The Neural Response to Maternal Stimuli: An ERP Study

PubMed Central

Wu, Lili; Gu, Ruolei; Cai, Huajian; Luo, Yu L. L.; Zhang, Jianxin

2014-01-01

Mothers are important to all humans. Research has established that maternal information affects individuals' cognition, emotion, and behavior. We measured event-related potentials (ERPs) to examine attentional and evaluative processing of maternal stimuli while participants completed a Go/No-go Association Task that paired mother or others words with good or bad evaluative words. Behavioral data showed that participants responded faster to mother words paired with good than the mother words paired with bad but showed no difference in response to these others across conditions, reflecting a positive evaluation of mother. ERPs showed larger P200 and N200 in response to mother than in response to others, suggesting that mother attracted more attention than others. In the subsequent time window, mother in the mother + bad condition elicited a later and larger late positive potential (LPP) than it did in the mother + good condition, but this was not true for others, also suggesting a positive evaluation of mother. These results suggest that people differentiate mother from others during initial attentional stage, and evaluative mother positively during later stage. PMID:25375157

An Evaluation of One- and Three-Parameter Logistic Tailored Testing Procedures for Use with Small Item Pools.

ERIC Educational Resources Information Center

McKinley, Robert L.; Reckase, Mark D.

A two-stage study was conducted to compare the ability estimates yielded by tailored testing procedures based on the one-parameter logistic (1PL) and three-parameter logistic (3PL) models. The first stage of the study employed real data, while the second stage employed simulated data. In the first stage, response data for 3,000 examinees were…

Predicting Outcomes After Chemo-Embolization in Patients with Advanced-Stage Hepatocellular Carcinoma: An Evaluation of Different Radiologic Response Criteria

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

Gunn, Andrew J., E-mail: agunn@uabmc.edu; Sheth, Rahul A.; Luber, Brandon

2017-01-15

PurposeThe purpse of this study was to evaluate the ability of various radiologic response criteria to predict patient outcomes after trans-arterial chemo-embolization with drug-eluting beads (DEB-TACE) in patients with advanced-stage (BCLC C) hepatocellular carcinoma (HCC).Materials and methodsHospital records from 2005 to 2011 were retrospectively reviewed. Non-infiltrative lesions were measured at baseline and on follow-up scans after DEB-TACE according to various common radiologic response criteria, including guidelines of the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver (EASL), and modified RECIST (mRECIST). Statistical analysis was performed to see which,more » if any, of the response criteria could be used as a predictor of overall survival (OS) or time-to-progression (TTP).Results75 patients met inclusion criteria. Median OS and TTP were 22.6 months (95 % CI 11.6–24.8) and 9.8 months (95 % CI 7.1–21.6), respectively. Univariate and multivariate Cox analyses revealed that none of the evaluated criteria had the ability to be used as a predictor for OS or TTP. Analysis of the C index in both univariate and multivariate models showed that the evaluated criteria were not accurate predictors of either OS (C-statistic range: 0.51–0.58 in the univariate model; range: 0.54–0.58 in the multivariate model) or TTP (C-statistic range: 0.55–0.59 in the univariate model; range: 0.57–0.61 in the multivariate model).ConclusionCurrent response criteria are not accurate predictors of OS or TTP in patients with advanced-stage HCC after DEB-TACE.« less

Predicting Outcomes After Chemo-Embolization in Patients with Advanced-Stage Hepatocellular Carcinoma: An Evaluation of Different Radiologic Response Criteria.

PubMed

Gunn, Andrew J; Sheth, Rahul A; Luber, Brandon; Huynh, Minh-Huy; Rachamreddy, Niranjan R; Kalva, Sanjeeva P

2017-01-01

The purpse of this study was to evaluate the ability of various radiologic response criteria to predict patient outcomes after trans-arterial chemo-embolization with drug-eluting beads (DEB-TACE) in patients with advanced-stage (BCLC C) hepatocellular carcinoma (HCC). Hospital records from 2005 to 2011 were retrospectively reviewed. Non-infiltrative lesions were measured at baseline and on follow-up scans after DEB-TACE according to various common radiologic response criteria, including guidelines of the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver (EASL), and modified RECIST (mRECIST). Statistical analysis was performed to see which, if any, of the response criteria could be used as a predictor of overall survival (OS) or time-to-progression (TTP). 75 patients met inclusion criteria. Median OS and TTP were 22.6 months (95 % CI 11.6-24.8) and 9.8 months (95 % CI 7.1-21.6), respectively. Univariate and multivariate Cox analyses revealed that none of the evaluated criteria had the ability to be used as a predictor for OS or TTP. Analysis of the C index in both univariate and multivariate models showed that the evaluated criteria were not accurate predictors of either OS (C-statistic range: 0.51-0.58 in the univariate model; range: 0.54-0.58 in the multivariate model) or TTP (C-statistic range: 0.55-0.59 in the univariate model; range: 0.57-0.61 in the multivariate model). Current response criteria are not accurate predictors of OS or TTP in patients with advanced-stage HCC after DEB-TACE.

A pilot study: sequential gemcitabine/cisplatin and icotinib as induction therapy for stage IIB to IIIA non-small-cell lung adenocarcinoma

PubMed Central

2013-01-01

Background A phase II clinical trial previously evaluated the sequential administration of erlotinib after chemotherapy for advanced non-small-cell lung cancer (NSCLC). This current pilot study assessed the feasibility of sequential induction therapy in patients with stage IIB to IIIA NSCLC adenocarcinoma. Methods Patients received gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 75 mg/m2 on day 1, followed by oral icotinib (125 mg, three times a day) on days 15 to 28. A repeatcomputed tomography(CT) scan evaluated the response to the induction treatment after two 4-week cycles and eligible patients underwent surgical resection. The primary objective was to assess the objective response rate (ORR), while EGFR and KRAS mutations and mRNA and protein expression levels of ERCC1 and RRM1 were analyzed in tumor tissues and blood samples. Results Eleven patients, most with stage IIIA disease, completed preoperative treatment. Five patients achieved partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (ORR=45%) and six patients underwent resection. Common toxicities included neutropenia, alanine transaminase (ALT) elevation, fatigue, dry skin, rash, nausea, alopecia and anorexia. No serious complications were recorded perioperatively. Three patients had exon 19 deletions and those with EGFR mutations were more likely to achieve a clinical response (P= 0.083). Furthermore, most cases who achieved a clinical response had low levels of ERCC1 expression and high levels of RRM1. Conclusions Two cycles of sequentially administered gemcitabine/cisplatin with icotinib as an induction treatment is a feasible and efficacious approach for stage IIB to IIIA NSCLC adenocarcinoma, which provides evidence for the further investigation of these chemotherapeutic and molecularly targeted therapies. PMID:23621919

VAC protocol for treatment of dogs with stage III hemangiosarcoma.

PubMed

Alvarez, Francisco J; Hosoya, Kenji; Lara-Garcia, Ana; Kisseberth, William; Couto, Guillermo

2013-01-01

Hemangiosarcomas (HSAs) are aggressive tumors with a high rate of metastasis. Clinical stage has been considered a negative prognostic factor for survival. The study authors hypothesized that the median survival time (MST) of dogs with metastatic (stage III) HSA treated with a vincristine, doxorubicin, and cyclophosphamide (VAC) chemotherapy protocol would not be different than those with stage I/II HSA. Sixty-seven dogs with HSA in different anatomic locations were evaluated retrospectively. All dogs received the VAC protocol as an adjuvant to surgery (n = 50), neoadjuvant (n = 3), or as the sole treatment modality (n = 14). There was no significant difference (P = 0.97) between the MST of dogs with stage III and stage I/II HSA. For dogs presenting with splenic HSA alone, there was no significant difference between the MST of dogs with stage III and stage I/II disease (P = 0.12). The overall response rate (complete response [CR] and partial response [PR]) was 86%). No unacceptable toxicities were observed. Dogs with stage III HSA treated with the VAC protocol have a similar prognosis to dogs with stage I/II HSA. Dogs with HSA and evidence of metastases at the time of diagnosis should not be denied treatment.

Evaluation of the Inertial Response of Variable-Speed Wind Turbines Using Advanced Simulation

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

Scholbrock, Andrew K; Muljadi, Eduard; Gevorgian, Vahan

In this paper, we focus on the temporary frequency support effect provided by wind turbine generators (WTGs) through the inertial response. With the implemented inertial control methods, the WTG is capable of increasing its active power output by releasing parts of the stored kinetic energy when the frequency excursion occurs. The active power can be boosted temporarily above the maximum power points, but the rotor speed deceleration follows and an active power output deficiency occurs during the restoration of rotor kinetic energy. We evaluate and compare the inertial response induced by two distinct inertial control methods using advanced simulation. Inmore » the first stage, the proposed inertial control methods are analyzed in offline simulation. Using an advanced wind turbine simulation program, FAST with TurbSim, the response of the researched wind turbine is comprehensively evaluated under turbulent wind conditions, and the impact on the turbine mechanical components are assessed. In the second stage, the inertial control is deployed on a real 600kW wind turbine - Controls Advanced Research Turbine, 3-bladed (CART3), which further verifies the inertial control through a hardware-in-the-loop (HIL) simulation. Various inertial control methods can be effectively evaluated based on the proposed two-stage simulation platform, which combines the offline simulation and real-time HIL simulation. The simulation results also provide insights in designing inertial control for WTGs.« less

Insight into phagocytosis of mature sexual (gametocyte) stages of Plasmodium falciparum using a human monocyte cell line.

PubMed

Bansal, Geetha P; Weinstein, Corey S; Kumar, Nirbhay

2016-05-01

During natural infection malaria parasites are injected into the bloodstream of a human host by the bite of an infected female Anopheles mosquito. Both asexual and mature sexual stages of Plasmodium circulate in the blood. Asexual forms are responsible for clinical malaria while sexual stages are responsible for continued transmission via the mosquitoes. Immune responses generated against various life cycle stages of the parasite have important roles in resistance to malaria and in reducing malaria transmission. Phagocytosis of free merozoites and erythrocytic asexual stages has been well studied, but very little is known about similar phagocytic clearance of mature sexual stages, which are critical for transmission. We evaluated phagocytic uptake of mature sexual (gametocyte) stage parasites by a human monocyte cell line in the absence of immune sera. We found that intact mature stages do not undergo phagocytosis, unless they are either killed or freed from erythrocytes. In view of this observation, we propose that the inability of mature gametocytes to be phagocytized may actually result in malaria transmission advantage. On the other hand, mature gametocytes that are not transmitted to mosquitoes during infection will eventually die and undergo phagocytosis, initiating immune responses that may have transmission blocking potential. A better understanding of early phagocytic clearance and immune responses to gametocytes may identify additional targets for transmission blocking strategies. Copyright © 2016 Elsevier B.V. All rights reserved.

Preliminary evaluation of the Environmental Research Institute of Michigan crop calendar shift algorithm for estimation of spring wheat development stage. [North Dakota, South Dakota, Montana, and Minnesota

NASA Technical Reports Server (NTRS)

Phinney, D. E. (Principal Investigator)

1980-01-01

An algorithm for estimating spectral crop calendar shifts of spring small grains was applied to 1978 spring wheat fields. The algorithm provides estimates of the date of peak spectral response by maximizing the cross correlation between a reference profile and the observed multitemporal pattern of Kauth-Thomas greenness for a field. A methodology was developed for estimation of crop development stage from the date of peak spectral response. Evaluation studies showed that the algorithm provided stable estimates with no geographical bias. Crop development stage estimates had a root mean square error near 10 days. The algorithm was recommended for comparative testing against other models which are candidates for use in AgRISTARS experiments.

Weed and Onion Response to multiple Applications of Goal Tender beginning at the 1-Leaf Stage of Onion

USDA-ARS?s Scientific Manuscript database

Broadleaf weed control in onion is difficult in part due to a lack of postemergence herbicide options at an early growth stage of onions. Onion tolerance to sequential applications of oxyfluorfen (Goal-Tender) alone and with bromoxynil (Buctril) beginning at the 1-lf stage of onions was evaluated n...

A pilot study of durvalumab and tremelimumab and immunogenomic dynamics in metastatic breast cancer

PubMed Central

Santa-Maria, Cesar August; Kato, Taigo; Park, Jae-Hyun; Kiyotani, Kazuma; Rademaker, Alfred; Shah, Ami N.; Gross, Leeaht; Blanco, Luis Z.; Jain, Sarika; Flaum, Lisa; Tellez, Claudia; Stein, Regina; Uthe, Regina; Gradishar, William J.; Cristofanilli, Massimo; Nakamura, Yusuke; Giles, Francis J.

2018-01-01

Immune checkpoint inhibitors produce modest responses in metastatic breast cancer, however, combination approaches may improve responses. A single arm pilot study was designed to determine the overall response rate (ORR) of durvalumab and tremelimumab, and evaluate immunogenomic dynamics in metastatic endocrine receptor (ER) positive or triple negative breast cancer (TNBC). Simon two-stage design indicated at least four responses from the first 18 patients were needed to proceed with the second stage. T-cell receptor (TCR) sequencing and immune-gene expression profiling were conducted at baseline and two months, whole exome sequencing was conducted at baseline. Eighteen evaluable patients were accrued (11 ER-positive; seven TNBC). Only three patients had a response (ORR = 17%), thus the study did not proceed to the second stage. Responses were only observed in patients with TNBC (ORR = 43%). Responders versus non-responders had upregulation of CD8, granzyme A, and perforin 1 gene expression, and higher mutational and neoantigen burden. Patients with TNBC had an oligoclonal shift of the most abundant TCR-beta clonotypes compared to those with ER-positive disease, p = 0.004. We conclude responses are low in unselected metastatic breast cancer, however, higher rates of clinical benefit were observed in TNBC. Immunogenomic dynamics may help identify phenotypes most likely to respond to immunotherapy. PMID:29721177

Evaluation of the Glasgow Prognostic Score in patients receiving chemoradiotherapy for stage III and IV esophageal cancer.

PubMed

Kimura, J; Kunisaki, C; Makino, H; Oshima, T; Ota, M; Oba, M; Takagawa, R; Kosaka, T; Ono, H A; Akiyama, H; Endo, I

2016-11-01

High Glasgow Prognostic scores (GPSs) have been associated with poor outcomes in various tumors, but the values of GPS and modified GPS (mGPS) in patients with advanced esophageal cancer receiving chemoradiotherapy (CRT) has not yet been reported. We have evaluated these with respect to predicting responsiveness to CRT and long-term survival. Between January 2002 and December 2011, tumor responses in 142 esophageal cancer patients (131 men and 11 women) with stage III (A, B and C) and IV receiving CRT were assessed. We assessed the value of the GPS as a predictor of a response to definitive CRT and also as a prognostic indicator in patients with esophageal cancer receiving CRT. We found that independent predictors of CRT responsiveness were Eastern Cooperative Oncology Group (ECOG) performance status, GPS and cTNM stage. Independent prognostic factors were ECOG performance status and GPS for progression-free survival and ECOG performance status, GPS and cTNM stage IV for disease-specific survival. GPS may be a novel predictor of CRT responsiveness and a prognostic indicator for progression-free and disease-specific survival in patients with advanced esophageal cancer. However, a multicenter study as same regime with large number of patients will be needed to confirm these outcomes. © 2015 International Society for Diseases of the Esophagus.

Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy.

PubMed

Miller, Marian; Ottesen, Rebecca A; Niland, Joyce C; Kruper, Laura; Chen, Steven L; Vito, Courtney

2014-10-01

Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods. Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I-III breast cancer who had NAC and pretreatment imaging at City of Hope (1997-2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0-0.4 (strong partial response, SPR), TRR > 0.4-1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan-Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders. There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016). TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.

Thymidine phosphorylase and hypoxia-inducible factor 1-α expression in clinical stage II/III rectal cancer: association with response to neoadjuvant chemoradiation therapy and prognosis.

