± 0.63/3.2 ml), transverse colon (2.4 ± 0.68/3.2 ml), and descending colon (2.08 ± 0.46/3.2 ml). Colorectal polyp patients with polyps in the rectum showed the highest CTC counts (2.2 ± 0.77/3.2 ml), followed by those with polyps in the ascending colon (1.82 ± 0.54/3.2 ml), sigmoid colon (1.38 ± 0.25/3.2 ml), transverse colon (0.75 ± 0.25/3.2 ml), and descending colon (0.33 ± 0.21/3.2 ml). The differences in CTC counts suggest that anatomical location of colorectal tumors may affect blood vessel metastasis. Meanwhile, patients with moderately differentiated and poorly differentiated tumors displayed higher peripheral blood CTC counts compared to those with well-differentiated tumors (P < 0.001). This result suggests that the type of tissue differentiation of colorectal tumors may act as another factor that affects blood vessel metastasis. Circulating tumor cells can be detected in the peripheral blood of colorectal cancer patients as well as patients with colorectal polyps. The differences in CTC counts suggest that anatomical location and the type of tissue differentiation of colorectal tumors may affect blood vessel metastasis.

Microfluidic chip for isolation of viable circulating tumor cells of hepatocellular carcinoma for their culture and drug sensitivity assay.

PubMed

Zhang, Yu; Zhang, Xiaofeng; Zhang, Jinling; Sun, Bin; Zheng, Lulu; Li, Jun; Liu, Sixiu; Sui, Guodong; Yin, Zhengfeng

2016-11-01

Circulating tumor cells (CTCs) have been proposed to be an active source of metastasis or recurrence of hepatocellular carcinoma (HCC). The enumeration and characterization of CTCs has important clinical significance in recurrence prediction and treatment monitoring in HCC patients. We previously developed a unique method to separate HCC CTCs based on the interaction of the asialoglycoprotein receptor (ASGPR) expressed on their membranes with its ligand. The current study applied the ligand-receptor binding assay to a CTC-chip in a microfluidic device. Efficient capture of HCC CTCs originates from the small dimensions of microfluidic channels and enhanced local topographic interactions between the microfluidic channel and extracellular extensions. With the optimized conditions, a capture yield reached > 85% for artificial CTC blood samples. Clinical utility of the system was further validated. CTCs were detected in all the examined 36 patients with HCC, with an average of 14 ± 10/2 mL. On the contrary, no CTCs were detected in healthy, benign liver disease or non-HCC cancer subjects. The current study also successfully demonstrated that the captured CTCs on our CTC-chip were readily released with ethylene diamine tetraacetic acid (EDTA); released CTCs remained alive and could be expanded to form a spheroid-like structure in a 3-dimensional cell culture assay; furthermore, sensitivity of released CTCs to chemotherapeutic agents (sorafenib or oxaliplatin) could be effectively tested utilizing this culture assay. In conclusion, the methodologies presented here offer great promise for accurate enumeration and easy release of captured CTCs, and released CTCs could be cultured for further functional studies.

Computer-aided marginal artery detection on computed tomographic colonography

NASA Astrophysics Data System (ADS)

Wei, Zhuoshi; Yao, Jianhua; Wang, Shijun; Liu, Jiamin; Summers, Ronald M.

2012-03-01

Computed tomographic colonography (CTC) is a minimally invasive technique for colonic polyps and cancer screening. The marginal artery of the colon, also known as the marginal artery of Drummond, is the blood vessel that connects the inferior mesenteric artery with the superior mesenteric artery. The marginal artery runs parallel to the colon for its entire length, providing the blood supply to the colon. Detecting the marginal artery may benefit computer-aided detection (CAD) of colonic polyp. It can be used to identify teniae coli based on their anatomic spatial relationship. It can also serve as an alternative marker for colon localization, in case of colon collapse and inability to directly compute the endoluminal centerline. This paper proposes an automatic method for marginal artery detection on CTC. To the best of our knowledge, this is the first work presented for this purpose. Our method includes two stages. The first stage extracts the blood vessels in the abdominal region. The eigenvalue of Hessian matrix is used to detect line-like structures in the images. The second stage is to reduce the false positives in the first step. We used two different masks to exclude the false positive vessel regions. One is a dilated colon mask which is obtained by colon segmentation. The other is an eroded visceral fat mask which is obtained by fat segmentation in the abdominal region. We tested our method on a CTC dataset with 6 cases. Using ratio-of-overlap with manual labeling of the marginal artery as the standard-of-reference, our method yielded true positive, false positive and false negative fractions of 89%, 33%, 11%, respectively.

Survivin gene levels in the peripheral blood of patients with gastric cancer independently predict survival

PubMed Central

2009-01-01

Background The detection of circulating tumor cells (CTC) is considered a promising tool for improving risk stratification in patients with solid tumors. We investigated on whether the expression of CTC related genes adds any prognostic power to the TNM staging system in patients with gastric carcinoma. Methods Seventy patients with TNM stage I to IV gastric carcinoma were retrospectively enrolled. Peripheral blood samples were tested by means of quantitative real time PCR (qrtPCR) for the expression of four CTC related genes: carcinoembryonic antigen (CEA), cytokeratin-19 (CK19), vascular endothelial growth factor (VEGF) and Survivin (BIRC5). Results Gene expression of Survivin, CK19, CEA and VEGF was higher than in normal controls in 98.6%, 97.1%, 42.9% and 38.6% of cases, respectively, suggesting a potential diagnostic value of both Survivin and CK19. At multivariable survival analysis, TNM staging and Survivin mRNA levels were retained as independent prognostic factors, demonstrating that Survivin expression in the peripheral blood adds prognostic information to the TNM system. In contrast with previously published data, the transcript abundance of CEA, CK19 and VEGF was not associated with patients' clinical outcome. Conclusions Gene expression levels of Survivin add significant prognostic value to the current TNM staging system. The validation of these findings in larger prospective and multicentric series might lead to the implementation of this biomarker in the routine clinical setting in order to optimize risk stratification and ultimately personalize the therapeutic management of these patients. PMID:20028510

Boar sperm storage capacity of BTS and Androhep Plus: viability, motility, capacitation, and tyrosine phosphorylation.

PubMed

Dubé, Charlotte; Beaulieu, Martin; Reyes-Moreno, Carlos; Guillemette, Christine; Bailey, Janice L

2004-09-01

Androhep Plus, a long-term extender (up to 7 days) and Beltsville Thawing Solution (BTS), a short-term extender (up to 3 days), are commonly used for liquid storage of porcine semen. To test the hypothesis that modifications in sperm viability, motility, chlortetracycline (CTC) fluorescence patterns, and protein tyrosine phosphorylation occur during semen storage in extenders, we compared these end points at different periods of storage in either Androhep Plus or BTS. Sperm from five boars were assessed daily over 12 days of storage (n = 5 ejaculates from different boars). Viability was not different (P < 0.05 between extenders, except on Day 2, when Androhep Plus maintained better viability. Differences in the percentage of motile (total) sperm due to extender were evident on Days 2, 4, 5, and 6, when Androhep Plus was superior to BTS (P < 0.05). The percentages of progressively motile sperm also differed, with Androhep Plus supporting higher rates on Days 2, 4, 5, 7, 8, 9, 10, and 11 (P < 0.05). The CTC fluorescence pattern distribution differed due to extender as early as Day 2; storage in Androhep Plus induced higher levels of pattern B sperm (P < 0.05) than storage in BTS. A tyrosine-phosphorylated protein of Mr 21,000 appeared after 10 days in sperm incubated in BTS, and was identified as a phospholipid hydroperoxide glutathione peroxidase. Therefore, modifications in viability, motility, CTC fluorescence patterns, and sperm protein tyrosine phosphorylation were apparent during sperm storage in extenders; these may affect the fertilizing capacity of the semen.

Social and Emotional Learning Competencies and Cross-Thematic Curriculum-Related Skills of Greek Students: A Multifactorial and Triangulation Analysis

ERIC Educational Resources Information Center

Tsolou, Olympia; Margaritis, Vasileios

2013-01-01

The cross-thematic curriculum (CTC) for school education has recently been implemented so that the quality of the Greek educational system is improved. This study aimed at assessing social and emotional learning competencies and CTC-related skills of 541 Greek students aged 11-13. Data triangulation was also used for validating these findings,…

Wedge-shaped microfluidic chip for circulating tumor cells isolation and its clinical significance in gastric cancer.

PubMed

Yang, Chaogang; Zhang, Nangang; Wang, Shuyi; Shi, Dongdong; Zhang, Chunxiao; Liu, Kan; Xiong, Bin

2018-05-23

Circulating tumor cells (CTCs) have great potential in both basic research and clinical application for the managements of cancer. However, the complicated fabrication processes and expensive materials of the existing CTCs isolation devices, to a large extent, limit their clinical translation and CTCs' clinical value. Therefore, it remains to be urgently needed to develop a new platform for achieving CTCs detection with low-cost, mass-producible but high performance. In the present study, we introduced a novel wedge-shaped microfluidic chip (named CTC-ΔChip) fabricated by two pieces of glass through wet etching and thermal bonding technique for CTCs isolation, which achieved CTCs enrichment by different size without cell surface expression markers and CTCs identification with three-color immunocytochemistry method (CK+/CD45-/Nucleus+). We validated the feasibility of CTC-ΔChip for detecting CTCs from different types of solid tumor. Furthermore, we applied the newly-developed platform to investigate the clinical significance of CTCs in gastric cancer (GC). Based on "label-free" characteristic, the capture efficiency of CTC-ΔChip can be as high as 93.7 ± 3.2% in DMEM and 91.0 ± 3.0% in whole blood sample under optimized conditions. Clinically, CTC-ΔChip exhibited the feasibility of detecting CTCs from different types of solid tumor, and it identified 7.30 ± 7.29 CTCs from 2 mL peripheral blood with a positive rate of 75% (30/40) in GC patients. Interestingly, we found that GC CTCs count was significantly correlated with multiple systemic inflammation indexes, including the lymphocyte count, platelet count, the level of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio. In addition, we also found that both the positivity rate and CTCs count were significantly associated with multiple clinicopathology parameters. Our novel CTC-ΔChip shows high performance for detecting CTCs from less volume of blood samples of cancer patients and important clinical significance in GC. Owing to the advantages of low-cost and mass-producible, CTC-ΔChip holds great potential of clinical application for cancer therapeutic guidance and prognostic monitoring in the future.

A cluster randomized non-inferiority field trial on the immunogenicity and safety of tetanus toxoid vaccine kept in controlled temperature chain compared to cold chain.

PubMed

Juan-Giner, Aitana; Domicent, Camille; Langendorf, Céline; Roper, Martha H; Baoundoh, Paul; Fermon, Florence; Gakima, Primitive; Zipursky, Simona; Tamadji, Mbaihol; Grais, Rebecca F

2014-10-29

In resource-poor settings, cold chain requirements present barriers for vaccine delivery. We evaluated the immunogenicity and safety of tetanus toxoid (TT) vaccine in "Controlled Temperature Chain" (CTC; up to 40 °C for <30 days before administration), compared to standard cold chain (SCC; 2-8 °C). Prior to the study, stability parameters of TT-CTC were shown to meet international requirements. A cluster randomized, non-inferiority trial was conducted in Moïssala district, Chad, December 2012-March 2013. Thirty-four included clusters were randomized to CTC or SCC. Women aged 14-49 years, eligible for TT vaccination and with a history of ≤1 TT dose, received two TT doses 4 weeks apart. Participants were blinded to allocation strategy. Tetanus antibody titers were measured using standard ELISA at inclusion and 4 weeks post-TT2. Primary outcome measures were post-vaccination seroconversion and fold-increase in geometric mean concentrations (GMC). Non-inferiority was by seroconversion difference (TTSCC-TTCTC) <5% and ratio of GMCs (TTSCC/TTCTC) <1.5. Adverse events were monitored at health centers and at next contact with participants. A total of 2128 women (CTC=1068; SCC=1060) were recruited. Primary intention to vaccinate analysis included 1830 participants; 272 of these were included in the seroconversion analysis. Seroconversion was reached by >95% of participants; upper 95%CI of the difference was 5.6%. Increases in GMC were over 4-fold; upper 95%CI of GMC ratio was 1.36 in the adjusted analysis. Few adverse events were recorded. This study demonstrates the immunogenicity and safety of TT in CTC at <40 °C for <30 days. The high proportion of participants protected at baseline results in a reduction of power to detect a 5% non-inferiority margin. However, results at a 10% non-inferiority margin, the comparable GMC increases and vaccine's stability demonstrated in the preliminary phase indicate that CTC can be an alternative strategy for TT delivery in situations where cold chain cannot be maintained. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Exploring the context in which different close-to-community sexual and reproductive health service providers operate in Bangladesh: a qualitative study.

PubMed

Mahmud, Ilias; Chowdhury, Sadia; Siddiqi, Bulbul Ashraf; Theobald, Sally; Ormel, Hermen; Biswas, Salauddin; Jahangir, Yamin Tauseef; Sarker, Malabika; Rashid, Sabina Faiz

2015-09-01

A range of formal and informal close-to-community (CTC) health service providers operate in an increasingly urbanized Bangladesh. Informal CTC health service providers play a key role in Bangladesh's pluralistic health system, yet the reasons for their popularity and their interactions with formal providers and the community are poorly understood. This paper aims to understand the factors shaping poor urban and rural women's choice of service provider for their sexual and reproductive health (SRH)-related problems and the interrelationships between these providers and communities. Building this evidence base is important, as the number and range of CTC providers continue to expand in both urban slums and rural communities in Bangladesh. This has implications for policy and future programme interventions addressing the poor women's SRH needs. Data was generated through 24 in-depth interviews with menstrual regulation clients, 12 focus group discussions with married men and women in communities and 24 semi-structured interviews with formal and informal CTC SRH service providers. Data was collected between July and September 2013 from three urban slums and one rural site in Dhaka and Sylhet, Bangladesh. Atlas.ti software was used to manage data analysis and coding, and a thematic analysis was undertaken. Poor women living in urban slums and rural areas visit a diverse range of CTC providers for SRH-related problems. Key factors influencing their choice of provider include the following: availability, accessibility, expenses and perceived quality of care, the latter being shaped by notions of trust, respect and familiarity. Informal providers are usually the first point of contact even for those clients who subsequently access SRH services from formal providers. Despite existing informal interactions between both types of providers and a shared understanding that this can be beneficial for clients, there is no effective link or partnership between these providers for referral, coordination and communication regarding SRH services. Training informal CTC providers and developing strategies to enable better links and coordination between this community-embedded cadre and the formal health sector has the potential to reduce service cost and improve availability of quality SRH (and other) care at the community level.

Sensitive detection of Escherichia coli O157:H7 in food and water by immunomagnetic separation and solid-phase laser cytometry

NASA Technical Reports Server (NTRS)

Pyle, B. H.; Broadaway, S. C.; McFeters, G. A.

1999-01-01

Rapid, direct methods are needed to assess active bacterial populations in water and foods. Our objective was to determine the efficiency of bacterial detection by immunomagnetic separation (IMS) and the compatibility of IMS with cyanoditolyl tetrazolium chloride (CTC) incubation to determine respiratory activity, using the pathogen Escherichia coli O157:H7. Counterstaining with a specific fluorescein-conjugated anti-O157 antibody (FAb) following CTC incubation was used to allow confirmation and visualization of bacteria by epifluorescence microscopy. Broth-grown E. coli O157:H7 was used to inoculate fresh ground beef (<17% fat), sterile 0.1% peptone, or water. Inoculated meat was diluted and homogenized in a stomacher and then incubated with paramagnetic beads coated with anti-O157 specific antibody. After IMS, cells with magnetic beads attached were stained with CTC and then an anti-O157 antibody-fluorescein isothiocyanate conjugate and filtered for microscopic enumeration or solid-phase laser cytometry. Enumeration by laser scanning permitted detection of ca. 10 CFU/g of ground beef or <10 CFU/ml of liquid sample. With inoculated meat, the regression results for log-transformed respiring FAb-positive counts of cells recovered on beads versus sorbitol-negative plate counts in the inoculum were as follows: intercept = 1.06, slope = 0.89, and r2 = 0. 95 (n = 13). The corresponding results for inoculated peptone were as follows: intercept = 0.67, slope = 0.88, and r2 = 0.98 (n = 24). Recovery of target bacteria on beads by the IMS-CTC-FAb method, compared with recovery by sorbitol MacConkey agar plating, yielded greater numbers (beef, 6.0 times; peptone, 3.0 times; water, 2.4 times). Thus, within 5 to 7 h, the IMS-CTC-FAb method detected greater numbers of E. coli O157 cells than were detected by plating. The results show that the IMS-CTC-FAb technique with enumeration by either fluorescence microscopy or solid-phase laser scanning cytometry gave results that compared favorably with plating following IMS.

The significance of circulating tumor cells in prostate cancer patients undergoing adjuvant or salvage radiation therapy

PubMed Central

Lowes, L E; Lock, M; Rodrigues, G; D'Souza, D; Bauman, G; Ahmad, B; Venkatesan, V; Allan, A L; Sexton, T

2015-01-01

Background: Following radical prostatectomy, success of adjuvant and salvage radiation therapy (RT) is dependent on the absence of micrometastatic disease. However, reliable prognostic/predictive factors for determining this are lacking. Therefore, novel biomarkers are needed to assist with clinical decision-making in this setting. Enumeration of circulating tumor cells (CTCs) using the regulatory-approved CellSearch System (CSS) is prognostic in metastatic prostate cancer. We hypothesize that CTCs may also be prognostic in the post-prostatectomy setting. Methods: Patient blood samples (n=55) were processed on the CSS to enumerate CTCs at 0, 6, 12 and 24 months after completion of RT. CTC values were correlated with predictive/prognostic factors and progression-free survival. Results: CTC status (presence/absence) correlated significantly with positive margins (increased likelihood of CTCneg disease; P=0.032), and trended toward significance with the presence of seminal vesicle invasion (CTCpos; P=0.113) and extracapsular extension (CTCneg; P=0.116). Although there was a trend toward a decreased time to biochemical failure (BCF) in baseline CTC-positive patients (n=9), this trend was not significant (hazard ratio (HR)=0.3505; P=0.166). However, CTC-positive status at any point (n=16) predicted for time to BCF (HR=0.2868; P=0.0437). Conclusions: One caveat of this study is the small sample size utilized (n=55) and the low number of patients with CTC-positive disease (n=16). However, our results suggest that CTCs may be indicative of disseminated disease and assessment of CTCs during RT may be helpful in clinical decision-making to determine, which patients may benefit from RT versus those who may benefit more from systemic treatments. PMID:26238233

Effect of the chlortetracycline addition method on methane production from the anaerobic digestion of swine wastewater.

PubMed

Huang, Lu; Wen, Xin; Wang, Yan; Zou, Yongde; Ma, Baohua; Liao, Xindi; Liang, Juanboo; Wu, Yinbao

2014-10-01

Effects of antibiotic residues on methane production in anaerobic digestion are commonly studied using the following two antibiotic addition methods: (1) adding manure from animals that consume a diet containing antibiotics, and (2) adding antibiotic-free animal manure spiked with antibiotics. This study used chlortetracycline (CTC) as a model antibiotic to examine the effects of the antibiotic addition method on methane production in anaerobic digestion under two different swine wastewater concentrations (0.55 and 0.22mg CTC/g dry manure). The results showed that CTC degradation rate in which manure was directly added at 0.55mg CTC/g (HSPIKE treatment) was lower than the control values and the rest of the treatment groups. Methane production from the HSPIKE treatment was reduced (p<0.05) by 12% during the whole experimental period and 15% during the first 7days. The treatments had no significant effect on the pH and chemical oxygen demand value of the digesters, and the total nitrogen of the 0.55mg CTC/kg manure collected from mediated swine was significantly higher than the other values. Therefore, different methane production under different antibiotic addition methods might be explained by the microbial activity and the concentrations of antibiotic intermediate products and metabolites. Because the primary entry route of veterinary antibiotics into an anaerobic digester is by contaminated animal manure, the most appropriate method for studying antibiotic residue effects on methane production may be using manure from animals that are given a particular antibiotic, rather than adding the antibiotic directly to the anaerobic digester. Copyright © 2014. Published by Elsevier B.V.

Degradation of Tetracyclines in Pig Manure by Composting with Rice Straw

PubMed Central

Chai, Rushan; Huang, Lidong; Li, Lingling; Gielen, Gerty; Wang, Hailong; Zhang, Yongsong

2016-01-01

A holistic approach was followed for utilizing tetracyclines (TCs)-contaminated pig manure, by composting this with rice straw in a greenhouse for CO2 fertilization and composted residue application. After composting, the composted residues can be applied to cropland as a supplemental source of synthetic fertilizers. The objective of this study was to determine the effect of pig manure-rice straw composting on the degradation of TCs in pig manure. The results showed that greenhouse composting significantly accelerated the degradation of TCs. Contents (150 mg·kg−1) of oxytetracycline (OTC), tetracycline (TC) and chlortetracycline (CTC) in the composting feedstock could be completely removed within 42 days for OTC and TC, and 14 days for CTC. However, in the control samples incubated at 25 °C in the dark, concentrations of OTC, TC and CTC only decreased 64.7%, 66.7% and 73.3%, respectively, after 49 days. The degradation rates of TCs in the composting feedstock were in the order of CTC > TC > OTC. During the composting process, CTC dissipated rapidly with the time required for 50% degradation (DT50) and 90% degradation (DT90) of 2.4 and 7.9 days, but OTC was more persistent with DT50 and DT90 values of 5.5 and 18.4 days. On the basis of the results obtained in this study, it could be concluded that pig manure-rice straw composting in a greenhouse can help to accelerate the degradation of TCs in pig manure and make composted residues safer for field application. This technology could be an acceptable practice for greenhouse farmers to utilize TCs-contaminated pig manure. PMID:26927136

Frequency analysis of gaze points with CT colonography interpretation using eye gaze tracking system

NASA Astrophysics Data System (ADS)

Tsutsumi, Shoko; Tamashiro, Wataru; Sato, Mitsuru; Okajima, Mika; Ogura, Toshihiro; Doi, Kunio

2017-03-01

It is important to investigate eye tracking gaze points of experts, in order to assist trainees in understanding of image interpretation process. We investigated gaze points of CT colonography (CTC) interpretation process, and analyzed the difference in gaze points between experts and trainees. In this study, we attempted to understand how trainees can be improved to a level achieved by experts in viewing of CTC. We used an eye gaze point sensing system, Gazefineder (JVCKENWOOD Corporation, Tokyo, Japan), which can detect pupil point and corneal reflection point by the dark pupil eye tracking. This system can provide gaze points images and excel file data. The subjects are radiological technologists who are experienced, and inexperienced in reading CTC. We performed observer studies in reading virtual pathology images and examined observer's image interpretation process using gaze points data. Furthermore, we examined eye tracking frequency analysis by using the Fast Fourier Transform (FFT). We were able to understand the difference in gaze points between experts and trainees by use of the frequency analysis. The result of the trainee had a large amount of both high-frequency components and low-frequency components. In contrast, both components by the expert were relatively low. Regarding the amount of eye movement in every 0.02 second we found that the expert tended to interpret images slowly and calmly. On the other hand, the trainee was moving eyes quickly and also looking for wide areas. We can assess the difference in the gaze points on CTC between experts and trainees by use of the eye gaze point sensing system and based on the frequency analysis. The potential improvements in CTC interpretation for trainees can be evaluated by using gaze points data.

Deep multi-spectral ensemble learning for electronic cleansing in dual-energy CT colonography

NASA Astrophysics Data System (ADS)

Tachibana, Rie; Näppi, Janne J.; Hironaka, Toru; Kim, Se Hyung; Yoshida, Hiroyuki

2017-03-01

We developed a novel electronic cleansing (EC) method for dual-energy CT colonography (DE-CTC) based on an ensemble deep convolution neural network (DCNN) and multi-spectral multi-slice image patches. In the method, an ensemble DCNN is used to classify each voxel of a DE-CTC image volume into five classes: luminal air, soft tissue, tagged fecal materials, and partial-volume boundaries between air and tagging and those between soft tissue and tagging. Each DCNN acts as a voxel classifier, where an input image patch centered at the voxel is generated as input to the DCNNs. An image patch has three channels that are mapped from a region-of-interest containing the image plane of the voxel and the two adjacent image planes. Six different types of spectral input image datasets were derived using two dual-energy CT images, two virtual monochromatic images, and two material images. An ensemble DCNN was constructed by use of a meta-classifier that combines the output of multiple DCNNs, each of which was trained with a different type of multi-spectral image patches. The electronically cleansed CTC images were calculated by removal of regions classified as other than soft tissue, followed by a colon surface reconstruction. For pilot evaluation, 359 volumes of interest (VOIs) representing sources of subtraction artifacts observed in current EC schemes were sampled from 30 clinical CTC cases. Preliminary results showed that the ensemble DCNN can yield high accuracy in labeling of the VOIs, indicating that deep learning of multi-spectral EC with multi-slice imaging could accurately remove residual fecal materials from CTC images without generating major EC artifacts.

Circulating tumor cell isolation during resection of colorectal cancer lung and liver metastases: a prospective trial with different detection techniques.

PubMed

Kaifi, Jussuf T; Kunkel, Miriam; Das, Avisnata; Harouaka, Ramdane A; Dicker, David T; Li, Guangfu; Zhu, Junjia; Clawson, Gary A; Yang, Zhaohai; Reed, Michael F; Gusani, Niraj J; Kimchi, Eric T; Staveley-O'Carroll, Kevin F; Zheng, Si-Yang; El-Deiry, Wafik S

2015-01-01

Colorectal cancer (CRC) metastasectomy improves survival, however most patient develop recurrences. Circulating tumor cells (CTCs) are an independent prognostic marker in stage IV CRC. We hypothesized that CTCs can be enriched during metastasectomy applying different isolation techniques. 25 CRC patients undergoing liver (16 (64%)) or lung (9 (36%)) metastasectomy were prospectively enrolled (clinicaltrial.gov identifier: NCT01722903). Central venous (liver) or radial artery (lung) tumor outflow blood (7.5 ml) was collected at incision, during resection, 30 min after resection, and on postoperative day (POD) 1. CTCs were quantified with 1. EpCAM-based CellSearch® system and 2. size-based isolation with a novel filter device (FMSA). CTCs were immunohistochemically identified using CellSearch®'s criteria (cytokeratin 8/18/19+, CD45- cells containing a nucleus (DAPI+)). CTCs were also enriched with a centrifugation technique (OncoQuick®). CTC numbers peaked during the resection with the FMSA in contrast to CellSearch® (mean CTC number during resection: FMSA: 22.56 (SEM 7.48) (p = 0.0281), CellSearch®: 0.87 (SEM ± 0.44) (p = 0.3018)). Comparing the 2 techniques, CTC quantity was significantly higher with the FMSA device (range 0-101) than CellSearch® (range 0-9) at each of the 4 time points examined (P < 0.05). Immunofluorescence staining of cultured CTCs revealed that CTCs have a combined epithelial (CK8/18/19) and macrophage (CD45/CD14) phenotype. Blood sampling during CRC metastasis resection is an opportunity to increase CTC capture efficiency. CTC isolation with the FMSA yields more CTCs than the CellSearch® system. Future studies should focus on characterization of single CTCs to identify targets for molecular therapy and immune escape mechanisms of cancer cells.

Deep learning of contrast-coated serrated polyps for computer-aided detection in CT colonography

NASA Astrophysics Data System (ADS)

Näppi, Janne J.; Pickhardt, Perry; Kim, David H.; Hironaka, Toru; Yoshida, Hiroyuki

2017-03-01

Serrated polyps were previously believed to be benign lesions with no cancer potential. However, recent studies have revealed a novel molecular pathway where also serrated polyps can develop into colorectal cancer. CT colonography (CTC) can detect serrated polyps using the radiomic biomarker of contrast coating, but this requires expertise from the reader and current computer-aided detection (CADe) systems have not been designed to detect the contrast coating. The purpose of this study was to develop a novel CADe method that makes use of deep learning to detect serrated polyps based on their contrast-coating biomarker in CTC. In the method, volumetric shape-based features are used to detect polyp sites over soft-tissue and fecal-tagging surfaces of the colon. The detected sites are imaged using multi-angular 2D image patches. A deep convolutional neural network (DCNN) is used to review the image patches for the presence of polyps. The DCNN-based polyp-likelihood estimates are merged into an aggregate likelihood index where highest values indicate the presence of a polyp. For pilot evaluation, the proposed DCNN-CADe method was evaluated with a 10-fold cross-validation scheme using 101 colonoscopy-confirmed cases with 144 biopsy-confirmed serrated polyps from a CTC screening program, where the patients had been prepared for CTC with saline laxative and fecal tagging by barium and iodine-based diatrizoate. The average per-polyp sensitivity for serrated polyps >=6 mm in size was 93+/-7% at 0:8+/-1:8 false positives per patient on average. The detection accuracy was substantially higher that of a conventional CADe system. Our results indicate that serrated polyps can be detected automatically at high accuracy in CTC.