PubMed

Lin, Shuhan; Lai, Hao; Qin, Yuzhou; Chen, Jiansi; Lin, Yuan

2015-01-01

The aim of this study was to determine whether pretreatment status of thymidine phosphorylase (TP), and hypoxia-inducible factor alpha (HIF-1α) could predict pathologic response to neoadjuvant chemoradiation therapy with oxaliplatin and capecitabine (XELOXART) and outcomes for clinical stage II/III rectal cancer patients. A total of 180 patients diagnosed with clinical stage II/III rectal cancer received XELOXART. The status of TP, and HIF-1α were determined in pretreatment biopsies by immunohistochemistry (IHC). Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. 5-year disease free survival (DFS) and 5-year overall survival (OS) were evaluated with the Kaplan-Meier method and were compared by the log-rank test. Over expression of TP and low expression of HIF-1α were associated with pathologic response to XELOXART and better outcomes (DFS and OS) in clinical stage II/III rectal cancer patients (P < 0.05). Our result suggested that pretreatment status of TP and HIF-1α were found to predict pathologic response and outcomes in clinical stage II/III rectal cancer received XELOXART. Additional well-designed, large sample, multicenter, prospective studies are needed to confirm the result of this study.

3D conformal radiation therapy for palliative treatment of canine nasal tumors.

PubMed

Buchholz, Julia; Hagen, Regine; Leo, Chiara; Ebling, Alessia; Roos, Malgorzata; Kaser-Hotz, Barbara; Bley, Carla Rohrer

2009-01-01

We evaluated the response of 38 dogs treated with a coarsely fractionated, palliative radiation protocol based on CT-based 3D treatment planning. Dogs with histologically confirmed malignant nasal tumors were studied. Treatment prescriptions consisted of 3-4 x 8 Gy, 4-5 x 6 Gy, or 10 x 3 Gy fractions. Selected patient and tumor factors were evaluated for an effect on outcome. Resolution of clinical signs was reported after irradiation in all dogs. Acute toxicities were mild and short lived. Thirty-seven of 38 dogs died or were euthanized due to tumor-related disease. Overall median progression-free interval (PFI) was 10 months. Tumor stage affected response, with modified stage 1 patients having a median PFI 21.3 months vs. a median PFI of 8.5 months for modified stage 2 patients (P = 0.0006). Modified stage was the only factor significantly related to outcome. Based on these findings, a palliative radiation prescription based on computerized treatment planning may be justified in some canine nasal tumor patients.

Electrochemotherapy efficacy evaluation for treatment of locally advanced stage III cutaneous squamous cell carcinoma: a 22-cases retrospective analysis.

PubMed

Di Monta, Gianluca; Caracò, Corrado; Simeone, Ester; Grimaldi, Antonio Maria; Marone, Ugo; Di Marzo, Massimiliano; Vanella, Vito; Festino, Lucia; Palla, Marco; Mori, Stefano; Mozzillo, Nicola; Ascierto, Paolo Antonio

2017-04-26

Extensive squamous cell carcinoma has few therapeutic options. In such cases, electrochemotherapy involving electroporation combined with antineoplastic drug appears to be a new potential option and may be considered as an alternative treatment. The aim of this retrospective single-center study was to evaluate electrochemotherapy efficacy in treatment of locally advanced stage III squamous cell carcinoma, in which surgical procedures would have entailed wide tissue sacrifice. Clinical features, treatment response, and adverse effects were evaluated in 22 patients treated with electrochemotherapy with intravenous injection of bleomycin for extensive stage III cutaneous squamous cell carcinoma. Treatment of cutaneous lesions were performed according to the European Standard Operating Procedures of Electrochemotherapy. Overall response to electrochemotherapy treatment was observed in 18 (81.8%) patients. Clinical response with necrosis of tumor mass was observed from the first session and lasted for all follow up period that ranged between 5 and 48 months with a median of 34 months. Overall the treatment was well tolerated with a very low complication rate. Electrochemotherapy represents a safe and effective therapeutic approach, associated with a good tolerability.

Efficacy and safety of Apatinib in stage IV sarcomas: experience of a major sarcoma center in China.

PubMed

Li, Feng; Liao, Zhichao; Zhao, Jun; Zhao, Gang; Li, Xubin; Du, Xiaoling; Yang, Yun; Yang, Jilong

2017-09-08

This study was conducted to review the efficacy and safety of Apatinib in stage IV sarcoma patients who failed previous chemotherapy. The clinical information on 16 patients with stage IV sarcomas who failed in prior chemotherapy and subsequently received Apatinib treatment was collected. Apatinib was given 500mg/daily and 4 weeks as a cycle. All patients had at least one measurable extracranial tumor according to Response Evaluation Criteria In Solid Tumors 1.0 criteria. Progression free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and treatment-related adverse effects (AEs) were reviewed and evaluated. Patients was administered Apatinib for 0 to 9 cycles with the median of 3.2 cycles. Median follow-up time was 8.4 months (1 to 12 months). Ten of 16 patients received at least 1 complete cycle of Apatinib treatment were eligible for the efficacy analysis. The median PFS was 8.84 months. Two patients achieved partial response (PR) and 6 patients achieved stable disease (SD). Two patients were evaluated as progression disease (PD) and one patient died of disease progression. The ORR was 20.0% (2/10) and the DCR was 80.0% (8/10). The most common grade 3/4 treatment-related AEs were hypertension (18.7%), hand-foot syndrome (12.5%) and proteinuria (6.3%). No drug-related severe AEs occurred. CApatinib treatment in this exploratory study exhibited objective efficacy and manageable toxicity in stage IV sarcoma patients who failed in chemotherapy. This result supports future random controlled trial to further define Apatinib activity in stage IV sarcomas.

Evaluation of the Inertial Response of Variable-Speed Wind Turbines Using Advanced Simulation: Preprint

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

Scholbrock, Andrew K; Muljadi, Eduard; Gevorgian, Vahan

In this paper, we focus on the temporary frequency support effect provided by wind turbine generators (WTGs) through the inertial response. With the implemented inertial control methods, the WTG is capable of increasing its active power output by releasing parts of the stored kinetic energy when the frequency excursion occurs. The active power can be boosted temporarily above the maximum power points, but the rotor speed deceleration follows and an active power output deficiency occurs during the restoration of rotor kinetic energy. In this paper, we evaluate and compare the inertial response induced by two distinct inertial control methods usingmore » advanced simulation. In the first stage, the proposed inertial control methods are analyzed in offline simulation. Using an advanced wind turbine simulation program, FAST with TurbSim, the response of the researched wind turbine is comprehensively evaluated under turbulent wind conditions, and the impact on the turbine mechanical components are assessed. In the second stage, the inertial control is deployed on a real 600-kW wind turbine, the three-bladed Controls Advanced Research Turbine, which further verifies the inertial control through a hardware-in-the-loop simulation. Various inertial control methods can be effectively evaluated based on the proposed two-stage simulation platform, which combines the offline simulation and real-time hardware-in-the-loop simulation. The simulation results also provide insights in designing inertial control for WTGs.« less

Development of guidance on the timeliness in response to acute kidney injury warning stage test results for adults in primary care: an appropriateness ratings evaluation

PubMed Central

Blakeman, Tom; Griffith, Kathryn; Lasserson, Dan; Lopez, Berenice; Tsang, Jung Y; Campbell, Stephen; Tomson, Charles

2016-01-01

Objectives Tackling the harm associated with acute kidney injury (AKI) is a global priority. In England, a national computerised AKI algorithm is being introduced across the National Health Service (NHS) to drive this change. The study sought to maximise its clinical utility and minimise the potential for burden on clinicians and patients in primary care. Design An appropriateness ratings evaluation using the RAND/UCLA Appropriateness Method. Setting Clinical scenarios were developed to test the timeliness in (1) communication of AKI warning stage test results from clinical pathology services to primary care, and (2) primary care clinician response to an AKI warning stage test result. Participants A 10-person panel was purposively sampled with representation from clinical biochemistry, acute and emergency medicine and general practice. General practitioners (GPs) represented typical practice in relation to rural and urban practice, out of hours care, GP commissioning and those interested in reducing the impact of medicalisation and ‘overdiagnosis’. Results There was agreement that delivery of AKI warning stage test results through interruptive methods of communication (ie, telephone) from laboratories to primary care was the appropriate next step for patients with an AKI warning stage 3 test result. In the context of acute illness, waiting up to 72 hours to respond to an AKI warning stage test result was deemed an inappropriate action in 62 out of the 65 (94.5%) cases. There was agreement that a clinician response was required within 6 hours, or less, in 39 out of 40 (97.5%) clinical cases relating AKI warning stage test results in the presence of moderate hyperkalaemia. Conclusions The study has informed national guidance to support a timely and calibrated response to AKI warning stage test results for adults in primary care. Further research is needed to support effective implementation, with a view to examine the effect on health outcomes and costs. PMID:27729353

Phenoloxidase activity among developmental stages and pupal cell types of the ground beetle Carabus (Chaetocarabus) lefebvrei (Coleoptera, Carabidae).

PubMed

Giglio, Anita; Giulianini, Piero Giulio

2013-04-01

In ecological immunology is of great importance the study of the immune defense plasticity as response to a variable environment. In holometabolous insects the fitness of each developmental stage depends on the capacity to mount a response (i.e. physiological, behavioral) under environmental pressure. The immune response is a highly dynamic trait closely related to the ecology of organism and the variation in the expression of an immune system component may affect another fitness relevant trait of organism (i.e. growth, reproduction). The present research quantified immune function (total and differential number of hemocytes, phagocytosis in vivo and activity of phenoloxidase) in the pupal stage of Carabus (Chaetocarabus) lefebvrei. Moreover, the cellular and humoral immune function was compared across the larval, pupal and adult stages to evaluate the changes in immunocompetence across the developmental stages. Four types of circulating hemocytes were characterized via transmission electron microscopy in the pupal stage: prohemocytes, plasmatocytes, granulocytes and oenocytoids. The artificial non-self-challenge treatments performed in vivo have shown that plasmatocytes and granulocytes are responsible for phagocytosis. The level of active phenoloxidase increases with the degree of pigmentation of the cuticle in each stage. In C. lefebvrei, there are different strategies in term of immune response to enhance the fitness of each life stage. The results have shown that the variation in speed and specificity of immune function across the developmental stages is correlated with differences in infection risk, life expectancy and biological function of the life cycle. Copyright © 2013 Elsevier Ltd. All rights reserved.

Life-stage dependent response in zebrafish (Danio rerio) to phototoxicity of TiO2 nanoparticles

EPA Science Inventory

The Zebrafish, and especially its embryo stage, has been increasingly used as a model to evaluate toxicity of manufactured nanomaterials. However, many studies have indicated that the chorion may protect developing embroys from the toxic effects of nanomaterials, suggesting that ...

Quantifying stimulus-response rehabilitation protocols by auditory feedback in Parkinson's disease gait pattern

NASA Astrophysics Data System (ADS)

Pineda, Gustavo; Atehortúa, Angélica; Iregui, Marcela; García-Arteaga, Juan D.; Romero, Eduardo

2017-11-01

External auditory cues stimulate motor related areas of the brain, activating motor ways parallel to the basal ganglia circuits and providing a temporary pattern for gait. In effect, patients may re-learn motor skills mediated by compensatory neuroplasticity mechanisms. However, long term functional gains are dependent on the nature of the pathology, follow-up is usually limited and reinforcement by healthcare professionals is crucial. Aiming to cope with these challenges, several researches and device implementations provide auditory or visual stimulation to improve Parkinsonian gait pattern, inside and outside clinical scenarios. The current work presents a semiautomated strategy for spatio-temporal feature extraction to study the relations between auditory temporal stimulation and spatiotemporal gait response. A protocol for auditory stimulation was built to evaluate the integrability of the strategy in the clinic practice. The method was evaluated in transversal measurement with an exploratory group of people with Parkinson's (n = 12 in stage 1, 2 and 3) and control subjects (n =6). The result showed a strong linear relation between auditory stimulation and cadence response in control subjects (R=0.98 +/-0.008) and PD subject in stage 2 (R=0.95 +/-0.03) and stage 3 (R=0.89 +/-0.05). Normalized step length showed a variable response between low and high gait velocity (0.2> R >0.97). The correlation between normalized mean velocity and stimulus was strong in all PD stage 2 (R>0.96) PD stage 3 (R>0.84) and controls (R>0.91) for all experimental conditions. Among participants, the largest variation from baseline was found in PD subject in stage 3 (53.61 +/-39.2 step/min, 0.12 +/- 0.06 in step length and 0.33 +/- 0.16 in mean velocity). In this group these values were higher than the own baseline. These variations are related with direct effect of metronome frequency on cadence and velocity. The variation of step length involves different regulation strategies and could need others specific external cues. In conclusion the current protocol (and their selected parameters, kind of sound time for training, step of variation, range of variation) provide a suitable gait facilitation method specially for patients with the highest gait disturbance (stage 2 and 3). The method should be adjusted for initial stages and evaluated in a rehabilitation program.

Evaluation of the response of concurrent high dose rate intracavitary brachytherapy with external beam radiotherapy in management of early stage carcinoma cervix.

PubMed

Patidar, Arvind Kumar; Kumar, H S; Walke, Rahul V; Hirapara, Pushpendra H; Jakhar, Shankar Lal; Bardia, M R

2012-10-01

To evaluate local disease control and early complications of concomitant brachytherapy with external beam-radiotherapy in early stage carcinoma cervix. Fifty patients of early stage carcinoma cervix (FIGO-IB/IIA) were randomly divided into study group concomitant external beam irradiation (EBRT) and HDR-ICBT (intra-cavitary brachytherapy, xrt = 50 Gy/25 Fr, HDR 5.2 Gy*5 Fr) and the control group EBRT followed by HDR-ICBT (xrt = 50 Gy/25 Fr, HDR 7.5 Gy*3 Fr). Acute reactions and local disease response were compared between treatment and at 6-month follow up. Median overall treatment times were 38 and 61 days in the study and the control groups, respectively. Acute skin reactions and diarrhea were more in the study but manageable. At the completion of the study, there were 80 and 68 % complete responses, 16 and 20 % partial responses, 0 and 8 % stable diseases in the study group and the control group, respectively. Response was better in the study group but statistically insignificant. Larger number of patients and longer follow up are required to arrive at concrete conclusion.

Impact of 18F-fluorodeoxyglucose positron emission tomography before and after definitive radiation therapy in patients with apparently solitary plasmacytoma.

PubMed

Kim, Paul J; Hicks, Rodney J; Wirth, Andrew; Ryan, Gail; Seymour, John F; Prince, H Miles; Mac Manus, Michael P

2009-07-01

To evaluate the impact of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) on management of patients with apparently isolated plasmacytoma. Twenty-one patients with apparently solitary plasmacytoma who underwent FDG-PET for staging or restaging were identified from a central PET database. They were either candidates for or had received definitive radiation therapy (RT). Seventeen patients had initial staging scans for bone (n = 11) or soft tissue (n = 6) plasmacytomas, and 11 had PET scans after RT. Only 1 of 14 known untreated sites of plasmacytoma was not identified on staging PET (lesion sensitivity = 93%). Three plasmacytomas were excised before PET. Staging PET influenced management in 6 of 17 patients (35%) by showing multiple myeloma (n = 1), discouraging RT after complete resection (n = 1), excluding plasmacytoma at a second site (n = 1), by increasing RT fields (n = 2), or by suggesting sarcoidosis (n = 1). Fifteen of 17 patients with initial staging PET scans received definitive RT. Restaging PET scans after RT showed complete metabolic response in 8 of 11 cases and progressive disease in 2. Two patients with either no response or partial metabolic response had late responses. Staging sestamibi and PET scans were concordant in five of six occasions (one sestamibi scan was false negative). FDG-PET has value for staging and RT planning in plasmacytoma and potentially could have a role in response-assessment after RT. Slow resolution of FDG uptake posttreatment does not necessarily imply an adverse prognosis.

Complete response in 5 out of 38 patients with advanced hepatocellular carcinoma treated with stem cell differentiation stage factors: case reports from a single centre.

PubMed

Livraghi, Tito; Ceriani, R; Palmisano, A; Pedicini, V; Pich, M G; Tommasini, M A; Torzilli, G

2011-02-01

Hepatocellular carcinoma (HCC) represents the third cause of cancer-related death. Because HCC is multi-centric with time, excluding the few transplanted patients, sooner or later it becomes untreatable with loco-regional therapies and, until some years ago, it was not responsive to systemic therapies. In 2005 a randomized trial indicated the efficacy of a product containing stem cell differentiation stage factors (SCDSF) taken from zebra fish embryos during the stage in which the totipotent stem cells are differentiating into the pluripotent adult stem cells. In such a trial the patients, with "intermediate" and "advanced" HCC according to BCLC/AASLD guidelines, presented benefit in terms of performance status (PS) and objective tumoral response, with some cases (2.4%) of complete response (CR). The aim of this cohort study is to report the experience of a tertiary referral center on the evidence of cases of CR in patients with "advanced" stage HCC treated with SCDSF as supportive care. CR was regarded as sustained disappearance of the neoplastic areas or blood supply therein, accompanied by normalization of AFP levels. Out of 49 patients consecutively recruited and retrospectively evaluated, 38 had "advanced" stage and 11 "terminal" stage. In 5 patients with "advanced" stage a sustained CR was reported (13.1%). Improvement on PS was obtained in 17 patients (34.6%). No side effects occurred. SCDSF treatment confirmed its efficacy in patients with "advanced" HCC, in terms of PS and tumoral response.