Effects of oral administration of tilmicosin on pulmonary inflammation in piglets experimentally infected with Actinobacillus pleuropneumoniae.

PubMed

Nerland, Erin M; LeBlanc, Justin M; Fedwick, Jason P; Morck, Douglas W; Merrill, John K; Dick, Paul; Paradis, Marie-Anne; Buret, Andre G

2005-01-01

To determine the effects of oral administration of tilmicosin in piglets experimentally infected with Actinobacillus pleuropneumoniae. Forty 3-week-old specific-pathogen free piglets. Piglets were assigned to 1 of 4 groups as follows: 1) uninfected sham-treated control piglets; 2) infected untreated piglets that were intratracheally inoculated with 10(7) CFUs of A pleuropneumoniae; 3) infected treated piglets that were intratracheally inoculated with A pleuropneumoniae and received tilmicosin in feed (400 ppm [microg/g]) for 7 days prior to inoculation; or 4) infected treated piglets that were intratracheally inoculated with A pleuropneumoniae and received chlortetracycline (CTC) in feed (1100 ppm [microg/gl) for 7 days prior to inoculation. Bronchoalveolar lavage (BAL) fluid and lung tissue specimens of piglets for each group were evaluated at 3 or 24 hours after inoculation. For each time point, 4 to 6 piglets/group were studied. Feeding of CTC and tilmicosin decreased bacterial load in lungs of infected piglets. Tilmicosin delivered in feed, but not CTC, enhanced apoptosis in porcine BAL fluid leukocytes. This was associated with a decrease in LTB4 concentrations in BAL fluid of tilmicosin-treated piglets, compared with untreated and CTC-treated piglets, and also with a significant decrease in the number of pulmonary lesions. Tilmicosin inhibited infection-induced increases in rectal temperatures, as measured in untreated and CTC-treated piglets. Pulmonary neutrophil infiltration and prostaglandin E2 concentrations in the BAL fluid were not significantly different among groups at any time. Oral administration of tilmicosin to infected piglets induces apoptosis in BAL fluid leukocytes and decreases BAL fluid LTB4 concentrations and inflammatory lung lesions.

Computed tomographic colonography for colorectal cancer screening: risk factors for the detection of advanced neoplasia.

PubMed

Hassan, Cesare; Pooler, B Dustin; Kim, David H; Rinaldi, Antonio; Repici, Alessandro; Pickhardt, Perry J

2013-07-15

The objective of this study was to determine whether age, sex, a positive family history of colorectal cancer, and body mass index (BMI) are important predictors of advanced neoplasia in the setting of screening computed tomographic colonography (CTC). Consecutive patients who were referred for first-time screening CTC from 2004 to 2011 at a single medical center were enrolled. Results at pathology were recorded for all patients who underwent polypectomy. Logistic regression was used to identify significant predictor variables for advanced neoplasia (any adenoma ≥ 10 mm or with villous component, high-grade dysplasia, or adenocarcinoma). Odds ratios (ORs) were used to express associations between the study variables (age, sex, BMI, and a positive family history of colorectal cancer) and advanced neoplasia. In total, 7620 patients underwent CTC screening. Of these, 276 patients (3.6%; 95% confidence interval [CI], 3.2%-4.1%) ultimately were diagnosed with advanced neoplasia. At multivariate analysis, age (mean OR per 10-year increase, 1.8; 95% CI, 1.6-2.0) and being a man (OR, 1.7; 95% CI, 1.3-2.2) were independent predictors of advanced neoplasia, whereas BMI and a positive family history of colorectal cancer were not. The number needed to screen to detect 1 case of advanced neoplasia varied from 51 among women aged ≤ 55 years to 10 among men aged >65 years. The number of post-CTC colonoscopies needed to detect 1 case of advanced neoplasia varied from 2 to 4. Age and sex were identified as important independent predictors of advanced neoplasia risk in individuals undergoing screening CTC, whereas BMI and a positive family history of colorectal cancer were not. These results have implications for appropriate patient selection. © 2013 American Cancer Society.

Virtual Colonoscopy Screening With Ultra Low-Dose CT and Less-Stressful Bowel Preparation: A Computer Simulation Study

NASA Astrophysics Data System (ADS)

Wang, Jing; Wang, Su; Li, Lihong; Fan, Yi; Lu, Hongbing; Liang, Zhengrong

2008-10-01

Computed tomography colonography (CTC) or CT-based virtual colonoscopy (VC) is an emerging tool for detection of colonic polyps. Compared to the conventional fiber-optic colonoscopy, VC has demonstrated the potential to become a mass screening modality in terms of safety, cost, and patient compliance. However, current CTC delivers excessive X-ray radiation to the patient during data acquisition. The radiation is a major concern for screening application of CTC. In this work, we performed a simulation study to demonstrate a possible ultra low-dose CT technique for VC. The ultra low-dose abdominal CT images were simulated by adding noise to the sinograms of the patient CTC images acquired with normal dose scans at 100 mA s levels. The simulated noisy sinogram or projection data were first processed by a Karhunen-Loeve domain penalized weighted least-squares (KL-PWLS) restoration method and then reconstructed by a filtered backprojection algorithm for the ultra low-dose CT images. The patient-specific virtual colon lumen was constructed and navigated by a VC system after electronic colon cleansing of the orally-tagged residue stool and fluid. By the KL-PWLS noise reduction, the colon lumen can successfully be constructed and the colonic polyp can be detected in an ultra low-dose level below 50 mA s. Polyp detection can be found more easily by the KL-PWLS noise reduction compared to the results using the conventional noise filters, such as Hanning filter. These promising results indicate the feasibility of an ultra low-dose CTC pipeline for colon screening with less-stressful bowel preparation by fecal tagging with oral contrast.

Degradation of Tetracyclines in Pig Manure by Composting with Rice Straw.

PubMed

Chai, Rushan; Huang, Lidong; Li, Lingling; Gielen, Gerty; Wang, Hailong; Zhang, Yongsong

2016-02-24

A holistic approach was followed for utilizing tetracyclines (TCs)-contaminated pig manure, by composting this with rice straw in a greenhouse for CO₂ fertilization and composted residue application. After composting, the composted residues can be applied to cropland as a supplemental source of synthetic fertilizers. The objective of this study was to determine the effect of pig manure-rice straw composting on the degradation of TCs in pig manure. The results showed that greenhouse composting significantly accelerated the degradation of TCs. Contents (150 mg·kg(-1)) of oxytetracycline (OTC), tetracycline (TC) and chlortetracycline (CTC) in the composting feedstock could be completely removed within 42 days for OTC and TC, and 14 days for CTC. However, in the control samples incubated at 25 °C in the dark, concentrations of OTC, TC and CTC only decreased 64.7%, 66.7% and 73.3%, respectively, after 49 days. The degradation rates of TCs in the composting feedstock were in the order of CTC > TC > OTC. During the composting process, CTC dissipated rapidly with the time required for 50% degradation (DT50) and 90% degradation (DT90) of 2.4 and 7.9 days, but OTC was more persistent with DT50 and DT90 values of 5.5 and 18.4 days. On the basis of the results obtained in this study, it could be concluded that pig manure-rice straw composting in a greenhouse can help to accelerate the degradation of TCs in pig manure and make composted residues safer for field application. This technology could be an acceptable practice for greenhouse farmers to utilize TCs-contaminated pig manure.

Characterization of the europium tetracycline complex as a biomarker for atherosclerosis

NASA Astrophysics Data System (ADS)

Courrol, Lilia C.; da Silva, Mônica N.; Sicchieri, Leticia B.

2016-04-01

Atherosclerosis is a narrowing of the arteries caused by an increase of atheromatous plaque: material formed by macrophage cells containing cholesterol and fatty acids, calcium and a variable amount of fibrous connective tissue. The elation between vulnerable plaques and cardiovascular events can be determined using plaque biomarkers. In this work, atherosclerotic plaques stained with different molar ratios of europium, in a potential plaque biomarker, europium tetracycline complex, were studied by fluorescence microscopy. The tetracycline antibiotic used was chlortetracycline. The growth of atherosclerotic plaque was followed during 60 days in New Zealand rabbits divided in two groups: an experimental group (EG), with nine animals and a control group (CG) with three animals. The animals in the EG received a diet with 1% of cholesterol and the animals of GC received a normal diet. The aortic arch of the animals with 60 days were cut in the vertical plane in 6 μm thick slices, which were mounted on glass slides and stained with hematoxylin an eosin and europium chlortetracycline complex (EuCTc). The fluorescence images were obtained exciting the EuCTc absorption band with a filter cube D (BP 355 - 425) and the emission was collected with a LP 470 suppression filter. Light intensity, detector gain and acquisition time were fixed for comparisons. The 20× magnified images were collected with 12 bit (or 4096 gray tones) resolution. The mean value of gray scale for each molar ratio of EuCTc was different, indicating that the complex interacts with the components of atherosclerotic plaque and the best molar ratio was 1.5 EuCTc. These results indicate the potential use of the EuCTc biomarker for atherosclerotic plaque characterization.

Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers.

PubMed

Murlidhar, Vasudha; Reddy, Rishindra M; Fouladdel, Shamileh; Zhao, Lili; Ishikawa, Martin K; Grabauskiene, Svetlana; Zhang, Zhuo; Lin, Jules; Chang, Andrew C; Carrott, Philip; Lynch, William R; Orringer, Mark B; Kumar-Sinha, Chandan; Palanisamy, Nallasivam; Beer, David G; Wicha, Max S; Ramnath, Nithya; Azizi, Ebrahim; Nagrath, Sunitha

2017-09-15

Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe ( P < 0.0001) and intraoperative Pe ( P < 0.001) blood. CTC clusters with large number of CTCs were observed in 50% of patients, with PV often revealing larger clusters. Long-term surveillance indicated that presence of clusters in preoperative Pe blood predicted a trend toward poor prognosis. Gene expression analysis by RT-qPCR revealed enrichment of p53 signaling and extracellular matrix involvement in PV and Pe samples. Ki67 expression was detected in 62.5% of PV samples and 59.2% of Pe samples, with the majority (72.7%) of patients positive for Ki67 expression in PV having single CTCs as opposed to clusters. Gene ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence. Cancer Res; 77(18); 5194-206. ©2017 AACR . ©2017 American Association for Cancer Research.

Colonic polyps: application value of computer-aided detection in computed tomographic colonography.

PubMed

Zhang, Hui-Mao; Guo, Wei; Liu, Gui-Feng; An, Dong-Hong; Gao, Shuo-Hui; Sun, Li-Bo; Yang, Hai-Shan

2011-02-01

Colonic polyps are frequently encountered in clinics. Computed tomographic colonography (CTC), as a painless and quick detection, has high values in clinics. In this study, we evaluated the application value of computer-aided detection (CAD) in CTC detection of colonic polyps in the Chinese population. CTC was performed with a GE 64-row multidetector computed tomography (MDCT) scanner. Data of 50 CTC patients (39 patients positive for at least one polyp of ≥ 0.5 cm in size and the other 11 patients negative by endoscopic detection) were retrospectively reviewed first without computer-aided detection (CAD) and then with CAD by four radiologists (two were experienced and another two inexperienced) blinded to colonoscopy findings. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of detected colonic polyps, as well as the areas under the ROC curves (Az value) with and without CAD were calculated. CAD increased the overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the colonic polyps detected by experienced and inexperienced readers. The sensitivity in detecting small polyps (5 - 9 mm) with CAD in experienced and inexperienced readers increased from 82% and 44% to 93% and 82%, respectively (P > 0.05 and P < 0.001). With the use of CAD, the overall false positive rate and false negative rate for the detection of polyps by experienced and inexperienced readers decreased in different degrees. Among 13 sessile polyps not detected by CAD, two were ≥ 1.0 cm, eleven were 5 - 9 mm in diameter, and nine were flat-shaped lesions. The application of CAD in combination with CTC can increase the ability to detect colonic polyps, particularly for inexperienced readers. However, CAD is of limited value for the detection of flat polyps.

Probabilistic vs. deterministic fiber tracking and the influence of different seed regions to delineate cerebellar-thalamic fibers in deep brain stimulation.

PubMed

Schlaier, Juergen R; Beer, Anton L; Faltermeier, Rupert; Fellner, Claudia; Steib, Kathrin; Lange, Max; Greenlee, Mark W; Brawanski, Alexander T; Anthofer, Judith M

2017-06-01

This study compared tractography approaches for identifying cerebellar-thalamic fiber bundles relevant to planning target sites for deep brain stimulation (DBS). In particular, probabilistic and deterministic tracking of the dentate-rubro-thalamic tract (DRTT) and differences between the spatial courses of the DRTT and the cerebello-thalamo-cortical (CTC) tract were compared. Six patients with movement disorders were examined by magnetic resonance imaging (MRI), including two sets of diffusion-weighted images (12 and 64 directions). Probabilistic and deterministic tractography was applied on each diffusion-weighted dataset to delineate the DRTT. Results were compared with regard to their sensitivity in revealing the DRTT and additional fiber tracts and processing time. Two sets of regions-of-interests (ROIs) guided deterministic tractography of the DRTT or the CTC, respectively. Tract distances to an atlas-based reference target were compared. Probabilistic fiber tracking with 64 orientations detected the DRTT in all twelve hemispheres. Deterministic tracking detected the DRTT in nine (12 directions) and in only two (64 directions) hemispheres. Probabilistic tracking was more sensitive in detecting additional fibers (e.g. ansa lenticularis and medial forebrain bundle) than deterministic tracking. Probabilistic tracking lasted substantially longer than deterministic. Deterministic tracking was more sensitive in detecting the CTC than the DRTT. CTC tracts were located adjacent but consistently more posterior to DRTT tracts. These results suggest that probabilistic tracking is more sensitive and robust in detecting the DRTT but harder to implement than deterministic approaches. Although sensitivity of deterministic tracking is higher for the CTC than the DRTT, targets for DBS based on these tracts likely differ. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Circulating tumor cells: advances in isolation and analysis, and challenges for clinical applications

PubMed Central

Harouaka, Ramdane; Kang, Zhigang; Zheng, Siyang; Cao, Liang

2013-01-01

Circulating tumor cells (CTCs) are rare cancer cells released from tumors into the bloodstream that are thought to have a key role in cancer metastasis. The presence of CTCs has been associated with worse prognosis in several major cancer types, including breast, prostate and colorectal cancer. There is considerable interest in CTC research and technologies for their potential use as cancer biomarkers that may enhance cancer diagnosis and prognosis, facilitate drug development, and improve the treatment of cancer patients. This review provides an update on recent progress in CTC isolation and molecular characterization technologies. Furthermore, the review covers significant advances and limitations in the clinical applications of CTC-based assays for cancer prognosis, response to anti-cancer therapies, and exploratory studies in biomarkers predictive of sensitivity and resistance to cancer therapies. PMID:24134902

Circulating tumor cells: advances in isolation and analysis, and challenges for clinical applications.

PubMed

Harouaka, Ramdane; Kang, Zhigang; Zheng, Si-Yang; Cao, Liang

2014-02-01

Circulating tumor cells (CTCs) are rare cancer cells released from tumors into the bloodstream that are thought to have a key role in cancer metastasis. The presence of CTCs has been associated with worse prognosis in several major cancer types, including breast, prostate and colorectal cancer. There is considerable interest in CTC research and technologies for their potential use as cancer biomarkers that may enhance cancer diagnosis and prognosis, facilitate drug development, and improve the treatment of cancer patients. This review provides an update on recent progress in CTC isolation and molecular characterization technologies. Furthermore, the review covers significant advances and limitations in the clinical applications of CTC-based assays for cancer prognosis, response to anti-cancer therapies, and exploratory studies in biomarkers predictive of sensitivity and resistance to cancer therapies. Published by Elsevier Inc.

Charge transfer complex states in diketopyrrolopyrrole polymers and fullerene blends: Implications for organic solar cell efficiency

NASA Astrophysics Data System (ADS)

Moghe, D.; Yu, P.; Kanimozhi, C.; Patil, S.; Guha, S.

2011-12-01

The spectral photocurrent characteristics of two donor-acceptor diketopyrrolopyrrole (DPP)-based copolymers (PDPP-BBT and TDPP-BBT) blended with a fullerene derivative [6,6]-phenyl C61-butyric acid methyl ester (PCBM) were studied using Fourier-transform photocurrent spectroscopy (FTPS) and monochromatic photocurrent (PC) method. PDPP-BBT:PCBM shows the onset of the lowest charge transfer complex (CTC) state at 1.42 eV, whereas TDPP-BBT:PCBM shows no evidence of the formation of a midgap CTC state. The FTPS and PC spectra of P3HT:PCBM are also compared. The larger singlet state energy difference of TDPP-BBT and PCBM compared to PDPP-BBT/P3HT and PCBM obliterates the formation of a midgap CTC state resulting in an enhanced photovoltaic efficiency over PDPP-BBT:PCBM.

Composite transform-convergent plate boundaries: description and discussion

USGS Publications Warehouse

Ryan, H.F.; Coleman, P.J.

1992-01-01

The leading edge of the overriding plate at an obliquely convergent boundary is commonly sliced by a system of strike-slip faults. This fault system is often structurally complex, and may show correspondingly uneven strain effects, with great vertical and translational shifts of the component blocks of the fault system. The stress pattern and strain effects vary along the length of the system and change through time. These margins are considered to be composite transform-convergent (CTC) plate boundaries. Examples are given of structures formed along three CTC boundaries: the Aleutian Ridge, the Solomon Islands, and the Philippines. The dynamism of the fault system along a CTC boundary can enhance vertical tectonism and basin formation. This concept provides a framework for the evaluation of petroleum resources related to basin formation, and mineral exploration related to igneous activity associated with transtensional processes. ?? 1992.

CTC Sentinel. Volume 2, Issue 6, June 2009

DTIC Science & Technology

2009-06-01

Pakistan also makes it easier for al-Qa`ida to manage local perceptions and deny involvement in controversial terrorist attacks within the country...Combating Terrorism Center (CTC) at West Point, where he manages the Harmony Program and is developing the CTC’s South Asian research program. Prior to...operational art. Police operational art is defined as the capacity to go beyond managing single tactical incidents to influencing the effects of multiple

Hyaluronan-Based Therapy for Metastatic Prostate Cancer

DTIC Science & Technology

2015-07-01

8217-AAG ACC CTT GTG CTC GTT GT-3’ and re- verse 5’-AGG TGG ACA CAA TCC CTC TG-3’ actin, forward 5’-TCC CTG GAG AAG AGC TAC GA-3’ and reverse 5’-AGC ACT... GTG TTG GCG TAC AG-3’. 2.2.5. Death-inducing signaling complex immunoprecipitation After HT-29 cells achieved 80% confluence, the cells were pretreated

Measurement of smaller colon polyp in CT colonography images using morphological image processing.

PubMed

Manjunath, K N; Siddalingaswamy, P C; Prabhu, G K

2017-11-01

Automated measurement of the size and shape of colon polyps is one of the challenges in Computed tomography colonography (CTC). The objective of this retrospective study was to improve the sensitivity and specificity of smaller polyp measurement in CTC using image processing techniques. A domain knowledge-based method has been implemented with hybrid method of colon segmentation, morphological image processing operators for detecting the colonic structures, and the decision-making system for delineating the smaller polyp-based on a priori knowledge. The method was applied on 45 CTC dataset. The key finding was that the smaller polyps were accurately measured. In addition to 6-9 mm range, polyps of even <5 mm were also detected. The results were validated qualitatively and quantitatively using both 2D MPR and 3D view. Implementation was done on a high-performance computer with parallel processing. It takes [Formula: see text] min for measuring the smaller polyp in a dataset of 500 CTC images. With this method, [Formula: see text] and [Formula: see text] were achieved. The domain-based approach with morphological image processing has given good results. The smaller polyps were measured accurately which helps in making right clinical decisions. Qualitatively and quantitatively the results were acceptable when compared to the ground truth at [Formula: see text].

PrediCTC, liquid biopsy in precision oncology: a technology transfer experience in the Spanish health system.

PubMed

Alonso-Alconada, L; Barbazan, J; Candamio, S; Falco, J L; Anton, C; Martin-Saborido, C; Fuster, G; Sampedro, M; Grande, C; Lado, R; Sampietro-Colom, L; Crego, E; Figueiras, S; Leon-Mateos, L; Lopez-Lopez, R; Abal, M

2018-05-01

Management of metastatic disease in oncology includes monitoring of therapy response principally by imaging techniques like CT scan. In addition to some limitations, the irruption of liquid biopsy and its application in personalized medicine has encouraged the development of more efficient technologies for prognosis and follow-up of patients in advanced disease. PrediCTC constitutes a panel of genes for the assessment of circulating tumor cells (CTC) in metastatic colorectal cancer patients, with demonstrated improved efficiency compared to CT scan for the evaluation of early therapy response in a multicenter prospective study. In this work, we designed and developed a technology transfer strategy to define the market opportunity for an eventual implementation of PrediCTC in the clinical practice. This included the definition of the regulatory framework, the analysis of the regulatory roadmap needed for CE mark, a benchmarking study, the design of a product development strategy, a revision of intellectual property, a cost-effectiveness study and an expert panel consultation. The definition and analysis of an appropriate technology transfer strategy and the correct balance among regulatory, financial and technical determinants are critical for the transformation of a promising technology into a viable technology, and for the decision of implementing liquid biopsy in the monitoring of therapy response in advanced disease.

Social networks and community prevention coalitions.

PubMed

Feinberg, Mark E; Riggs, Nathaniel R; Greenberg, Mark T

2005-07-01

This study investigates the links between community readiness and the social networks among participants in Communities That Care (CTC), community-based prevention coalitions. The coalitions targeted adolescent behavior problems through community risk factor assessments, prioritization of risk factors, and selection/implementation of corresponding evidence-based family, school, and community programs. Key leaders (n = 219) in 23 new CTC sites completed questionnaires focusing on community readiness to implement CTC and the respondents' personal, work, and social organization links to other key leaders in the community. Outside technical assistants also completed ratings of each community's readiness and early CTC functioning. Measures of network cohesion/integration were positively associated with readiness, while centralization was negatively associated. These results suggest that non-centralized networks in which ties between members are close and direct may be an indicator of community readiness. In addition, we found different associations between readiness and different domains of social relations. EDITORS' STRATEGIC IMPLICATIONS: The authors present the promising practice of using social network analysis to characterize the functioning of local prevention coalitions and their readiness to implement a community-based prevention initiative. Researchers and community planners will benefit from the lessons in this article, which capitalizes on a large sample and multiple informants. This work raises interesting questions about how to combine the promotion of coalition functioning while simultaneously encouraging diversity of coalition membership.

Emerging Role of Nanomaterials in Circulating Tumor Cell Isolation and Analysis

PubMed Central

2015-01-01

Circulating tumor cells (CTCs) are low frequency cells found in the bloodstream after having been shed from a primary tumor. These cells are research targets because of the information they may potentially provide about both an individual cancer as well as the mechanisms through which cancer spreads in the process of metastasis. Established technologies exist for CTC isolation, but the recent progress and future of this field lie in nanomaterials. In this review, we provide perspective into historical CTC capture as well as current research being conducted, emphasizing the significance of the materials being used to fabricate these devices. The modern investigation into CTCs initially featured techniques that have since been commercialized. A major innovation in the field was the development of a microfluidic capture device, first fabricated in silicon and followed up with glass and thermopolymer devices. We then specifically highlight the technologies incorporating magnetic nanoparticles, carbon nanotubes, nanowires, nanopillars, nanofibers, and nanoroughened surfaces, graphene oxide and their fabrication methods. The nanoscale provides a new set of tools that has the potential to overcome current limitations associated with CTC capture and analysis. We believe the current trajectory of the field is in the direction of nanomaterials, allowing the improvements necessary to further CTC research. PMID:24601556

Cerebro-retinal microangiopathy with calcifications and cysts due to recessive mutations in the CTC1 gene.

PubMed

Bisserbe, A; Tertian, G; Buffet, C; Turhan, A; Lambotte, O; Nasser, G; Alvin, P; Tardieu, M; Riant, F; Bergametti, F; Tournier-Lasserve, E; Denier, C

2015-05-01

Cerebro-retinal microangiopathy with calcifications and cysts (CRMCC) or Coats plus syndrome is a pleiotropic disorder affecting the eyes, brain, bone and gastrointestinal tract. Its primary pathogenesis involves small vessel obliterative microangiopathy. Recently, autosomal recessively inherited mutations in CTC1 have been reported in CRMCC patients. We herein report an adolescent referred to our hospital following new seizures in a context of an undefined multisystem disorder. Cerebral imaging disclosed asymmetrical leukopathy, intracranial calcifications and cysts. In addition, he presented other typical CRMCC features i.e. a history of intrauterine growth retardation, skeletal demineralization and osteopenia, bilateral exudative vitreo-retinopathy reminiscent of Coats disease, recurrent gastrointestinal hemorrhages secondary to watermelon stomach and variceal bleeding of the esophagus due to idiopathic portal hypertension and telangiectatic and angiodysplasic changes in the small intestine and colon, and anemia due to recurrent bleeding and bone marrow abnormalities. The patient was diagnosed with Coats plus syndrome. CTC1 gene screening confirmed the diagnosis with the identification of heterozygous deleterious mutations. CRMCC due to CTC1 mutations has a broad clinical expressivity. Our case report illustrates the main possible associated phenotypes and their complications, demonstrating the need for a careful etiological search in order to initiate appropriate therapeutic and preventive measures. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Lab on a fabric: Mass producible and low-cost fabric filters for the high-throughput viable isolation of circulating tumor cells.

PubMed

Bu, Jiyoon; Kang, Yoon-Tae; Lee, Yong-Seok; Kim, Jeongsuk; Cho, Young-Ho; Moon, Byung-In

2017-05-15

Circulating tumor cells (CTCs) play an important role in estimating the presence and the metastatic relapse of tumor. Despite of their importance, isolation of viable CTCs is still struggling, since chemical or mechanical damages are unavoidable when separating less than 1000 of CTCs out of billions of other blood components. Furthermore, the current CTC isolation devices show low productivity, since they are produced after a series of complicated fabrication processes. Here, we present a low-cost and mass-producible fabric filters for the viable CTC isolation and the further molecular assay for profiling cancer-associated markers. The fabric filter, produced by polyester monofilament yarns, can be massively produced at extremely low-cost, by showing productivity of ~22filters/s at ~59filters/USD. By utilizing size-based sorting method, the fabric filter is capable to isolate both epithelial and mesenchymal CTCs, while slots with curved walls are beneficial for preventing the cell rupture by reducing 21.6% of mechanical stress compared to the conventional straight-walled slots. We applied our filter to 11 human blood samples and found that the number of CTCs was closely related to the expression level of Ki-67, which is highly overexpressed in proliferative tumors. The fabric filter might be an appropriate caner-screening tool in developing countries, where people suffer from insufficient healthcare services. Copyright © 2017 Elsevier B.V. All rights reserved.

CTC Sentinel. Volume 6, Issue 7, July 2013

DTIC Science & Technology

2013-07-01

researched means to disable fire suppression systems to increase the impact of a plot that was ultimately disrupted by authorities. These failed plots...7 About the CTC Sentinel The Combating Terrorism Center is an independent educational and research institution based in the Department of social...old, after “watching videos of children getting killed in countries like Kashmir and Palestine.”6 He described his actions on behalf of TeaMp0isoN

The Roles of the Bone Marrow Microenvironment in Controlling Tumor Dormancy

DTIC Science & Technology

2017-10-01

Prostate cancer patients often have long time periods betweencurative intent surgery or radiation therapy until the time of biochemical recurrence or...incurred by the consequent excision of some benign masses. Radiation triggers EMT Above we reviewed some evidence that chemotherapy and mechanical...tissue disruption give rise to CTC and EMT in surviving cells. Below we review data showing radiation causes CTC and EMT as well.45,46 For a few specific

Liquid biopsy on chip: a paradigm shift towards the understanding of cancer metastasis.

PubMed

Tadimety, Amogha; Syed, Abeer; Nie, Yuan; Long, Christina R; Kready, Kasia M; Zhang, John X J

2017-01-23

This comprehensive review serves as a guide for developing scalable and robust liquid biopsies on chip for capture, detection, and analysis of circulating tumor cells (CTCs). Liquid biopsy, the detection of biomarkers from body fluids, has proven challenging because of CTC rarity and the heterogeneity of CTCs shed from tumors. The review starts with the underlying biological mechanisms that make liquid biopsy a challenge before moving into an evaluation of current technological progress. Then, a framework for evaluation of the technologies is presented with special attention to throughput, capture rate, and cell viability for analysis. Technologies for CTC capture, detection, and analysis will be evaluated based on these criteria, with a focus on current approaches, limitations and future directions. The paper provides a critical review for microchip developers as well as clinical investigators to build upon the existing progress towards the goal of designing CTC capture, detection, and analysis platforms.