Colorectal cancer: intrinsic characteristics modulate cancer energy expenditure and the risk of cachexia.

PubMed

Ravasco, Paula; Monteiro-Grillo, Isabel; Camilo, Maria

2007-08-01

To conduct a prospective longitudinal study in colorectal cancer (CRC) patients: 1) to evaluate resting energy expenditure (REE), weight/dietary intake changes, and response to treatment, taking into consideration cancer stage and histology; 2) to determine their potential interrelations; and 3) to quantify the relative contributions to REE of cancer/nutrition/treatment. 101 CRC patients proposed for neoadjuvant radiotherapy (RT) were evaluated before and after RT: REE (indirect calorimetry measurements), percentage of weight loss, usual diet (diet history), current diet (24 hour recall), and treatment response. REE was higher in Stages III/IV versus I/II, at the RT onset (p < 0.002) and end (p = 0.02), and in moderately/poorly/undifferentiated cancers vs well differentiated (onset, p < 0.001) and (RT end, p = 0.01); weight/intake reductions were also greater in Stages III/IV versus I/II (p < 0.01) and in moderately/poorly/undifferentiated cancers versus well differentiated (p < 0.02). According to patients' response to treatment, REE was increased in Stage III/IV (p < 0.005) and Grade 2/3 histology (p < 0.003). In nonresponders, REE increased 7.2 +/- 1.3 kcal/kg/day and decreased 2.8 +/- 0.4 kcal/kg/day in responders. REE changes were not-significantly influenced by weight/intake. Relative contributions to baseline REE were determined in 25 percent by stage, in 25 percent by histology, in 3 percent by intake and in 4 percent by weight loss. At the end of RT, higher REE was attributed in 26 percent to stage, in 27 percent to histology, in 30 percent to nontreatment response, in 9 percent to intake, and in 8 percent to weight loss. In this CRC patient population, higher metabolic rates were mainly determined by the tumor burden and aggressiveness in association with response to treatment clearly disclaiming the effect of weight loss and/or dietary intake reductions.

The relationship between facilitators' questions and the level of reflection in postsimulation debriefing.

PubMed

Husebø, Sissel Eikeland; Dieckmann, Peter; Rystedt, Hans; Søreide, Eldar; Friberg, Febe

2013-06-01

Simulation-based education is a learner-active method that may enhance teamwork skills such as leadership and communication. The importance of postsimulation debriefing to promote reflection is well accepted, but many questions concerning whether and how faculty promote reflection remain largely unanswered in the research literature. The aim of this study was therefore to explore the depth of reflection expressed in questions by facilitators and responses from nursing students during postsimulation debriefings. Eighty-one nursing students and 4 facilitators participated. The data were collected in February and March 2008, the analysis being conducted on 24 video-recorded debriefings from simulated resuscitation teamwork involving nursing students only. Using Gibbs' reflective cycle, we graded the facilitators' questions and nursing students' responses into stages of reflection and then correlated these. Facilitators asked most evaluative and fewest emotional questions, whereas nursing students answered most evaluative and analytic responses and fewest emotional responses. The greatest difference between facilitators and nursing students was in the analytic stage. Only 23 (20%) of 117 questions asked by the facilitators were analytic, whereas 45 (35%) of 130 students' responses were rated as analytic. Nevertheless, the facilitators' descriptive questions also elicited student responses in other stages such as evaluative and analytic responses. We found that postsimulation debriefings provide students with the opportunity to reflect on their simulation experience. Still, if the debriefing is going to pave the way for student reflection, it is necessary to work further on structuring the debriefing to facilitate deeper reflection. Furthermore, it is important that facilitators consider what kind of questions they ask to promote reflection. We think future research on debriefing should focus on developing an analytical framework for grading reflective questions. Such research will inform and support facilitators in devising strategies for the promotion of learning through reflection in postsimulation debriefings.

Positron Emission Tomography in Breast Cancer

PubMed Central

Vercher-Conejero, Jose Luis; Pelegrí-Martinez, Laura; Lopez-Aznar, Diego; Cózar-Santiago, María del Puig

2015-01-01

Gradually, FDG-PET/CT has been strengthening within the diagnostic algorithms of oncological diseases. In many of these, PET/CT has shown to be useful at different stages of the disease: diagnosis, staging or re-staging, treatment response assessment, and recurrence. Some of the advantages of this imaging modality versus CT, MRI, bone scan, mammography, or ultrasound, are based on its great diagnostic capacity since, according to the radiopharmaceutical used, it reflects metabolic changes that often occur before morphological changes and therefore allows us to stage at diagnosis. Moreover, another advantage of this technique is that it allows us to evaluate the whole body so it can be very useful for the detection of distant disease. With regard to breast cancer, FDG-PET/CT has proven to be important when recurrence is suspected or in the evaluation of treatment response. The technological advancement of PET equipment through the development of new detectors and equipment designed specifically for breast imaging, and the development of more specific radiopharmaceuticals for the study of the different biological processes of breast cancer, will allow progress not only in making the diagnosis of the disease at an early stage but also in enabling personalized therapy for patients with breast cancer. PMID:26854143

Interpersonal relationship modulates brain responses to outcome evaluation when gambling for/against others: an electrophysiological analysis.

PubMed

Leng, Yue; Zhou, Xiaolin

2014-10-01

When individuals play a gambling task and their actions have consequences for observers, how are the brain responses of the performers modulated by their interpersonal relationship with the observers? To address this issue, we examined the event-related potentials responses in performers while they played two gambling games: one during which they tried to earn money for the observers instead of themselves (i.e., Experiment 1) and another gambling game during which they attempted to earn money from the observers (i.e., Experiment 2). In Experiment 1, ERP results showed that when gambling for either the friends or the strangers, the feedback-related negativity (FRN) responses were more negative-going to the losses than to the gains. The FRN effect (loss minus gain) was significantly larger when gambling for the friends than for the strangers. The general P300 response was more positive-going when gambling for the friends than for the strangers. These results suggested that gambling for others enables individuals to assess the outcome from the interests of the other people, consequently, the FRN response may be driven by the evaluative process related to interests of the others. Because one׳s own economic interests were not involved, the performers׳ brain responses during both the early, semi-automatic stage (i.e., the FRN) and the later, controlled stage (i.e., the P300) of outcome evaluation were modulated by the interpersonal relationship between the performers and the observers. In Experiment 2, ERP results revealed that when gambling against others, the FRN response was more negative-going to the losses than to the gains, as well. However, neither the FRN effect nor the general FRN response was modulated by interpersonal relationship. The general P300 response was more positive-going when gambling against the stranger than against the friend. These results suggested that when gambling against others, the performers׳ FRN response may be driven by two evaluative processes: one is related to the interests of their own, and another is related to the interests of the other people; and the former one plays a dominant role. Because of highly self-involvement, only the performers׳ brain responses during the later controlled stage of outcome evaluation were modulated by interpersonal relationship. The present study extended previous research on brain responses to outcome evaluation when decision making actions have consequences for the other people by suggesting that the FRN response in the performer could also be driven by two evaluative processes. In addition, whether the FRN in the performer was modulated by interpersonal relationship depends on which evaluative process plays a dominant role. However, the P300 in the performer could always be modulated by interpersonal relationship. These findings provide evidence on outcome evaluation being composed of an early semi-automatic primitive process and a later controlled cognitive/affective appraisal process. Copyright © 2014 Elsevier Ltd. All rights reserved.

A phase 2 trial of dasatinib in patients with locally advanced or stage IV mucosal, acral, or vulvovaginal melanoma: A trial of the ECOG-ACRIN Cancer Research Group (E2607).

PubMed

Kalinsky, Kevin; Lee, Sandra; Rubin, Krista M; Lawrence, Donald P; Iafrarte, Anthony J; Borger, Darell R; Margolin, Kim A; Leitao, Mario M; Tarhini, Ahmad A; Koon, Henry B; Pecora, Andrew L; Jaslowski, Anthony J; Cohen, Gary I; Kuzel, Timothy M; Lao, Christopher D; Kirkwood, John M

2017-07-15

KIT-directed tyrosine kinase inhibitors such as imatinib have demonstrated benefits in KIT-mutant (KIT+) mucosal, acral, vulvovaginal, and chronically sun-damaged (CSD) melanoma. Dasatinib has superior preclinical activity in comparison with other tyrosine kinase inhibitors against cells with the most common KIT mutation, exon 11 L576P . The ECOG-ACRIN E2607 trial assessed dasatinib in patients with these melanoma subtypes. Patients received 70 mg of oral dasatinib twice daily. The primary objective for this 2-stage phase 2 trial was response rate. Stage I was open to KIT+ and wild-type KIT (KIT-) mucosal, acral, and CSD melanoma (n = 57). Stage II accrued only KIT+ tumors (n = 30). To enrich the trial for KIT+ tumors, vulvovaginal melanoma was added, and CSD melanoma was removed from eligibility. Secondary objectives included progression-free survival (PFS), overall survival (OS), and safety. From May 2009 to December 2010, the first stage enrolled 57 patients. Among the evaluable patients, 3 of 51 (5.9%) achieved a partial response: all were KIT-. Stage II closed early because of slow accrual (November 2011 to December 2015). In stage II, 4 of 22 evaluable patients (18.2%) had a partial response; the median duration was 4.2 months. The median PFS was 2.1 months (n = 73; 95% confidence interval [CI], 1.5-2.9 months). The median OS was 7.5 months (95% CI, 6.0-11.9 months). In exploratory analyses, no differences were seen in PFS or OS with the KIT status or subtype. Dasatinib was discontinued because of adverse events in 9 of 75 patients (12%). The dasatinib response rate among KIT+ melanoma patients was low. In view of its clinical activity, it is recommended that imatinib remain the KIT tyrosine kinase inhibitor of choice for unresectable KIT+ melanoma. Cancer 2017;123:2688-97. © 2017 American Cancer Society. © 2017 American Cancer Society.

Fear of negative evaluation moderates effects of social exclusion on selective attention to social signs.

PubMed

Tanaka, Hiroaki; Ikegami, Tomoko

2015-01-01

Previous studies demonstrated that fear of negative evaluation (FNE) moderates responses to exclusion in late-stage social outcomes (e.g., social judgements and behaviours). People with low levels of FNE show affiliative responses, feeling compelled to recover their sense of belonging, whereas people with high levels of FNE do not. This study examined whether FNE also moderates responses to exclusion in early-stage interpersonal perception, manifested in selective attention. The experiment using a dot-probe task revealed that exclusion led participants with low levels of FNE to increase attention to signs of social acceptance (i.e., smiling faces). It also revealed that exclusion led those with high levels of FNE to pay more attention to signs of social threat (i.e., angry faces) relative to those of social acceptance. Thus, exclusion makes the motivation to protect oneself from social threats dominant over the motivation to reestablish social bonds among those who fear negative evaluation.

In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay as a Predictor of Clinical Response to Fluorouracil-Based Adjuvant Chemotherapy in Stage II Colorectal Cancer

PubMed Central

Kwon, Hye Youn; Kim, Im-kyung; Kang, Jeonghyun; Sohn, Seung-Kook; Lee, Kang Young

2016-01-01

Purpose We evaluated the usefulness of the in vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) for prediction of clinical response to fluorouracil-based adjuvant chemotherapy in stage II colorectal cancer. Materials and Methods Tumor specimens of 86 patients with pathologically confirmed stage II colorectal adenocarcinoma were tested for chemosensitivity to fluorouracil. Chemosensitivity was determined by cell death rate (CDR) of drug-exposed cells, calculated by comparing the intracellular ATP level with that of untreated controls. Results Among the 86 enrolled patients who underwent radical surgery followed by fluorouracil-based adjuvant chemotherapy, recurrence was found in 11 patients (12.7%). The CDR ≥ 20% group was associated with better disease-free survival than the CDR < 20% group (89.4% vs. 70.1%, p=0.027). Multivariate analysis showed that CDR < 20% and T4 stage were poor prognostic factors for disease-free survival after fluorouracil-based adjuvant chemotherapy. Conclusion In stage II colorectal cancer, the in vitro ATP-CRA may be useful in identifying patients likely to benefit from fluorouracil-based adjuvant chemotherapy. PMID:26511802

Treatment of Early-stage Extracranial Arteriovenous Malformations with Intralesional Interstitial Bleomycin Injection: A Pilot Study.

PubMed

Jin, Yunbo; Zou, Yun; Hua, Chen; Chen, Hui; Yang, Xi; Ma, Gang; Chang, Lei; Qiu, Yajing; Lyu, Dongze; Wang, Tianyou; Chang, Shih-Jen; Qiao, Congzhen; Luo, Chunfen; Tremp, Mathias; Lin, Xiaoxi

2018-04-01

Purpose To assess the efficacy and safety of intralesional interstitial bleomycin injection in the treatment of early-stage (Schobinger stage I or II) extracranial arteriovenous malformations (AVMs). Materials and Methods This prospective study involved 34 patients with early-stage AVMs, as defined by the Schobinger staging system. The patients received intralesional interstitial bleomycin injected at a maximum dose of 15 000 IU or 1000 IU per kilogram of body weight for children who weighed less than 15 kg per procedure for a total of 6 months (once every month). Therapeutic outcome was evaluated by the degree of devascularization at angiography and the clinical outcome 3 months after the last treatment. Further follow-up was evaluated based on further clinical outcome. Adverse events were recorded according to the Society of Interventional Radiology classification. Results Of the 34 patients with early-stage AVM, 32 (mean age, 20.5 years; 24 female [75%]) completed the study. The results showed that 27 (84.4%, 95% confidence interval [CI]: 71.1, 97.7) patients were responsive to bleomycin injection, including nine (28.1%) with a complete response. Four (12.5%) patients showed no response, and one (3.1%) patient experienced worsening 3 months after the last treatment. During further follow-up (mean follow-up time, 20.7 months; range, 5-28 months), the outcome remained stable in 31 (96.9%) of the 32 patients. A major complication, anaphylactic shock, was observed in one (3.1%, 95% CI: 0, 9.5) patient. Common minor complications included hyperpigmentation, nausea, pruritus, and bullae. Conclusion Intralesional interstitial bleomycin injection is a feasible approach for early-stage AVMs and yields safe and effective outcomes. © RSNA, 2017.

Time-varying SMART design and data analysis methods for evaluating adaptive intervention effects.

PubMed

Dai, Tianjiao; Shete, Sanjay

2016-08-30

In a standard two-stage SMART design, the intermediate response to the first-stage intervention is measured at a fixed time point for all participants. Subsequently, responders and non-responders are re-randomized and the final outcome of interest is measured at the end of the study. To reduce the side effects and costs associated with first-stage interventions in a SMART design, we proposed a novel time-varying SMART design in which individuals are re-randomized to the second-stage interventions as soon as a pre-fixed intermediate response is observed. With this strategy, the duration of the first-stage intervention will vary. We developed a time-varying mixed effects model and a joint model that allows for modeling the outcomes of interest (intermediate and final) and the random durations of the first-stage interventions simultaneously. The joint model borrows strength from the survival sub-model in which the duration of the first-stage intervention (i.e., time to response to the first-stage intervention) is modeled. We performed a simulation study to evaluate the statistical properties of these models. Our simulation results showed that the two modeling approaches were both able to provide good estimations of the means of the final outcomes of all the embedded interventions in a SMART. However, the joint modeling approach was more accurate for estimating the coefficients of first-stage interventions and time of the intervention. We conclude that the joint modeling approach provides more accurate parameter estimates and a higher estimated coverage probability than the single time-varying mixed effects model, and we recommend the joint model for analyzing data generated from time-varying SMART designs. In addition, we showed that the proposed time-varying SMART design is cost-efficient and equally effective in selecting the optimal embedded adaptive intervention as the standard SMART design.