Assessment of Capacity to Consent by Nurses Who Deliver Health Care to Patients Who Misuse Substances

PubMed Central

Taylor, Darlene; Ho, Anita; Mâsse, Louise C.; Van Borek, Natasha; Li, Neville; Patterson, Michelle; Ogilvie, Gina; Buxton, Jane A.

2016-01-01

This qualitative study explored the current practice that nurses use to assess capacity to consent to health care (CTC-HC) in street outreach settings. Key informant interviews were conducted with a purposive sample of nurses from each of British Columbia’s five regional health authorities, allowing nurses to describe their lived experiences with assessing CTC-HC. Content analysis was used to summarize information captured in the data. A total of 19 nurses participated in the study. Five themes emerged from the data: (a) internal guiding forces that contribute to the nurses’ assessment, (b) external influences that contribute to the nurses’ assessment, (c) measures that are important for assessing CTC-HC, (d) threshold setting, and (e) context (physical and interpersonal) within which assessment of capacity takes place. These elements will be incorporated into a capacity assessment tool that can be used in nursing best practices. PMID:28462344

Treatment of tetracycline antibiotics by laccase in the presence of 1-hydroxybenzotriazole.

PubMed

Suda, Tomoyo; Hata, Takayuki; Kawai, Shingo; Okamura, Hideo; Nishida, Tomoaki

2012-01-01

Tetracycline antibiotics are widely used in human and veterinary medicine; however, residual amounts of these antibiotics in the environment are of concern since they could contribute to selection of resistant bacteria. In this study, tetracycline (TC), chlortetracycline (CTC), doxycycline (DC) and oxytetracycline (OTC) were treated with laccase from the white rot fungus Trametes versicolor in the presence of the redox mediator 1-hydroxybenzotriazole (HBT). High performance liquid chromatography demonstrated that DC and CTC were completely eliminated after 15 min, while TC and CTC were eliminated after 1 h. This system also resulted in a complete loss of inhibition of growth of Escherichia coli and Bacillus subtilis and the green alga Pseudokirchneriella subcapitata with decreasing tetracycline antibiotic concentration. These results suggest that the laccase-HBT system is effective in eliminating tetracycline antibiotics and removing their ecotoxicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Using communities that care for community child maltreatment prevention.

PubMed

Salazar, Amy M; Haggerty, Kevin P; de Haan, Benjamin; Catalano, Richard F; Vann, Terri; Vinson, Jean; Lansing, Michaele

2016-03-01

The prevention of mental, emotional, and behavioral (MEB) disorders among children and adolescents is a national priority. One mode of implementing community-wide MEB prevention efforts is through evidence-based community mobilization approaches such as Communities That Care (CTC). This article provides an overview of the CTC framework and discusses the adaptation process of CTC to prevent development of MEBs through preventing child abuse and neglect and bolstering child well-being in children aged 0 to 10. Adaptations include those to the intervention itself as well as those to the evaluation approach. Preliminary findings from the Keeping Families Together pilot study of this evolving approach suggest that the implementation was manageable for sites, and community board functioning and community adoption of a science-based approach to prevention in pilot sites looks promising. Implications and next steps are outlined. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Phenomenal enhancement of optical nonlinearity in PTZ-I based ZnS/ZnSe nanocomposites

NASA Astrophysics Data System (ADS)

Divyasree, M. C.; Shiju, E.; Vijisha, M. V.; Ramesan, M. T.; Chandrasekharan, K.

2018-05-01

The enhanced nonlinear optical properties of phenothiazine-iodine (PTZ-I) charge transfer complex (CTC) on composite formation with ZnS/ZnSe nanostructures are reported. The interaction between the components was confirmed by the FTIR spectra. Structural and morphological changes on nanocomposite formation were analyzed by scanning electron microscopy and X-ray diffraction spectra. The absorption and emission features of both the nanocomposites and their constituent components were studied. Nonlinear optical properties of all the samples in nanosecond regime were investigated by the Z-scan technique using Nd: YAG laser with 532 nm wavelength and 7 ns pulse width. The optical nonlinearity of PTZ-I CTC was found to be improved considerably on composite formation and the new systems can be proposed as excellent candidates for photonic devices. Enhanced optical nonlinearity of the composites could be attributed to charge/energy transfer mechanism between PTZ-I CTC and the nanostructures.

A "live" biopsy in a small-cell lung cancer patient by detection of circulating tumor cells.

PubMed

Bevilacqua, Simona; Gallo, Marianna; Franco, Renato; Rossi, Antonio; De Luca, Antonella; Rocco, Gaetano; Botti, Gerardo; Gridelli, Cesare; Normanno, Nicola

2009-07-01

A 71-year-old patient with a pulmonary lesion was diagnosed with a low-grade neuroendocrine tumor following examination of a fine needle aspiration biopsy. Analysis of a peripheral blood sample with the CellSearch system revealed the presence of putative circulating tumor cells (CTC) that were positive for EpCAM and cytokeratin (CK) expression. Since EpCAM is not usually expressed in neuroendocrine tumors, we performed a biopsy of liver metastases. Morphological and immunophenotypical characterization revealed that the patient had an EpCAM and CK positive small-cell lung cancer (SCLC). By using the CellSearch apparatus, EpCAM/CK positive CTC were detected in peripheral blood samples from 3 out of 4 additional SCLC patients. This study is the first to demonstrate that CTC can be identified in SCLC patients by using the CellSearch system.

Final Technical Report

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

Alexander Fridman

2005-06-01

This DOE project DE-FC36-04GO14052 ''Plasma Pilot Plant Test for Treating VOC Emissions from Wood Products Plants'' was conducted by Drexel University in cooperation with Georgia-Pacific (G-P) and Kurchatov Institute (KI). The objective of this project was to test the Plasma Pilot Plant capabilities in wood industry. The final goal of the project was to replace the current state-of-the-art, regenerative thermal oxidation (RTO) technology by Low-Temperature Plasma Technology (LTPT) in paper and wood industry for Volatile Organic Components (VOC) destruction in High Volume Low Concentration (HVLC) vent emissions. MetPro Corporation joined the team as an industrial partner from the environmental controlmore » business and a potential leader for commercialization. Concurrent Technology Corporation (CTC) has a separate contract with DOE for this technology evaluation. They prepared questionnaires for comparison of this technology and RTO, and made this comparison. These data are presented in this report along with the description of the technology itself. Experiments with the pilot plant were performed with average plasma power up to 3.6 kW. Different design of the laboratory and pilot plant pulsed coronas, as well as different analytical methods revealed many new peculiarities of the VOC abatement process. The work reported herein describes the experimental results for the VOCs removal efficiency with respect to energy consumption, residence time, water effect and initial concentration.« less

Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology.

PubMed

Che, James; Yu, Victor; Dhar, Manjima; Renier, Corinne; Matsumoto, Melissa; Heirich, Kyra; Garon, Edward B; Goldman, Jonathan; Rao, Jianyu; Sledge, George W; Pegram, Mark D; Sheth, Shruti; Jeffrey, Stefanie S; Kulkarni, Rajan P; Sollier, Elodie; Di Carlo, Dino

2016-03-15

Circulating tumor cells (CTCs) are emerging as rare but clinically significant non-invasive cellular biomarkers for cancer patient prognosis, treatment selection, and treatment monitoring. Current CTC isolation approaches, such as immunoaffinity, filtration, or size-based techniques, are often limited by throughput, purity, large output volumes, or inability to obtain viable cells for downstream analysis. For all technologies, traditional immunofluorescent staining alone has been employed to distinguish and confirm the presence of isolated CTCs among contaminating blood cells, although cells isolated by size may express vastly different phenotypes. Consequently, CTC definitions have been non-trivial, researcher-dependent, and evolving. Here we describe a complete set of objective criteria, leveraging well-established cytomorphological features of malignancy, by which we identify large CTCs. We apply the criteria to CTCs enriched from stage IV lung and breast cancer patient blood samples using the High Throughput Vortex Chip (Vortex HT), an improved microfluidic technology for the label-free, size-based enrichment and concentration of rare cells. We achieve improved capture efficiency (up to 83%), high speed of processing (8 mL/min of 10x diluted blood, or 800 μL/min of whole blood), and high purity (avg. background of 28.8±23.6 white blood cells per mL of whole blood). We show markedly improved performance of CTC capture (84% positive test rate) in comparison to previous Vortex designs and the current FDA-approved gold standard CellSearch assay. The results demonstrate the ability to quickly collect viable and pure populations of abnormal large circulating cells unbiased by molecular characteristics, which helps uncover further heterogeneity in these cells.

Effect of Daytime Blue-enriched LED Light on the Nighttime Circadian Melatonin Inhibition of Hepatoma 7288CTC Warburg Effect and Progression.

PubMed

Dauchy, Robert T; Wren-Dail, Melissa A; Dupepe, Lynell M; Hill, Steven M; Xiang, Shulin; Anbalagan, Muralidharan; Belancio, Victoria P; Dauchy, Erin M; Blask, David E

2018-06-06

Liver cancer is the second leading cause of cancer death worldwide. Metabolic pathways within the liver and liver cancersare highly regulated by the central circadian clock in the suprachiasmatic nuclei (SCN). Daily light and dark cycles regulate the SCN-driven pineal production of the circadian anticancer hormone melatonin and temporally coordinate circadianrhythms of metabolism and physiology in mammals. In previous studies, we demonstrated that melatonin suppresses linoleicacid metabolism and the Warburg effect (aerobic glycolysis)in human breast cancer xenografts and that blue-enriched light(465-485 nm) from light-emitting diode lighting at daytime (bLAD) amplifies nighttime circadian melatonin levels in ratsby 7-fold over cool white fluorescent (CWF) lighting. Here we tested the hypothesis that daytime exposure of tissue-isolatedMorris hepatoma 7288CTC-bearing male rats to bLAD amplifies the nighttime melatonin signal to enhance the inhibition oftumor growth. Compared with rats housed under a 12:12-h light:dark cycle in CWF light, rats in bLAD light evinced a 7-fold higher peak plasma melatonin level at the mid-dark phase; in addition, high melatonin levels were prolonged until 4 h intothe light phase. After implantation of tissue-isolated hepatoma 7288CTC xenografts, tumor growth rates were markedly delayed,and tumor cAMP levels, LA metabolism, the Warburg effect, and growth signaling activities were decreased in rats inbLAD compared with CWF daytime lighting. These data show that the increased nighttime circadian melatonin levels dueto bLAD exposure decreases hepatoma metabolic, signaling, and proliferative activities beyond what occurs after normalmelatonin signaling under CWF light.

Effects of the Communities That Care system on cross-sectional profiles of adolescent substance use and delinquency.

PubMed

Van Horn, M Lee; Fagan, Abigail A; Hawkins, J David; Oesterle, Sabrina

2014-08-01

Adolescent substance use and delinquency are major public health problems. Although community-based prevention strategies have been recommended to produce population-level reductions in rates of substance use and delinquency, few models show evidence of effectiveness. To test the efficacy of a community-based prevention system, Communities That Care (CTC), in reducing community rates of problem behaviors, particularly effects on specific profiles of adolescent substance use and delinquency in eighth- and tenth-graders. Twenty-four communities were randomized to CTC intervention or control groups. Data were collected from 14,099 8th- and 10th-grade students in these communities using anonymous cross-sectional surveys in 2004 and 2010 and analyzed in 2012. Outcomes were four different profiles of self-reported substance use and delinquency in 8th grade and five profiles in 10th grade. In the cross-sectional 2010 data, there was no intervention effect on the probability of experimenting with substances or of substance use coupled with delinquent activities for either grade. However, tenth-graders in intervention communities were significantly less likely to be alcohol users than those in control communities (OR=0.69, CI=0.48, 1.00). Cross-sectional population surveys showed evidence of CTC effects in reducing tenth-grade alcohol users but not experimenters. A community-wide reduction in adolescent alcohol use is important because alcohol is the most commonly used illicit substance during adolescence, and early initiation of alcohol use has been associated with alcohol-related disorders in adulthood. Failure to find hypothesized effects on experimenters qualifies these results. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology

PubMed Central

Che, James; Yu, Victor; Dhar, Manjima; Renier, Corinne; Matsumoto, Melissa; Heirich, Kyra; Garon, Edward B.; Goldman, Jonathan; Rao, Jianyu; Sledge, George W.; Pegram, Mark D.; Sheth, Shruti; Jeffrey, Stefanie S.; Kulkarni, Rajan P.; Sollier, Elodie; Di Carlo, Dino

2016-01-01

Circulating tumor cells (CTCs) are emerging as rare but clinically significant non-invasive cellular biomarkers for cancer patient prognosis, treatment selection, and treatment monitoring. Current CTC isolation approaches, such as immunoaffinity, filtration, or size-based techniques, are often limited by throughput, purity, large output volumes, or inability to obtain viable cells for downstream analysis. For all technologies, traditional immunofluorescent staining alone has been employed to distinguish and confirm the presence of isolated CTCs among contaminating blood cells, although cells isolated by size may express vastly different phenotypes. Consequently, CTC definitions have been non-trivial, researcher-dependent, and evolving. Here we describe a complete set of objective criteria, leveraging well-established cytomorphological features of malignancy, by which we identify large CTCs. We apply the criteria to CTCs enriched from stage IV lung and breast cancer patient blood samples using the High Throughput Vortex Chip (Vortex HT), an improved microfluidic technology for the label-free, size-based enrichment and concentration of rare cells. We achieve improved capture efficiency (up to 83%), high speed of processing (8 mL/min of 10x diluted blood, or 800 μL/min of whole blood), and high purity (avg. background of 28.8±23.6 white blood cells per mL of whole blood). We show markedly improved performance of CTC capture (84% positive test rate) in comparison to previous Vortex designs and the current FDA-approved gold standard CellSearch assay. The results demonstrate the ability to quickly collect viable and pure populations of abnormal large circulating cells unbiased by molecular characteristics, which helps uncover further heterogeneity in these cells. PMID:26863573

Detection of Circulating Tumor Cells in Hepatocellular Carcinoma Using Antibodies against Asialoglycoprotein Receptor, Carbamoyl Phosphate Synthetase 1 and Pan-Cytokeratin

PubMed Central

Zhang, Yu; Liu, Huiying; Sun, Bin; Zhao, Linlin; Ge, Naijian; Qian, Haihua; Yang, Yefa; Wu, Mengchao; Yin, Zhengfeng

2014-01-01

Background Asialoglycoprotein receptor (ASGPR)-ligand-based separation combined with identification with Hep Par 1 or pan-cytokeratin (P-CK) antibody have been demonstrated to detect circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC). The aim of this study was to develop an improved enrichment and identification system that allows the detection of all types of HCC CTCs. Methods The specificity of the prepared anti-ASGPR monoclonal antibody was characterized. HCC cells were bound by ASGPR antibody and subsequently magnetically isolated by second antibody-coated magnetic beads. Isolated HCC cells were identified by immunofluorescence staining using a combination of anti-P-CK and anti-carbamoyl phosphate synthetase 1 (CPS1) antibodies. Blood samples spiked with HepG2 cells were used to determine recovery and sensitivity. CTCs were detected in blood samples from HCC patients and other patients. Results ASGPR was exclusively expressed in human hepatoma cell line, normal hepatocytes and HCC cells in tissue specimens detected by the ASGPR antibody staining. More HCC cells could be identified by the antibody cocktail for CPS1 and P-CK compared with a single antibody. The current approach obtained a higher recovery rate of HepG2 cells and more CTC detection from HCC patients than the previous method. Using the current method CTCs were detected in 89% of HCC patients and no CTCs were found in the other test subjects. Conclusions Our anti-ASGPR antibody could be used for specific and efficient HCC CTC enrichment, and anti-P-CK combined with anti-CPS1 antibodies is superior to identification with one antibody alone in the sensitivity for HCC CTC detection. PMID:24763545

Analogous detection of circulating tumor cells using the AccuCyte® -CyteFinder® system and ISET system in patients with locally advanced and metastatic prostate cancer.

PubMed

van der Toom, Emma E; Groot, Vincent P; Glavaris, Stephanie A; Gemenetzis, Georgios; Chalfin, Heather J; Wood, Laura D; Wolfgang, Christopher L; de la Rosette, Jean J M C H; de Reijke, Theo M; Pienta, Kenneth J

2018-03-01

Circulating tumor cells (CTCs) can provide important information on patient's prognosis and treatment efficacy. Currently, a plethora of methods is available for the detection of these rare cells. We compared the outcomes of two of those methods to enumerate and characterize CTCs in patients with locally advanced and metastatic prostate cancer (PCa). First, the selection-free AccuCyte ® - CyteFinder ® system (RareCyte ® , Inc., Seattle, WA) and second, the ISET system (Rarecells Diagnostics, France), a CTC detection method based on cell size-exclusion. Peripheral blood samples were obtained from 15 patients with metastatic PCa and processed in parallel, using both methods according to manufacturer's protocol. CTCs were identified by immunofluorescence, using commercially available antibodies to pancytokeratin (PanCK), EpCAM, CD45/CD66b/CD34/CD11b/CD14 (AccuCyte ® - CyteFinder ® system), and pancytokeratin, vimentin (Vim) and CD45 (ISET system). The median CTC count was 5 CTCs/7.5 mL (range, 0-20) for the AccuCyte ® - CyteFinder ® system and 37 CTCs/7.5 mL (range, 8-139) for the ISET system (P < 0.001). Total CTC counts obtained for the two methods were correlated (r = 0.750, P = 0.001). When separating the total CTC count obtained with the ISET system in PanCK+/Vim- and PanCK+/Vim+ CTCs, the total CTC count obtained with the AccuCyte ® - CyteFinder ® system was moderately correlated with the PanCK+/Vim- CTCs, and strongly correlated with the PanCK+/Vim+ CTCs (r = 0.700, P = 0.004 and r = 0.810, P < 0.001, respectively). Our results highlight significant disparities in the enumeration and phenotype of CTCs detected by both techniques. Although the median amount of CTCs/7.5 mL differed significantly, total CTC counts of both methods were strongly correlated. For future studies, a more uniform approach to the isolation and definition of CTCs based on immunofluorescent stains is needed to provide reproducible results that can be correlated with clinical outcomes. © 2017 Wiley Periodicals, Inc.

CTC Sentinel. Volume 2, Issue 9, September 2009

DTIC Science & Technology

2009-09-01

For a detailed analysis of this plot and its international links, see Reinares. 20 “ NEFA Exclusives: Video Interviews with Top Paki- stani Taliban...Spokesman Maulvi Omar,” NEFA Foun- dation, August 29, 2008. 21 Reinares. 22 “Taliban’s Foreign Support Vexes U.S.,” Wall Street Journal, June 1...CTC Sentinel 1:4 (2008). 27 “Interview with Taliban Commander Sirajuddin Haqqani,” NEFA Foundation, August 18, 2008. 28 “Taliban’s Siraj Haqqani

[Virtual colonoscopy is now reality].

PubMed

Pedersen, Bodil Ginnerup; Achiam, Michael P; Arnesen, Regnar Bøge

2005-10-31

Virtual colonoscopy involves a helical CT or MR scan of the abdomen and pelvis to detect colorectal polyps and cancer. Both modalities have shown promising sensitivity in revealing larger polyps, in comparison with colonoscopy. Caution should be exercised in its clinical implementation due to significant interobserver variation and individual learning curves. A Danish study indicates that CT colonography (CTC) can be performed cost-effectively compared to colonoscopy. CTC is recommended in preference to double-contrast barium enema after incomplete colonoscopy.

Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis

DTIC Science & Technology

2015-10-01

from breast cancer patients are very distinct from breast cancer cell lines that are widely used for drug discovery, a finding which raises the...These findings are of relevance because the formation of invadopodia in CTC is required for the in vivo extravasation through blood-brain barrier as...Optimization of PCR conditions to prepare distinct Notch1/HPSE shRNAs with the establishment of an effective cloning protocol to construct pINDUCER11-shRNA

Laser-induced tissue autofluorescence versus exogenous chemical probe induced fluorescence as an arterial layer detection method: a comparative study

NASA Astrophysics Data System (ADS)

Papazoglou, Theodore G.; Arakawa, Koh; Grundfest, Warren S.; Papaioannou, Thanassis; Fishbein, Michael C.; Litvack, Frank

1990-07-01

The goal ofihis sludy was o develop a reliable laser inducedfluorescence specira analysis system using the 308nm Excimer Laser as an ablaiion andfluorescence inducing source. During our analysis we also aflempled lo determine whether exogenous chloroeiracycline hydrocloride (CTC) increased the discrimination capacity of the LIFS system. We then assessed the ability of CTC to improve the detection of the boundary between atheroma and normal media.

Isolation of circulating tumor cells by a magnesium-embedded filter

NASA Astrophysics Data System (ADS)

Liu, Yang; Xu, Tong; Xu, Yucheng; Kang, Dongyang; Xu, Lei; Park, Jungwook; Han-Chieh Chang, Jay; Zhang, Xiaoxiao; Goldkorn, Amir; Tai, Yu-Chong

2015-10-01

Circulating tumor cells (CTCs) are rare cancer cells that are shed by tumors into the bloodstream and that can be valuable biomarkers for various types of cancers. However, CTCs captured on the filter could not be released easily using the existing CTC analysis platforms based on size. To address this limitation, we have developed a novel magnesium (Mg)-embedded cell filter for capture, release and isolation of CTCs. The CTC-filter consists of a thin Ebeam-deposited Mg layer embedded between two parylene-C (PA-C) layers with designed slots for filtration and CTC capture. Thin Mg film has proved highly biocompatible and can be etched in saline, PBS and Dulbecco’s modified eagle medium (DMEM) etc, properties that are of great benefit to help dissociate the filter and thus release the cells. The finite element method (FEM) analysis was performed on the Mg etching process in DMEM for the structure design. After the filtration process, the filter was submerged in DMEM to facilitate Mg etching. The top PA-C filter pieces break apart from the bottom after Mg completely dissolves, enabling captured CTCs to detach. The released CTC can be easily aspirated into a micropipette for further analysis. Thus, the Mg-embedded cell filter provides a new and effective approach for CTCs isolation from the filter, making this a promising new strategy for cancer detection.

Model-based iterative reconstruction in low-dose CT colonography-feasibility study in 65 patients for symptomatic investigation.

PubMed

Vardhanabhuti, Varut; James, Julia; Nensey, Rehaan; Hyde, Christopher; Roobottom, Carl

2015-05-01

To compare image quality on computed tomographic colonography (CTC) acquired at standard dose (STD) and low dose (LD) using filtered-back projection, adaptive statistical iterative reconstruction, and model-based iterative reconstruction (MBIR) techniques. A total of 65 symptomatic patients were prospectively enrolled for the study and underwent STD and LD CTC with filtered-back projection, adaptive statistical iterative reconstruction, and MBIR to allow direct per-patient comparison. Objective image noise, subjective image analyses, and polyp detection were assessed. Objective image noise analysis demonstrates significant noise reduction using MBIR technique (P < .05) despite being acquired at lower doses. Subjective image analyses were superior for LD MBIR in all parameters except visibility of extracolonic lesions (two-dimensional) and visibility of colonic wall (three-dimensional) where there were no significant differences. There was no significant difference in polyp detection rates (P > .05). Doses: LD (dose-length product, 257.7), STD (dose-length product, 483.6). LD MBIR CTC objectively shows improved image noise using parameters in our study. Subjectively, image quality is maintained. Polyp detection shows no significant difference but because of small numbers needs further validation. Average dose reduction of 47% can be achieved. This study confirms feasibility of using MBIR in this context of CTC in symptomatic population. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

Circulating Tumor Cell Count Correlates with Colorectal Neoplasm Progression and Is a Prognostic Marker for Distant Metastasis in Non-Metastatic Patients

NASA Astrophysics Data System (ADS)

Tsai, Wen-Sy; Chen, Jinn-Shiun; Shao, Hung-Jen; Wu, Jen-Chia; Lai-Ming, Jr.; Lu, Si-Hong; Hung, Tsung-Fu; Chiu, Yen-Chi; You, Jeng-Fu; Hsieh, Pao-Shiu; Yeh, Chien-Yuh; Hung, Hsin-Yuan; Chiang, Sum-Fu; Lin, Geng-Ping; Tang, Reiping; Chang, Ying-Chih

2016-04-01

Enumeration of circulating tumor cells (CTCs) has been proven as a prognostic marker for metastatic colorectal cancer (m-CRC) patients. However, the currently available techniques for capturing and enumerating CTCs lack of required sensitivity to be applicable as a prognostic marker for non-metastatic patients as CTCs are even more rare. We have developed a microfluidic device utilizing antibody-conjugated non-fouling coating to eliminate nonspecific binding and to promote the multivalent binding of target cells. We then established the correlation of CTC counts and neoplasm progression through applying this platform to capture and enumerate CTCs in 2 mL of peripheral blood from healthy (n = 27), benign (n = 21), non-metastatic (n = 95), and m-CRC (n = 15) patients. The results showed that the CTC counts progressed from 0, 1, 5, to 36. Importantly, after 2-year follow-up on the non-metastatic CRC patients, we found that those who had ≥5 CTCs were 8 times more likely to develop distant metastasis within one year after curable surgery than those who had <5. In conclusion, by employing a sensitive device, CTC counts show good correlation with colorectal neoplasm, thus CTC may be as a simple, independent prognostic marker for the non-metastatic CRC patients who are at high risk of early recurrence.

A Rationale for Music Training to Enhance Executive Functions in Parkinson's Disease: An Overview of the Problem.

PubMed

Lesiuk, Teresa; Bugos, Jennifer A; Murakami, Brea

2018-04-22

Music listening interventions such as Rhythmic Auditory Stimulation can improve mobility, balance, and gait in Parkinson’s Disease (PD). Yet, the impact of music training on executive functions is not yet known. Deficits in executive functions (e.g., attention, processing speed) in patients with PD result in gait interference, deficits in emotional processing, loss of functional capacity (e.g., intellectual activity, social participation), and reduced quality of life. The model of temporal prediction and timing suggests two networks collectively contribute to movement generation and execution: the basal ganglia-thalamocortical network (BGTC) and the cerebellar-thalamocortical network (CTC). Due to decreases in dopamine responsible for the disruption of the BGTC network in adults with PD, it is hypothesized that rhythmic auditory cues assist patients through recruiting an alternate network, the CTC, which extends to the supplementary motor areas (SMA) and the frontal cortices. In piano training, fine motor finger movements activate the cerebellum and SMA, thereby exercising the CTC network. We hypothesize that exercising the CTC network through music training will contribute to enhanced executive functions. Previous research suggested that music training enhances cognitive performance (i.e., working memory and processing speed) in healthy adults and adults with cognitive impairments. This review and rationale provides support for the use of music training to enhance cognitive outcomes in patients with Parkinson’s Disease (PD).

Contralateral cortico-ponto-cerebellar pathways reconstruction in humans in vivo: implications for reciprocal cerebro-cerebellar structural connectivity in motor and non-motor areas.

PubMed

Palesi, Fulvia; De Rinaldis, Andrea; Castellazzi, Gloria; Calamante, Fernando; Muhlert, Nils; Chard, Declan; Tournier, J Donald; Magenes, Giovanni; D'Angelo, Egidio; Gandini Wheeler-Kingshott, Claudia A M

2017-10-09

Cerebellar involvement in cognition, as well as in sensorimotor control, is increasingly recognized and is thought to depend on connections with the cerebral cortex. Anatomical investigations in animals and post-mortem humans have established that cerebro-cerebellar connections are contralateral to each other and include the cerebello-thalamo-cortical (CTC) and cortico-ponto-cerebellar (CPC) pathways. CTC and CPC characterization in humans in vivo is still challenging. Here advanced tractography was combined with quantitative indices to compare CPC to CTC pathways in healthy subjects. Differently to previous studies, our findings reveal that cerebellar cognitive areas are reached by the largest proportion of the reconstructed CPC, supporting the hypothesis that a CTC-CPC loop provides a substrate for cerebro-cerebellar communication during cognitive processing. Amongst the cerebral areas identified using in vivo tractography, in addition to the cerebral motor cortex, major portions of CPC streamlines leave the prefrontal and temporal cortices. These findings are useful since provide MRI-based indications of possible subtending connectivity and, if confirmed, they are going to be a milestone for instructing computational models of brain function. These results, together with further multi-modal investigations, are warranted to provide important cues on how the cerebro-cerebellar loops operate and on how pathologies involving cerebro-cerebellar connectivity are generated.