Essential fatty acids supplementation in different-stage atopic dogs fed on a controlled diet.

PubMed

Abba, C; Mussa, P P; Vercelli, A; Raviri, G

2005-01-01

The aim of this trial was to evaluate the effects of polyunsaturated fatty acid (PUFA) supplementation in different-stages atopic dogs fed on a controlled diet. Twenty-two non-seasonal atopic dogs of different breeds and ages were included in the 2-month trial. All the patients were given an essential fatty acid (EFA) supplementation [17 mg/kg eicosapentaenoic acid (EPA) + 5 mg/kg docosahexaenoic acid (DHA) + 35 mg/kg gammalinolenic acid (GLA)], the global (diet + supplementation) omega-6 to omega-3 ratio was 5.5-1. Two groups of dogs were considered: group A 'pre-immunotherapy' (15 cases) included dogs with early stages atopy, which had not been submitted to any treatment yet; group B 'post-immunotherapy' (seven cases) included dogs with chronic atopy immunotherapy non-responsive. Clinical evaluations were performed at the beginning, on day 30 and at the end of the trial. Blood serum fatty acids profile was determined at the beginning and at the end of the study. Better clinical results were obtained in group A, a great difference was found between the two groups on pruritus score. Serum arachidonic acid (AA) was significantly lower at the end of the trial in group A while GLA was significantly higher in group B. We hypothesized that different-stages atopic dogs could have different response to EFA supplementation, maybe because of a different fatty acids metabolism. Early stages cases seem to be more responsive to EFA supplementation.

[¹³¹I]Metaiodobenzylguanidine therapy in neural crest tumors: varying outcome in different histopathologies.

PubMed

Rachh, Swati Hiren; Abhyankar, Suman; Basu, Sandip

2011-12-01

To evaluate the response of [¹³¹I] metaiodobenzylguanidine ([¹³¹I]MIBG) therapy in patients with neuroectodermal tumors and to assess their quality of life using the functional assessment of cancer therapy - general quality-of-life questionnaire for patients who are on follow-up after MIBG therapy. Thirty-two patients diagnosed with various subtypes of neuroectodermal tumors and treated with [¹³¹I]MIBG were included in this retrospective analysis. Response to therapy was evaluated objectively by comparing pretherapy and posttherapy biochemical markers, radiological investigations, and follow-up MIBG scans. Symptomatic response and quality of life were also evaluated in the follow-up visits. In seven patients with stage III neuroblastoma, an objective response rate was seen in 57% and a symptomatic response rate was seen in 29% of the patients. Among 11 patients with stage IV neuroblastoma, an objective response was observed in 36% and a symptomatic response in 36% of the patients. Among 12 patients with pheochomocytoma and paraganglioma, an objective response was noticed in 8%, but symptomatic improvement and stabilization of disease were seen in 75% of the patients belonging to this category. One patient with medullary carcinoma of the thyroid and one patient with mediastinal carcinoid did not show an objective response but had a stable disease; both patients showed symptomatic improvement. Quality of life has improved in all 11 patients who are still on follow-up. [¹³¹I]MIBG therapy can be of significant value in the treatment of patients with chemotherapy-resistant stage III and IV neuroblastomas who demonstrate good tracer uptake in diagnostic scans. MIBG therapy has the potential to stabilize the disease and provide symptomatic improvement in patients with metastatic/recurrent pheochomocytoma/paraganglioma and medullary carcinoma thyroid and carcinoid in which there is evidence of tracer accumulation in the tumor. Both single high dose or multiple fractionated doses are equally effective in improving the quality of life in metastatic/recurrent pheochomocytoma/paraganglioma.

Clinical effects of laser immunotherapy on metastatic cancer patients

NASA Astrophysics Data System (ADS)

Naylor, Mark F.; Lam, Anh K.; Bahavar, Cody F.; Nordquist, Robert E.; Chen, Wei R.

2016-03-01

Clinical trials of late-stage breast cancer patients and late-stage melanoma patients treated by laser immunotherapy (LIT) have shown promising results. In a 2010 study of Li et al, eleven late-stage melanoma patients received LIT in one or multiple 6-week treatment cycles applied to a 200-cm2 treatment site, which usually contained multiple cutaneous metastases. Long-term, positive response was observed in six patients. All lesions in the treatment area of the patients responded to LIT, eight of which achieved complete local response (CLR). CLR was observed in the non-treatment site (regional) lesions in four patients. Five patients were still alive at the time of last follow-up. The probability of 12-month overall survival was 70%.2 In 2011, Li et al, treated ten late stage breast cancer patients with LIT.1 In 8 patients available for evaluation, the objective response rate was 62.5% and the clinical beneficial response rate was 75%.1 This review demonstrates that LIT is safe and well tolerated, so it can be easily applied on an outpatient basis and can be combined with other pharmaceutical modalities to improve the therapeutic response of metastatic cancers.

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography evaluation of subcutaneous panniculitis-like T cell lymphoma and treatment response

PubMed Central

Gorodetskiy, Vadim R; Mukhortova, Olga V; Aslanidis, Irakli P; Klapper, Wolfram; Probatova, Natalya A

2016-01-01

Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a very rare variant of non-Hodgkin’s lymphoma. Currently, there is no standard imaging method for staging of SPTCL nor for assessment of treatment response. Here, we describe our use of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for staging and monitoring of treatment response in 3 cases of SPTCL. Primary staging by PET/CT showed that all 3 patients had multiple foci in the subcutaneous fat tissue, with SUVmax from 10.5 to 14.6. Involvement of intra-abdominal fat with high SUVmax was identified in 2 of the patients. Use of the triple drug regimen of gemcitabine, cisplatin and methylprednisolone (commonly known as “GEM-P”) as first-line therapy or second-line therapy facilitated complete metabolic response for all 3 cases. FDG PET/CT provides valuable information for staging and monitoring of treatment response and can reveal occult involvement of the intra-abdominal visceral fat. High FDG uptake on pre-treatment PET can identify patients with aggressive disease and help in selection of first-line therapy. PMID:27672640

Estimation of Supersonic Stage Separation Aerodynamics of Winged-Body Launch Vehicles Using Response Surface Methods

NASA Technical Reports Server (NTRS)

Erickson, Gary E.

2010-01-01

Response surface methodology was used to estimate the longitudinal stage separation aerodynamic characteristics of a generic, bimese, winged multi-stage launch vehicle configuration at supersonic speeds in the NASA LaRC Unitary Plan Wind Tunnel. The Mach 3 staging was dominated by shock wave interactions between the orbiter and booster vehicles throughout the relative spatial locations of interest. The inference space was partitioned into several contiguous regions within which the separation aerodynamics were presumed to be well-behaved and estimable using central composite designs capable of fitting full second-order response functions. The underlying aerodynamic response surfaces of the booster vehicle in belly-to-belly proximity to the orbiter vehicle were estimated using piecewise-continuous lower-order polynomial functions. The quality of fit and prediction capabilities of the empirical models were assessed in detail, and the issue of subspace boundary discontinuities was addressed. Augmenting the central composite designs to full third-order using computer-generated D-optimality criteria was evaluated. The usefulness of central composite designs, the subspace sizing, and the practicality of fitting lower-order response functions over a partitioned inference space dominated by highly nonlinear and possibly discontinuous shock-induced aerodynamics are discussed.

Impact of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography Before and After Definitive Radiation Therapy in Patients With Apparently Solitary Plasmacytoma

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

Kim, Paul J.; Hicks, Rodney J.; Wirth, Andrew

2009-07-01

Purpose: To evaluate the impact of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) on management of patients with apparently isolated plasmacytoma. Methods and Materials: Twenty-one patients with apparently solitary plasmacytoma who underwent FDG-PET for staging or restaging were identified from a central PET database. They were either candidates for or had received definitive radiation therapy (RT). Results: Seventeen patients had initial staging scans for bone (n = 11) or soft tissue (n = 6) plasmacytomas, and 11 had PET scans after RT. Only 1 of 14 known untreated sites of plasmacytoma was not identified on staging PET (lesion sensitivity = 93%).more » Three plasmacytomas were excised before PET. Staging PET influenced management in 6 of 17 patients (35%) by showing multiple myeloma (n = 1), discouraging RT after complete resection (n = 1), excluding plasmacytoma at a second site (n = 1), by increasing RT fields (n = 2), or by suggesting sarcoidosis (n = 1). Fifteen of 17 patients with initial staging PET scans received definitive RT. Restaging PET scans after RT showed complete metabolic response in 8 of 11 cases and progressive disease in 2. Two patients with either no response or partial metabolic response had late responses. Staging sestamibi and PET scans were concordant in five of six occasions (one sestamibi scan was false negative). Conclusions: FDG-PET has value for staging and RT planning in plasmacytoma and potentially could have a role in response-assessment after RT. Slow resolution of FDG uptake posttreatment does not necessarily imply an adverse prognosis.« less

Research on Evaluation Ethics: What Have We Learned and Why Is It Important?

ERIC Educational Resources Information Center

Morris, Michael

1999-01-01

Findings from empirical research on evaluation ethics indicate an apparent lack of consensus within the field concerning what constitutes an ethical issue, the frequent occurrence of problems in the later stages of evaluation projects, and the perceived ethical significance of the tendency of evaluators to be more responsive to some stakeholders…

Development of guidance on the timeliness in response to acute kidney injury warning stage test results for adults in primary care: an appropriateness ratings evaluation.

PubMed

Blakeman, Tom; Griffith, Kathryn; Lasserson, Dan; Lopez, Berenice; Tsang, Jung Y; Campbell, Stephen; Tomson, Charles

2016-10-11

Tackling the harm associated with acute kidney injury (AKI) is a global priority. In England, a national computerised AKI algorithm is being introduced across the National Health Service (NHS) to drive this change. The study sought to maximise its clinical utility and minimise the potential for burden on clinicians and patients in primary care. An appropriateness ratings evaluation using the RAND/UCLA Appropriateness Method. Clinical scenarios were developed to test the timeliness in (1) communication of AKI warning stage test results from clinical pathology services to primary care, and (2) primary care clinician response to an AKI warning stage test result. A 10-person panel was purposively sampled with representation from clinical biochemistry, acute and emergency medicine and general practice. General practitioners (GPs) represented typical practice in relation to rural and urban practice, out of hours care, GP commissioning and those interested in reducing the impact of medicalisation and 'overdiagnosis'. There was agreement that delivery of AKI warning stage test results through interruptive methods of communication (ie, telephone) from laboratories to primary care was the appropriate next step for patients with an AKI warning stage 3 test result. In the context of acute illness, waiting up to 72 hours to respond to an AKI warning stage test result was deemed an inappropriate action in 62 out of the 65 (94.5%) cases. There was agreement that a clinician response was required within 6 hours, or less, in 39 out of 40 (97.5%) clinical cases relating AKI warning stage test results in the presence of moderate hyperkalaemia. The study has informed national guidance to support a timely and calibrated response to AKI warning stage test results for adults in primary care. Further research is needed to support effective implementation, with a view to examine the effect on health outcomes and costs. 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/.

Conceptual Knowledge Influences Decision Making Differently in Individuals with High or Low Cognitive Flexibility: An ERP Study.

PubMed

Dong, Xiaofei; Du, Xiumin; Qi, Bing

2016-01-01

Studies using the Iowa Gambling Task (IGT) have distinguished between good and bad decision makers and have provided an explanation for deficits in decision making. Previous studies have demonstrated a link between Wisconsin Card Sorting Test (WCST) performance and IGT performance, but the results were not consistent and failed to explain why WCST performance can predict IGT performance. The present study aimed to demonstrate that WCST performance can predict IGT performance and to identify the cognitive component of the WCST that affects IGT performance using event-related potentials (ERPs). In this study, 39 healthy subjects (5 subjects were excluded) were divided into a high group and a low group based on their global score on the WCST. A single-choice version of the IGT was used to eliminate the impact of retrieval strategies on the choice evaluation process and interference due to uncorrelated decks. Differences in the underlying neural mechanisms and explicit knowledge between the two groups during the three stages of the decision-making process were described. Based on the information processing perspective, we divided the decision-making process into three stages: choice evaluation, response selection, and feedback processing. The behavioral results showed that the highly cognitively flexible participants performed better on the IGT and acquired more knowledge of the task. The ERP results showed that during the choice evaluation stage, the P300 recorded from central and parietal regions when a bad deck appeared was larger in the high group participants than in the low group participants. During the response selection stage, the effect of choice type was significant only in the frontal region in the high group, with a larger effect for passing. During the feedback evaluation stage, a larger FRN was evoked for a loss than for a win in the high group, whereas the FRN effect was absent in the low group. Compared with the participants with low cognitive flexibility, the participants with high cognitive flexibility performed better on the IGT, acquired more knowledge of the task, and displayed more obvious somatic markers. The low group participants showed reduced working memory abilities during the choice evaluation stage. The appropriate somatic markers reflected by the DPN is formed only when conceptual knowledge is gained in the response selection stage. The absence of an FRN effect in the subjects who performed poorly on the WCST suggests a significant deficit in feedback learning and reward prediction.

Conceptual Knowledge Influences Decision Making Differently in Individuals with High or Low Cognitive Flexibility: An ERP Study

PubMed Central

Dong, Xiaofei; Du, Xiumin; Qi, Bing

2016-01-01

Objective Studies using the Iowa Gambling Task (IGT) have distinguished between good and bad decision makers and have provided an explanation for deficits in decision making. Previous studies have demonstrated a link between Wisconsin Card Sorting Test (WCST) performance and IGT performance, but the results were not consistent and failed to explain why WCST performance can predict IGT performance. The present study aimed to demonstrate that WCST performance can predict IGT performance and to identify the cognitive component of the WCST that affects IGT performance using event-related potentials (ERPs). Methods In this study, 39 healthy subjects (5 subjects were excluded) were divided into a high group and a low group based on their global score on the WCST. A single-choice version of the IGT was used to eliminate the impact of retrieval strategies on the choice evaluation process and interference due to uncorrelated decks. Differences in the underlying neural mechanisms and explicit knowledge between the two groups during the three stages of the decision-making process were described. Results Based on the information processing perspective, we divided the decision-making process into three stages: choice evaluation, response selection, and feedback processing. The behavioral results showed that the highly cognitively flexible participants performed better on the IGT and acquired more knowledge of the task. The ERP results showed that during the choice evaluation stage, the P300 recorded from central and parietal regions when a bad deck appeared was larger in the high group participants than in the low group participants. During the response selection stage, the effect of choice type was significant only in the frontal region in the high group, with a larger effect for passing. During the feedback evaluation stage, a larger FRN was evoked for a loss than for a win in the high group, whereas the FRN effect was absent in the low group. Conclusion Compared with the participants with low cognitive flexibility, the participants with high cognitive flexibility performed better on the IGT, acquired more knowledge of the task, and displayed more obvious somatic markers. The low group participants showed reduced working memory abilities during the choice evaluation stage. The appropriate somatic markers reflected by the DPN is formed only when conceptual knowledge is gained in the response selection stage. The absence of an FRN effect in the subjects who performed poorly on the WCST suggests a significant deficit in feedback learning and reward prediction. PMID:27479484

Screening tool for oropharyngeal dysphagia in stroke - Part I: evidence of validity based on the content and response processes.

PubMed

Almeida, Tatiana Magalhães de; Cola, Paula Cristina; Pernambuco, Leandro de Araújo; Magalhães, Hipólito Virgílio; Magnoni, Carlos Daniel; Silva, Roberta Gonçalves da

2017-08-17

The aim of the present study was to identify the evidence of validity based on the content and response process of the Rastreamento de Disfagia Orofaríngea no Acidente Vascular Encefálico (RADAVE; "Screening Tool for Oropharyngeal Dysphagia in Stroke"). The criteria used to elaborate the questions were based on a literature review. A group of judges consisting of 19 different health professionals evaluated the relevance and representativeness of the questions, and the results were analyzed using the Content Validity Index. In order to evidence validity based on the response processes, 23 health professionals administered the screening tool and analyzed the questions using a structured scale and cognitive interview. The RADAVE structured to be applied in two stages. The first version consisted of 18 questions in stage I and 11 questions in stage II. Eight questions in stage I and four in stage II did not reach the minimum Content Validity Index, requiring reformulation by the authors. The cognitive interview demonstrated some misconceptions. New adjustments were made and the final version was produced with 12 questions in stage I and six questions in stage II. It was possible to develop a screening tool for dysphagia in stroke with adequate evidence of validity based on content and response processes. Both validity evidences obtained so far allowed to adjust the screening tool in relation to its construct. The next studies will analyze the other evidences of validity and the measures of accuracy.