Single-cell vs. bulk activity properties of coastal bacterioplankton over an annual cycle in a temperate ecosystem.

PubMed

Morán, Xosé Anxelu G; Calvo-Díaz, Alejandra

2009-01-01

The connections between single-cell activity properties of heterotrophic planktonic bacteria and whole community metabolism are still poorly understood. Here, we show flow cytometry single-cell analysis of membrane-intact (live), high nucleic acid (HNA) content and actively respiring (CTC+) bacteria with samples collected monthly during 2006 in northern Spain coastal waters. Bulk activity was assessed by measuring 3H-Leucine incorporation and specific growth rates. Consistently, different single-cell relative abundances were found, with 60-100% for live, 30-84% for HNA and 0.2-12% for CTC+ cells. Leucine incorporation rates (2-153 pmol L(-1) h(-1)), specific growth rates (0.01-0.29 day(-1)) and the total and relative abundances of the three single-cell groups showed marked seasonal patterns. Distinct depth distributions during summer stratification and different relations with temperature, chlorophyll and bacterial biovolume suggest the existence of different controlling factors on each single-cell property. Pooled leucine incorporation rates were similarly correlated with the abundance of all physiological groups, while specific growth rates were only substantially explained by the percentage of CTC+ cells. However, the ability to reduce CTC proved notably better than the other two single-cell properties at predicting bacterial bulk rates within seasons, suggesting a tight linkage between bacterial individual respiration and biomass production at the community level.

Feasibility of Using the Marginal Blood Vessels as Reference Landmarks for CT Colonography

PubMed Central

Wei, Zhuoshi; Yao, Jianhua; Wang, Shijun; Liu, Jiamin; Dwyer, Andrew J.; Pickhardt, Perry J.; Nowinski, Wieslaw L.; Summers, Ronald M.

2015-01-01

OBJECTIVE The purpose of this study was to show the spatial relationship of the colonic marginal blood vessels and the teniae coli on CT colonography (CTC) and the use of the marginal blood vessels for supine-prone registration of polyps and for determination of proper connectivity of collapsed colonic segments. MATERIALS AND METHODS We manually labeled the marginal blood vessels on 15 CTC examinations. Colon segmentation, centerline extraction, teniae detection, and teniae identification were automatically performed. For assessment of their spatial relationships, the distances from the marginal blood vessels to the three teniae coli and to the colon were measured. Student t tests (paired, two-tailed) were performed to evaluate the differences among these distances. To evaluate the reliability of the marginal vessels as reference points for polyp correlation, we analyzed 20 polyps from 20 additional patients who underwent supine and prone CTC. The average difference of the circumferential polyp position on the supine and prone scans was computed. Student t tests (paired, two-tailed) were performed to evaluate the supine-prone differences of the distance. We performed a study on 10 CTC studies from 10 patients with collapsed colonic segments by manually tracing the marginal blood vessels near the collapsed regions to resolve the ambiguity of the colon path. RESULTS The average distances (± SD) from the marginal blood vessels to the tenia mesocolica, tenia omentalis, and tenia libera were 20.1 ± 3.1 mm (95% CI, 18.5–21.6 mm), 39.5 ± 4.8 mm (37.1–42.0 mm), and 36.9 ± 4.2 mm (34.8–39.1 mm), respectively. Pairwise comparison showed that these distances to the tenia libera and tenia omentalis were significantly different from the distance to the tenia mesocolica (p < 0.001). The average distance from the marginal blood vessels to the colon wall was 15.3 ± 2.0 mm (14.2–16.3 mm). For polyp localization, the average difference of the circumferential polyp position on the supine and prone scans was 9.6 ± 9.4 mm (5.5–13.7 mm) (p = 0.15) and expressed as a percentage of the colon circumference was 3.1% ± 2.0% (2.3–4.0%) (p = 0.83). We were able to trace the marginal blood vessels for 10 collapsed colonic segments and determine the paths of the colon in these regions. CONCLUSION The marginal blood vessels run parallel to the colon in proximity to the tenia mesocolica and enable accurate supine-prone registration of polyps and localization of the colon path in areas of collapse. Thus, the marginal blood vessels may be used as reference landmarks complementary to the colon centerline and teniae coli. PMID:24370165

Cauchy problem in spacetimes with closed timelike curves

NASA Astrophysics Data System (ADS)

Friedman, John; Morris, Michael S.; Novikov, Igor D.; Echeverria, Fernando; Klinkhammer, Gunnar; Thorne, Kip S.; Yurtsever, Ulvi

1990-09-01

The laws of physics might permit the existence, in the real Universe, of closed timelike curves (CTC's). Macroscopic CTC's might be a semiclassical consequence of Planck-scale, quantum gravitational, Lorentzian foam, if such foam exists. If CTC's are permitted, then the semiclassical laws of physics (the laws with gravity classical and other fields quantized or classical) should be augmented by a principle of self-consistency, which states that a local solution to the equations of physics can occur in the real Universe only if it can be extended to be part of a global solution, one which is well defined throughout the (nonsingular regions of) classical spacetime. The consequences of this principle are explored for the Cauchy problem of the evolution of a classical, massless scalar field Φ (satisfying □Φ=0) in several model spacetimes with CTC's. In general, self-consistency constrains the initial data for the field Φ. For a family of spacetimes with traversible wormholes, which initially possess no CTC's and then evolve them to the future of a stable Cauchy horizon scrH, self-consistency seems to place no constraints on initial data for Φ that are posed on past null infinity, and none on data posed on spacelike slices which precede scrH. By contrast, initial data posed in the future of scrH, where the CTC's reside, are constrained; but the constraints appear to be mild in the sense that in some neighborhood of every event one is free to specify initial data arbitrarily, with the initial data elsewhere being adjusted to guarantee self-consistent evolution. A spacetime whose self-consistency constraints have this property is defined to be ``benign with respect to the scalar field Φ.'' The question is posed as to whether benign spacetimes in some sense form a generic subset of all spacetimes with CTC's. It is shown that in the set of flat, spatially and temporally closed, 2-dimensional spacetimes the benign ones are not generic. However, it seems likely that every 4-dimensional, asymptotically flat space-time that is stable and has a topology of the form R×(S-one point), where S is a closed 3-manifold, is benign. Wormhole spacetimes are of this type, with S=S1×S2. We suspect that these types of self-consistency behavior of the scalar field Φ are typical for noninteracting (linearly superposing), classical fields. However, interacting classical systems can behave quite differently, as is demonstrated by a study of the motion of a hard-sphere billiard ball in a wormhole spacetime with closed timelike curves: If the ball is classical, then some choices of initial data (some values of the ball's initial position and velocity) give rise to unique, self-consistent motions of the ball; other choices produce two different self-consistent motions; and others might (but we are not yet sure) produce no self-consistent motions whatsoever. By contrast, in a path-integral formulation of the nonrelativistic quantum mechanics of such a billiard ball, there appears to be a unique, self-consistent set of probabilities for the outcomes of all measurements. This paper's conclusion, that CTC's may not be as nasty as people have assumed, is reinforced by the fact that they do not affect Gauss's theorem and thus do not affect the derivation of global conservation laws from differential ones. The standard conservation laws remain valid globally, and in asymptotically flat, wormhole spacetimes they retain a natural, quasilocal interpretation.

Circulating Tumor Cell Counts Are Prognostic of Overall Survival in SWOG S0421: A Phase III Trial of Docetaxel With or Without Atrasentan for Metastatic Castration-Resistant Prostate Cancer

PubMed Central

Goldkorn, Amir; Ely, Benjamin; Quinn, David I.; Tangen, Catherine M.; Fink, Louis M.; Xu, Tong; Twardowski, Przemyslaw; Van Veldhuizen, Peter J.; Agarwal, Neeraj; Carducci, Michael A.; Monk, J. Paul; Datar, Ram H.; Garzotto, Mark; Mack, Philip C.; Lara, Primo; Higano, Celestia S.; Hussain, Maha; Thompson, Ian Murchie; Cote, Richard J.; Vogelzang, Nicholas J.

2014-01-01

Purpose Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan. Patients and Methods CTCs were enumerated at baseline (day 0) and before cycle two (day 21) using CellSearch. Baseline counts and changes in counts from day 0 to 21 were evaluated for association with OS, prostate-specific antigen (PSA), and RECIST response using Cox regression as well as receiver operator characteristic (ROC) curves, integrated discrimination improvement (IDI) analysis, and regression trees. Results Median day-0 CTC count was five cells per 7.5 mL, and CTCs < versus ≥ five per 7.5 mL were significantly associated with baseline PSA, bone pain, liver disease, hemoglobin, alkaline phosphatase, and subsequent PSA and RECIST response. Median OS was 26 months for < five versus 13 months for ≥ five CTCs per 7.5 mL at day 0 (hazard ratio [HR], 2.74 [adjusting for covariates]). ROC curves had higher areas under the curve for day-0 CTCs than for PSA, and IDI analysis showed that adding day-0 CTCs to baseline PSA and other covariates increased predictive accuracy for survival by 8% to 10%. Regression trees yielded new prognostic subgroups, and rising CTC count from day 0 to 21 was associated with shorter OS (HR, 2.55). Conclusion These data validate the prognostic utility of CTC enumeration in a large docetaxel-based prospective cohort. Baseline CTC counts were prognostic, and rising CTCs at 3 weeks heralded significantly worse OS, potentially serving as an early metric to help redirect and optimize therapy in this clinical setting. PMID:24616308

Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer.

PubMed

Goldkorn, Amir; Ely, Benjamin; Quinn, David I; Tangen, Catherine M; Fink, Louis M; Xu, Tong; Twardowski, Przemyslaw; Van Veldhuizen, Peter J; Agarwal, Neeraj; Carducci, Michael A; Monk, J Paul; Datar, Ram H; Garzotto, Mark; Mack, Philip C; Lara, Primo; Higano, Celestia S; Hussain, Maha; Thompson, Ian Murchie; Cote, Richard J; Vogelzang, Nicholas J

2014-04-10

Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan. CTCs were enumerated at baseline (day 0) and before cycle two (day 21) using CellSearch. Baseline counts and changes in counts from day 0 to 21 were evaluated for association with OS, prostate-specific antigen (PSA), and RECIST response using Cox regression as well as receiver operator characteristic (ROC) curves, integrated discrimination improvement (IDI) analysis, and regression trees. Median day-0 CTC count was five cells per 7.5 mL, and CTCs < versus ≥ five per 7.5 mL were significantly associated with baseline PSA, bone pain, liver disease, hemoglobin, alkaline phosphatase, and subsequent PSA and RECIST response. Median OS was 26 months for < five versus 13 months for ≥ five CTCs per 7.5 mL at day 0 (hazard ratio [HR], 2.74 [adjusting for covariates]). ROC curves had higher areas under the curve for day-0 CTCs than for PSA, and IDI analysis showed that adding day-0 CTCs to baseline PSA and other covariates increased predictive accuracy for survival by 8% to 10%. Regression trees yielded new prognostic subgroups, and rising CTC count from day 0 to 21 was associated with shorter OS (HR, 2.55). These data validate the prognostic utility of CTC enumeration in a large docetaxel-based prospective cohort. Baseline CTC counts were prognostic, and rising CTCs at 3 weeks heralded significantly worse OS, potentially serving as an early metric to help redirect and optimize therapy in this clinical setting.

Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: a Gynecologic Oncology Group study

PubMed Central

Behbakht, Kian; Sill, Michael W.; Darcy, Kathleen M.; Rubin, Stephen C.; Mannel, Robert S.; Waggoner, Steven; Schilder, Russell J.; Cai, Kathy Q.; Godwin, Andrew K.; Alpaugh, R. Katherine

2012-01-01

Purpose Patients with persistent/recurrent epithelial ovarian cancer/primary peritoneal cancer (EOC/PPC) have limited treatment options. AKT and PI3K pathway activation is common in EOC/PPC, resulting in constitutive activation of downstream mTOR. The GOG conducted a phase II evaluation of efficacy and safety for the mTOR inhibitor, temsirolimus in EOC/PPC and explored circulating tumor cells (CTC) and AKT/mTOR/downstream tumor markers. Methods Eligible women with measurable, persistent/recurrent EOC/PPC who had received 1–3 prior regimens were treated with 25 mg weekly IV temsirolimus until progression or intolerable toxicity. Primary endpoints were progression-free survival (PFS) ≥6-months, tumor response, and toxicity. CellSearch® system was used to examine CTC, and AKT/mTOR/downstream markers were evaluated by archival tumor immunohistochemistry. Kendall’s tau-b correlation coefficient (r) and Cox regression modeling were used to explore marker associations with baseline characteristics and outcome. Results Sixty patients were enrolled in a two-stage sequential design. Of 54 eligible and evaluable patients, 24.1% (90%CI 14.9%–38.6%) had PFS ≥6 months (median 3.1 months), 9.3% (90%CI 3.7%–23.4%) experienced a partial response. Grade 3/4 adverse events included metabolic(8), gastrointestinal(8), pain(6), constitutional(5) and pulmonary(4). Suggested associations were between cyclin D1 and PFS ≥6 months, PFS or survival; positive CTC pre-treatment and lack of response; and high CTC expression of M30 and PFS ≥6 months/longer PFS. Conclusions Temsirolimus appears to have modest activity in persistent/recurrent EOC/PPC; however, PFS is just below that required to warrant inclusion in phase III studies in unselected patients. Cyclin D1 as a selection marker and CTC measures merit further study. PMID:21752435

Single‐dose pharmacokinetics of co‐crystal of tramadol–celecoxib: Results of a four‐way randomized open‐label phase I clinical trial in healthy subjects

PubMed Central

Lahjou, Mounia; Vaqué, Anna; Sust, Mariano; Encabo, Mercedes; Soler, Lluis; Sans, Artur; Sicard, Eric; Gascón, Neus; Encina, Gregorio; Plata‐Salamán, Carlos

2017-01-01

Aims Co‐crystal of tramadol–celecoxib (CTC) is a novel co‐crystal molecule containing two active pharmaceutical ingredients under development by Esteve (E‐58425) and Mundipharma Research (MR308). This Phase I study compared single‐dose pharmacokinetics (PK) of CTC with those of the individual reference products [immediate‐release (IR) tramadol and celecoxib] alone and in open combination. Methods Healthy adults aged 18–55 years were orally administered four treatments under fasted conditions (separated by 7‐day wash‐out period): 200 mg IR CTC (equivalent to 88 mg tramadol and 112 mg celecoxib; Treatment 1); 100 mg IR tramadol (Treatment 2); 100 mg celecoxib (Treatment 3); and 100 mg IR tramadol and 100 mg celecoxib (Treatment 4). Treatment sequence was assigned using computer‐generated randomization. PK parameters were calculated using noncompartmental analysis with parameters for CTC adjusted according to reference product dose (100 mg). Results Thirty‐six subjects (28 male, mean age 36 years) participated. Tramadol PK parameters for Treatments‐1, –2 and –4, respectively, were 263, 346 and 349 ng ml–1 (mean maximum plasma concentration); 3039, 2979 and 3119 ng h ml–1 (mean cumulative area under the plasma concentration–time curve); and 2.7, 1.8 and 1.8 h (median time to maximum plasma concentration). For Treatments 1, 3 and 4, the respective celecoxib PK parameters were 313, 449 and 284 ng ml–1; 2183, 3093 and 2856 ng h ml–1; and 1.5, 2.3 and 3.0 h. No unexpected adverse events were reported. Conclusion PK parameters of each API in CTC were modified by co‐crystallization compared with marketed formulations of tramadol, celecoxib, and their open combination. PMID:28810061

Single-dose pharmacokinetics of co-crystal of tramadol-celecoxib: Results of a four-way randomized open-label phase I clinical trial in healthy subjects.

PubMed

Videla, Sebastián; Lahjou, Mounia; Vaqué, Anna; Sust, Mariano; Encabo, Mercedes; Soler, Lluis; Sans, Artur; Sicard, Eric; Gascón, Neus; Encina, Gregorio; Plata-Salamán, Carlos

2017-12-01

Co-crystal of tramadol-celecoxib (CTC) is a novel co-crystal molecule containing two active pharmaceutical ingredients under development by Esteve (E-58425) and Mundipharma Research (MR308). This Phase I study compared single-dose pharmacokinetics (PK) of CTC with those of the individual reference products [immediate-release (IR) tramadol and celecoxib] alone and in open combination. Healthy adults aged 18-55 years were orally administered four treatments under fasted conditions (separated by 7-day wash-out period): 200 mg IR CTC (equivalent to 88 mg tramadol and 112 mg celecoxib; Treatment 1); 100 mg IR tramadol (Treatment 2); 100 mg celecoxib (Treatment 3); and 100 mg IR tramadol and 100 mg celecoxib (Treatment 4). Treatment sequence was assigned using computer-generated randomization. PK parameters were calculated using noncompartmental analysis with parameters for CTC adjusted according to reference product dose (100 mg). Thirty-six subjects (28 male, mean age 36 years) participated. Tramadol PK parameters for Treatments-1, -2 and -4, respectively, were 263, 346 and 349 ng ml -1 (mean maximum plasma concentration); 3039, 2979 and 3119 ng h ml -1 (mean cumulative area under the plasma concentration-time curve); and 2.7, 1.8 and 1.8 h (median time to maximum plasma concentration). For Treatments 1, 3 and 4, the respective celecoxib PK parameters were 313, 449 and 284 ng ml -1 ; 2183, 3093 and 2856 ng h ml -1 ; and 1.5, 2.3 and 3.0 h. No unexpected adverse events were reported. PK parameters of each API in CTC were modified by co-crystallization compared with marketed formulations of tramadol, celecoxib, and their open combination. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Career and Technology Center Guides Students in Real-Life Careers | Poster

Cancer.gov

By Carolynne Keenan, Contributing Writer Frederick County Public School students have a unique opportunity—a chance to get a real-world, hands-on experience in biomedical science and biotechnology before they even graduate from high school, thanks to the Frederick County Career and Technology Center (CTC). Several years ago, the CTC established its biomedical sciences program with a curriculum from Project Lead the Way (PLTW), a nonprofit, nationwide developer of science, technology, engineering, and mathematics (STEM) education in elementary, middle, and high schools.

Causal Structure around Spinning 5-DIMENSIONAL Cosmic Strings

NASA Astrophysics Data System (ADS)

Slagter, Reinoud Jan

2008-09-01

We present a numerical solution of a stationary 5-dimensional spinning cosmic string in the Einstein-Yang-Mills (EYM) model, where the extra bulk coordinate ψ is periodic. It turns out that when gψψ approaches zero, i.e., a closed time-like curve (CTC) would appear, the solution becomes singular. We also investigated the geometrical structure of the static 5D cosmic string. Two opposite moving 5D strings could, in contrast with the 4D case, fulfil the Gott condition for CTC formation.

CTC Sentinel. Volume 9, Issue 8

DTIC Science & Technology

2016-08-01

607 Cullum Road, Lincoln Hall West Point, NY 10996 Phone: (845) 938-8495 Email: sentinel@usma.edu Web : www.ctc.usma.edu/sentinel/ SUBSMISSIONS...Hallberg Tønnes- sen, “The Islamic Emirate of Fallujah,” paper presented at ISA conference, Montreal, March 16-19, 2011. See also Ben Hubbard, “Iraq...It’s difficult, therefore, to dry up the financing to a point where the money isn’t there to sponsor it. What we do set as our goal is to weaken the

CTC Sentinel. Volume 1, Issue 1, December 2007. West Point Releases First Issue of CTC Sentinel

DTIC Science & Technology

2007-12-01

Shaykh Ahmad Yusuf, the amir of the Bani Suwayf group, and Shaykh Nabil al - Mughrabi , who was serving two life sentences in Egyptian prison.4...Center Department of Social Sciences U.S. Military Academy RepoRts Abu Mus`ab al -Suri’s Critique of Hard Line Salafists in the Jihadist Current By...Brynjar Lia the recent scholarly literature on al - Qa`ida has focused on studying internal divisions and ideological schisms in the global jihadist

Hyaluronan-Based Therapy for Metastatic Prostate Cancer

DTIC Science & Technology

2016-09-01

forward 5′-TGT GAC TTT GGT TGT TCC GTT GC-3′ and reverse 5′-ACC TGA GCC GAT GCA ACA ACA G-3′; DR5, forward 5′- AAG ACC CTT GTG CTC GTT GT-3′ and...reverse 5′-AGG TGG ACA CAA TCC CTC TG-3′; actin, forward 5′- TCC CTG GAG AAG AGC TAC GA-3′ and reverse 5′-AGC ACT GTG TTG GCG TAC AG-3′. 2.2.5. Death

Old Receptors, New Treatment Strategies for Breast Cancer

DTIC Science & Technology

2012-04-01

48. Page DL, Gray R, Allred DC, Dressler LG, Hatfield AK, Martino S, et al. Prediction of node-negative breast cancer outcome by his- tologic grading...GCG GTC ACA GTG ACC TGC GAG GTC ACA GTG ACC TGC GAG GTC ACA GTG ACC TGC GA-30 and 50-AGC TTC GCA GGT CAC TGT GAC CTC GCA GGT CAC TGT GAC CTC GCA GGT...VS, Bobseine K, Gray Jr LE. Development and characterization of a cell line thatstablyexpresses anestrogen-responsive luciferase reporter

Reducing image noise in computed tomography (CT) colonography: effect of an integrated circuit CT detector.

PubMed

Liu, Yu; Leng, Shuai; Michalak, Gregory J; Vrieze, Thomas J; Duan, Xinhui; Qu, Mingliang; Shiung, Maria M; McCollough, Cynthia H; Fletcher, Joel G

2014-01-01

To investigate whether the integrated circuit (IC) detector results in reduced noise in computed tomography (CT) colonography (CTC). Three hundred sixty-six consecutive patients underwent clinically indicated CTC using the same CT scanner system, except for a difference in CT detectors (IC or conventional). Image noise, patient size, and scanner radiation output (volume CT dose index) were quantitatively compared between patient cohorts using each detector system, with separate comparisons for the abdomen and pelvis. For the abdomen and pelvis, despite significantly larger patient sizes in the IC detector cohort (both P < 0.001), image noise was significantly lower (both P < 0.001), whereas volume CT dose index was unchanged (both P > 0.18). Based on the observed image noise reduction, radiation dose could alternatively be reduced by approximately 20% to result in similar levels of image noise. Computed tomography colonography images acquired using the IC detector had significantly lower noise than images acquired using the conventional detector. This noise reduction can permit further radiation dose reduction in CTC.

Label-free isolation of a prostate cancer cell among blood cells and the single-cell measurement of drug accumulation using an integrated microfluidic chip.

PubMed

Khamenehfar, A; Beischlag, T V; Russell, P J; Ling, M T P; Nelson, C; Li, P C H

2015-11-01

Circulating tumor cells (CTCs) are found in the blood of patients with cancer. Although these cells are rare, they can provide useful information for chemotherapy. However, isolation of these rare cells from blood is technically challenging because they are small in numbers. An integrated microfluidic chip, dubbed CTC chip, was designed and fabricated for conducting tumor cell isolation. As CTCs usually show multidrug resistance (MDR), the effect of MDR inhibitors on chemotherapeutic drug accumulation in the isolated single tumor cell is measured. As a model of CTC isolation, human prostate cancer cells were mixed with mouse blood cells and the label-free isolation of the tumor cells was conducted based on cell size difference. The major advantages of the CTC chip are the ability for fast cell isolation, followed by multiple rounds of single-cell measurements, suggesting a potential assay for detecting the drug responses based on the liquid biopsy of cancer patients.

Size-based separation methods of circulating tumor cells.

PubMed

Hao, Si-Jie; Wan, Yuan; Xia, Yi-Qiu; Zou, Xin; Zheng, Si-Yang

2018-02-01

Circulating tumor cells (CTCs) originate from the primary tumor mass and enter into the peripheral bloodstream. Compared to other "liquid biopsy" portfolios such as exosome, circulating tumor DNA/RNA (ctDNA/RNA), CTCs have incomparable advantages in analyses of transcriptomics, proteomics, and signal colocalization. Hence, CTCs hold the key to understanding the biology of metastasis and play a vital role in cancer diagnosis, treatment monitoring, and prognosis. Size-based enrichment features are prominent in CTC isolation. It is a label-free, simple and fast method. Enriched CTCs remain unmodified and viable for a wide range of subsequent analyses. In this review, we comprehensively summarize the differences of size and deformability between CTCs and blood cells, which would facilitate the development of technologies of size-based CTC isolation. Then we review representative size-/deformability-based technologies available for CTC isolation and highlight the recent achievements in molecular analysis of isolated CTCs. To wrap up, we discuss the substantial challenges facing the field, and elaborate on prospects. Copyright © 2018 Elsevier B.V. All rights reserved.

Lipid-Polymer Nanoparticles Encapsulating Curcumin for Modulating the Vascular Deposition of Breast Cancer Cells

PubMed Central

Palange, Anna L.; Di Mascolo, Daniele; Carallo, Claudio; Gnasso, Agostino; Decuzzi, Paolo

2014-01-01

Vascular adhesion and endothelial transmigration are critical steps in the establishment of distant metastasis by circulating tumor cells (CTCs). Also, vascular inflammation plays a pivotal role in steering CTCs out of the blood stream. Here, long circulating lipid-polymer nanoparticles encapsulating curcumin (NANOCurc) are proposed for modulating the vascular deposition of CTCs. Upon treatment with NANOCurc, the adhesion propensity of highly metastatic breast cancer cells (MDA-MB-231) onto TNF-α stimulated endothelial cells (HUVECs) reduces by ~ 70%, in a capillary flow. Remarkably, the CTC vascular deposition already reduces up to ~ 50% by treating solely the inflamed HUVECs. The CTC arrest is mediated by the interaction between ICAM-1 on HUVECs and MUC-1 on cancer cells, and moderate doses of curcumin down-regulate the expression of both molecules. This suggests that NANOCurc could prevent metastasis and limit the progression of the disease by modulating vascular inflammation and impairing the CTC arrest. PMID:24566270

Current sources of carbon tetrachloride (CCl4) in our atmosphere

NASA Astrophysics Data System (ADS)

Sherry, David; McCulloch, Archie; Liang, Qing; Reimann, Stefan; Newman, Paul A.

2018-02-01

Carbon tetrachloride (CCl4 or CTC) is an ozone-depleting substance whose emissive uses are controlled and practically banned by the Montreal Protocol (MP). Nevertheless, previous work estimated ongoing emissions of 35 Gg year-1 of CCl4 into the atmosphere from observation-based methods, in stark contrast to emissions estimates of 3 (0-8) Gg year-1 from reported numbers to UNEP under the MP. Here we combine information on sources from industrial production processes and legacy emissions from contaminated sites to provide an updated bottom-up estimate on current CTC global emissions of 15-25 Gg year-1. We now propose 13 Gg year-1 of global emissions from unreported non-feedstock emissions from chloromethane and perchloroethylene plants as the most significant CCl4 source. Additionally, 2 Gg year-1 are estimated as fugitive emissions from the usage of CTC as feedstock and possibly up to 10 Gg year-1 from legacy emissions and chlor-alkali plants.

How has the economic downturn affected communities and implementation of science-based prevention in the randomized trial of communities that care?

PubMed

Kuklinski, Margaret R; Hawkins, J David; Plotnick, Robert D; Abbott, Robert D; Reid, Carolina K

2013-06-01

This study examined implications of the economic downturn that began in December 2007 for the Community Youth Development Study (CYDS), a longitudinal randomized controlled trial of the Communities That Care (CTC) prevention system. The downturn had the potential to affect the internal validity of the CYDS research design and implementation of science-based prevention in study communities. We used archival economic indicators and community key leader reports of economic conditions to assess the extent of the economic downturn in CYDS communities and potential internal validity threats. We also examined whether stronger economic downturn effects were associated with a decline in science-based prevention implementation. Economic indicators suggested the downturn affected CYDS communities to different degrees. We found no evidence of systematic differences in downturn effects in CTC compared to control communities that would threaten internal validity of the randomized trial. The Community Economic Problems scale was a reliable measure of community economic conditions, and it showed criterion validity in relation to several objective economic indicators. CTC coalitions continued to implement science-based prevention to a significantly greater degree than control coalitions 2 years after the downturn began. However, CTC implementation levels declined to some extent as unemployment, the percentage of students qualifying for free lunch, and community economic problems worsened. Control coalition implementation levels were not related to economic conditions before or after the downturn, but mean implementation levels of science-based prevention were also relatively low in both periods.

Cost-Benefit Analysis of Communities That Care Outcomes at Eighth Grade

PubMed Central

Kuklinski, Margaret R.; Briney, John S.; Hawkins, J. David; Catalano, Richard F.