Diagnosis and evaluation of gastric cancer by positron emission tomography

PubMed Central

Wu, Chen-Xi; Zhu, Zhao-Hui

2014-01-01

Gastric cancer is the second leading cause of cancer mortality worldwide. The diagnosis of gastric cancer has been significantly improved with the broad availability of gastrointestinal endoscopy. Effective technologies for accurate staging and quantitative evaluation are still in demand to merit reasonable treatment and better prognosis for the patients presented with advanced disease. Preoperative staging using conventional imaging tools, such as computed tomography (CT) and endoscopic ultrasonography, is inadequate. Positron emission tomography (PET), using 18F-fluorodeoxyglucose (FDG) as a tracer and integrating CT for anatomic localization, holds a promise to detect unsuspected metastasis and has been extensively used in a variety of malignancies. However, the value of FDG PET/CT in diagnosis and evaluation of gastric cancer is still controversial. This article reviews the current literature in diagnosis, staging, response evaluation, and relapse monitoring of gastric cancer, and discusses the current understanding, improvement, and future prospects in this area. PMID:24782610

Multimodal imaging evaluation in staging of rectal cancer

PubMed Central

Heo, Suk Hee; Kim, Jin Woong; Shin, Sang Soo; Jeong, Yong Yeon; Kang, Heoung-Keun

2014-01-01

Rectal cancer is a common cancer and a major cause of mortality in Western countries. Accurate staging is essential for determining the optimal treatment strategies and planning appropriate surgical procedures to control rectal cancer. Endorectal ultrasonography (EUS) is suitable for assessing the extent of tumor invasion, particularly in early-stage or superficial rectal cancer cases. In advanced cases with distant metastases, computed tomography (CT) is the primary approach used to evaluate the disease. Magnetic resonance imaging (MRI) is often used to assess preoperative staging and the circumferential resection margin involvement, which assists in evaluating a patient’s risk of recurrence and their optimal therapeutic strategy. Positron emission tomography (PET)-CT may be useful in detecting occult synchronous tumors or metastases at the time of initial presentation. Restaging after neoadjuvant chemoradiotherapy (CRT) remains a challenge with all modalities because it is difficult to reliably differentiate between the tumor mass and other radiation-induced changes in the images. EUS does not appear to have a useful role in post-therapeutic response assessments. Although CT is most commonly used to evaluate treatment responses, its utility for identifying and following-up metastatic lesions is limited. Preoperative high-resolution MRI in combination with diffusion-weighted imaging, and/or PET-CT could provide valuable prognostic information for rectal cancer patients with locally advanced disease receiving preoperative CRT. Based on these results, we conclude that a combination of multimodal imaging methods should be used to precisely assess the restaging of rectal cancer following CRT. PMID:24764662

Neoadjuvant conformal chemoradiation with induction chemotherapy for rectal adenocarcinoma. A prospective observational study.

PubMed

Fekete, Zsolt; Muntean, Alina-Simona; Hica, Ştefan; Rancea, Alin; Resiga, Liliana; Csutak, Csaba; Todor, Nicolae; Nagy, Viorica Magdalena

2014-06-01

The purpose of this prospective observational study was to evaluate the rate and the prognostic factors for down-staging and complete response for rectal adenocarcinoma after induction chemotherapy and neoadjuvant chemoradiation followed by surgery, and to analyze the rate of sphincter-saving surgery. We included from March 2011 to October 2013 a number of 88 patients hospitalized with locally advanced rectal adenocarcinoma in the Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj. The treatment schedule included 2-4 cycles of Oxaliplatin plus a fluoropyrimidine followed by concomitant chemoradiation with a dose of 50 Gy in 25 fractions combined with a fluoropyrimidine monotherapy. The rate of T down-staging was 49.4% (40/81 evaluable patients). Independent prognostic factors for T down-staging were: age >57 years (p<0.01), cN0 (p<0.01), distance from anal verge >5 cm (p<0.01), initial CEA <6.2 ng/ml (p<0.01), higher number of chemotherapy cycles with Oxaliplatin (pROC=0.05) and protraction of radiotherapy of >35 days (p<0.01). Nine patients from 81 (11.1%) presented complete response (7 pathological and 2 clinical); the independent prognostic factors were stage cT2 versus cT3-4 (p<0.01), initial tumor size ≤3.5 cm and distance from anal verge >5 cm (p=0.03). Sixty-eight patients (79.1%) underwent radical surgery and among them 35 patients (51.5 %) had a sphincter saving procedure. Induction chemotherapy with neoadjuvant chemoradiation produced important down-staging in rectal adenocarcinoma. Independent prognostic factors for T down-staging were: age, cN0, distance from anal verge, initial CEA, the number of Oxaliplatin cycles and duration of radiotherapy; for complete response: cT2, initial tumor size and distance from the anal verge.

High serum soluble tumor necrosis factor receptor 1 predicts poor treatment response in acute-stage schizophrenia.

PubMed

Nishimon, Shohei; Ohnuma, Tohru; Takebayashi, Yuto; Katsuta, Narimasa; Takeda, Mayu; Nakamura, Toru; Sannohe, Takahiro; Higashiyama, Ryoko; Kimoto, Ayako; Shibata, Nobuto; Gohda, Tomohito; Suzuki, Yusuke; Yamagishi, Sho-Ichi; Tomino, Yasuhiko; Arai, Heii

2017-06-02

Inflammation may be involved in the pathophysiology of schizophrenia. However, few cross-sectional or longitudinal studies have examined changes in biomarker expression to evaluate diagnostic and prognostic efficacy in acute-stage schizophrenia. We compared serum inflammatory biomarker concentrations in 87 patients with acute-stage schizophrenia on admission to 105 age-, sex-, and body mass index (BMI)-matched healthy controls. The measured biomarkers were soluble tumor necrosis factor receptor 1 (sTNFR1) and adiponectin, which are associated with inflammatory responses, and pigment epithelium-derived factor (PEDF), which has anti-inflammatory properties. We then investigated biomarker concentrations and associations with clinical factors in 213 patients (including 42 medication-free patients) and 110 unmatched healthy controls to model conditions typical of clinical practice. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale and Global Assessment of Function. In 121 patients, biomarker levels and clinical status were evaluated at both admission and discharge. Serum sTNFR1 was significantly higher in patients with acute-stage schizophrenia compared to matched controls while no significant group differences were observed for the other markers. Serum sTNFR1 was also significantly higher in the 213 patients compared to unmatched controls. The 42 unmedicated patients had significantly lower PEDF levels compared to controls. Between admission and discharge, sTNFR1 levels decreased significantly; however, biomarker changes did not correlate with clinical symptoms. The discriminant accuracy of sTNFR1 was 93.2% between controls and patients, showing no symptom improvement during care. Inflammation and a low-level anti-inflammatory state may be involved in both schizophrenia pathogenesis and acute-stage onset. High serum sTNFR1 in the acute stage could be a useful prognostic biomarker for treatment response in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Phyllostomid Bat Occurrence in Successional Stages of Neotropical Dry Forests

PubMed Central

Avila-Cabadilla, Luis Daniel; Stoner, Kathryn Elizabeth; Nassar, Jafet M.; Espírito-Santo, Mario M.; Alvarez-Añorve, Mariana Yolotl; Aranguren, Carla I.; Henry, Mickael; González-Carcacía, José A.; Dolabela Falcão, Luiz A.; Sanchez-Azofeifa, Gerardo Arturo

2014-01-01

Tropical dry forests (TDFs) are highly endangered tropical ecosystems being replaced by a complex mosaic of patches of different successional stages, agricultural fields and pasturelands. In this context, it is urgent to understand how taxa playing critical ecosystem roles respond to habitat modification. Because Phyllostomid bats provide important ecosystem services (e.g. facilitate gene flow among plant populations and promote forest regeneration), in this study we aimed to identify potential patterns on their response to TDF transformation in sites representing four different successional stages (initial, early, intermediate and late) in three Neotropical regions: México, Venezuela and Brazil. We evaluated bat occurrence at the species, ensemble (abundance) and assemblage level (species richness and composition, guild composition). We also evaluated how bat occurrence was modulated by the marked seasonality of TDFs. In general, we found high seasonal and regional specificities in phyllostomid occurrence, driven by specificities at species and guild levels. For example, highest frugivore abundance occurred in the early stage of the moistest TDF, while highest nectarivore abundance occurred in the same stage of the driest TDF. The high regional specificity of phyllostomid responses could arise from: (1) the distinctive environmental conditions of each region, (2) the specific behavior and ecological requirements of the regional bat species, (3) the composition, structure and phenological patterns of plant assemblages in the different stages, and (4) the regional landscape composition and configuration. We conclude that, in tropical seasonal environments, it is imperative to perform long-term studies considering seasonal variations in environmental conditions and plant phenology, as well as the role of landscape attributes. This approach will allow us to identify potential patterns in bat responses to habitat modification, which constitute an invaluable tool for not only bat biodiversity conservation but also for the conservation of the key ecological processes they provide. PMID:24404175

Repeated iodine-125 seed implantations combined with external beam radiotherapy for the treatment of locally recurrent or metastatic stage III/IV non-small cell lung cancer: a retrospective study.

PubMed

Li, Wei; Dan, Gang; Jiang, Jianqing; Zheng, Yifeng; Zheng, Xiushan; Deng, Dan

2016-09-13

Recurrent or metastatic lung cancer is difficult to manage. This retrospective study aimed to assess the efficacy of repeated iodine-125 seed implantations combined with external beam radiotherapy (EBRT) for locally recurrent or metastatic stage-III/IV non-small cell lung cancer (NSCLC). Eighteen previously treated stage-III/IV NSCLC patients with local or metastatic recurrences underwent 1-to-3 iodine-125 implantations. Six of these patients received palliative EBRT and six patients received combined chemotherapy using gemcitabine and cisplatin. Near-term treatment efficacy was evaluated 3 months after seed implantation by comparing changes in tumor size on computed tomography images; the evaluated outcomes were complete response, partial response, stable disease, and local tumor control rate. Long-term efficacy was assessed based on 1- and 2-year survival rates. Patients were followed up for 6 to 50 months. The overall (i.e., complete + partial) response rate was 87.4 %. The local control rates after the first, second, and third years were 94.1, 58.8 and 41.2 %, respectively. The results of this study demonstrated that repeated implantation of radioactive particles combined with EBRT is a safe treatment that effectively controlled local recurrence and metastasis of stage III/IV NSCLC.

Clinical End Points and Response Criteria in Mycosis Fungoides and Sézary Syndrome: A Consensus Statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer

PubMed Central

Olsen, Elise A.; Whittaker, Sean; Kim, Youn H.; Duvic, Madeleine; Prince, H. Miles; Lessin, Stuart R.; Wood, Gary S.; Willemze, Rein; Demierre, Marie-France; Pimpinelli, Nicola; Bernengo, Maria Grazia; Ortiz-Romero, Pablo L.; Bagot, Martine; Estrach, Teresa; Guitart, Joan; Knobler, Robert; Sanches, José Antonio; Iwatsuki, Keiji; Sugaya, Makoto; Dummer, Reinhard; Pittelkow, Mark; Hoppe, Richard; Parker, Sareeta; Geskin, Larisa; Pinter-Brown, Lauren; Girardi, Michael; Burg, Günter; Ranki, Annamari; Vermeer, Maartan; Horwitz, Steven; Heald, Peter; Rosen, Steve; Cerroni, Lorenzo; Dreno, Brigette; Vonderheid, Eric C.

2011-01-01

Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS. PMID:21576639

Front-line window therapy with cisplatin in patients with primary disseminated Ewing sarcoma: A study by the Associazione Italiana di Ematologia ed Oncologia Pediatrica and Italian Sarcoma Group.

PubMed

Luksch, Roberto; Grignani, Giovanni; D'Angelo, Paolo; Prete, Arcangelo; Puma, Nadia; Podda, Marta; Casanova, Michela; Ferrari, Andrea; Morosi, Carlo; Fagioli, Franca; Aglietta, Massimo; Ferrari, Stefano; Picci, Piero; Massimino, Maura

2017-12-01

The aim was to assess the activity of cisplatin (CDDP) in Ewing sarcoma (ES). The study consisted of front-line window therapy with CDDP 120 mg/sqm every 3 weeks for two courses in children and young adults with primary disseminated ES. Response was assessed using the Response Evaluation Criteria in Solid Tumours criteria, and Simon's two-stage design was applied. Twelve consecutive patients were enrolled in stage 1. Only one objective response was observed. Since the target response rate was not achieved, accrual was stopped and CDDP as a single agent in ES was judged unworthy of further assessment. © 2017 Wiley Periodicals, Inc.

2-[18F]fluoro-2-deoxyglucose positron-emission tomography in staging, response evaluation, and treatment planning of lymphomas.

PubMed

Specht, Lena

2007-07-01

2-[18F]fluoro-2-deoxyglucose positron-emission tomography (FDG-PET) is used increasingly in the clinical management of lymphomas. With regard to staging, FDG-PET is more sensitive and specific than conventional staging methods in FDG avid lymphomas (ie, Hodgkin lymphoma and most aggressive non-Hodgkin lymphomas). Despite methodological problems, in particular the lack of a valid reference test, FDG-PET is approved and generally used for this purpose. With regard to response evaluation, FDG-PET at the end of treatment seems to aid considerably in differentiating between residual masses with or without residual lymphoma. Hence, new revised response criteria have been proposed, incorporating the result of FDG-PET at the end of treatment. An early interim FDG-PET scan after 1 to 3 cycles of chemotherapy is a very strong predictor of outcome, and trials are now in progress testing treatment modifications on this basis. With regard to treatment planning, in the context of combined-modality therapy, radiotherapy for lymphomas is moving toward more conformal techniques reducing the irradiated volume to include only the macroscopic lymphoma. In this situation, accurate imaging is essential, and FDG-PET coregistered with the planning computed tomography (CT) scan is used increasingly. The availability of PET/CT scanners suited for virtual simulation has aided this process. However, clinical data evaluating this technique are at present sparse.

Evaluation of third molar development in the estimation of chronological age.

PubMed

Soares, Caio Belém Rodrigues Barros; Figueiroa, José Natal; Dantas, Renata Moura Xavier; Kurita, Lúcio Mitsuo; Pontual, Andréa dos Anjos; Ramos-Perez, Flávia Maria de Moraes; Perez, Danyel Elias da Cruz; Pontual, Maria Luiza dos Anjos

2015-09-01

The purpose of this study was to evaluate the correlation between chronological age and the degree of third molar mineralization by Demirjian's developmental stages (Demirjian et al., 1973) using panoramic radiography. From a total of 11.396 digital panoramic radiographs of patients from three oral radiology private clinics from the northeast region of Brazil, obtained from January to June 2009, 2097 radiographic images from patients aged between 6 and 22 years were selected. The images were analyzed individually by two obsevers using a 21-inch computer screen and Windows Picture and Fax Viewer. Reliability was achieved by intra- and interobserver evaluation, using the Kappa test. Chronological age, calcification stage, gender and third molar were interrelated using a multiple linear regression model, considering age as a response variable. There was reliability with Demirjian et al.'s developmental stage assesment, displaying a significant relationship between mineralization stages and patients' age (P<0.05). There was no significant difference between the average age and the calcification stage taking gender and localization of the third molar into consideration. It is possible to estimate chronological age based on Demirjian's stage of a third molar, regardless of gender and location. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Assessment of Parametrial Response by Growth Pattern in Patients With International Federation of Gynecology and Obstetrics Stage IIB and IIIB Cervical Cancer: Analysis of Patients From a Prospective, Multicenter Trial (EMBRACE)

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

Yoshida, Kenji; Kobe University Graduate School of Medicine, Kobe; Jastaniyah, Noha

Purpose: To assess disease response along the parametrial space according to tumor morphology in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB and IIIB cervical cancer at the time of image-guided adaptive brachytherapy. Methods and Materials: Patients with FIGO stage IIB and IIIB cervical cancer registered as of November 2013 in the EMBRACE study were evaluated. Tumors were stratified according to morphologic subtype on magnetic resonance imaging (expansive and infiltrative), and the characteristics of those subtypes were analyzed. Parametrial involvement at diagnosis and at brachytherapy was evaluated, and the response to chemo-radiotherapy was classified as good, moderate,more » or poor. The response grade was compared between the 2 groups and analyzed with regard to tumor volumes, and dosimetric parameters. Results: A total of 452 patients were evaluated, of whom 186 had expansive growth type and 266 had infiltrative morphology. Patients with infiltrative tumors had more extensive disease, as indicated by a higher rate of FIGO stage IIIB disease, as well as radiologic evidence of extension into the distal parametrial space and to the pelvic side wall on magnetic resonance imaging. Cervical necrosis was more common in the infiltrative group. Good response was more common in the expansive group (34% vs 24%; P=.02), and poor response was more common in the infiltrative group (11% and 19%; P=.02). Mean gross tumor volume at diagnosis was equal in both groups (51.7 cm{sup 3}). The high-risk clinical target volume was larger in infiltrative tumors (37.9 cm{sup 3} vs 33.3 cm{sup 3}, P=.005). The mean high-risk clinical target volume D{sub 90} was slightly higher in expansive tumors (92.7 Gy and 89.4 Gy, P<.001). Conclusion: Infiltrative tumors are more advanced at presentation and respond less favorably to chemo-radiotherapy when compared with expansive tumors that are more or less equivalent in size. The use of image-guided adaptive brachytherapy allows achieving reasonably high doses in both groups.« less

Phase II Trial of Sorafenib in Combination with Carboplatin and Paclitaxel in Patients with Metastatic Uveal Melanoma: SWOG S0512

PubMed Central

Bhatia, Shailender; Moon, James; Margolin, Kim A.; Weber, Jeffrey S.; Lao, Christopher D.; Othus, Megan; Aparicio, Ana M.; Ribas, Antoni; Sondak, Vernon K.

2012-01-01

Background Sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, inhibits the mitogen-activated protein kinase pathway that is activated in most uveal melanoma tumors. This phase II study was conducted by the SWOG cooperative group to evaluate the efficacy of sorafenib in combination with carboplatin and paclitaxel (CP) in metastatic uveal melanoma. Methods Twenty-five patients with stage IV uveal melanoma who had received 0–1 prior systemic therapy were enrolled. Treatment included up to 6 cycles of carboplatin (AUC = 6) and paclitaxel (225 mg/m2) administered IV on day 1 plus sorafenib (400 mg PO twice daily), followed by sorafenib monotherapy until disease progression. The primary endpoint was objective response rate (ORR); a two-stage design was used with the study to be terminated if no confirmed responses were observed in the first 20 evaluable patients. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS). Results No confirmed objective responses occurred among the 24 evaluable patients (ORR = 0% [95% CI: 0–14%]) and the study was terminated at the first stage. Minor responses (tumor regression less than 30%) were seen in eleven of 24 (45%) patients. The median PFS was 4 months [95% CI: 1–6 months] and the 6-month PFS was 29% [95% CI: 13%–48%]. The median OS was 11 months [95% CI: 7–14 months]. Conclusion In this study, the overall efficacy of CP plus sorafenib in metastatic uveal melanoma did not warrant further clinical testing when assessed by ORR, although minor tumor responses and stable disease were observed in some patients. Trial Registration ClinicalTrials.gov NCT00329641 PMID:23226204

Targeting personalized medicine in a non-Hodgkin lymphoma patient with 18F-FDG and 18F-choline PET/CT.

PubMed

Ribeiro, Thalles H; S, Raul; Castro, Ana Carolina G; Paulino, Eduardo; Mamede, Marcelo

2017-02-01

Early diagnosis and staging of non-Hodgkin lymphoma (NHL) is essential for therapeutic strategy decision. Positron emission tomography/computed tomography (PET/CT) with fluordeoxyglucose (FDG), a glucose analogue, labeled with fluor-18 (18F-FDG) has been used to evaluate staging, therapy response and prognosis in NHL patients. However, in some cases, 18F-FDG has shown false-positive uptake due to inflammatory reaction after chemo and/or radiation therapy. In this case report, we present a NHL patient evaluated with 18F-FDG and 18F-choline PET/CT scan imaging pre- and post-therapy. 18F-FDG and 18F-choline PET/CT were performed for the purpose of tumor staging and have shown intense uptake in infiltrative tissue as well as in the lymph node, but with some mismatching in the tumor. Post-treatment 18F-FDG and 18F-choline PET/ CT scans revealed no signs of radiotracer uptake, suggesting complete remission of the tumor. 18F-choline may be a complimentary tool for staging and assessment of therapeutic response in non-Hodgkin lymphoma, while non-18F-FDG tracer can be used for targeted therapy and patient management.

Stage-Dependent Expression of Deltamethrin Toxicity and Resistance in Triatoma infestans (Hemiptera: Reduviidae) From Argentina.

PubMed

Germano, Mónica D; Picollo, María I

2018-02-20

Triatoma infestans Klug (Hemiptera: Reduviidae) is the main vector of Chagas disease in Latin America. This insect has been controlled with pyrethroids since the 1980s, although the emergence of resistance to deltamethrin has decreased control success in some areas of the Gran Chaco ecoregion. The response of T. infestans to deltamethrin was evaluated per developmental stage. In addition, we evaluated the possible stage-dependent expression of deltamethrin resistance. The bioassays were conducted by topical application of the insecticide in acetone. The drop size, age at the time of exposure, and mortality measuring time were standardized per stage. The lethal dose of deltamethrin moderately increased with the developmental stage. The resistance to deltamethrin was expressed in every instar, and was the highest in the fourth- and fifth-instar nymphs. While increasing, weight plays a relevant role in lethal dose stage dependency, a number of contributing factors such as degradative metabolism are probably involved in the variability of insecticide effect and resistance described for different T. infestans developmental stages. Possible explanations for these differences and their implications on resistance management and chemical control are discussed.

Prognostic Significance of NSCLC and Response to EGFR-TKIs of EGFR-Mutated NSCLC Based on PD-L1 Expression.

PubMed

Kobayashi, Kenichi; Seike, Masahiro; Zou, Fenfei; Noro, Rintaro; Chiba, Mika; Ishikawa, Arimi; Kunugi, Shinobu; Kubota, Kaoru; Gemma, Akihiko

2018-02-01

Recent clinical trials have shown that immune checkpoint blockades that target either PD-1 or PD-L1 yield remarkable responses in a subgroup of patients with non-small cell lung cancer (NSCLC). We retrospectively examined, by immunohistochemical analysis, 211 NSCLC samples. Using 32 independent samples, we also evaluated PD-L1 expression in NSCLC patients with EGFR gene mutations treated by EGFR-TKIs. Overall survival of PD-L1-positive stages I-III NSCLC and stage I NSCLC and stages I-III squamous cell carcinoma (SQ) were significantly shorter than those of PD-L1-negative NSCLC (p<0.01 and p=0.02 and p=0.01, respectively). In stage I NSCLC and stages I-III SQ, PD-L1 expression was found to be independent predictor of death after multivariate analysis. Response to EGFR-TKIs was not significantly different between PD-L1-positive and PD-L1-negative NSCLC patients with EGFR mutations. PD-L1 expression was a significant independent predictor of poor outcome in NSCLC patients. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Pupillary Responses to Full-Field Chromatic Stimuli Are Reduced in Patients with Early-Stage Primary Open-Angle Glaucoma.

PubMed

Najjar, Raymond P; Sharma, Sourabh; Atalay, Eray; Rukmini, Annadata V; Sun, Christopher; Lock, Jing Zhan; Baskaran, Mani; Perera, Shamira A; Husain, Rahat; Lamoureux, Ecosse; Gooley, Joshua J; Aung, Tin; Milea, Dan

2018-03-21

To evaluate the ability of chromatic pupillometry to reveal abnormal pupillary responses to light in patients with early-stage primary open-angle glaucoma (POAG) and to test whether the degree of pupillometric impairment correlates with structural hallmarks of optic nerve damage in the disease. Cross-sectional study. Forty-six patients with early-stage POAG (63.4±8.3 years, 63% male, 87% ethnic-Chinese) and 90 age-matched healthy controls (61.4±8.6 years, 34% male, 89% ethnic-Chinese). Patients with POAG had a visual field mean deviation (VFMD) of -6 decibels or better on automated perimetry. Each participant underwent a monocular 2-minute exposure to blue light (462 nm) followed by another 2-minute exposure to red light (638 nm) using a modified Ganzfeld dome equipped with a light-emitting diode lighting system. The light stimuli intensity was increased logarithmically to evaluate the combined extrinsic and intrinsic response of intrinsically photosensitive retinal ganglion cells (ipRGCs). Light-induced changes in horizontal pupil diameter were assessed monocularly using infrared pupillography. Baseline-adjusted, light-induced pupillary constriction amplitudes were calculated, and individual irradiance-response curves were constructed for each stimulus. Pupillary constriction amplitudes were compared between groups and across light intensities using a linear mixed model analysis. The linear relationship between pupillometric parameters and different structural and functional features of glaucoma was assessed using Pearson's correlation analysis. Light-induced pupillary constriction was reduced in patients with early-stage POAG compared with controls at moderate to high irradiances (≥11 Log photons/cm 2 /s) of blue (P = 0.003) and red (P < 0.001) light. Maximal pupillary constriction amplitude was correlated with retinal nerve fiber layer thickness (RNFL) thickness (blue: r = 0.51, P < 0.001; red: r = 0.45, P = 0.002) in patients with POAG but not in controls. Conversely, pupillometric parameters were not correlated with visual field scores in patients with early-stage POAG. Patients with early-stage POAG exhibit reduced pupillary responses to moderate and high irradiances of blue and red lights. This wavelength-independent functional alteration correlates with structural thinning of the RNFL and could be the consequence of dysfunction or loss of melanopsin expressing ipRGCs in the early stages of the disease. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Development of a new Rasch-based scoring algorithm for the National Eye Institute Visual Functioning Questionnaire to improve its interpretability.

PubMed

Petrillo, Jennifer; Bressler, Neil M; Lamoureux, Ecosse; Ferreira, Alberto; Cano, Stefan

2017-08-14

The NEI VFQ-25 has undergone psychometric evaluation in patients with varying ocular conditions and the general population. However, important limitations which may affect the interpretation of clinical trial results have been previously identified, such as concerns with reliability and validity. The purpose of this study was to evaluate the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) and make recommendations for a revised scoring structure, with a view to improving its psychometric performance and interpretability. Rasch Measurement Theory analyses were conducted in two stages using pooled baseline NEI VFQ-25 data for 2487 participants with retinal diseases enrolled in six clinical trials. In stage 1, we examined: scale-to-sample targeting; thresholds for item response options; item fit statistics; stability; local dependence; and reliability. In stage 2, a post-hoc revision of the scoring structure (VFQ-28R) was created and psychometrically re-evaluated. In stage 1, we found that the NEI VFQ-25 was mis-targeted to the sample, and had disordered response thresholds (15/25 items) and mis-fitting items (8/25 items). However, items appeared to be stable (differential item functioning for three items), have minimal item dependency (one pair of items) and good reliability (person-separation index, 0.93). In stage 2, the modified Rasch-scored NEI VFQ-28-R was assessed. It comprised two broad domains: Activity Limitation (19 items) and Socio-Emotional Functioning (nine items). The NEI VFQ-28-R demonstrated improved performance with fewer disordered response thresholds (no items), less item misfit (three items) and improved population targeting (reduced ceiling effect) compared with the NEI VFQ-25. Compared with the original version, the proposed NEI VFQ-28-R, with Rasch-based scoring and a two-domain structure, appears to offer improved psychometric performance and interpretability of the vision-related quality of life scale for the population analysed.

Genome-wide analysis identifies chickpea (Cicer arietinum) heat stress transcription factors (Hsfs) responsive to heat stress at the pod development stage.

PubMed

Chidambaranathan, Parameswaran; Jagannadham, Prasanth Tej Kumar; Satheesh, Viswanathan; Kohli, Deshika; Basavarajappa, Santosh Halasabala; Chellapilla, Bharadwaj; Kumar, Jitendra; Jain, Pradeep Kumar; Srinivasan, R

2018-05-01

The heat stress transcription factors (Hsfs) play a prominent role in thermotolerance and eliciting the heat stress response in plants. Identification and expression analysis of Hsfs gene family members in chickpea would provide valuable information on heat stress responsive Hsfs. A genome-wide analysis of Hsfs gene family resulted in the identification of 22 Hsf genes in chickpea in both desi and kabuli genome. Phylogenetic analysis distinctly separated 12 A, 9 B, and 1 C class Hsfs, respectively. An analysis of cis-regulatory elements in the upstream region of the genes identified many stress responsive elements such as heat stress elements (HSE), abscisic acid responsive element (ABRE) etc. In silico expression analysis showed nine and three Hsfs were also expressed in drought and salinity stresses, respectively. Q-PCR expression analysis of Hsfs under heat stress at pod development and at 15 days old seedling stage showed that CarHsfA2, A6, and B2 were significantly upregulated in both the stages of crop growth and other four Hsfs (CarHsfA2, A6a, A6c, B2a) showed early transcriptional upregulation for heat stress at seedling stage of chickpea. These subclasses of Hsfs identified in this study can be further evaluated as candidate genes in the characterization of heat stress response in chickpea.

Glass-eel-stage American Eels respond to conspecific odor as a function of concentration

USGS Publications Warehouse

Schmucker, Andrew K.; Johnson, Nicholas; Galbraith, Heather S.; Li, Weiming

2016-01-01

The American Eel Anguilla rostrata has experienced staggering population declines in recent decades and is now the focus of restoration efforts. Studies have demonstrated that olfaction is critical to anguillid behavior and that glass eels (the life stage which migrates inland from saltwater to freshwater) are attracted to conspecific washings. We evaluated conspecific cueing as a potential mechanism for American Eel inland migration coordination by assessing (1) the affinity of glass eels to conspecific washings, (2) the concentration–response relationships, and (3) changes in responsiveness to washings during the glass eel-to-elver transition. In two-choice maze assays, glass eels were attracted to glass eel washings over a wide range of concentrations (0.20–0.40 g of glass eels·L−1·h−1), and a logarithmic function provided the best fit to the concentration–response relationship. When given a choice between two conspecific washings of higher and lower concentrations, the glass eels generally preferred the higher concentration. Responses to undiluted glass eel washings did not significantly differ among stage-3–7 glass eels, although stage-7 eels were not attracted to the washings, whereas the other stages were. Washing affinity remained similar over the course of several weeks. These results support aspects of the conspecific cueing hypothesis at the glass eel life stage under laboratory conditions, suggesting that conspecific cueing is an important component of migration coordination among juvenile American Eels and warrants additional study.

Early stage response problem for post-disaster incidents

NASA Astrophysics Data System (ADS)

Kim, Sungwoo; Shin, Youngchul; Lee, Gyu M.; Moon, Ilkyeong

2018-07-01

Research on evacuation plans for reducing damages and casualties has been conducted to advise defenders against threats. However, despite the attention given to the research in the past, emergency response management, designed to neutralize hazards, has been undermined since planners frequently fail to apprehend the complexities and contexts of the emergency situation. Therefore, this study considers a response problem with unique characteristics for the duration of the emergency. An early stage response problem is identified to find the optimal routing and scheduling plan for responders to prevent further hazards. Due to the complexity of the proposed mathematical model, two algorithms are developed. Data from a high-rise building, called Central City in Seoul, Korea, are used to evaluate the algorithms. Results show that the proposed algorithms can procure near-optimal solutions within a reasonable time.

Biological soil crust response to late season prescribed fire in a Great Basin juniper woodland

Treesearch

Steven D. Warren; Larry L. St.Clair; Jeffrey R. Johansen; Paul Kugrens; L. Scott Baggett; Benjamin J. Bird

2015-01-01

Expansion of juniper on U.S. rangelands is a significant environmental concern. Prescribed fire is often recommended to control juniper. To that end, a prescribed burn was conducted in a Great Basin juniper woodland. Conditions were suboptimal; fire did not encroach into mid- or late-seral stages and was patchy in the early-seral stage. This study evaluated the effects...