2011-01-01

This paper presents a cost-benefit analysis of the Communities That Care (CTC) prevention system, a public health approach to reducing risk, enhancing protection, and reducing the prevalence of adolescent health and behavior problems community wide. The analysis is based on outcomes from a panel of students followed from Grade 5 through Grade 8 in a randomized controlled trial involving 24 communities in 7 states. Previous analyses have shown that CTC prevented the initiation of cigarette smoking, alcohol use, and delinquency by the end of 8th grade in CTC communities compared to controls. This paper estimates long-term monetary benefits associated with significant intervention effects on cigarette smoking and delinquency as compared to the cost of conducting the intervention. Under conservative cost assumptions, the net present benefit is $5,250 per youth, including $812 from the prevention of cigarette smoking and $4,438 from the prevention of delinquency. The benefit-cost ratio indicates a return of $5.30 per $1.00 invested. Under less conservative but still viable cost assumptions, the benefit-cost ratio due to prevention of cigarette smoking and delinquency increases to $10.23 per $1.00 invested. Benefits from CTC’s reduction in alcohol initiation as well as broader inclusion of quality-of-life gains would further increase CTC’s benefit-cost ratio. Results provide evidence that CTC is a cost-beneficial preventive intervention and a good investment of public dollars, even under very conservative cost and benefit assumptions. PMID:22108900

Dynamic Repertoire of Intrinsic Brain States Is Reduced in Propofol-Induced Unconsciousness

PubMed Central

Liu, Xiping; Pillay, Siveshigan

2015-01-01

Abstract The richness of conscious experience is thought to scale with the size of the repertoire of causal brain states, and it may be diminished in anesthesia. We estimated the state repertoire from dynamic analysis of intrinsic functional brain networks in conscious sedated and unconscious anesthetized rats. Functional resonance images were obtained from 30-min whole-brain resting-state blood oxygen level-dependent (BOLD) signals at propofol infusion rates of 20 and 40 mg/kg/h, intravenously. Dynamic brain networks were defined at the voxel level by sliding window analysis of regional homogeneity (ReHo) or coincident threshold crossings (CTC) of the BOLD signal acquired in nine sagittal slices. The state repertoire was characterized by the temporal variance of the number of voxels with significant ReHo or positive CTC. From low to high propofol dose, the temporal variances of ReHo and CTC were reduced by 78%±20% and 76%±20%, respectively. Both baseline and propofol-induced reduction of CTC temporal variance increased from lateral to medial position. Group analysis showed a 20% reduction in the number of unique states at the higher propofol dose. Analysis of temporal variance in 12 anatomically defined regions of interest predicted that the largest changes occurred in visual cortex, parietal cortex, and caudate-putamen. The results suggest that the repertoire of large-scale brain states derived from the spatiotemporal dynamics of intrinsic networks is substantially reduced at an anesthetic dose associated with loss of consciousness. PMID:24702200

Fluid tagging for CT colonography: effectiveness of a 2-hour iodinated oral preparation after incomplete optical colonoscopy.

PubMed

Chang, Kevin J; Rekhi, Satinder S; Anderson, Stephan W; Soto, Jorge A

2011-01-01

To evaluate the distal extent and attenuation of bowel opacification achieved after administration of a single low volume dose of oral contrast 2 hours before computed tomographic colonography (CTC) after incomplete optical colonoscopy. This retrospective study included 144 patients undergoing CTC after incomplete colonoscopy from April 2006 to July 2008 at 2 separate medical centers. Each patient received 20 to 30 mL of diatrizoate meglumine and diatrizoate sodium solution 2 hours before being scanned. The distalmost extent of opacification was: stomach/small bowel, n = 13; cecum, n = 2; ascending colon, n = 7; transverse colon, n = 19; descending colon, n = 14; sigmoid colon, n = 24; rectum, n = 65. The mean attenuation of each opacified segment was: cecum, 449 Hounsfield units (HU); ascending colon, 474 HU; transverse colon, 468 HU; descending colon, 421 HU; sigmoid colon, 391 HU; and rectum, 382 HU. In 103 (71.5%) patients, oral contrast reached the distal colon (descending colon, sigmoid colon, or rectum). The oral contrast did not reach the colon in only 13 (9.0%) patients. Oral administration of a small volume hyperosmolar oral contrast agent 2 hours before CTC results in satisfactory colonic opacification in the majority of patients. Adding same-day fluid tagging in incomplete colonoscopy patients presenting for completion CTC should result in adequate fluid opacification for most of the colon, especially proximal segments not visualized at the time of incomplete colonoscopy.

How Has the Economic Downturn Affected Communities and Implementation of Science-Based Prevention in the Randomized Trial of Communities That Care?

PubMed Central

Kuklinski, Margaret R.; Hawkins, J. David; Plotnick, Robert D.; Abbott, Robert D.; Reid, Carolina K.

2013-01-01

This study examined implications of the economic downturn that began in December 2007 for the Community Youth Development Study (CYDS), a longitudinal randomized controlled trial of the Communities That Care (CTC) prevention system. The downturn had the potential to affect the internal validity of the CYDS research design and implementation of science-based prevention in study communities. We used archival economic indicators and community key leader reports of economic conditions to assess the extent of the economic downturn in CYDS communities and potential internal validity threats. We also examined whether stronger economic downturn effects were associated with a decline in science-based prevention implementation. Economic indicators suggested the downturn affected CYDS communities to different degrees. We found no evidence of systematic differences in downturn effects in CTC compared to control communities that would threaten internal validity of the randomized trial. The Community Economic Problems scale was a reliable measure of community economic conditions, and it showed criterion validity in relation to several objective economic indicators. CTC coalitions continued to implement science-based prevention to a significantly greater degree than control coalitions 2 years after the downturn began. However, CTC implementation levels declined to some extent as unemployment, the percentage of students qualifying for free lunch, and community economic problems worsened. Control coalition implementation levels were not related to economic conditions before or after the downturn, but mean implementation levels of science-based prevention were also relatively low in both periods. PMID:23054169

2011 Joint Missions Conference Held in Bloomington, Indiana on August 29-31, 2011

DTIC Science & Technology

2011-08-31

Breakfast Sponsored by CTC Foyer 8:00 AM – 8:15 AM NSWC Crane Welcome Remarks Great Hall  Mr. Duane Embree (SES), Technical...Director, NSWC Crane 8:15 AM – 8:30 AM NDIA Welcome Remarks Great Hall  MG Barry D. Bates, USA (Ret), VP Operations, NDIA 8:30 AM...Agile Response • Test and Evaluation Design • Concurrent systems evolution NPS Perspective on FX Research Dimensions HADR FX COCOM FX (Proposed)SOF FX

CTC Sentinel. Volume 1, Issue 4, March 2008. Jihad After Iraq: Lessons from the Arab Afghans Phenomenon

DTIC Science & Technology

2008-03-01

hydrogen peroxide of low concentration (35% in this case) could be “ enriched ” using flour . The suspects had purchased large quantities of flour and...announced that they have discovered the body of who they believe is top Jemaah Islamiyah bomb expert Dulmatin, who is suspected of involvement in the...2002 Bali bombings. The body was discovered in a shallow grave on Tawi-Tawi Island, and the FBI is involved in testing DNA from the body to

Circulating tumor cells (CTCs) from metastatic breast cancer patients linked to decreased immune function and response to treatment.

PubMed

Green, Taryn L; Cruse, Julius M; Lewis, Robert E; Craft, Barbara S

2013-10-01

We aimed to examine the use of circulating tumor cells (CTCs) as an effective measure of treatment efficacy and immune system function in metastatic breast cancer patients. CTCs are believed to be indicators of residual disease and thus pose an increased risk of metastasis and poorer outcomes to those patients who are CTC-positive. We obtained peripheral blood samples from 45 patients previously diagnosed with metastatic disease originating in the breast. Using TLR agonists that bind TLR ligands and upregulate immune effects versus unstimulated cells, we calculated a percent specific lysis using chromium-51 assay to illustrate the functional abilities of patient natural killer (NK) cells. We found those with greater than 5 CTCs per 7.5 mL blood had significantly decreased responses by their immune cells when compared with those patients who had 5 CTCs or less. We furthermore found a correlation between disease progression and CTC-positive patients, indicating that those who have a positive test should be closely monitored by their clinician. CTCs represent an exciting new clinical opportunity that will ideally utilize their low invasiveness and quick turnaround time to best benefit clinical scenarios. © 2013.

Immunomagnetic Nano-Screening Chip for Circulating Tumor Cells Detection in Blood

NASA Astrophysics Data System (ADS)

Horton, A. P.; Lane, N.; Tam, J.; Sokolov, K.; Garner, H. R.; Uhr, J. W.; Zhang, X. J.

2010-03-01

We present a novel method towards diagnose cancer at an early stage via a blood test. Early diagnosis is high on the future agenda of oncologists because of significant evidence that it will result in a higher cure rate. Capture of circulating tumor cells (CTCs) which are known to escape from carcinomas at an early stage offers such an opportunity. We design, fabricate and optimize the nanomagnetic-screening chip that captures the CTCs in microfluid, and further integrate the nano-chip with the new multispectral imaging system so that it can quantify different tumor markers and automate the entire instrument. Specifically, hybrid plasmonic (Fe2O3-core Au shell) nanoparticles, conjugated a collection of antibodies especially chosen to target breast cancer CTCs, with high magnetic susceptibility will be used for effective immunomagnetic CTC isolation. Greatly increased sensitivity over previous attempts is demonstrated by decreasing the length scale for interactions between the magnetic-nanoparticle-tagged CTCs and the isolative magnetic field, while increasing the effective cross-sectional area over which this interaction takes place. The screening chip is integrated with a novel hyperspectral microscopic imaging (HMI) platform capable of recording the entire emission spectra in a single pass evaluation. The combined system will precisely quantify up to 10 tumor markers on CTCs.

In vivo, label-free, and noninvasive detection of melanoma metastasis by photoacoustic flow cytometry

NASA Astrophysics Data System (ADS)

Liu, Rongrong; Wang, Cheng; Hu, Cheng; Wang, Xueding; Wei, Xunbin

2014-02-01

Melanoma, a malignant tumor of melanocytes, is the most serious type of skin cancer in the world. It accounts for about 80% of deaths of all skin cancer. For cancer detection, circulating tumor cells (CTCs) serve as a marker for metastasis development, cancer recurrence, and therapeutic efficacy. Melanoma tumor cells have high content of melanin, which has high light absorption and can serve as endogenous biomarker for CTC detection without labeling. Here, we have developed an in vivo photoacoustic flow cytometry (PAFC) to monitor the metastatic process of melanoma cancer by counting CTCs of melanoma tumor bearing mice in vivo. To test in vivo PAFC's capability of detecting melanoma cancer, we have constructed a melanoma tumor model by subcutaneous inoculation of highly metastatic murine melanoma cancer cells, B16F10. In order to effectively distinguish the targeting PA signals from background noise, we have used the algorithm of Wavelet denoising method to reduce the background noise. The in vivo flow cytometry (IVFC) has shown a great potential for detecting circulating tumor cells quantitatively in the blood stream. Compared with fluorescence-based in vivo flow cytometry (IVFC), PAFC technique can be used for in vivo, label-free, and noninvasive detection of circulating tumor cells (CTCs).

Crush the Crave: Development and Formative Evaluation of a Smartphone App for Smoking Cessation.

PubMed

Baskerville, Neill B; Struik, Laura L; Dash, Darly

2018-03-02

Emerging evidence supports the use of smartphone apps for smoking cessation, especially in young adults given their high smoking rates and high smartphone ownership rates. Although evaluative evidence is encouraging for supporting smoking cessation, there remains a paucity of research describing the design and development processes of mobile health (mHealth) interventions. The aim of this paper was to describe the process of developing Crush the Crave (CTC), an evidence-informed app to support smoking cessation in young adults, and the results of a formative evaluation of app usage behavior, as part of a broader program of research that seeks to establish the effectiveness of the CTC app. The Spiral Technology Action Research (STAR) 5-cycle model (listen, plan, do, act, and study) was employed to guide the development, implementation, and dissemination of CTC. The approach to development and formative evaluation included focus groups with young adult smokers (n=78) across 2 phases, analysis of the content of existing apps, 2 sessions with content experts, and Google Analytics to assess user behavior during a 12-month pilot. LISTEN-focus groups revealed young adult smoker preferences of (1) positive reinforcement, (2) personalization, (3) social support, (4) quit support, (5) tracking the behavior, and (6) tracking quit benefits. PLAN-informed by evidence for smoking cessation, young adult preferences and an assessment of popular cessation apps, content experts produced a mind map and a storyboard describing app content and structure. DO-focus groups with young adult smokers provided feedback on the first version of the app with opinions on content and suggestions for improvement such as providing alerts and distractions from craving. ACT-refinements were made, and app content was organized using the 4 key design components informed by principles of persuasive technology for behavior change: credibility, task support, dialogue support, and social support. CTC was launched in April 2013 and piloted from the period July 2013 to June 2014 where 1987 Android users had 18,567 sessions, resulting in 59,384 page views and 89.58% (1780/1987) of users returning within the same day to use CTC. STUDY-a pragmatic randomized controlled trial of CTC was launched in August 2014 to demonstrate that including mHealth technology as a population-based intervention can help young adult smokers to quit. The results of this phase will be presented in a subsequent publication. CTC is one of the first smoking cessation apps designed to meet the needs of young adult smokers. The development was informed by the inclusion of young adults in the design and the systematic application of multiple stakeholder input, scientific evidence, and theory. The STAR model approach was followed from the beginning of intervention development, which should facilitate optimization of mHealth interventions in the future. ClinicalTrials.gov NCT01983150; http://clinicaltrials.gov/ct2/show/NCT01983150 (Archived by WebCite at http://www.webcitation.org/6VGyc0W0i). ©Neill B Baskerville, Laura L Struik, Darly Dash. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 02.03.2018.

Crush the Crave: Development and Formative Evaluation of a Smartphone App for Smoking Cessation

PubMed Central

2018-01-01

Background Emerging evidence supports the use of smartphone apps for smoking cessation, especially in young adults given their high smoking rates and high smartphone ownership rates. Although evaluative evidence is encouraging for supporting smoking cessation, there remains a paucity of research describing the design and development processes of mobile health (mHealth) interventions. Objective The aim of this paper was to describe the process of developing Crush the Crave (CTC), an evidence-informed app to support smoking cessation in young adults, and the results of a formative evaluation of app usage behavior, as part of a broader program of research that seeks to establish the effectiveness of the CTC app. Methods The Spiral Technology Action Research (STAR) 5-cycle model (listen, plan, do, act, and study) was employed to guide the development, implementation, and dissemination of CTC. The approach to development and formative evaluation included focus groups with young adult smokers (n=78) across 2 phases, analysis of the content of existing apps, 2 sessions with content experts, and Google Analytics to assess user behavior during a 12-month pilot. Results LISTEN—focus groups revealed young adult smoker preferences of (1) positive reinforcement, (2) personalization, (3) social support, (4) quit support, (5) tracking the behavior, and (6) tracking quit benefits. PLAN—informed by evidence for smoking cessation, young adult preferences and an assessment of popular cessation apps, content experts produced a mind map and a storyboard describing app content and structure. DO—focus groups with young adult smokers provided feedback on the first version of the app with opinions on content and suggestions for improvement such as providing alerts and distractions from craving. ACT—refinements were made, and app content was organized using the 4 key design components informed by principles of persuasive technology for behavior change: credibility, task support, dialogue support, and social support. CTC was launched in April 2013 and piloted from the period July 2013 to June 2014 where 1987 Android users had 18,567 sessions, resulting in 59,384 page views and 89.58% (1780/1987) of users returning within the same day to use CTC. STUDY—a pragmatic randomized controlled trial of CTC was launched in August 2014 to demonstrate that including mHealth technology as a population-based intervention can help young adult smokers to quit. The results of this phase will be presented in a subsequent publication. Conclusions CTC is one of the first smoking cessation apps designed to meet the needs of young adult smokers. The development was informed by the inclusion of young adults in the design and the systematic application of multiple stakeholder input, scientific evidence, and theory. The STAR model approach was followed from the beginning of intervention development, which should facilitate optimization of mHealth interventions in the future. Trial Registration ClinicalTrials.gov NCT01983150; http://clinicaltrials.gov/ct2/show/NCT01983150 (Archived by WebCite at http://www.webcitation.org/6VGyc0W0i) PMID:29500157

All-in-one centrifugal microfluidic device for size-selective circulating tumor cell isolation with high purity.

PubMed

Lee, Ada; Park, Juhee; Lim, Minji; Sunkara, Vijaya; Kim, Shine Young; Kim, Gwang Ha; Kim, Mi-Hyun; Cho, Yoon-Kyoung

2014-11-18

Circulating tumor cells (CTCs) have gained increasing attention owing to their roles in cancer recurrence and progression. Due to the rarity of CTCs in the bloodstream, an enrichment process is essential for effective target cell characterization. However, in a typical pressure-driven microfluidic system, the enrichment process generally requires complicated equipment and long processing times. Furthermore, the commonly used immunoaffinity-based positive selection method is limited, as its recovery rate relies on EpCAM expression of target CTCs, which shows heterogeneity among cell types. Here, we propose a centrifugal-force-based size-selective CTC isolation platform that can isolate and enumerate CTCs from whole blood within 30 s with high purity. The device was validated using the MCF-7 breast cancer cell line spiked in phosphate-buffered saline and whole blood, and an average capture efficiency of 61% was achieved, which is typical for size-based filtration. The capture efficiency for whole blood samples varied from 44% to 84% under various flow conditions and dilution factors. Under the optimized operating conditions, a few hundred white blood cells per 1 mL of whole blood were captured, representing a 20-fold decrease compared to those obtained using a commercialized size-based CTC isolation device. In clinical validation, normalized CTC counts varied from 10 to 60 per 7.5 mL of blood from gastric and lung cancer patients, yielding a detection rate of 50% and 38%, respectively. Overall, our CTC isolation device enables rapid and label-free isolation of CTCs with high purity, which should greatly improve downstream molecular analyses of captured CTCs.

Clinical impact of circulating tumor cells and therapy response in pancreatic cancer.

PubMed

Okubo, K; Uenosono, Y; Arigami, T; Mataki, Y; Matsushita, D; Yanagita, S; Kurahara, H; Sakoda, M; Kijima, Y; Maemura, K; Natsugoe, S

2017-06-01

Among gastrointestinal cancers, the prognosis of pancreatic cancer is one of the poorest, with a large number of patients being diagnosed with unresectable tumors at the first visit to a doctor. The aims of the present study were to investigate the circulating tumor cells (CTC) in peripheral blood in order to assess their clinical significance in patients with pancreatic cancer. Sixty-five patients with advanced pancreatic cancer were enrolled. Borderline resectable pancreatic tumor patients were 9, and Unresectable patients were 56. The CellSearch system was used to isolate and enumerate CTCs. CTCs were identified in 21 out of 65 patients (32.3%) with only unresectable tumors. The overall survival rate was significantly lower in unresectable patients with than in those without CTCs (P = 0.0051). CTC positivity was significantly higher in patients with than in those without liver metastasis. A multivariate analysis identified the presence or absence of CTCs as an independent prognostic factor. Follow-up blood specimens were obtained from 40 patients treated with chemotherapy or chemoradiotherapy. The incidences of CTC positivity at three months after beginning of treatments in patients with progressive disease and stable disease or a partial response were 45.4% and 24.1%, respectively. The overall survival rate was significantly lower in patients with than in those without CTCs even after treatments (P = 0.045). CTC numbers represents a useful tool for predicting prognoses and therapeutic responses to chemotherapy among patients with advanced pancreatic cancer. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Wavelet method for CT colonography computer-aided polyp detection.

PubMed

Li, Jiang; Van Uitert, Robert; Yao, Jianhua; Petrick, Nicholas; Franaszek, Marek; Huang, Adam; Summers, Ronald M

2008-08-01

Computed tomographic colonography (CTC) computer aided detection (CAD) is a new method to detect colon polyps. Colonic polyps are abnormal growths that may become cancerous. Detection and removal of colonic polyps, particularly larger ones, has been shown to reduce the incidence of colorectal cancer. While high sensitivities and low false positive rates are consistently achieved for the detection of polyps sized 1 cm or larger, lower sensitivities and higher false positive rates occur when the goal of CAD is to identify "medium"-sized polyps, 6-9 mm in diameter. Such medium-sized polyps may be important for clinical patient management. We have developed a wavelet-based postprocessor to reduce false positives for this polyp size range. We applied the wavelet-based postprocessor to CTC CAD findings from 44 patients in whom 45 polyps with sizes of 6-9 mm were found at segmentally unblinded optical colonoscopy and visible on retrospective review of the CT colonography images. Prior to the application of the wavelet-based postprocessor, the CTC CAD system detected 33 of the polyps (sensitivity 73.33%) with 12.4 false positives per patient, a sensitivity comparable to that of expert radiologists. Fourfold cross validation with 5000 bootstraps showed that the wavelet-based postprocessor could reduce the false positives by 56.61% (p <0.001), to 5.38 per patient (95% confidence interval [4.41, 6.34]), without significant sensitivity degradation (32/45, 71.11%, 95% confidence interval [66.39%, 75.74%], p=0.1713). We conclude that this wavelet-based postprocessor can substantially reduce the false positive rate of our CTC CAD for this important polyp size range.

A Joint Model for the Kinetics of CTC Count and PSA Concentration During Treatment in Metastatic Castration-Resistant Prostate Cancer*

PubMed Central

Wilbaux, M; Tod, M; De Bono, J; Lorente, D; Mateo, J; Freyer, G; You, B; Hénin, E

2015-01-01

Assessment of treatment efficacy in metastatic castration-resistant prostate cancer (mCRPC) is limited by frequent nonmeasurable bone metastases. The count of circulating tumor cells (CTCs) is a promising surrogate marker that may replace the widely used prostate-specific antigen (PSA). The purpose of this study was to quantify the dynamic relationships between the longitudinal kinetics of these markers during treatment in patients with mCRPC. Data from 223 patients with mCRPC treated by chemotherapy and/or hormonotherapy were analyzed for up to 6 months of treatment. A semimechanistic model was built, combining the following several pharmacometric advanced features: (1) Kinetic-Pharmacodynamic (K-PD) compartments for treatments (chemotherapy and hormonotherapy); (2) a latent variable linking both marker kinetics; (3) modeling of CTC kinetics with a cell lifespan model; and (4) a negative binomial distribution for the CTC random sampling. Linked with survival, this model would potentially be useful for predicting treatment efficacy during drug development or for therapeutic adjustment in treated patients. PMID:26225253

Nanotechnology-Based Strategies for Early Cancer Diagnosis Using Circulating Tumor Cells as a Liquid Biopsy

PubMed Central

Huang, Qinqin; Wang, Yin; Chen, Xingxiang; Wang, Yimeng; Li, Zhiqiang; Du, Shiming; Wang, Lianrong; Chen, Shi

2018-01-01

Circulating tumor cells (CTCs) are cancer cells that shed from a primary tumor and circulate in the bloodstream. As a form of “tumor liquid biopsy”, CTCs provide important information for the mechanistic investigation of cancer metastasis and the measurement of tumor genotype evolution during treatment and disease progression. However, the extremely low abundance of CTCs in the peripheral blood and the heterogeneity of CTCs make their isolation and characterization major technological challenges. Recently, nanotechnologies have been developed for sensitive CTC detection; such technologies will enable better cell and molecular characterization and open up a wide range of clinical applications, including early disease detection and evaluation of treatment response and disease progression. In this review, we summarize the nanotechnology-based strategies for CTC isolation, including representative nanomaterials (such as magnetic nanoparticles, gold nanoparticles, silicon nanopillars, nanowires, nanopillars, carbon nanotubes, dendrimers, quantum dots, and graphene oxide) and microfluidic chip technologies that incorporate nanoroughened surfaces and discuss their key challenges and perspectives in CTC downstream analyses, such as protein expression and genetic mutations that may reflect tumor aggressiveness and patient outcome. PMID:29291161

Droplet Digital PCR Based Androgen Receptor Variant 7 (AR-V7) Detection from Prostate Cancer Patient Blood Biopsies.

PubMed

Ma, Yafeng; Luk, Alison; Young, Francis P; Lynch, David; Chua, Wei; Balakrishnar, Bavanthi; de Souza, Paul; Becker, Therese M

2016-08-04

Androgen receptor splice variant V7 (AR-V7) was recently identified as a valuable predictive biomarker in metastatic castrate-resistant prostate cancer. Here, we report a new, sensitive and accurate screen for AR-V7 mRNA expression directly from circulating tumor cells (CTCs): We combined EpCAM-based immunomagnetic CTC isolation using the IsoFlux microfluidic platform with droplet digital polymerase chain reaction (ddPCR) to analyze total AR and AR-V7 expression from prostate cancer patients CTCs. We demonstrate that AR-V7 is reliably detectable in enriched CTC samples with as little as five CTCs, even considering tumor heterogeneity, and confirm detection of AR-V7 in CTC samples from advanced prostate cancer (PCa) patients with AR-V7 detection limited to castrate resistant disease status in our sample set. Sensitive molecular analyses of circulating tumor cells (CTCs) or circulating tumor nucleic acids present exciting strategies to detect biomarkers, such as AR-V7 from non-invasive blood samples, so-called blood biopsies.

Cerebellar dentate nuclei lesions reduce motivation in appetitive operant conditioning and open field exploration.

PubMed

Bauer, David J; Kerr, Abigail L; Swain, Rodney A

2011-02-01

Recently identified pathways from the dentate nuclei of the cerebellum to the rostral cerebral cortex via the thalamus suggest a cerebellar role in frontal and prefrontal non-motor functioning. Disturbance of cerebellar morphology and connectivity, particularly involving these cerebellothalamocortical (CTC) projections, has been implicated in motivational and cognitive deficits. The current study explored the effects of CTC disruption on motivation in male Long Evans rats. The results of two experiments demonstrate that electrolytic lesions of the cerebellar dentate nuclei lower breaking points on an operant conditioning progressive ratio schedule and decrease open field exploration compared to sham controls. Changes occurred in the absence of motor impairment, assessed via lever pressing frequency and rotarod performance. Similar elevated plus maze performances between lesioned and sham animals indicated that anxiety did not influence task performance. Our results demonstrate hedonic and purposive motivational reduction and suggest a CTC role in global motivational processes. These implications are discussed in terms of psychiatric disorders such as schizophrenia and autism, in which cerebellar damage and motivational deficits often present concomitantly. Copyright © 2010 Elsevier Inc. All rights reserved.

Optimizing computer-aided colonic polyp detection for CT colonography by evolving the Pareto front1

PubMed Central

Li, Jiang; Huang, Adam; Yao, Jack; Liu, Jiamin; Van Uitert, Robert L.; Petrick, Nicholas; Summers, Ronald M.

2009-01-01

A multiobjective genetic algorithm is designed to optimize a computer-aided detection (CAD) system for identifying colonic polyps. Colonic polyps appear as elliptical protrusions on the inner surface of the colon. Curvature-based features for colonic polyp detection have proved to be successful in several CT colonography (CTC) CAD systems. Our CTC CAD program uses a sequential classifier to form initial polyp detections on the colon surface. The classifier utilizes a set of thresholds on curvature-based features to cluster suspicious colon surface regions into polyp candidates. The thresholds were previously chosen experimentally by using feature histograms. The chosen thresholds were effective for detecting polyps sized 10 mm or larger in diameter. However, many medium-sized polyps, 6–9 mm in diameter, were missed in the initial detection procedure. In this paper, the task of finding optimal thresholds as a multiobjective optimization problem was formulated, and a genetic algorithm to solve it was utilized by evolving the Pareto front of the Pareto optimal set. The new CTC CAD system was tested on 792 patients. The sensitivities of the optimized system improved significantly, from 61.68% to 74.71% with an increase of 13.03% (95% CI [6.57%, 19.5%], p=7.78×10−5) for the size category of 6–9 mm polyps, from 65.02% to 77.4% with an increase of 12.38% (95% CI [6.23%, 18.53%], p=7.95×10−5) for polyps 6 mm or larger, and from 82.2% to 90.58% with an increase of 8.38% (95%CI [0.75%, 16%], p=0.03) for polyps 8 mm or larger at comparable false positive rates. The sensitivities of the optimized system are nearly equivalent to those of expert radiologists. PMID:19235388

Automated image-based colon cleansing for laxative-free CT colonography computer-aided polyp detection

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

Linguraru, Marius George; Panjwani, Neil; Fletcher, Joel G.