Brunnstrom Recovery Stage and Motricity Index for the Evaluation of Upper Extremity in Stroke: Analysis for Correlation and Responsiveness

ERIC Educational Resources Information Center

Safaz, Ismail; Ylmaz, Bilge; Yasar, Evren; Alaca, Rdvan

2009-01-01

The aim of this study was to find out first whether Brunnstrom recovery stage (BRS) and motricity index (MI) were correlated with each other and second to observe whether the two assessment tools were sensitive to changes regarding the rehabilitation outcome. Forty-six stroke patients who were admitted to the Stroke Rehabilitation Unit at our…

Performance of the Natural Mortality Factors of Aphis gossypii (Hemiptera: Aphididae) as a Function of Cotton Plant Variety and Phenology.

PubMed

Chamuene, António; Araújo, Tamíris Alves; Silva, Gerson; Costa, Thiago Leandro; Berger, Paulo Geraldo; Picanço, Marcelo Coutinho

2018-04-05

Natural mortality factors are responsible for regulating pest populations in the field. However, plant attributes such as the variety and phenological stage can influence the performance of these factors. Therefore, we investigated the performance of the natural mortality factors of Aphis gossypii (Glover; Hemiptera: Aphididae) as a function of the plant variety and phenology. To investigate the performance of these factors, we evaluated the mortality of A. gossypii caused by natural mortality factors for 2 yr in field conditions in transgenic (Bacillus thuringiensis/Roundup Ready) and non-transgenic cotton crops during vegetative, flowering, and fruiting stages. The natural mortality factors were affected similarly between the transgenic and non-transgenic plants; however, differences were observed in their performance, depending on the phenological stage of the cotton plant. Compared with other stages, predation was higher in the flowering stage, whereas the mortality caused by rainfall was higher in the vegetative stage. Coccinellid beetles were primarily responsible for the predation on A. gossypii. These findings highlight that the performance of the natural mortality factors of A. gossypii varied more as a function of the phenological stage of cotton than of the variety.

Differential Effects of Motor Efference Copies and Proprioceptive Information on Response Evaluation Processes

PubMed Central

Stock, Ann-Kathrin; Wascher, Edmund; Beste, Christian

2013-01-01

It is well-kown that sensory information influences the way we execute motor responses. However, less is known about if and how sensory and motor information are integrated in the subsequent process of response evaluation. We used a modified Simon Task to investigate how these streams of information are integrated in response evaluation processes, applying an in-depth neurophysiological analysis of event-related potentials (ERPs), time-frequency decomposition and sLORETA. The results show that response evaluation processes are differentially modulated by afferent proprioceptive information and efference copies. While the influence of proprioceptive information is mediated via oscillations in different frequency bands, efference copy based information about the motor execution is specifically mediated via oscillations in the theta frequency band. Stages of visual perception and attention were not modulated by the interaction of proprioception and motor efference copies. Brain areas modulated by the interactive effects of proprioceptive and efference copy based information included the middle frontal gyrus and the supplementary motor area (SMA), suggesting that these areas integrate sensory information for the purpose of response evaluation. The results show how motor response evaluation processes are modulated by information about both the execution and the location of a response. PMID:23658624

Ethical dilemmas and human rights considerations arising from the evaluation of a smoking policy in a health promoting setting.

PubMed

Harvey, Harold D; Fleming, Paul; Patterson, Michael

2002-09-01

One of the key challenges in managing the Health Promoting Workplace is the development of an effective policy for the control of environmental tobacco smoke (ETS). This paper explores the ethical consequences raised when the implementation of such a policy was evaluated in a large multi-campus university. In a three-stage evaluation, the first stage involved a qualitative enquiry with the Health and Safety Committee to obtain the management perspective on the working of the policy. A survey of the perception of the ETS policy and smoking behaviours with a representative sample of staff and students constituted the second stage. In the final stage the Health and Safety Committee was engaged with the findings of stages 1 and 2 to develop a response to the evaluation. The ethical implications which arise from this evaluation centre, firstly, on the underlying reasons for undertaking an evaluation. Secondly, consideration is given to the consequences of applying utilitarian principles to smoking policy for the minority who smoke and thus find their work or study patterns affected by a smoking ban. Such a ban limits their autonomy and while it may be helpful (beneficent) in terms of their longer-term physical health, it may have harmful (maleficent) effects on their psychological wellbeing and the potential for negative consequences if they choose to contravene the ban on smoking. The implications of addressing this situation are explored.

Positive interaction of social comparison and personal responsibility for outcomes.

PubMed

Grygolec, Jaroslaw; Coricelli, Giorgio; Rustichini, Aldo

2012-01-01

We formulate and test a model that allows sharp separation between two different ways in which environment affects evaluation of outcomes, by comparing social vs. private and personal responsibility vs. chance. In the experiment, subjects chose between two lotteries, one low-risk and one high-risk. They could then observe the outcomes. By varying the environment between private (they could observe the outcome of the chosen lottery and the outcome of the lottery they had not chosen) and social (they could observe the outcome of the lottery chosen by another subject) we can differentiate the response and brain activity following the feedback in social and private settings. The evidence suggests that envy and pride are significant motives driving decisions and outcomes evaluation, stronger than private emotions like regret and rejoice, with ventral striatum playing a key role. When we focus on the outcome evaluation stage we demonstrate that BOLD signal in ventral striatum is increasing in the difference between obtained and counterfactual payoffs. For a given difference in payoffs, striatal responses are more pronounced in social than in private environment. Moreover, a positive interaction (complementarity) between social comparison and personal responsibility is reflected in the pattern of activity in the ventral striatum. At decision stage we observe getting ahead of the Joneses effect in ventral striatum with subjective value of risk larger in social than in private environment.

Age Influence on Sexual Behavior of the Lesser Cornstalk Borer, Elasmopalpus lignosellus (Zeller) (Lepidoptera: Pyralidae).

PubMed

Xavier, L M S; Magalhães, D M; Viana, P A; Blassioli-Moraes, M C; Borges, M; Barrigossi, J A F; Vilela, E F; Laumann, R A

2018-04-01

The objective of this work was to evaluate the reproductive behavior and response of Elasmopalpus lignosellus (Zeller) males to calling females. Frequency of mating was recorded in couples during the first 7 days of the adult stage. Calling behavior of females was observed during the first 4 days of the adult stage and responses of males, in the same age intervals, to calling females were recorded in wind tunnel bioassays. The maximum number of matings occurred when the couple was between 24 and 48 h old. The scotophase period significantly influenced mating behavior, which peaked between 6 and 8 h of darkness and the mean mating duration was 93.9 ± 4.2 min. Calling females, when evaluated in a wind tunnel, attracted significantly more males than in bioassays with clean air (control). The number of individuals in calling behavior was significantly lower for females that were between 0 to 24 h old compared to the other females evaluated, but this did not influence male response. A lower proportion of males between 48 to 72 h old responded to calling females and these responses were delayed in comparison with males of other ages (0 to 24, 24 to 48, and 72 to 96 h old). These results indicate that the age of E. lignosellus males influences the response to conspecific calling females.

Positive Interaction of Social Comparison and Personal Responsibility for Outcomes

PubMed Central

Grygolec, Jaroslaw; Coricelli, Giorgio; Rustichini, Aldo

2012-01-01

We formulate and test a model that allows sharp separation between two different ways in which environment affects evaluation of outcomes, by comparing social vs. private and personal responsibility vs. chance. In the experiment, subjects chose between two lotteries, one low-risk and one high-risk. They could then observe the outcomes. By varying the environment between private (they could observe the outcome of the chosen lottery and the outcome of the lottery they had not chosen) and social (they could observe the outcome of the lottery chosen by another subject) we can differentiate the response and brain activity following the feedback in social and private settings. The evidence suggests that envy and pride are significant motives driving decisions and outcomes evaluation, stronger than private emotions like regret and rejoice, with ventral striatum playing a key role. When we focus on the outcome evaluation stage we demonstrate that BOLD signal in ventral striatum is increasing in the difference between obtained and counterfactual payoffs. For a given difference in payoffs, striatal responses are more pronounced in social than in private environment. Moreover, a positive interaction (complementarity) between social comparison and personal responsibility is reflected in the pattern of activity in the ventral striatum. At decision stage we observe getting ahead of the Joneses effect in ventral striatum with subjective value of risk larger in social than in private environment. PMID:22371706

Ecdysone receptor (EcR) and ultraspiracle (USP) genes from the cyclopoid copepod Paracyclopina nana: Identification and expression in response to water accommodated fractions (WAFs).

PubMed

Puthumana, Jayesh; Lee, Min-Chul; Han, Jeonghoon; Kim, Hui-Su; Hwang, Dae-Sik; Lee, Jae-Seong

2017-02-01

Ecdysteroid hormones are pivotal in the development, growth, and molting of arthropods, and the hormone pathway is triggered by binding ecdysteroid to a heterodimer of the two nuclear receptors; ecdysone receptors (EcR) and ultraspiracle (USP). We have characterized EcR and USP genes, and their 5'-untranslated region (5'-UTR) from the copepod Paracyclopina nana, and studied mRNA transcription levels in post-embryonic stages and in response to water accommodated fractions (WAFs) of crude oil. The open reading frames (ORF) of EcR and USP were 1470 and 1287bp that encoded 490 and 429 amino acids with molecular weight of 121.18 and 105.03kDa, respectively. Also, a well conserved DNA-binding domain (DBD) and ligand-binding domain (LBD) were identified which confirmed by phylogenetic analysis. Messenger RNA transcriptional levels of EcR and USP were developmental stage-specific in early post-embryonic stages (N3-4). However, an evoked expression of USP was observed throughout copepodid stage and in adult females. WAFs (40 and 80%) were acted as an ecdysone agonist in P. nana, and elicited the mRNA transcription levels in adults. Developmental stage-specific transcriptional activation of EcR and USP in response to WAFs was observed. USP gene was down-regulated in the nauplius in response to WAF, whereas up-regulation of USP was observed in the adults. This study represents the first data of molecular elucidation of EcR and USP genes and their regulatory elements from P. nana and the developmental stage specific expression in response to WAFs, which can be used as potential biomarkers for environmental stressors with ecotoxicological evaluations in copepods. Copyright © 2016 Elsevier Inc. All rights reserved.

Investigating Robustness of Item Response Theory Proficiency Estimators to Atypical Response Behaviors under Two-Stage Multistage Testing. ETS GRE® Board Research Report. ETS GRE®-16-03. ETS Research Report No. RR-16-22

ERIC Educational Resources Information Center

Kim, Sooyeon; Moses, Tim

2016-01-01

The purpose of this study is to evaluate the extent to which item response theory (IRT) proficiency estimation methods are robust to the presence of aberrant responses under the "GRE"® General Test multistage adaptive testing (MST) design. To that end, a wide range of atypical response behaviors affecting as much as 10% of the test items…

Importance of positron emission tomography for assessing the response of primary and metastatic lesions to induction treatments in T4 esophageal cancer.

PubMed

Makino, Tomoki; Yamasaki, Makoto; Tanaka, Koji; Tatsumi, Mitsuaki; Takiguchi, Shuji; Hatazawa, Jun; Mori, Masaki; Doki, Yuichiro

2017-10-01

There is no consensus strategy for treatment of T4 esophageal cancer, and because of this, a better evaluation of treatment response is crucial to establish personalized therapies. This study aimed to establish a useful system for evaluating treatment response in T4 esophageal cancer. This study included 130 patients with cT4 esophageal cancer without distant metastasis who underwent 18 F-fluorodeoxyglucose-positron emission tomography before and after a series of induction treatments comprising chemoradiation or chemotherapy. We evaluated the maximal standardized uptake value and treatment response. The mean ± standard deviation of standardized uptake value in the primary tumor before and after induction treatments were 13.8 ± 4.4 and 5.4 ± 4.1, respectively, and the mean standardized uptake value decrease was 58.4%. The most significant difference in survival between positron emission tomography-primary tumor responders and nonresponders was at a decrease of 60% standardized uptake value, based on every 10% stepwise cutoff analysis (2-year cause-specific survival: 60.2 vs 23.5%; hazard ratio = 2.705; P < .0001). With this cutoff value, the resectability (P = .0307), pathologic response (P = .0004), and pT stage (P < .0001) were associated with positron emission tomography-primary tumor response. Univariate analysis of 2-year cause-specific survival indicated a correlation between cause-specific survival and clinical stages according to TNM classification, esophageal perforation, positron emission tomography-primary tumor response, lymph node status evaluated by positron emission tomography before and after induction treatments, and operative resection. Multivariate analysis further identified positron emission tomography-primary tumor response (hazard ratio = 2.354; P = .0107), lymph node status evaluated by positron emission tomography after induction treatments (hazard ratio = 1.966; P = .0089), and operative resection (hazard ratio = 2.012; P = .0245) as independent prognostic predictors. Positron emission tomography evaluation of the response of primary and metastatic lesions to induction treatments is important to formulate treatment strategies for cT4 esophageal cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Stress anisotropy and velocity anisotropy in low porosity shale

NASA Astrophysics Data System (ADS)

Kuila, U.; Dewhurst, D. N.; Siggins, A. F.; Raven, M. D.

2011-04-01

Shales are known for often marked intrinsic anisotropy of many of their properties, including strength, permeability and velocity for example. In addition, it is well known that anisotropic stress fields can also have a significant impact on anisotropy of velocity, even in an isotropic medium. This paper sets out to investigate the ultrasonic velocity response of well-characterised low porosity shales from the Officer Basin in Western Australia to both isotropic and anisotropic stress fields and to evaluate the velocity response to the changing stress field. During consolidated undrained multi-stage triaxial tests on core plugs cut normal to bedding, V pv increases monotonically with increasing effective stress and V s1 behaves similarly although with some scatter. V ph and V sh remain constant initially but then decrease within each stage of the multi-stage test, although velocity from stage to stage at any given differential stress increases. This has the impact of decreasing both P-wave (ɛ) and S-wave anisotropy (γ) through application of differential stress within each loading stage. However, increasing the magnitude of an isotropic stress field has little effect on the velocity anisotropies. The intrinsic anisotropy of the shale remains reasonably high at the highest confining pressures. The results indicate the magnitude and orientation of the stress anisotropy with respect to the shale microfabric has a significant impact on the velocity response to changing stress fields.

Serologic response to a 23-valent pneumococcal vaccine administered prior to autologous stem cell transplantation in patients with multiple myeloma.

PubMed

Hinge, Maja; Ingels, Helene A S; Slotved, Hans-Christian; Mølle, Ingolf

2012-11-01

Patients with multiple myeloma are known to have an increased risk of infections with Streptococcus pneumoniae and vaccination is recommended. We retrospectively investigated the response of a 23-valent polysaccharide-based pneumococcal vaccine in 60 patients with multiple myeloma administered prior to autologous stem cell transplantation (ASCT). Specific antibody titers were measured before and after vaccination. Disease stage was evaluated and associated to the response. We found that 33% of the patients responded to the vaccine. There was a statistic significant association between response to the vaccine and disease stage (p = 0.01). We conclude that vaccination against S. pneumoniae prior to ASCT is reasonable at least in patients responding well to induction therapy, but still it is important to be aware that the response is frequently poor and the duration of it is unknown. © 2012 The Authors APMIS © 2012 APMIS.

Assessment of Stage of Change, Decisional Balance, Self-Efficacy, and Use of Processes of Change of Low-Income Parents for Increasing Servings of Fruits and Vegetables to Preschool-Aged Children

ERIC Educational Resources Information Center

Hildebrand, Deana A.; Betts, Nancy M.

2009-01-01

Objective: Use the Transtheoretical Model of Behavior Change (TTM) to determine the proportionate stage of change of low-income parents and primary caregivers (PPC) for increasing accessibility, measured as servings served, of fruits and vegetables (FV) to their preschool-aged children and evaluate response differences for theoretical constructs.…

ypTNM staging after neoadjuvant chemotherapy in the Chinese gastric cancer population: an evaluation on the prognostic value of the AJCC eighth edition cancer staging system.