2011-12-15

Purpose: To evaluate the performance of a computer-aided detection (CAD) system for detecting colonic polyps at noncathartic computed tomography colonography (CTC) in conjunction with an automated image-based colon cleansing algorithm. Methods: An automated colon cleansing algorithm was designed to detect and subtract tagged-stool, accounting for heterogeneity and poor tagging, to be used in conjunction with a colon CAD system. The method is locally adaptive and combines intensity, shape, and texture analysis with probabilistic optimization. CTC data from cathartic-free bowel preparation were acquired for testing and training the parameters. Patients underwent various colonic preparations with barium or Gastroview in divided dosesmore » over 48 h before scanning. No laxatives were administered and no dietary modifications were required. Cases were selected from a polyp-enriched cohort and included scans in which at least 90% of the solid stool was visually estimated to be tagged and each colonic segment was distended in either the prone or supine view. The CAD system was run comparatively with and without the stool subtraction algorithm. Results: The dataset comprised 38 CTC scans from prone and/or supine scans of 19 patients containing 44 polyps larger than 10 mm (22 unique polyps, if matched between prone and supine scans). The results are robust on fine details around folds, thin-stool linings on the colonic wall, near polyps and in large fluid/stool pools. The sensitivity of the CAD system is 70.5% per polyp at a rate of 5.75 false positives/scan without using the stool subtraction module. This detection improved significantly (p = 0.009) after automated colon cleansing on cathartic-free data to 86.4% true positive rate at 5.75 false positives/scan. Conclusions: An automated image-based colon cleansing algorithm designed to overcome the challenges of the noncathartic colon significantly improves the sensitivity of colon CAD by approximately 15%.« less

A chip assisted immunomagnetic separation system for the efficient capture and in situ identification of circulating tumor cells.

PubMed

Tang, Man; Wen, Cong-Ying; Wu, Ling-Ling; Hong, Shao-Li; Hu, Jiao; Xu, Chun-Miao; Pang, Dai-Wen; Zhang, Zhi-Ling

2016-04-07

The detection of circulating tumor cells (CTCs), a kind of "liquid biopsy", represents a potential alternative to noninvasive detection, characterization and monitoring of carcinoma. Many previous studies have shown that the number of CTCs has a significant relationship with the stage of cancer. However, CTC enrichment and detection remain notoriously difficult because they are extremely rare in the bloodstream. Herein, aided by a microfluidic device, an immunomagnetic separation system was applied to efficiently capture and in situ identify circulating tumor cells. Magnetic nanospheres (MNs) were modified with an anti-epithelial-cell-adhesion-molecule (anti-EpCAM) antibody to fabricate immunomagnetic nanospheres (IMNs). IMNs were then loaded into the magnetic field controllable microfluidic chip to form uniform IMN patterns. The IMN patterns maintained good stability during the whole processes including enrichment, washing and identification. Apart from its simple manufacture process, the obtained microfluidic device was capable of capturing CTCs from the bloodstream with an efficiency higher than 94%. The captured cells could be directly visualized with an inverted fluorescence microscope in situ by immunocytochemistry (ICC) identification, which decreased cell loss effectively. Besides that, the CTCs could be recovered completely just by PBS washing after removal of the permanent magnets. It was observed that all the processes showed negligible influence on cell viability (viability up to 93%) and that the captured cells could be re-cultured for more than 5 passages after release without disassociating IMNs. In addition, the device was applied to clinical samples and almost all the samples from patients showed positive results, which suggests it could serve as a valuable tool for CTC enrichment and detection in the clinic.

A Novel Tumor Antigen and Foxp3 Dual Targeting Tumor Cell Vaccine Enhances the Immunotherapy in a Murine Model of Renal Cell Carcinoma

DTIC Science & Technology

2015-12-01

GTA TCC GAT GTC CAC AAT-30; CD206_fw 50-GCA AAT GGA GCC GTC TGT GC-30, CD206_rev 50-CTC GTG GAT CTC CGT GAC AC-30; Arg-1_fw 50- GTG AAG AAC CCA CGG TCT...GT-30, Arg-1_rev 50-CTG GTT GTC AGG GGA GTG TT-30; iNOS_fw 50-TGG TGG TGA CAA GCA CAT TT-30, iNOS_rev 50- AAG GCC AAA CAC AGC ATA CC-30; Cxcl9_fw 50

A Monte Carlo Technique Suitable for Obtaining Complex Space System Reliability Confidence Limits from Component Test Data with Three Unknown Parameters.

DTIC Science & Technology

1982-12-01

093 .031 .026 E 116,292 56,424 44,906 12,354 L.L.S. c 2280 802 351 OW Average k .360 .074* .022* .009* Slope f 116,892 51,187 35,276 8,318 Modified c...LE.O.)THEN gELY =1. RGE1=RGE 1.1 ELS E X (CT-C) /THETA)**KI IF(XeLTo20.)THE4. RErLY=EXP(-X) ELSE RELY=O. END IF E"’D IF RETURN EN) 66 I APPENDIX B

Detection of Activating Estrogen Receptor Gene (ESR1) Mutations in Single Circulating Tumor Cells.

PubMed

Paolillo, Carmela; Mu, Zhaomei; Rossi, Giovanna; Schiewer, Matthew J; Nguyen, Thomas; Austin, Laura; Capoluongo, Ettore; Knudsen, Karen; Cristofanilli, Massimo; Fortina, Paolo

2017-10-15

Purpose: Early detection is essential for treatment plans before onset of metastatic disease. Our purpose was to demonstrate feasibility to detect and monitor estrogen receptor 1 ( ESR1 ) gene mutations at the single circulating tumor cell (CTC) level in metastatic breast cancer (MBC). Experimental Design: We used a CTC molecular characterization approach to investigate heterogeneity of 14 hotspot mutations in ESR1 and their correlation with endocrine resistance. Combining the CellSearch and DEPArray technologies allowed recovery of 71 single CTCs and 12 WBC from 3 ER-positive MBC patients. Forty CTCs and 12 WBC were subjected to whole genome amplification by MALBAC and Sanger sequencing. Results: Among 3 selected patients, 2 had an ESR1 mutation (Y537). One showed two different ESR1 variants in a single CTC and another showed loss of heterozygosity. All mutations were detected in matched cell-free DNA (cfDNA). Furthermore, one had 2 serial blood samples analyzed and showed changes in both cfDNA and CTCs with emergence of mutations in ESR1 (Y537S and T570I), which has not been reported previously. Conclusions: CTCs are easily accessible biomarkers to monitor and better personalize management of patients with previously demonstrated ER-MBC who are progressing on endocrine therapy. We showed that single CTC analysis can yield important information on clonal heterogeneity and can be a source of discovery of novel and potential driver mutations. Finally, we also validate a workflow for liquid biopsy that will facilitate early detection of ESR1 mutations, the emergence of endocrine resistance and the choice of further target therapy. Clin Cancer Res; 23(20); 6086-93. ©2017 AACR . ©2017 American Association for Cancer Research.

Technical Insights into Highly Sensitive Isolation and Molecular Characterization of Fixed and Live Circulating Tumor Cells for Early Detection of Tumor Invasion.

PubMed

Laget, Sophie; Broncy, Lucile; Hormigos, Katia; Dhingra, Dalia M; BenMohamed, Fatima; Capiod, Thierry; Osteras, Magne; Farinelli, Laurent; Jackson, Stephen; Paterlini-Bréchot, Patrizia

2017-01-01

Circulating Tumor Cells (CTC) and Circulating Tumor Microemboli (CTM) are Circulating Rare Cells (CRC) which herald tumor invasion and are expected to provide an opportunity to improve the management of cancer patients. An unsolved technical issue in the CTC field is how to obtain highly sensitive and unbiased collection of these fragile and heterogeneous cells, in both live and fixed form, for their molecular study when they are extremely rare, particularly at the beginning of the invasion process. We report on a new protocol to enrich from blood live CTC using ISET® (Isolation by SizE of Tumor/Trophoblastic Cells), an open system originally developed for marker-independent isolation of fixed tumor cells. We have assessed the impact of our new enrichment method on live tumor cells antigen expression, cytoskeleton structure, cell viability and ability to expand in culture. We have also explored the ISET® in vitro performance to collect intact fixed and live cancer cells by using spiking analyses with extremely low number of fluorescent cultured cells. We describe results consistently showing the feasibility of isolating fixed and live tumor cells with a Lower Limit of Detection (LLOD) of one cancer cell per 10 mL of blood and a sensitivity at LLOD ranging from 83 to 100%. This very high sensitivity threshold can be maintained when plasma is collected before tumor cells isolation. Finally, we have performed a comparative next generation sequencing (NGS) analysis of tumor cells before and after isolation from blood and culture. We established the feasibility of NGS analysis of single live and fixed tumor cells enriched from blood by our system. This study provides new protocols for detection and characterization of CTC collected from blood at the very early steps of tumor invasion.

Atrial fibrillation ablation: "perpetual motion" of open irrigated tip catheters at 50 W is safe and improves outcomes.

PubMed

Winkle, Roger A; Mead, R Hardwin; Engel, Gregory; Patrawala, Rob A

2011-05-01

Point-by-point use of open irrigated tip catheters (OITCs) at 50 W increases atrial fibrillation (AF) ablation cure rates but also increases complications. We determined if constantly moving the OITC (perpetual motion) when using 50 W increases ablation cure rates without increasing complications. We evaluated procedural data, complications, and individual procedure cure rates (IPCRs) for AF ablation using closed tip catheters (CTC) versus OITC at 40, 45, and 50 W in 1,122 ablations. We used "perpetual motion" to move the OITC at 50 W every 3-10 seconds. The OITC showed higher IPCR than CTC at 45 W (P = 0.012) and 50 W (P < 0.0005). For the OITC, IPCR increased from 44.6% to 60.7% as power increased from 40 to 50 W (P = 0.008). The OITC appeared superior to the CTC for all types of AF. For paroxysmal AF, increasing OITC power from 40 to 50 W provided no increase in IPCR (70.6% vs 71.2%, P = 0.827). For persistent AF, increasing power from 40 to 50 W increased IPCR from 34.5% to 59.5% (P = 0.001). Complications were similar for the CTC and the OITC at any power. The OITC at 50 W had shorter procedure, left atrial, and fluoroscopy times (P < 0.0005). Increasing OITC power from 40 to 50 W increases IPCR with no increase in complications as long as the 50 W setting is done using "perpetual motion." The OITC 50 W power setting results in shorter procedure and fluoroscopy times and should be considered for AF ablations. ©2010, The Authors. Journal compilation ©2010 Wiley Periodicals, Inc.

Quantitation of circulating tumor cells in blood samples from ovarian and prostate cancer patients using tumor-specific fluorescent ligands.

PubMed

He, Wei; Kularatne, Sumith A; Kalli, Kimberly R; Prendergast, Franklyn G; Amato, Robert J; Klee, George G; Hartmann, Lynn C; Low, Philip S

2008-10-15

Quantitation of circulating tumor cells (CTCs) can provide information on the stage of a malignancy, onset of disease progression and response to therapy. In an effort to more accurately quantitate CTCs, we have synthesized fluorescent conjugates of 2 high-affinity tumor-specific ligands (folate-AlexaFluor 488 and DUPA-FITC) that bind tumor cells >20-fold more efficiently than fluorescent antibodies. Here we determine whether these tumor-specific dyes can be exploited for quantitation of CTCs in peripheral blood samples from cancer patients. A CTC-enriched fraction was isolated from the peripheral blood of ovarian and prostate cancer patients by an optimized density gradient centrifugation protocol and labeled with the aforementioned fluorescent ligands. CTCs were then quantitated by flow cytometry. CTCs were detected in 18 of 20 ovarian cancer patients (mean 222 CTCs/ml; median 15 CTCs/ml; maximum 3,118 CTCs/ml), whereas CTC numbers in 16 gender-matched normal volunteers were negligible (mean 0.4 CTCs/ml; median 0.3 CTCs/ml; maximum 1.5 CTCs/ml; p < 0.001, chi(2)). CTCs were also detected in 10 of 13 prostate cancer patients (mean 26 CTCs/ml, median 14 CTCs/ml, maximum 94 CTCs/ml) but not in 18 gender-matched healthy donors (mean 0.8 CTCs/ml, median 1, maximum 3 CTC/ml; p < 0.0026, chi(2)). Tumor-specific fluorescent antibodies were much less efficient in quantitating CTCs because of their lower CTC labeling efficiency. Use of tumor-specific fluorescent ligands to label CTCs in peripheral blood can provide a simple, accurate and sensitive method for determining the number of cancer cells circulating in the bloodstream.

Variation in hospital mortality in an Australian neonatal intensive care unit network.

PubMed

Abdel-Latif, Mohamed E; Nowak, Gen; Bajuk, Barbara; Glass, Kathryn; Harley, David

2018-07-01

Studying centre-to-centre (CTC) variation in mortality rates is important because inferences about quality of care can be made permitting changes in practice to improve outcomes. However, comparisons between hospitals can be misleading unless there is adjustment for population characteristics and severity of illness. We sought to report the risk-adjusted CTC variation in mortality among preterm infants born <32 weeks and admitted to all eight tertiary neonatal intensive care units (NICUs) in the New South Wales and the Australian Capital Territory Neonatal Network (NICUS), Australia. We analysed routinely collected prospective data for births between 2007 and 2014. Adjusted mortality rates for each NICU were produced using a multiple logistic regression model. Output from this model was used to construct funnel plots. A total of 7212 live born infants <32 weeks gestation were admitted consecutively to network NICUs during the study period. NICUs differed in their patient populations and severity of illness.The overall unadjusted hospital mortality rate for the network was 7.9% (n=572 deaths). This varied from 5.3% in hospital E to 10.4% in hospital C. Adjusted mortality rates showed little CTC variation. No hospital reached the +99.8% control limit level on adjusted funnel plots. Characteristics of infants admitted to NICUs differ, and comparing unadjusted mortality rates should be avoided. Logistic regression-derived risk-adjusted mortality rates plotted on funnel plots provide a powerful visual graphical tool for presenting quality performance data. CTC variation is readily identified, permitting hospitals to appraise their practices and start timely intervention. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

National CT Colonography Trial (ACRIN 6664): Comparison of Three Full-Laxative Bowel Preparations in More Than 2500 Average-Risk Patients

PubMed Central

Hara, Amy K.; Kuo, Mark D.; Blevins, Meridith; Chen, Mei-Hsiu; Yee, Judy; Dachman, Abraham; Menias, Christine O.; Siewert, Betina; Cheema, Jugesh I.; Obregon, Richard G.; Fidler, Jeff L.; Zimmerman, Peter; Horton, Karen M.; Coakley, Kevin; Iyer, Revathy B.; Halvorsen, Robert A.; Casola, Giovanna; Johnson, C. Daniel

2011-01-01

OBJECTIVE The purpose of our study was to compare the effect of three different full-laxative bowel preparations on patient compliance, residual stool and fluid, reader confidence, and polyp detection at CT colonography (CTC). SUBJECTS AND METHODS A total of 2531 patients underwent CTC followed by colonoscopy for the American College of Radiology Imaging Network (ACRIN) National CTC Trial. Of this total, 2525 patients used one of three bowel preparations with bisacodyl tablets and stool and fluid tagging: 4 L of polyethylene glycol (PEG); 90 mL of phosphosoda; or 300 mL of magnesium citrate. Patients reported percent compliance with the bowel preparation and radiologists graded each CTC examination for the amount of residual fluid and stool on a scale from 1 (none) to 4 (nondiagnostic). Reader confidence for true-positive findings was reported on a 5-point scale: 1 (low) to 5 (high). Sensitivity and specificity for detecting polyps ≥ 6 mm and ≥ 1 cm compared with colonoscopy were calculated for each preparation. RESULTS The most commonly prescribed preparation was phosphosoda (n = 1403) followed by PEG (n = 1020) and magnesium citrate (n = 102). Phosphosoda had the highest patient compliance (p = 0.01), least residual stool (p < 0.001), and highest reader confidence versus PEG for examinations with polyps (p = 0.06). Magnesium citrate had significantly more residual fluid compared with PEG and phosphosoda (p = 0.006). The sensitivity and specificity for detecting colon polyps ≥ 6 mm and ≥ 1 cm did not differ significantly between preparations. CONCLUSION Polyp detection was comparable for all three preparations, although phosphosoda had significantly higher patient compliance and the least residual stool. PMID:21512073

Separable Bilayer Microfiltration Device for Viable Label-free Enrichment of Circulating Tumour Cells

NASA Astrophysics Data System (ADS)

Zhou, Ming-Da; Hao, Sijie; Williams, Anthony J.; Harouaka, Ramdane A.; Schrand, Brett; Rawal, Siddarth; Ao, Zheng; Brennaman, Randall; Gilboa, Eli; Lu, Bo; Wang, Shuwen; Zhu, Jiyue; Datar, Ram; Cote, Richard; Tai, Yu-Chong; Zheng, Si-Yang

2014-12-01

The analysis of circulating tumour cells (CTCs) in cancer patients could provide important information for therapeutic management. Enrichment of viable CTCs could permit performance of functional analyses on CTCs to broaden understanding of metastatic disease. However, this has not been widely accomplished. Addressing this challenge, we present a separable bilayer (SB) microfilter for viable size-based CTC capture. Unlike other single-layer CTC microfilters, the precise gap between the two layers and the architecture of pore alignment result in drastic reduction in mechanical stress on CTCs, capturing them viably. Using multiple cancer cell lines spiked in healthy donor blood, the SB microfilter demonstrated high capture efficiency (78-83%), high retention of cell viability (71-74%), high tumour cell enrichment against leukocytes (1.7-2 × 103), and widespread ability to establish cultures post-capture (100% of cell lines tested). In a metastatic mouse model, SB microfilters successfully enriched viable mouse CTCs from 0.4-0.6 mL whole mouse blood samples and established in vitro cultures for further genetic and functional analysis. Our preliminary studies reflect the efficacy of the SB microfilter device to efficiently and reliably enrich viable CTCs in animal model studies, constituting an exciting technology for new insights in cancer research.

Tracking metastatic breast cancer: the future of biology in biosensors.

PubMed

Lim, Y C; Wiegmans, A P

2016-04-01

Circulating tumour cells associated with breast cancer (brCTCs) represent cells that have the capability to establish aggressive secondary metastatic tumours. The isolation and characterization of CTCs from blood in a single device is the future of oncology diagnosis and treatment. The methods of enrichment of CTCs have primarily utilized simple biological interactions with bimodal reporting with biased high purity and low numbers or low purity and high background. In this review, we will discuss the advances in microfluidics that has allowed the use of more complex selection criteria and biological methods to identify CTC populations. We will also discuss a potential new method of selection based on the response of the oncogenic DNA repair pathways within brCTCs. This method would allow insight into not only the oncogenic signalling at play but the chemoresistance mechanisms that could guide future therapeutic intervention at any stage of disease progression.

Identification of Pro-Differentiation p53 Target Genes and Evaluation of Expression in Normal and Malignant Mammary Gland

DTIC Science & Technology

2008-04-01

genes such as c -myc and Klf-4, frequently upregulated in tumors also have been shown to establish and preserve the ES cell phenotype and the rapid...proliferation of ES cells in culture. More importantly, the introduction of these four factors (Oct3/4, Sox-2, c -myc and Klf-4) into mouse embryonic or...GTA-3’; mouse nanog: sense 5’-AAG TAC CTC AGC CTC CAG CA-3’, antisense 5’-CGT AAG GCT GCA GAA AGT GC-3’; mouse c -myc: sense 5’-CAC CAT GCC CCT CAA CGT

Novel Therapeutic Strategy for the Prevention of Bone Fractures

DTIC Science & Technology

2013-06-01

AGA GAG GGA GAT GCT CAG TGT TGG M32599 18S AGT GCG GGT CAT AAG CTT GC GGG CCT CAC TAA AC CAT CCA V00851 β-actin GTT TGA GAC CTT CAA CAC CCC GTG ...GCC ATC TCC TGC TCG AAG TC Meredith et al 2011* Mstn ACT GGA CCT CTC GAT AGA ACA CTC ACT TAG TGC TGT GTG TGT GGA GAT NM_010834.2 IGF-1 CAG...ACA GGA GCC CAG GAA AG AAG TGC CGT ATC CCA GAG GA NM_184052 MHC ACA GTC AGA GGT GTG ACTC AGC CG CCG ACT TGC GGA GGA AAG GTG C NM_001099635 Murf1

Novel Therapeutic Strategy for the Prevention of Bone Fractures

DTIC Science & Technology

2014-08-01

GAC CTT CAA CAC CCC GTG GCC ATC TCC TGC TCG AAG TC Meredith et al 2011* Mstn ACT GGA CCT CTC GAT AGA ACA CTC ACT TAG TGC TGT GTG TGT GGA GAT...NM_010834.2 IGF-1 CAG ACA GGA GCC CAG GAA AG AAG TGC CGT ATC CCA GAG GA NM_184052 MHC ACA GTC AGA GGT GTG ACTC AGC CG CCG ACT TGC GGA GGA AAG GTG C...AGC AGA GA TGA GTG CCT GCG GTA CAG AT NM_007553.2 RUNX-2 GGA AAG GCA CTG ACT GAC CTA ACA AAT TCT AAG CTT GGG AGG A NM_009820 Osx ACT ACC CAC CCT TCC

Protein evaluation of four oat (Avena sativa L.) cultivars adapted for cultivation in the south of Brazil.

PubMed

Pedó, I; Sgarbieri, V C; Gutkoski, L C

1999-01-01

Four oat cultivars adapted for soil and climate conditions in the southern region of Brazil were evaluated for protein nutritive value. Evaluations were done both in vitro and in vivo. In vitro evaluation was done by essential amino acid profile, available lysine, amino acid scoring, and protein digestibility corrected amino acid-scoring (PDCAAS). Nitrogen balance indices and PER were determined in vivo with rats. In all four cultivars (UFP-15, UFP-16, CTC-03, UFRGS-14), lysine was the most limiting amino acid. Available lysine, amino acid score and PDCAAS were highest for cultivar UFRGS-14 and lowest for CTC-03. When compared to casein, only nitrogen retention for UFRGS-14 did not differ statistically (p>0.05); all other indices of protein quality were inferior to casein for the oat cultivars. The oat cultivars tended to be identical among themselves, except for apparent protein digestibility which was significantly higher in the UFRGS-14 and CTC-03 cultivars. On average, the PER values of the oat cultivars were 82% of casein; the net protein utilization was 88% of casein as determined in vivo and 49% by the estimation in vitro (PDCAAS).

Aptamer-Based Methods for Detection of Circulating Tumor Cells and Their Potential for Personalized Diagnostics.

PubMed

Zamay, Anna S; Zamay, Galina S; Kolovskaya, Olga S; Zamay, Tatiana N; Berezovski, Maxim V

2017-01-01

Cancer diagnostics and treatment monitoring rely on sensing and counting of rare cells such as cancer circulating tumor cells (CTCs) in blood. Many analytical techniques have been developed to reliably detect and quantify CTCs using unique physical shape and size of tumor cells and/or distinctive patterns of cell surface biomarkers. Main problems of CTC bioanalysis are in the small number of cells that are present in the circulation and heterogeneity of CTCs. In this chapter, we describe recent progress towards the selection and application of synthetic DNA or RNA aptamers to capture and detect CTCs in blood. Antibody-based approaches for cell isolation and purification are limited because of an antibody's negative effect on cell viability and purity. Aptamers transform cell isolation technology, because they bind and release cells on-demand. The unique feature of anti-CTC aptamers is that the aptamers are selected for cell surface biomarkers in their native state, and conformation without previous knowledge of their biomarkers. Once aptamers are produced, they can be used to identify CTC biomarkers using mass spectrometry. The biomarkers and corresponding aptamers can be exploited to improve cancer diagnostics and therapies .

Acceptability of oral iodinated contrast media: a head-to-head comparison of four media.

PubMed

Pollentine, A; Ngan-Soo, E; McCoubrie, P

2013-05-01

To assess the palatability of iodinated oral contrast media commonly used in abdominopelvic CT and CT colonography (CTC). 80 volunteers assessed the palatability of a 20-ml sample of a standard 30 mg ml(-1) dilution of Omnipaque® (iohexol; GE Healthcare, Cork, Ireland), Telebrix® (meglumine ioxithalamate; Guerbet, Aulnay-sous-Bois, France), Gastromiro® (iopamidol; Bracco, High Wycombe, UK) and Gastrografin® (sodium diatrizoate and meglumine diatrizoate; Bayer, Newbury, UK) in a computer-generated random order. Gastrografin is rated significantly less palatable than the remaining media (p<0.005). Omnipaque and Telebrix are significantly more palatable than Gastromiro. No difference existed between Omnipaque and Telebrix. 39% of participants would refuse to consume the quantities of Gastrografin required for a CTC examination compared with Telebrix (7%) and Omnipaque (9%) (p<0.05). Omnipaque and Telebrix are significantly more palatable than both Gastromiro and Gastrografin, with participants more willing to ingest them in larger quantities as well as being less expensive. Omnipaque and Telebrix are significantly more palatable iodinated oral contrast media than both Gastromiro and Gastrografin, which has potential implications in compliance with both abdominopelvic CT and CTC.

Acceptability of oral iodinated contrast media: a head-to-head comparison of four media

PubMed Central

Ngan-Soo, E; McCoubrie, P

2013-01-01

Objective: To assess the palatability of iodinated oral contrast media commonly used in abdominopelvic CT and CT colonography (CTC). Methods: 80 volunteers assessed the palatability of a 20-ml sample of a standard 30 mg ml−1 dilution of Omnipaque® (iohexol; GE Healthcare, Cork, Ireland), Telebrix® (meglumine ioxithalamate; Guerbet, Aulnay-sous-Bois, France), Gastromiro® (iopamidol; Bracco, High Wycombe, UK) and Gastrografin® (sodium diatrizoate and meglumine diatrizoate; Bayer, Newbury, UK) in a computer-generated random order. Results: Gastrografin is rated significantly less palatable than the remaining media (p<0.005). Omnipaque and Telebrix are significantly more palatable than Gastromiro. No difference existed between Omnipaque and Telebrix. 39% of participants would refuse to consume the quantities of Gastrografin required for a CTC examination compared with Telebrix (7%) and Omnipaque (9%) (p<0.05). Conclusion: Omnipaque and Telebrix are significantly more palatable than both Gastromiro and Gastrografin, with participants more willing to ingest them in larger quantities as well as being less expensive. Advances in knowledge: Omnipaque and Telebrix are significantly more palatable iodinated oral contrast media than both Gastromiro and Gastrografin, which has potential implications in compliance with both abdominopelvic CT and CTC. PMID:23564884

Lack of Detection of Bt Sugarcane Cry1Ab and NptII DNA and Proteins in Sugarcane Processing Products Including Raw Sugar

PubMed Central

Cheavegatti-Gianotto, Adriana; Gentile, Agustina; Oldemburgo, Danielle Angeloni; Merheb, Graciela do Amaral; Sereno, Maria Lorena; Lirette, Ron Peter; Ferreira, Thais Helena Silva; de Oliveira, Wladecir Salles

2018-01-01

Brazil is the largest sugarcane producer and the main sugar exporter in the world. The industrial processes applied by Brazilian mills are very efficient in producing highly purified sugar and ethanol. Literature presents evidence of lack of DNA/protein in these products, regardless of the nature of sugarcane used as raw material. Recently CTNBio, the Brazilian biosafety authority, has approved the first biotechnology-derived sugarcane variety for cultivation, event CTC175-A, which expresses the Cry1Ab protein to control the sugarcane borer (Diatraea saccharalis). The event also expresses neomycin-phosphotransferase type II (NptII) protein used as selectable marker during the transformation process. Because of the high purity of sugar and ethanol produced from genetically modified sugarcane, these end-products should potentially be classified as “pure substances, chemically defined,” by Brazilian Biosafety Law No. 11.105. If this classification is to be adopted, these substances are not considered as “GMO derivatives” and fall out of the scope of Law No. 11.105. In order to assess sugar composition and quality, we evaluate Cry1Ab and NptII expression in several sugarcane tissues and in several fractions from laboratory-scale processing of event CTC175-A for the presence of these heterologous proteins as well as for the presence of traces of recombinant DNA. The results of these studies show that CTC175-A presents high expression of Cry1Ab in leaves and barely detectable expression of heterologous proteins in stalks. We also evaluated the presence of ribulose-1,5-bisphosphate carboxylase/oxygenase protein and DNA in the fractions of the industrial processing of conventional Brazilian sugarcane cultivars. Results from both laboratory and industrial processing were concordant, demonstrating that DNA and protein are not detected in the clarified juice and downstream processed fractions, including ethanol and raw sugar, indicating that protein and DNA are removed and/or degraded during processing. In conclusion, the processing of conventional sugarcane and CTC175-A Bt event results in downstream products with no detectable concentrations of heterologous DNA or new protein. These results help in the classification of sugar and ethanol derived from CTC175-A event as pure, chemically defined substances in Brazil and may relieve regulatory burdens in countries that import Brazilian sugar. PMID:29637070

Ocean acidification effect on prokaryotic metabolism tested in two diverse trophic regimes in the Mediterranean Sea

NASA Astrophysics Data System (ADS)

Celussi, Mauro; Malfatti, Francesca; Annalisa, Franzo; Gazeau, Frédéric; Giannakourou, Antonia; Pitta, Paraskevi; Tsiola, Anastasia; Del Negro, Paola

2017-02-01

Notwithstanding the increasing amount of researches on the effect of ocean acidification (OA) on marine ecosystems, no consent has emerged on its consequences on many prokaryote-mediated processes. Two mesocosm experiments were performed in coastal Mediterranean areas with different trophic status: the summer oligotrophic Bay of Calvi (BC, Corsica, France) and the winter mesotrophic Bay of Villefranche (BV, France). During these experiments, nine enclosures (∼54 m3) were deployed: 3 unamended controls and 6 elevated CO2, following a gradient up to 1250 μatm. We present results involving free-living viral and prokaryotic standing stocks, bacterial carbon production, abundance of highly active cells (CTC+), and degradation processes (beta-glucosidase, chitinase, leucine-aminopeptidase, lipase and alkaline phosphatase activities). The experiments revealed clear differences in the response of the two prokaryotic communities to CO2 manipulation. Only abundances of heterotrophic prokaryotes, viruses and lipase activity were not affected by CO2 manipulation at both locations. On the contrary, the percent of CTC+ was positively correlated to CO2 only in BC, concomitantly to a bulk reduction of [3H]-leucine uptake. The other tested parameters showed a different response at the two sites suggesting that the trophic regime of the systems plays a fundamental role on the effect of OA on prokaryotes through indirect modifications of the available substrate. Modified degradation rates may affect considerably the export of organic matter to the seafloor and thus ecosystem functioning within the water column. Our results highlight the need to further analyse the consequences of OA in oligotrophic ecosystems with particular focus on dissolved organic matter.

Soil moisture detection by Skylab's microwave sensors. [radiometer/scatterometer measurements of Texas

NASA Technical Reports Server (NTRS)

Moore, R. K.; Ulaby, F. T. (Principal Investigator); Barr, J. C.; Sobti, A.

1974-01-01

The author has identified the following significant results. Terrain microwave backscatter and emission response to soil moisture variations were investigated using Skylab's 13.9 GHz RADSCAT (radiometer/scatterometer) system. Data acquired on June 5, 1973, over a test site in west-central Texas indicated a fair degree of correlation with composite rainfall. The scan made was cross-track contiguous (CTC) with a pitch of 29.4 deg and no roll effect. Vertical polarization was employed with both radiometer and scatterometer. The composite rainfall was computed according to the flood prediction technique using rainfall data supplied by weather reporting stations.

ESR1 Methylation: A Liquid Biopsy-Based Epigenetic Assay for the Follow-up of Patients with Metastatic Breast Cancer Receiving Endocrine Treatment.

PubMed

Mastoraki, Sophia; Strati, Areti; Tzanikou, Eleni; Chimonidou, Maria; Politaki, Eleni; Voutsina, Alexandra; Psyrri, Amanda; Georgoulias, Vassilis; Lianidou, Evi

2018-03-15

Purpose: Liquid biopsy provides real-time monitoring of tumor evolution and response to therapy through analysis of circulating tumor cells (CTCs) and plasma-circulating tumor DNA (ctDNA). ESR1 epigenetic silencing potentially affects response to endocrine treatment. We evaluated ESR1 methylation in CTCs and paired plasma ctDNA. We evaluated ESR1 methylation in CTCs and paired plasma ctDNA as a potential biomarker for response to everolimus/exemestane treatment. Experimental Design: A highly sensitive and specific real-time MSP assay for ESR1 methylation was developed and validated in (i) 65 primary breast tumors formalin-fixed paraffin-embedded (FFPE), (ii) EpCAM + CTC fractions (122 patients and 30 healthy donors; HD), (iii) plasma ctDNA (108 patients and 30HD), and (iv) in CTCs (CellSearch) and in paired plasma ctDNA for 58 patients with breast cancer. ESR1 methylation status was investigated in CTCs isolated from serial peripheral blood samples of 19 patients with ER + /HER2 - advanced breast cancer receiving everolimus/exemestane. Results: ESR1 methylation was detected in: (i) 25/65 (38.5%) FFPEs, (ii) EpCAM + CTC fractions : 26/112 (23.3%) patients and 1/30 (3.3%) HD, and (iii) plasma ctDNA: 8/108 (7.4%) patients and 1/30 (3.3%) HD. ESR1 methylation was highly concordant in 58 paired DNA samples, isolated from CTCs (CellSearch) and corresponding plasma. In serial peripheral blood samples of patients treated with everolimus/exemestane, ESR1 methylation was observed in 10/36 (27.8%) CTC-positive samples, and was associated with lack of response to treatment ( P = 0.023, Fisher exact test). Conclusions: We report for the first time the detection of ESR1 methylation in CTCs and a high concordance with paired plasma ctDNA. ESR1 methylation in CTCs was associated with lack of response to everolimus/exemestane regimen. ESR1 methylation should be further evaluated as a potential liquid biopsy-based biomarker. Clin Cancer Res; 24(6); 1500-10. ©2017 AACR . ©2017 American Association for Cancer Research.

Parylene as a new membrane material for BioMEMS applications

NASA Astrophysics Data System (ADS)

Lu, Bo

The work in this thesis aims to use MEMS and microfabrication technologies to develop two types of parylene membrane devices for biomedical applications. The first device is the parylene membrane filter for cancer detection. The presence of circulating tumor cells (CTC) in patient blood is an important sign of cancer metastasis. However, currently there are two big challenges for CTC detection. First, CTCs are extremely rare, especially at the early stage of cancer metastasis. Secondly, CTCs are very fragile, and are very likely to be damaged during the capturing process. By using size-based membrane filtration through the specially designed parylene filters, together with a constant-pressure filtration system, we are able to capture the CTCs from patient blood with high capture efficiency, high viability, moderate enrichment, and high throughput. Both immunofluorescence enumeration and telomerase activity detection have been used to detect and differentiate the captured CTCs. The feasibility of further cell culture of the captured CTCs has also been demonstrated, which could be a useful way to increase the number of CTCs for future studies. Models of the time-dependent cell membrane damage are developed to predict and prevent CTC damage during this detection process. The results of clinical trials further demonstrate that the parylene membrane filter is a promising device for cancer detection. The second device is the parylene artificial Bruch's membrane for age-related macular degeneration (AMD). AMD is usually characterized by an impaired Bruch's membrane with much lowered permeability, which impedes the transportation of nutrients from choroid vessels to nourish the retinal pigment epithelial (RPE) cells and photoreceptors. Parylene is selected as a substitute material because of its good mechanical properties, transparency, biocompatibility, and machinability. More importantly, it is found that the permeability of submicron parylene is very similar to that of healthy human Bruch's membrane. A mesh-supported submicron parylene membrane structure has been designed and its feasibility as an artificial Bruch's membrane has been demonstrated by diffusion experiments, cell perfusion culture, and pressure deflection tests. RPE cells are able to adhere, proliferate and develop into normal in vivo-like morphology and functions. Currently this artificial membrane is under clinical trials.

Energy-momentum restrictions on the creation of Gott time machines

NASA Astrophysics Data System (ADS)

Carroll, Sean M.; Farhi, Edward; Guth, Alan H.; Olum, Ken D.

1994-11-01

The discovery by Gott of a remarkably simple spacetime with closed timelike curves (CTC's) provides a tool for investigating how the creation of time machines is prevented in classical general relativity. The Gott spacetime contains two infinitely long, parallel cosmic strings, which can equivalently be viewed as point masses in (2+1)-dimensional gravity. We examine the possibility of building such a time machine in an open universe. Specifically, we consider initial data specified on an edgeless, noncompact, spacelike hypersurface, for which the total momentum is timelike (i.e., not the momentum of a Gott spacetime). In contrast to the case of a closed universe (in which Gott pairs, although not CTC's, can be produced from the decay of stationary particles), we find that there is never enough energy for a Gott-like time machine to evolve from the specified data; it is impossible to accelerate two particles to a sufficiently high velocity. Thus, the no-CTC theorems of Tipler and Hawking are enforced in an open (2+1)-dimensional universe by a mechanism different from that which operates in a closed universe. In proving our result, we develop a simple method to understand the inequalities that restrict the result of combining momenta in (2+1)-dimensional gravity.

Feasibility of simultaneous computed tomographic colonography and fully automated bone mineral densitometry in a single examination.

PubMed

Summers, Ronald M; Baecher, Nicolai; Yao, Jianhua; Liu, Jiamin; Pickhardt, Perry J; Choi, J Richard; Hill, Suvimol

2011-01-01

To show the feasibility of calculating the bone mineral density (BMD) from computed tomographic colonography (CTC) scans using fully automated software. Automated BMD measurement software was developed that measures the BMD of the first and second lumbar vertebrae on computed tomography and calculates the mean of the 2 values to provide a per patient BMD estimate. The software was validated in a reference population of 17 consecutive women who underwent quantitative computed tomography and in a population of 475 women from a consecutive series of asymptomatic patients enrolled in a CTC screening trial conducted at 3 medical centers. The mean (SD) BMD was 133.6 (34.6) mg/mL (95% confidence interval, 130.5-136.7; n = 475). In women aged 42 to 60 years (n = 316) and 61 to 79 years (n = 159), the mean (SD) BMDs were 143.1 (33.5) and 114.7 (28.3) mg/mL, respectively (P < 0.0001). Fully automated BMD measurements were reproducible for a given patient with 95% limits of agreement of -9.79 to 8.46 mg/mL for the mean difference between paired assessments on supine and prone CTC. Osteoporosis screening can be performed simultaneously with screening for colorectal polyps.

Context- and Template-Based Compression for Efficient Management of Data Models in Resource-Constrained Systems.

PubMed

Macho, Jorge Berzosa; Montón, Luis Gardeazabal; Rodriguez, Roberto Cortiñas

2017-08-01

The Cyber Physical Systems (CPS) paradigm is based on the deployment of interconnected heterogeneous devices and systems, so interoperability is at the heart of any CPS architecture design. In this sense, the adoption of standard and generic data formats for data representation and communication, e.g., XML or JSON, effectively addresses the interoperability problem among heterogeneous systems. Nevertheless, the verbosity of those standard data formats usually demands system resources that might suppose an overload for the resource-constrained devices that are typically deployed in CPS. In this work we present Context- and Template-based Compression (CTC), a data compression approach targeted to resource-constrained devices, which allows reducing the resources needed to transmit, store and process data models. Additionally, we provide a benchmark evaluation and comparison with current implementations of the Efficient XML Interchange (EXI) processor, which is promoted by the World Wide Web Consortium (W3C), and it is the most prominent XML compression mechanism nowadays. Interestingly, the results from the evaluation show that CTC outperforms EXI implementations in terms of memory usage and speed, keeping similar compression rates. As a conclusion, CTC is shown to be a good candidate for managing standard data model representation formats in CPS composed of resource-constrained devices.

Prevention System Mediation of Communities That Care Effects on Youth Outcomes

PubMed Central

Hawkins, J. David; Rhew, Isaac C.; Shapiro, Valerie B.; Abbott, Robert D.; Oesterle, Sabrina; Arthur, Michael W.; Briney, John S.; Catalano, Richard F.

2013-01-01

This study examined whether the significant intervention effects of the Communities That Care (CTC) prevention system on youth problem behaviors observed in a panel of eighth-grade students (Hawkins et al. Archives of Pediatrics and Adolescent Medicine 163:789–798 2009) were mediated by community-level prevention system constructs posited in the CTC theory of change. Potential prevention system constructs included the community’s degree of (a) adoption of a science-based approach to prevention, (b) collaboration on prevention activities, (c) support for prevention, and (d) norms against adolescent drug use as reported by key community leaders in 24 communities. Higher levels of community adoption of a science-based approach to prevention and support for prevention in 2004 predicted significantly lower levels of youth problem behaviors in 2007, and higher levels of community norms against adolescent drug use predicted lower levels of youth drug use in 2007. Effects of the CTC intervention on youth problem behaviors by the end of eighth grade were mediated fully by community adoption of a science-based approach to prevention. No other significant mediated effects were found. Results support CTC’s theory of change that encourages communities to adopt a science- based approach to prevention as a primary mechanism for improving youth outcomes. PMID:23828448

Antimicrobial growth promoters modulate host responses in mice with a defined intestinal microbiota

PubMed Central

Brown, Kirsty; Zaytsoff, Sarah J. M.; Uwiera, Richard R. E.; Inglis, G. Douglas

2016-01-01

Antibiotics can promote growth in livestock (antimicrobial growth promoters, AGPs), however lack of knowledge regarding mechanisms has hampered the development of effective non-antibiotic alternatives. Antibiotics affect eukaryotic cells at therapeutic concentrations, yet effects of AGPs on host physiology are relatively understudied, partially due to the complexity of host-microorganism interactions within the gastrointestinal tract. To determine the direct effects of AGPs on the host, we generated Altered Schaedler Flora (ASF) mice, and administered chlortetracycline (CTC) and tylosin phosphate (TYL) in feed. Mice were challenged with Citrobacter rodentium to determine how AGPs alter host responses to physiological stress. Although CTC and TYL had inconsistent effects on the ASF taxa, AGPs protected mice from weight loss following C. rodentium inoculation. Mice treated with either CTC or TYL had lower expression of βd1 and Il17a in the intestine and had a robust induction of Il17a and Il10. Furthermore, AGP administration resulted in a lower hepatic expression of acute phase proteins (Saa1, Hp, and Cp) in liver tissue, and ameliorated C. rodentium-induced reductions in the expression of genes involved in lipogenesis (Hmgcl and Fabp1). Collectively, this indicates that AGPs directly affect host physiology, and highlights important considerations in the development of non-antibiotic alternatives. PMID:27929072

Context- and Template-Based Compression for Efficient Management of Data Models in Resource-Constrained Systems

PubMed Central

Montón, Luis Gardeazabal

2017-01-01

The Cyber Physical Systems (CPS) paradigm is based on the deployment of interconnected heterogeneous devices and systems, so interoperability is at the heart of any CPS architecture design. In this sense, the adoption of standard and generic data formats for data representation and communication, e.g., XML or JSON, effectively addresses the interoperability problem among heterogeneous systems. Nevertheless, the verbosity of those standard data formats usually demands system resources that might suppose an overload for the resource-constrained devices that are typically deployed in CPS. In this work we present Context- and Template-based Compression (CTC), a data compression approach targeted to resource-constrained devices, which allows reducing the resources needed to transmit, store and process data models. Additionally, we provide a benchmark evaluation and comparison with current implementations of the Efficient XML Interchange (EXI) processor, which is promoted by the World Wide Web Consortium (W3C), and it is the most prominent XML compression mechanism nowadays. Interestingly, the results from the evaluation show that CTC outperforms EXI implementations in terms of memory usage and speed, keeping similar compression rates. As a conclusion, CTC is shown to be a good candidate for managing standard data model representation formats in CPS composed of resource-constrained devices. PMID:28763013

Strategies for Isolation and Molecular Profiling of Circulating Tumor Cells.

PubMed

Chen, Jia-Yang; Chang, Ying-Chih

2017-01-01

Cancer is the leading cause of death by disease worldwide, and metastasis is responsible for more than 90% of the mortality of cancer patients. Metastasis occurs when tumor cells leave the primary tumor, travel through the blood stream as circulating tumor cells (CTCs), and then colonize secondary tumors at sites distant from the primary tumor. The capture, identification, and analysis of CTCs offer both scientific and clinical benefits. On the scientific side, the analysis of CTCs could help elucidate possible genetic alterations and signaling pathway aberrations during cancer progression, which could then be used to find new methods to stop cancer progression. On the clinical side, non-invasive testing of a patient's blood for CTCs can be used for patient diagnosis and prognosis, as well as subsequent monitoring of treatment efficacy in routine clinical practice. Additionally, investigation of CTCs early in the progression of cancer may reveal targets for initial cancer detection and for anti-cancer treatment. This chapter will evaluate strategies and devices used for the isolation and identification of CTCs directly from clinical samples of blood. Recent progress in the understanding of the significance of both single CTCs and circulating tumor microemboli will be discussed. Also, advancements in the use of CTC-based liquid biopsy in clinical diagnosis and the potential of CTC-based molecular characterization for use in clinical applications will be summarized.

Residues of chlortetracycline, doxycycline and sulfadiazine-trimethoprim in intestinal content and feces of pigs due to cross-contamination of feed.

PubMed

Peeters, Laura E J; Daeseleire, Els; Devreese, Mathias; Rasschaert, Geertrui; Smet, Annemieke; Dewulf, Jeroen; Heyndrickx, Marc; Imberechts, Hein; Haesebrouck, Freddy; Butaye, Patrick; Croubels, Siska

2016-09-20

Cross-contamination of feed with low concentrations of antimicrobials can occur at production, transport and/or farm level. Concerns are rising about possible effects of this contaminated feed on resistance selection in the intestinal microbiota. Therefore, an experiment with pigs was set up, in which intestinal and fecal concentrations of chlortetracycline (CTC), doxycycline (DOX) and sulfadiazine-trimethoprim (SDZ-TRIM) were determined after administration of feed containing a 3 % carry-over level of these antimicrobials. The poor oral bioavailability of tetracyclines resulted in rather high concentrations in cecal and colonic content and feces at steady-state conditions. A mean concentration of 10 mg/kg CTC and 4 mg/kg DOX in the feces was reached, which is higher than concentrations that were shown to cause resistance selection. On the other hand, lower mean levels of SDZ (0.7 mg/kg) and TRIM (< limit of detection of 0.016 mg/kg) were found in the feces, corresponding with the high oral bioavailability of SDZ and TRIM in pigs. The relation between the oral bioavailability and intestinal concentrations of the tested antimicrobials, may be of help in assessing the risks of cross-contaminated feed. However, future research is needed to confirm our results and to evaluate the effects of these detected concentrations on resistance selection in the intestinal microbiota of pigs.

First Wave of the 2016-17 Cholera Outbreak in Hodeidah City, Yemen - ACF Experience and Lessons Learned.

PubMed

Altmann, Mathias; Suarez-Bustamante, Miguel; Soulier, Celine; Lesavre, Celine; Antoine, Caroline

2017-10-13

Although cases were reported only in 2010 and 2011, cholera is probably endemic in Yemen. In the context of a civil war, a cholera outbreak was declared in different parts of the country October 6th, 2016. This paper describes the ACF outbreak response in Hodeidah city from October 28th, 2016 to February 28th, 2017 in order to add knowledge to this large outbreak. The ACF outbreak response in Hodeidah city included a case management component and prevention measures in the community. In partnership with the Ministry of Public Health and Population of Yemen (MoPHP), the case management component included a Cholera Treatment Center (CTC) implemented in the Al Thoraw hospital, 11 Oral Rehydration Therapy Corners (ORTCs) and an active case finding system. In partnership with other stakeholders, prevention measures in the community, including access to safe water and hygiene promotion, were implemented in the most affected communities of the city. From October 28th, 2016 until February 28th, 2017, ACF provided care to 8,270 Acute Watery Diarrhea (AWD) cases, of which 5,210 (63%) were suspected cholera cases, in the CTC and the 11 ORTCs implemented in Hodeidah city. The attack rate was higher among people living in Al Hali district, with a peak in November 2016. At the CTC, 8% of children under 5 years-old also presented with Severe Acute Malnutrition (SAM). The Case-Fatality Rate (CFR) was low (0.07%) but 15% of admitted cases defaulted for cultural and security reasons. Environmental management lacked the information to appropriately target affected areas. Financial resources did not allow complete coverage of the city. Response to the first wave of a large cholera outbreak in Hodeidah city was successful in maintaining a CFR <1% in the CTC. However, considering the actual context of Yemen and its water infrastructure, much more efforts are needed to control the current outbreak resurgence.

First Wave of the 2016-17 Cholera Outbreak in Hodeidah City, Yemen - ACF Experience and Lessons Learned

PubMed Central

Altmann, Mathias; Suarez-Bustamante, Miguel; Soulier, Celine; Lesavre, Celine; Antoine, Caroline

2017-01-01

Introduction: Although cases were reported only in 2010 and 2011, cholera is probably endemic in Yemen. In the context of a civil war, a cholera outbreak was declared in different parts of the country October 6th, 2016. This paper describes the ACF outbreak response in Hodeidah city from October 28th, 2016 to February 28th, 2017 in order to add knowledge to this large outbreak. Methods: The ACF outbreak response in Hodeidah city included a case management component and prevention measures in the community. In partnership with the Ministry of Public Health and Population of Yemen (MoPHP), the case management component included a Cholera Treatment Center (CTC) implemented in the Al Thoraw hospital, 11 Oral Rehydration Therapy Corners (ORTCs) and an active case finding system. In partnership with other stakeholders, prevention measures in the community, including access to safe water and hygiene promotion, were implemented in the most affected communities of the city. Results: From October 28th, 2016 until February 28th, 2017, ACF provided care to 8,270 Acute Watery Diarrhea (AWD) cases, of which 5,210 (63%) were suspected cholera cases, in the CTC and the 11 ORTCs implemented in Hodeidah city. The attack rate was higher among people living in Al Hali district, with a peak in November 2016. At the CTC, 8% of children under 5 years-old also presented with Severe Acute Malnutrition (SAM). The Case-Fatality Rate (CFR) was low (0.07%) but 15% of admitted cases defaulted for cultural and security reasons. Environmental management lacked the information to appropriately target affected areas. Financial resources did not allow complete coverage of the city. Conclusion: Response to the first wave of a large cholera outbreak in Hodeidah city was successful in maintaining a CFR <1% in the CTC. However, considering the actual context of Yemen and its water infrastructure, much more efforts are needed to control the current outbreak resurgence. PMID:29188130

Texture-based CAD improves diagnosis for low-dose CT colonography

NASA Astrophysics Data System (ADS)

Liang, Zhengrong; Cohen, Harris; Posniak, Erica; Fiore, Eddie; Wang, Zigang; Li, Bin; Andersen, Joseph; Harrington, Donald

2008-03-01

Computed tomography (CT)-based virtual colonoscopy or CT colonography (CTC) currently utilizes oral contrast solutions to tag the colonic fluid and possibly residual stool for differentiation from the colon wall and polyps. The enhanced image density of the tagged colonic materials causes a significant partial volume (PV) effect into the colon wall as well as the lumen space (filled with air or CO II). The PV effect on the colon wall can "bury" polyps of size as large as 5mm by increasing their image densities to a noticeable level, resulting in false negatives. It can also create false positives when PV effect goes into the lumen space. We have been modeling the PV effect for mixture-based image segmentation and developing text-based computer-aided detection of polyp (CADpolyp) by utilizing the PV mixture-based image segmentation. This work presents some preliminary results of developing and applying texture-based CADpolyp technique to low-dose CTC studies. A total of 114 studies of asymptomatic patients older than 50, who underwent CTC and then optical colonoscopy (OC) on the same day, were selected from a database, which was accumulated in the past decade and contains various bowel preparations and CT scanning protocols. The participating radiologists found ten polyps of greater than 5 mm from a total of 16 OC proved polyps, i.e., a detection sensitivity of 63%. They scored 23 false positives from the database, i.e., a 20% false positive rate. Approximately 70% of the datasets were marked as imperfect bowel cleansing and/or presence of image artifacts. The impact of imperfect bowel cleansing and image artifacts on VC performance is significant. The texture-based CADpolyp detected all the polyps with an average of 2.68 false positives per patient. This indicates that texture-based CADpolyp can improve the CTC performance in the cases of imperfect cleansed bowels and presence of image artifacts.

Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry.

PubMed

Biggs, Colleen N; Siddiqui, Khurram M; Al-Zahrani, Ali A; Pardhan, Siddika; Brett, Sabine I; Guo, Qiu Q; Yang, Jun; Wolf, Philipp; Power, Nicholas E; Durfee, Paul N; MacMillan, Connor D; Townson, Jason L; Brinker, Jeffrey C; Fleshner, Neil E; Izawa, Jonathan I; Chambers, Ann F; Chin, Joseph L; Leong, Hon S

2016-02-23

Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/µL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer.

Effects of ionic strength, temperature, and pH on degradation of selected antibiotics

USGS Publications Warehouse

Loftin, K.A.; Adams, C.D.; Meyer, M.T.; Surampalli, R.

2008-01-01

Aqueous degradation rates, which include hydrolysis and epimerization, for chlorretracycline (CTC), oxytetracycline (OTC), tetracycline (TET), lincomycin (LNC), sulfachlorpyridazine (SCP), sulfadimethoxine (SDM), sulfathiazole (STZ), trimethoprim (TRM), and tylosin A (TYL) were studied as a function of ionic strength (0.0015, 0.050, or 0.084 mg/L as Na2HPO4), temperature (7, 22, and 35??C), and pH (2, 5, 7, 9, and 11). Multiple linear regression revealed that ionic strength did not significantly affect (?? = 0.05) degradation rates for all compounds, but temperature and pH affected rates for CTC, OTC, and TET significandy (?? = 0.05). Degradation also was observed for TYL at pH 2 and 11. No significant degradation was observed for LNC, SCR SDM, STZ, TRM, and TYL (pH 5, 7, and 9) under study conditions. Pseudo first-order rate constants, half-lives, and Arrhenius coefficients were calculated where appropriate. In general, hydrolysis rates for CTC, OTC, and TET increased as pH and temperature increased following Arrhenius relationships. Known degradation products were used to confirm that degradation had occurred, but these products were not quantified. Half-lives ranged from less than 6 h up to 9.7 wk for the tetracyclines and for TYL (pH 2 and 11), but no degradation of LIN, the sulfonamides, or TRM was observed during the study period. These results indicate that tetracyclines and TYL at pH 2 and 11 are prone to pH-mediated transformation and hydrolysis in some cases, but not the sulfonamides, LIN nor TRM are inclined to degrade under study conditions. This indicates that with the exception of CTC OTC, and TET, pH-mediated reactions such as hydrolysis and epimerization are not likely removal mechanisms in surface water, anaerobic swine lagoons, wastewater, and ground water. Copyright ?? 2008 by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America. All rights reserved.

Technical Insights into Highly Sensitive Isolation and Molecular Characterization of Fixed and Live Circulating Tumor Cells for Early Detection of Tumor Invasion

PubMed Central

Laget, Sophie; Dhingra, Dalia M.; BenMohamed, Fatima; Capiod, Thierry; Osteras, Magne; Farinelli, Laurent; Jackson, Stephen; Paterlini-Bréchot, Patrizia

2017-01-01

Circulating Tumor Cells (CTC) and Circulating Tumor Microemboli (CTM) are Circulating Rare Cells (CRC) which herald tumor invasion and are expected to provide an opportunity to improve the management of cancer patients. An unsolved technical issue in the CTC field is how to obtain highly sensitive and unbiased collection of these fragile and heterogeneous cells, in both live and fixed form, for their molecular study when they are extremely rare, particularly at the beginning of the invasion process. We report on a new protocol to enrich from blood live CTC using ISET® (Isolation by SizE of Tumor/Trophoblastic Cells), an open system originally developed for marker-independent isolation of fixed tumor cells. We have assessed the impact of our new enrichment method on live tumor cells antigen expression, cytoskeleton structure, cell viability and ability to expand in culture. We have also explored the ISET® in vitro performance to collect intact fixed and live cancer cells by using spiking analyses with extremely low number of fluorescent cultured cells. We describe results consistently showing the feasibility of isolating fixed and live tumor cells with a Lower Limit of Detection (LLOD) of one cancer cell per 10 mL of blood and a sensitivity at LLOD ranging from 83 to 100%. This very high sensitivity threshold can be maintained when plasma is collected before tumor cells isolation. Finally, we have performed a comparative next generation sequencing (NGS) analysis of tumor cells before and after isolation from blood and culture. We established the feasibility of NGS analysis of single live and fixed tumor cells enriched from blood by our system. This study provides new protocols for detection and characterization of CTC collected from blood at the very early steps of tumor invasion. PMID:28060956

Safety of multiple repeated cycles of 177Lu-octreotate in patients with recurrent neuroendocrine tumour.

PubMed

Yordanova, Anna; Mayer, Karin; Brossart, Peter; Gonzalez-Carmona, Maria A; Strassburg, Christian P; Essler, Markus; Ahmadzadehfar, Hojjat

2017-07-01

Peptide receptor radionuclide therapy (PRRT) is an effective therapy in patients with a somatostatin receptor-positive neuroendocrine tumour (NET). Still unclear is how many cycles of 177 Lu-octreotate can be repeated while maintaining an acceptable toxicity profile. The purpose of this study was to assess the safety of repeated PRRT in patients with recurrent NET. We retrospectively evaluated data from 15 patients treated with repeated PRRT between 2004 and 2015. The median administered activity was 63.8 GBq (range 52-96.6 GBq) in a median of 9 cycles (range 8-13 cycles). Nonhaematological and haematological toxicities were assessed from clinical reports and laboratory data. The rates of adverse events in three therapy groups were compared: during cycles 1 to 4, cycles 5 to 8, and cycles 9 to 13. Baseline laboratory assessments were also compared with data obtained at the end of treatment. The overall survival in the study patients was compared with survival data in patients who received only a baseline PRRT of three or four cycles. We observed no life-threatening adverse events (CTC-4) during 177 Lu-octreotate treatment. Reversible haematological toxicity (CTC-3) occurred in two patients (13%). No CTC-3/4 nephrotoxicity was recorded. More CTC-3 adverse events were recorded in the first therapy group than in the other two groups. Furthermore, there were no significant changes in the mean values of thrombocytes, leucocytes and serum creatinine before and after therapy. However, the mean haemoglobin levels fell from 14 g/dL to 11 g/dL. Finally, compared with those patients who received three or four cycles, there was a survival benefit in patients treated with repeated PRRT (censored overall survival 85.6 vs. 69.7 months, p < 0.001). Therapy with eight or more cycles of 177 Lu-octreotate was well tolerated and led to a survival benefit in patients with recurrent NET.

A study of oral contrast coating on the surface of polyps: an implication for computer-aided detection and classification of polyps

NASA Astrophysics Data System (ADS)

Singh, Harmanpreet; Li, Lihong C.; Pomeroy, Marc; Pickhardt, Perry J.; Barish, Matthew A.; Harrington, Donald P.; Liang, Zhengrong

2017-03-01

Accurate identification of polyps is the ultimate goal of Computed Tomography Colonography (CTC). While oral contrast agents were originally used to tag stool and fluid for the ultimate goal of CTC, recently their effect on coating the surface of polyps has been observed. This study aims to evaluate (1) the frequency at which the oral contrast adhered to polyp surfaces and (2) if there was a difference in contrast adherence with respect to diverse polyp types. To eliminate gravity as a factor in this study, the polyps in contact with tagged fluid pools, particularly on the bottom of the colon wall were excluded. A total of 150 polyps were selected under the above condition from a CTC database and screened for any adherent contrast on the luminal edge. Among the total, 53% of the screened polyps had adherent contrast. Serrated adenomas and hyperplastic polyps had a higher tagging percentage, 77.80% and 62.50% respectively, than tubular adenomas and tubulovillous adenomas, 44.40% and 43% respectively. Other factors that were analyzed for the effect on coating include size and location of the polyps. The higher tagging percentage of serrated adenomas and hyperplastic polyps may be due to their similar cellular features. The average size of the polyps was 8.9 mm. When the polyps were separated by size into small (5-9mm) and large (10-26mm) groups, the large group had a higher tagging percentage. The polyp types were also classified by location with the major findings being: 1) Tubular adenomas were present in all segments of the colon and 2) that serrated adenomas were present at a higher percentage in the proximal colon. These findings shall facilitate characterizing tagging agents and improve computer aided detection and classification of polyps via CTC.

Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry

PubMed Central

Al-Zahrani, Ali A.; Pardhan, Siddika; Brett, Sabine I.; Guo, Qiu Q.; Yang, Jun; Wolf, Philipp; Power, Nicholas E.; Durfee, Paul N.; MacMillan, Connor D.; Townson, Jason L.; Brinker, Jeffrey C.; Fleshner, Neil E.; Izawa, Jonathan I.; Chambers, Ann F.; Chin, Joseph L.; Leong, Hon S.

2016-01-01

Background Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Patients and Methods Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/μL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. Results PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. Conclusions PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer. PMID:26814433

Small cell lung cancer: Recruitment of macrophages by circulating tumor cells

PubMed Central

Hamilton, Gerhard; Rath, Barbara; Klameth, Lukas; Hochmair, Maximilan J.

2016-01-01

ABSTRACT Tumor-associated macrophages (TAMs) play an important role in tumor progression, suppression of antitumor immunity and dissemination. Blood monocytes infiltrate the tumor region and are primed by local microenvironmental conditions to promote tumor growth and invasion. Although many of the interacting cytokines and factors are known for the tumor-macrophage interactions, the putative contribution of circulating tumor cells (CTCs) is not known so far. These specialized cells are characterized by increased mobility, ability to degrade the extracellular matrix (ECM) and to enter the blood stream and generate secondary lesions which is a leading cause of death for the majority of tumor patients. The first establishment of two permanent CTC lines, namely BHGc7 and 10, from blood samples of advanced stage small cell lung cancer (SCLC) patients allowed us to investigate the CTC-immune cell interaction. Cocultures of peripheral blood mononuclear cells (PBMNCs) with CTCs or addition of CTC-conditioned medium (CTC-CM) in vitro resulted in monocyte-macrophage differentiation and appearance of CD14+, CD163weak and CD68+ macrophages expressing markers of TAMs. Furthermore, we screened the supernatants of CTC-primed macrophages for presence of approximately 100 cytokines and compared the expression with those induced by the local metastatic SCLC26A cell line. Macrophages recruited by SCLC26A-CM showed expression of osteopontin (OPN), monocyte chemoattractant protein-1 (MCP-1), IL-8, chitinase3-like 1 (CHI3L1), platelet factor (Pf4), IL-1ra and matrix metalloproteinase-9 (MMP-9) among other minor cytokines/chemokines. In contrast, BHGc7-CM induced marked overexpression of complement factor D (CFD)/adipsin and vitamin D-BP (VDBP), as well as increased secretion of OPN, lipocalin-2 (LCN2), CHI3L1, uPAR, MIP-1 and GDF-15/MIC-1. BHGc10, derived independently from relapsed SCLC, revealed an almost identical pattern with added expression of ENA-78/CXCL5. CMs of the non-tumor HEK293 cell line revealed no induction of macrophages, whereas incubation of PBMNCs with recombinant CHI3L1 gave positive results. Thus, the specific contributions of CTCs in SCLC affect CFD/adipsin, possibly involved in immunity/cachexia, VDBP which gives rise to group-specific component protein-derived macrophage-activating factor (GcMAF), GDF-15/MIC-1 which enhances the malignant phenotype of tumor cells and ENA-78/CXCL5 which attracts angiogenic neutrophils. In conclusion, CTCs are competent to specifically manipulate TAMs to increase invasiveness, angiogenesis, immunosuppression and possibly lipid catabolism. PMID:27141354

Small cell lung cancer: Recruitment of macrophages by circulating tumor cells.

PubMed

Hamilton, Gerhard; Rath, Barbara; Klameth, Lukas; Hochmair, Maximilan J

2016-03-01

Tumor-associated macrophages (TAMs) play an important role in tumor progression, suppression of antitumor immunity and dissemination. Blood monocytes infiltrate the tumor region and are primed by local microenvironmental conditions to promote tumor growth and invasion. Although many of the interacting cytokines and factors are known for the tumor-macrophage interactions, the putative contribution of circulating tumor cells (CTCs) is not known so far. These specialized cells are characterized by increased mobility, ability to degrade the extracellular matrix (ECM) and to enter the blood stream and generate secondary lesions which is a leading cause of death for the majority of tumor patients. The first establishment of two permanent CTC lines, namely BHGc7 and 10, from blood samples of advanced stage small cell lung cancer (SCLC) patients allowed us to investigate the CTC-immune cell interaction. Cocultures of peripheral blood mononuclear cells (PBMNCs) with CTCs or addition of CTC-conditioned medium (CTC-CM) in vitro resulted in monocyte-macrophage differentiation and appearance of CD14 + , CD163 weak and CD68 + macrophages expressing markers of TAMs. Furthermore, we screened the supernatants of CTC-primed macrophages for presence of approximately 100 cytokines and compared the expression with those induced by the local metastatic SCLC26A cell line. Macrophages recruited by SCLC26A-CM showed expression of osteopontin (OPN), monocyte chemoattractant protein-1 (MCP-1), IL-8, chitinase3-like 1 (CHI3L1), platelet factor (Pf4), IL-1ra and matrix metalloproteinase-9 (MMP-9) among other minor cytokines/chemokines. In contrast, BHGc7-CM induced marked overexpression of complement factor D (CFD)/adipsin and vitamin D-BP (VDBP), as well as increased secretion of OPN, lipocalin-2 (LCN2), CHI3L1, uPAR, MIP-1 and GDF-15/MIC-1. BHGc10, derived independently from relapsed SCLC, revealed an almost identical pattern with added expression of ENA-78/CXCL5. CMs of the non-tumor HEK293 cell line revealed no induction of macrophages, whereas incubation of PBMNCs with recombinant CHI3L1 gave positive results. Thus, the specific contributions of CTCs in SCLC affect CFD/adipsin, possibly involved in immunity/cachexia, VDBP which gives rise to group-specific component protein-derived macrophage-activating factor (GcMAF), GDF-15/MIC-1 which enhances the malignant phenotype of tumor cells and ENA-78/CXCL5 which attracts angiogenic neutrophils. In conclusion, CTCs are competent to specifically manipulate TAMs to increase invasiveness, angiogenesis, immunosuppression and possibly lipid catabolism.

Comparison of routine and unprepped CT colonography augmented by low fiber diet and stool tagging: a pilot study.

PubMed

Dachman, Abraham H; Dawson, Damien O; Lefere, Philippe; Yoshida, Hiro; Khan, Nasreen U; Cipriani, Nicole; Rubin, David T

2007-01-01

We performed a pilot study examining the feasibility of a new unprepped CT colonography (CTC) strategy: low fiber diet and tagging (unprepped) vs. low fiber diet, tagging and a magnesium citrate cleansing preparation (prepped). Prior reports of tagging were limited in that the residual stool was neither measured and stratified by size nor did prior reports subjectively evaluate the ease of interpretation by a reader experienced in interpreting CTC examinations. Prospective randomized to unprepped n = 14 and prepped n = 14. Colonic segments were subjectively evaluated for residual stool that would potentially interfere with interpretation. Scores were given in the following categories: percentage of residual stool that was touching or nearly touching mucosa, the largest piece of retained stool, effectiveness of tagging, height of residual fluid, degree of distention, ease of interpretation, and reading time. Ease of the CT read (scale where 4 = optimal read) averaged 1.3 for the unprepped group and 2.3 for the prepped group. The mean read time averaged 17.5 min for unprepped and 17.9 min for prepped. The degree of distention (scale where 4 = well distended) averaged 3.7 for unprepped and 3.6 for prepped. Supine and prone images combined, the unprepped group had 160 segments with stool; prepped group had 58 segments. The amount of stool covering the mucosa in all segments averaged 1.6 (33%-66% coverage) in the unprepped group and 0.35 (<33% mucosal coverage) in the prepped group. The mean size of the largest piece of stool was 33.67 mm for unprepped and 4.01 mm for prepped. Percentage of tagged stool was not significantly different between the groups (range of 94-98%). The height of residual fluid averaged 8.37 mm for unprepped and 13.4 mm for prepped. Three polyps in three patients were found during optical colonoscopy (OC) in the unprepped group (5, 6, and 10 mm), none of which were prospectively detected at CTC. Three polyps in three patients were detected during OC in the prepped group (5, 10, and 15 mm), two of which were prospectively detected at CTC. Two false-positive lesions were observed at CTC in one patient in the prepped group. There was more stool in the unprepped group and while this factor did not slow down the reading time, it made the examination subjectively harder to interpret and likely caused the three polyps in this group to be missed. We conclude that a truly unprepped strategy that leaves significant residual stool, even if well tagged, is not desirable.

Comparison of the Effects of Two Whitening Toothpastes on Microhardness of the Enamel and a Microhybride Composite Resin: An in Vitro Study

PubMed Central

Khamverdi, Z.; Kasraie, Sh.; Rezaei-Soufi, L.; Jebeli, S.

2010-01-01

Introduction: Whitening toothpastes which have been accepted in populations may affect properties of enamel and restorative materials. The aim of this study was to compare the microhardness of human enamel and Z250 microhybrid composite resin after brushing with two whitening toothpastes. Materials and Methods: In this experimental study of enamel specimens, forty five freshly extracted human incisors were prepared and divided into three groups of control enamel (ClE), Crest enamel (CtE) and Aquafresh enamel (AfE). For composite resin specimens, forty five cylindrical-shaped specimens of light-cured Z250 composite were prepared and divided into three groups of control composite (ClC), Crest composite (CtC) and Aquafresh composite (AfC). The control groups were brushed without toothpaste. Crest and Aquafresh group specimens were brushed with Crest and Aquafresh whitening toothpastes, respectively. Vickers microhardness test was performed for all groups. Data were analyzed by One-way ANOVA and Tukey tests. Results: Microhardness values of ClE, CtE, AfE, ClC, CtC and AfC groups were 332.99 ± 26.59, 313.99 ± 20.56, 323.57 ± 27.96, 137.1 ± 3.16, 122.95 ± 3.27 and 130.36 ± 4.8, respectively. One-way ANOVA showed no significant differences among three enamel groups but there was significant difference among composite groups (p<0.01). Conclusion: Crest and Aquafresh whitening toothpastes did not affect enamel hardness but reduced the microhardness value of Z-250 composite resin. However, Crest whitening toothpaste decreased the microhardness more than Aquafresh. PMID:21998788

The characterization of four gene expression analysis in circulating tumor cells made by Multiplex-PCR from the AdnaTest kit on the lab-on-a-chip Agilent DNA 1000 platform.

PubMed

Škereňová, Markéta; Mikulová, Veronika; Čapoun, Otakar; Zima, Tomáš

2016-01-01

Nowadays, on-a-chip capillary electrophoresis is a routine method for the detection of PCR fragments. The Agilent 2100 Bioanalyzer was one of the first commercial devices in this field. Our project was designed to study the characteristics of Agilent DNA 1000 kit in PCR fragment analysis as a part of circulating tumour cell (CTC) detection technique. Despite the common use of this kit a complex analysis of the results from a long-term project is still missing. A commercially available Agilent DNA 1000 kit was used as a final step in the CTC detection (AdnaTest) for the determination of the presence of PCR fragments generated by Multiplex PCR. Data from 30 prostate cancer patients obtained during two years of research were analyzed to determine the trueness and precision of the PCR fragment size determination. Additional experiments were performed to demonstrate the precision (repeatability, reproducibility) and robustness of PCR fragment concentration determination. The trueness and precision of the size determination was below 3% and 2% respectively. The repeatability of the concentration determination was below 15%. The difference in concentration determination increases when Multiplex-PCR/storage step is added between the two measurements of one sample. The characteristics established in our study are in concordance with the manufacturer's specifications established for a ladder as a sample. However, the concentration determination may vary depending on chip preparation, sample storage and concentration. The 15% variation of concentration determination repeatability was shown to be partly proportional and can be suppressed by proper normalization.

Spray Characteristics and Tribo-Mechanical Properties of High-Velocity Arc-Sprayed WC-W2C Iron-Based Coatings

NASA Astrophysics Data System (ADS)

Tillmann, W.; Hagen, L.; Kokalj, D.

2017-10-01

In terms of arc-sprayed coatings, the lamellar coating microstructure is mainly affected by the atomization behavior of the molten electrode tips. When using compressed air, oxide formations occur during atomization, across the particle-laden spray plume and when the molten droplets splash onto the substrate. Within the scope of this study, the potential of a high-velocity arc-spraying process due to elevated atomization gas pressures and its effect on the spray and coating characteristics was analyzed using a cast tungsten carbide (CTC)-reinforced FeCMnSi cored wire. Since the atomization behavior corresponds with the electrode phenomena, the power spectrum and the droplet formation were observed during spraying. The tribo-mechanical properties of CTC-FeCMnSi coatings were examined in dry sliding experiments and indentation tests. In addition, adhesion tests and metallographic investigations were carried out to analyze the bonding strength, cohesive behavior, and lamellar microstructure. The occurrence of oxide phases was evaluated by x-ray diffraction and electron microscopy. Moreover, the oxygen content was determined by using glow discharge optical emission spectroscopy as well as energy-dispersive x-ray spectroscopy. With respect to elevated atomization gas pressures, a dense microstructure with improved adhesion to the substrate and reduced surface roughness was observed. Dry sliding experiments revealed an advanced wear behavior of specimens, when using above average increased atomization gas pressures. Analytic methods verified the existence of oxide phases, which were generated during spraying. A significant change of the extent and type of oxides, when applying an increased flow rate of the atomization gas, cannot be observed. Besides an enhanced coating quality, the use of increased atomization gas pressure exhibited good process stability.

Differences between genders in colorectal morphology on CT colonography using a quantitative approach: a pilot study.

PubMed

Weber, Charles N; Poff, Jason A; Lev-Toaff, Anna S; Levine, Marc S; Zafar, Hanna M

To explore quantitative differences between genders in morphologic colonic metrics and determine metric reproducibility. Quantitative colonic metrics from 20 male and 20 female CTC datasets were evaluated twice by two readers; all exams were performed after incomplete optical colonoscopy. Intra-/inter-reader reliability was measured with intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC). Women had overall decreased colonic volume, increased tortuosity and compactness and lower sigmoid apex height on CTC compared to men (p<0.0001,all). Quantitative measurements in colonic metrics were highly reproducible (ICC=0.9989 and 0.9970; CCC=0.9945). Quantitative morphologic differences between genders can be reproducibility measured. Copyright © 2017 Elsevier Inc. All rights reserved.

A portable circulating tumor cell capture microdevice

NASA Astrophysics Data System (ADS)

Datar, Ram H.

2009-03-01

Sensitive detection of earliest metastatic spread of tumors in a minimally invasive and user-friendly manner will revolutionize the clinical management of cancer patients. The current methodologies for circulating tumor cell (CTC) capture and identification have significant limitations including time, cost, limited capture efficiency and lack of standardization. We have developed and optimized a novel parylene membrane filter-based portable microdevice for size-based isolation of CTC from human peripheral blood. Following characterization with a model system to study the recovery rate and enrichment factor, a comparison of the microdevice with the commercially available system using blood from cancer patients demonstrated superior recovery rate and the promise of clinical utility of the microdevice. The development of the microdevice and its potential clinical applicability will be discussed.

Exploring multiple feature combination strategies with a recurrent neural network architecture for off-line handwriting recognition

NASA Astrophysics Data System (ADS)

Mioulet, L.; Bideault, G.; Chatelain, C.; Paquet, T.; Brunessaux, S.

2015-01-01

The BLSTM-CTC is a novel recurrent neural network architecture that has outperformed previous state of the art algorithms in tasks such as speech recognition or handwriting recognition. It has the ability to process long term dependencies in temporal signals in order to label unsegmented data. This paper describes different ways of combining features using a BLSTM-CTC architecture. Not only do we explore the low level combination (feature space combination) but we also explore high level combination (decoding combination) and mid-level (internal system representation combination). The results are compared on the RIMES word database. Our results show that the low level combination works best, thanks to the powerful data modeling of the LSTM neurons.

The potential diagnostic power of circulating tumor cell analysis for non-small-cell lung cancer.

PubMed

Ross, Kirsty; Pailler, Emma; Faugeroux, Vincent; Taylor, Melissa; Oulhen, Marianne; Auger, Nathalie; Planchard, David; Soria, Jean-Charles; Lindsay, Colin R; Besse, Benjamin; Vielh, Philippe; Farace, Françoise

2015-01-01

In non-small-cell lung cancer (NSCLC), genotyping tumor biopsies for targetable somatic alterations has become routine practice. However, serial biopsies have limitations: they may be technically difficult or impossible and could incur serious risks to patients. Circulating tumor cells (CTCs) offer an alternative source for tumor analysis that is easily accessible and presents the potential to identify predictive biomarkers to tailor therapies on a personalized basis. Examined here is our current knowledge of CTC detection and characterization in NSCLC and their potential role in EGFR-mutant, ALK-rearranged and ROS1-rearranged patients. This is followed by discussion of the ongoing issues such as the question of CTC partnership as diagnostic tools in NSCLC.

Evaluation of a HDR image sensor with logarithmic response for mobile video-based applications

NASA Astrophysics Data System (ADS)

Tektonidis, Marco; Pietrzak, Mateusz; Monnin, David

2017-10-01

The performance of mobile video-based applications using conventional LDR (Low Dynamic Range) image sensors highly depends on the illumination conditions. As an alternative, HDR (High Dynamic Range) image sensors with logarithmic response are capable to acquire illumination-invariant HDR images in a single shot. We have implemented a complete image processing framework for a HDR sensor, including preprocessing methods (nonuniformity correction (NUC), cross-talk correction (CTC), and demosaicing) as well as tone mapping (TM). We have evaluated the HDR sensor for video-based applications w.r.t. the display of images and w.r.t. image analysis techniques. Regarding the display we have investigated the image intensity statistics over time, and regarding image analysis we assessed the number of feature correspondences between consecutive frames of temporal image sequences. For the evaluation we used HDR image data recorded from a vehicle on outdoor or combined outdoor/indoor itineraries, and we performed a comparison with corresponding conventional LDR image data.

Making sense of health care delivery Where does the close to community health care worker fit in? – The case for congestive heart failure

PubMed Central

Iyngkaran, P.; Biddargardi, N.; Bastiampillai, T.; Beneby, G.

2015-01-01

Close to community health care workers (CTC-HCW) is an increasingly used term to describe the emergence of a new partner in health services delivery. In strengthening arguments for this part of the health workforce the authorities, health staffers, supporters, sceptics and perhaps clients will look to the academicians and the evidence base to determine the fate of this group. There is no doubt, CTC-HCW are a vital resource, whose importance is tied to socio-demo-geographic variables. Regardless of what the common perceptions of its importance are, the evolving evidence base could suggest either way. In this short commentary we would like to highlight the importance of a balanced and common sense approach in these arguments. An important example is heart failure where the majority have an associated comorbidity and one in four would also suffer with cognitive or mood disturbances. It is unclear how the CTC-HCW would fare for this devastating syndrome. In moving forward it is important we understand there are: strengths and limitations in the evidence gathering processes; indecision as to the questions; uncertainty of the starting points to gather evidence; and sociodemogeographic biases, which have to be factored before determining the fate of this much needed health care resource. PMID:26138183

Polyester fabric sheet layers functionalized with graphene oxide for sensitive isolation of circulating tumor cells.

PubMed

Bu, Jiyoon; Kim, Young Jun; Kang, Yoon-Tae; Lee, Tae Hee; Kim, Jeongsuk; Cho, Young-Ho; Han, Sae-Won

2017-05-01

The metastasis of cancer is strongly associated with the spread of circulating tumor cells (CTCs). Based on the microfluidic devices, which offer rapid recovery of CTCs, a number of studies have demonstrated the potential of CTCs as a diagnostic tool. However, not only the insufficient specificity and sensitivity derived from the rarity and heterogeneity of CTCs, but also the high-cost fabrication processes limit the use of CTC-based medical devices in commercial. Here, we present a low-cost fabric sheet layers for CTC isolation, which are composed of polyester monofilament yarns. Fabric sheet layers are easily functionalized with graphene oxide (GO), which is beneficial for improving both sensitivity and specificity. The GO modification to the low-cost fabrics enhances the binding of anti-EpCAM antibodies, resulting in 10-25% increase of capture efficiency compared to the surface without GO (anti-EpCAM antibodies directly onto the fabric sheets), while achieving high purity by isolating only 50-300 leukocytes in 1 mL of human blood. We investigated CTCs in ten human blood samples and successfully isolated 4-42 CTCs/mL from cancer patients, while none of cancerous cells were found among healthy donors. This remarkable results show the feasibility of GO-functionalized fabric sheet layers to be used in various CTC-based clinical applications, with high sensitivity and selectivity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Circulating tumor cells in lung cancer.

PubMed

Young, Rachel; Pailler, Emma; Billiot, Fanny; Drusch, Françoise; Barthelemy, Amélie; Oulhen, Marianne; Besse, Benjamin; Soria, Jean-Charles; Farace, Françoise; Vielh, Philippe

2012-01-01

Circulating tumor cells (CTCs) have emerged as potential biomarkers in several cancers such as colon, prostate, and breast carcinomas, with a correlation between CTC number and patient prognosis being established by independent research groups. The detection and enumeration of CTCs, however, is still a developing field, with no universal method of detection suitable for all types of cancer. CTC detection in lung cancer in particular has proven difficult to perform, as CTCs in this type of cancer often present with nonepithelial characteristics. Moreover, as many detection methods rely on the use of epithelial markers to identify CTCs, the loss of these markers during epithelial-to-mesenchymal transition in certain metastatic cancers can render these methods ineffective. The development of personalized medicine has led to an increase in the advancement of molecular characterization of CTCs. The application of techniques such as FISH and RT-PCR to detect EGFR, HER2, and KRAS abnormalities in lung, breast, and colon cancer, for example, could be used to characterize CTCs in real time. The use of CTCs as a 'liquid biopsy' is therefore an exciting possibility providing information on patient prognosis and treatment efficacy. This review summarizes the state of CTC detection today, with particular emphasis on lung cancer, and discusses the future applications of CTCs in helping the clinician to develop new strategies in patient treatment. Copyright © 2012 S. Karger AG, Basel.

Effect of Reduced Tube Voltage on Diagnostic Accuracy of CT Colonography.

PubMed

Futamata, Yoshihiro; Koide, Tomoaki; Ihara, Riku

2017-01-01

The normal tube voltage in computed tomography colonography (CTC) is 120 kV. Some reports indicate that the use of a low tube voltage (lower than 120 kV) technique plays a significant role in reduction of radiation dose. However, to determine whether a lower tube voltage can reduce radiation dose without compromising diagnostic accuracy, an evaluation of images that are obtained while maintaining the volume CT dose index (CTDI vol ) is required. This study investigated the effect of reduced tube voltage in CTC, without modifying radiation dose (i.e. constant CTDI vol ), on image quality. Evaluation of image quality involved the shape of the noise power spectrum, surface profiling with volume rendering (VR), and receiver operating characteristic (ROC) analysis. The shape of the noise power spectrum obtained with a tube voltage of 80 kV and 100 kV was not similar to the one produced with a tube voltage of 120 kV. Moreover, a higher standard deviation was observed on volume-rendered images that were generated using the reduced tube voltages. In addition, ROC analysis revealed a statistically significant drop in diagnostic accuracy with reduced tube voltage, revealing that the modification of tube voltage affects volume-rendered images. The results of this study suggest that reduction of tube voltage in CTC, so as to reduce radiation dose, affects image quality and diagnostic accuracy.

Growth of the Bacteriocin-Producing Lactobacillus sakei Strain CTC 494 in MRS Broth Is Strongly Reduced Due to Nutrient Exhaustion: a Nutrient Depletion Model for the Growth of Lactic Acid Bacteria

PubMed Central

Leroy, Frédéric; De Vuyst, Luc

2001-01-01

Although commercial MRS broth has been designed to allow excellent growth of lactobacilli, most of these bacteria are still subjected to a self-inhibiting process. The most likely explanation is the accumulation of lactic acid or other toxic end products and the depletion of nutrients. In this study, the self-inhibition of Lactobacillus sakei CTC 494 was analyzed in a kinetic way, and a nutrient depletion model was set up to describe the growth inhibition process. This simple model has considerable advantages compared to commonly used descriptive models such as the logistic growth equation. It offers a better fit and a more realistic description of the growth data by taking into account both growth inhibition due to lactic acid production and changes in growth rates due to nutrient depletion. Depending on the fermentation conditions, in MRS broth there appears to be a strong decrease of the specific growth rate over time. Some undefined compounds present in the complex nitrogen source of MRS broth appear to be of crucial importance because of their limited availability. Moreover, nutrient availability affects bacteriocin production through its effect on cell growth as well as on the bacteriocin production per cell. A plateau value for the bacteriocin production by L. sakei CTC 494 was observed. PMID:11571136

Making sense of health care delivery Where does the close to community health care worker fit in? - The case for congestive heart failure.

PubMed

Iyngkaran, P; Biddargardi, N; Bastiampillai, T; Beneby, G

2015-01-01

Close to community health care workers (CTC-HCW) is an increasingly used term to describe the emergence of a new partner in health services delivery. In strengthening arguments for this part of the health workforce the authorities, health staffers, supporters, sceptics and perhaps clients will look to the academicians and the evidence base to determine the fate of this group. There is no doubt, CTC-HCW are a vital resource, whose importance is tied to socio-demo-geographic variables. Regardless of what the common perceptions of its importance are, the evolving evidence base could suggest either way. In this short commentary we would like to highlight the importance of a balanced and common sense approach in these arguments. An important example is heart failure where the majority have an associated comorbidity and one in four would also suffer with cognitive or mood disturbances. It is unclear how the CTC-HCW would fare for this devastating syndrome. In moving forward it is important we understand there are: strengths and limitations in the evidence gathering processes; indecision as to the questions; uncertainty of the starting points to gather evidence; and sociodemogeographic biases, which have to be factored before determining the fate of this much needed health care resource. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.