PubMed

Li, Ziyu; Wang, Yinkui; Shan, Fei; Ying, Xiangji; Wu, Zhouqiao; Xue, Kan; Miao, Rulin; Zhang, Yan; Ji, Jiafu

2018-05-10

This study aims to evaluate the new ypTNM staging system in Chinese gastric cancer patients. We conducted retrospective survival and regression analyses using a database of gastric cancer patients who underwent neoadjuvant chemotherapy at the Peking University Cancer Hospital and Institute from January 2007 to January 2015. A total of 473 patients were included in the study with 28 pathological complete response (pCR) cases, 3 ypT0N1 cases, 65 stage I cases, 126 stage II cases, and 251 stage III cases. The pCR cases had similar survival to stage I patients (p > 0.05). The 3-year disease-free survival (DFS) and 5-year overall survival (OS) rates of stage I, II and III patients were significantly different (3-year DFS: 89.0, 75.5, and 39.6%, p < 0.001; 5-year OS: 89.6, 65.5, and 36.5%, p = 0.001). Both ypT and ypN are independent predictors of patient survival, while further log-rank tests showed that the ypN stage is of better prognostic value than ypT. Subgrouping analysis revealed that stage III patients of ypT4b and ypN3 had worse survival compared to the rest of stage III cases (p < 0.001). The c-index values of the ypTNM stage and modified ypTNM stage (stage III divided into IIIa and IIIb) were 0.657 and 0.708, respectively (p < 0.001). Our data showed significant differences in survival among gastric cancer patients at different ypTNM stages, indicating its prognostic value in the Chinese population. Further detailed analyses may facilitate the subgrouping of each stage to allow for a more accurate evaluation of disease prognosis in gastric cancer patients.

Vinorelbine and paclitaxel for locoregional advanced or metastatic non-small-cell lung cancer.

PubMed

Pérez, Juan E; Machiavelli, Mario R; Romero, Alberto O; Romero Acuña, Luis A; Domínguez, María E; Fasce, Hebe; Flores Acosta, Luis; Marrone, Nora; Romero Acuña, Juan M; Langhi, Mario J; Amato, Sonia; Bologna, Fabrina; Ortiz, Eduardo H; Leone, Bernardo A; Lacava, Juan A; Vallejo, Carlos T

2002-08-01

A phase II trial was performed to evaluate the efficacy and toxicity of the novel combination of vinorelbine and paclitaxel as first-line chemotherapy in patients with stages IIIB and IV non-small-cell lung cancer. From January 1997 to September 1999, 34 patients (9 stage IIIB and 25 stage IV) received a regimen consisting of the following: vinorelbine 30 mg/m2 20 minutes intravenous (i.v.) infusion, days 1 and 8; and paclitaxel 135 mg/m2 3-hour i.v. (starting 1 hour after vinorelbine) on day 1. Cycles were repeated every 28 days until progression of disease or unacceptable toxicity development. The median age was 57 years (range 41-70 years); median performance status was 1. Histology was as follows: squamous cell in 24 (71%), large cell in 1 (3%), and adenocarcinoma in 9 (26%). All patients are evaluable for toxicity, whereas 30 are evaluable for response (4 patients refused treatment). Objective response was recorded in 4 of 30 patients (13%, 95% CI 1-25%). No complete response was observed. Partial response was recorded in 4 patients (13%), no change in 10 patients (34%), and progressive disease in 16 patients (53%). The median time to treatment failure was 4 months and median survival was 9 months. The limiting toxicity was myelosuppression: leukopenia in 23 patients (68%), whereas neutropenia was observed in 25 patients (78%). Peripheral neurotoxicity developed in 14 patients (41%) (without G3 or G4 episodes), and constipation (G1-G2: 10 patients), myalgia (G1-G2: 11 patients), diarrhea (G1-G2: 7 patients), and stomatitis were observed in 7 patients. Vinorelbine-paclitaxel combination showed only modest activity against locoregionally advanced or metastatic NSCLC.

Value of diffusion-weighted MRI and apparent diffusion coefficient measurements for predicting the response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy.

PubMed

Iannicelli, Elsa; Di Pietropaolo, Marco; Pilozzi, Emanuela; Osti, Mattia Falchetto; Valentino, Maria; Masoni, Luigi; Ferri, Mario

2016-10-01

The aim of our study was to assess the performance value of magnetic resonance imaging (MRI) in the restaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy (CRT) and in the identification of good vs. poor responders to neoadjuvant therapy. A total of 34 patients with locally advanced rectal cancer underwent MRI prior to and after CRT. T stage and tumor regression grade (TRG) on post-CRT MRI was compared with the pathological staging ypT and TRG. Tumor volume and the apparent diffusion coefficient (ADC) were measured using diffusion-weighted imaging (DWI) before and after neoadjuvant CRT; the percentage of tumor volume reduction and the change of ADC (ΔADC) was also calculated. ADC parameters and the percentage of tumor volume reduction were correlated to histopathological results. The diagnostic performance of ADC and volume reduction to assess tumor response was evaluated by calculating the area under the ROC curve and the optimal cut-off values. A significant correlation between the T stage and the TRG defined in DW-MRI after CRT and the ypT and the TRG observed on the surgical specimens was found (p = 0.001; p < 0.001). The mean post-CRT ADC and ΔADC in responder patients was significantly higher compared to non-responder ones (p = 0.001; p = 0.01). Furthermore, the mean post-CRT ADC values were significantly higher in tumors with T-downstage (p = 0.01). DW-MRI may have a significant role in the restaging and in the evaluation of post-CRT response of locally advanced rectal cancer. Quantitative analysis of DWI through ADC map may result in a promising noninvasive tool to evaluate the response to therapy.

Experimental evaluation of reproductive response to climate warming in an oviparous skink.

PubMed

Lu, Hongliang; Wang, Yong; Tang, Wenqi; DU, Weiguo

2013-06-01

The impact of climate warming on organisms is increasingly being recognized. The experimental evaluation of phenotypically plastic responses to warming is a critical step in understanding the biological effects and adaptive capacity of organisms to future climate warming. Oviparous Scincella modesta live in deeply-shaded habitats and they require low optimal temperatures during embryonic development, which makes them suitable subjects for testing the effects of warming on reproduction. We raised adult females and incubated their eggs under different thermal conditions that mimicked potential climate warming. Female reproduction, embryonic development and hatchling traits were monitored to evaluate the reproductive response to warming. Experimental warming induced females to lay eggs earlier, but it did not affect the developmental stage of embryos at oviposition or the reproductive output. The high temperatures experienced by gravid females during warming treatments reduced the incubation period and increased embryonic mortality. The locomotor performance of hatchlings was not affected by the maternal thermal environment, but it was affected by the warming treatment during embryonic development. Our results suggest that climate warming might have a profound effect on fitness-relevant traits both at embryonic and post-embryonic stages in oviparous lizards. © 2012 Wiley Publishing Asia Pty Ltd, ISZS and IOZ/CAS.

The Application of Kohlberg's Moral Development Model to College Students' Technology Ethics Decisions

ERIC Educational Resources Information Center

Kiser, Angelina I. T.; Morrison, Eileen E.; Craven, Annette

2009-01-01

This study examined undergraduate university students' (n=121) responses to six ethical dilemmas within the realm of information technology (IT). Using a framework based on Kohlberg's stages of moral development, the study evaluated the level of moral development as demonstrated in these responses. An apriori coding system was used to analyze the…

Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients With Cutaneous T-Cell Lymphoma

PubMed Central

Piekarz, Richard L.; Frye, Robin; Turner, Maria; Wright, John J.; Allen, Steven L.; Kirschbaum, Mark H.; Zain, Jasmine; Prince, H. Miles; Leonard, John P.; Geskin, Larisa J.; Reeder, Craig; Joske, David; Figg, William D.; Gardner, Erin R.; Steinberg, Seth M.; Jaffe, Elaine S.; Stetler-Stevenson, Maryalice; Lade, Stephen; Fojo, A. Tito; Bates, Susan E.

2009-01-01

Purpose Romidepsin (depsipeptide or FK228) is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. On the basis of observed responses in a phase I trial, a phase II trial of romidepsin in patients with T-cell lymphoma was initiated. Patients and Methods The initial cohort was limited to patients with cutaneous T-cell lymphoma (CTCL), or subtypes mycosis fungoides or Sézary syndrome, who had received no more than two prior cytotoxic regimens. There were no limits on other types of therapy. Subsequently, the protocol was expanded to enroll patients who had received more than two prior cytotoxic regimens. Results Twenty-seven patients were enrolled onto the first cohort, and a total of 71 patients are included in this analysis. These patients had undergone a median of four prior treatments, and 62 patients (87%) had advanced-stage disease (stage IIB, n = 15; stage III, n= 6; or stage IV, n = 41). Toxicities included nausea, vomiting, fatigue, and transient thrombocytopenia and granulocytopenia. Pharmacokinetics were evaluated with the first administration of romidepsin. Complete responses were observed in four patients, and partial responses were observed in 20 patients for an overall response rate of 34% (95% CI, 23% to 46%). The median duration of response was 13.7 months. Conclusion The histone deacetylase inhibitor romidepsin has single-agent clinical activity with significant and durable responses in patients with CTCL. PMID:19826128

Pre- and post-test evaluation of a project to facilitate research development in practice in a hospital setting.

PubMed

Clifford, C; Murray, S

2001-12-01

This paper describes a project designed to facilitate the use of research in nursing practice in one acute hospital. A university team worked in collaboration with staff from the hospital to develop and evaluate the impact of development work designed to enhance knowledge and use of research in practice. A research utilization questionnaire was administered as a pre-test (stage 1); a development phase was implemented (stage 2) and a post-test survey (stage 3) was administered to evaluate the impact of the development work. In stage 1, the total population of nursing and midwifery staff in the hospital (n=473) were targeted and 235 returned the questionnaire, giving a response rate of 50%. Data from the pre-test and focus group discussions with staff were used to plan stage 2 of the project. The development stage involved an educational strand in which open learning research materials were made available to staff, who were also offered tutorial support in their learning. A second strand supported the development of clinical research projects and funds were identified for clinical staff to apply for project development awards to enable them to develop skills in research and development activity under the supervision of a research fellow. Stage 3 involved a post-test survey of staff who had completed the questionnaire in stage 1 (n=81). There were no significant differences in findings between the pre-test and post-test. Qualitative data from those involved in the clinical projects in stage 2 indicated factors impacting on the feasibility of undertaking research in practice.

Malaria vaccines: past, present and future.

PubMed

von Seidlein, Lorenz; Bejon, Philip

2013-12-01

The currently available malaria control tools have allowed malaria elimination in many regions but there remain many regions where malaria control has made little progress. A safe and protective malaria vaccine would be a huge asset for malaria control. Despite the many challenges, efforts continue to design and evaluate malaria vaccine candidates. These candidates target different stages in the life cycle of Plasmodia. The most advanced vaccine candidates target the pre-erythrocytic stages in the life cycle of the parasite and include RTS,S/AS01, which has progressed through clinical development to the stage that it may be licensed in 2015. Attenuated whole-parasite vaccine candidates are highly protective, but there are challenges to manufacture and to administration. Cellular immunity is targeted by the prime-boost approach. Priming vectors trigger only modest responses but these are focused on the recombinant antigen. Boosting vectors trigger strong but broad non-specific responses. The heterologous sequence produces strong immunological responses to the recombinant antigen. Candidates that target the blood stages of the parasite have to result in an immune response that is more effective than the response to an infection to abort or control the infection of merozoites and hence disease. Finally, the sexual stages of the parasite offer another target for vaccine development, which would prevent the transmission of malaria. Today it seems unlikely that any candidate targeting a single antigen will provide complete protection against an organism of the complexity of Plasmodium. A systematic search for vaccine targets and combinations of antigens may be a more promising approach.

Cat-Scratch Disease: A Pitfall for Lymphoma Evaluation by FDG-PET/CT.

PubMed

Dubreuil, Julien; Dony, Arthur; Salles, Gilles; Traverse-Glehen, Alexandra; Giammarile, Francesco; Skanjeti, Andrea

2017-02-01

FDG-PET/CT is a standard of care in staging and response assessment of Hodgkin lymphoma. Hence, it is important to recognize pitfalls owing to the potential therapeutic impact. We report a case of a 29-year-old woman affected by stage III bulky Hodgkin lymphoma. The interim FDG-PET/CT showed a complete metabolic response. After three new cycles of chemotherapy, the patient showed fever and lymphadenopathy at clinic examination, PET/CT revealed several FDG uptakes at lymph nodes in inguinal and iliac region. Pathologic analyses, after biopsy and serologic examinations, led to the diagnosis of cat-scratch disease.

Endoscopic Criteria for Evaluating Tumor Stage after Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer.

PubMed

Han, Kyung Su; Sohn, Dae Kyung; Kim, Dae Yong; Kim, Byung Chang; Hong, Chang Won; Chang, Hee Jin; Kim, Sun Young; Baek, Ji Yeon; Park, Sung Chan; Kim, Min Ju; Oh, Jae Hwan

2016-04-01

Local excision may be an another option for selected patients with markedly down-staged rectal cancer after preoperative chemoradiation therapy (CRT), and proper evaluation of post-CRT tumor stage (ypT) is essential prior to local excision of these tumors. This study was designed to determine the correlations between endoscopic findings and ypT of rectal cancer. In this study, 481 patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection between 2004 and 2013 at a single institution were evaluated retrospectively. Pathological good response (p-GR) was defined as ypT ≤ 1, and pathological minimal or no response (p-MR) as ypT ≥ 2. The patients were randomly classified according to two groups, a testing (n=193) and a validation (n=288) group. Endoscopic criteria were determined from endoscopic findings and ypT in the testing group and used in classifying patients in the validation group as achieving or not achieving p-GR. Based on findings in the testing group, the endoscopic criteria for p-GR included scarring, telangiectasia, and erythema, whereas criteria for p-MR included nodules, ulcers, strictures, and remnant tumors. In the validation group, the kappa statistic was 0.965 (p < 0.001), and the sensitivity, specificity, positive predictive value, and negative predictive value were 0.362, 0.963, 0.654, and 0.885, respectively. The endoscopic criteria presented are easily applicable for evaluation of ypT after preoperative CRT for rectal cancer. These criteria may be used for selection of patients for local excision of down-staged rectal tumors, because patients with p-MR could be easily ruled out.

Dilatation and curettage is more accurate than endometrial aspiration biopsy in early-stage endometrial cancer patients treated with high dose oral progestin and levonorgestrel intrauterine system

PubMed Central

2017-01-01

Objective To determine whether less invasive endometrial (EM) aspiration biopsy is adequately accurate for evaluating treatment outcomes compared to the dilatation and curettage (D&C) biopsy in early-stage endometrial cancer (EC) patients treated with high dose oral progestin and levonorgestrel intrauterine system (LNG-IUS). Methods We conducted a prospective observational study with patients younger than 40 years who were diagnosed with clinical stage IA, The International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid adenocarcinoma and sought to maintain their fertility. The patients were treated with medroxyprogesterone acetate 500 mg/day and LNG-IUS. Treatment responses were evaluated every 3 months. EM aspiration biopsy was conducted after LNG-IUS removal followed D&C. The tissue samples were histologically compared. The diagnostic concordance rate of the two tests was examined with κ statistics. Results Twenty-eight pairs of EM samples were obtained from five patients. The diagnostic concordance rate of D&C and EM aspiration biopsy was 39.3% (κ value=0.26). Of the seven samples diagnosed as normal with D&C, three (42.8%) were diagnosed as normal by using EM aspiration biopsy. Of the eight samples diagnosed with endometrioid adenocarcinoma by using D&C, three (37.5%) were diagnosed with endometrioid adenocarcinoma by using EM aspiration biopsy. Of the 13 complex EM hyperplasia samples diagnosed with the D&C, five (38.5%) were diagnosed with EM hyperplasia by using EM aspiration biopsy. Of the samples obtained through EM aspiration, 46.4% were insufficient for histological evaluation. Conclusion To evaluate the treatment responses of patients with early-stage EC treated with high dose oral progestin and LNG-IUS, D&C should be conducted after LNG-IUS removal. PMID:27670255

Dilatation and curettage is more accurate than endometrial aspiration biopsy in early-stage endometrial cancer patients treated with high dose oral progestin and levonorgestrel intrauterine system.

PubMed

Kim, Da Hee; Seong, Seok Ju; Kim, Mi Kyoung; Bae, Hyo Sook; Kim, Mi La; Yun, Bo Seong; Jung, Yong Wook; Shim, Jeong Yun

2017-01-01

To determine whether less invasive endometrial (EM) aspiration biopsy is adequately accurate for evaluating treatment outcomes compared to the dilatation and curettage (D&C) biopsy in early-stage endometrial cancer (EC) patients treated with high dose oral progestin and levonorgestrel intrauterine system (LNG-IUS). We conducted a prospective observational study with patients younger than 40 years who were diagnosed with clinical stage IA, The International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid adenocarcinoma and sought to maintain their fertility. The patients were treated with medroxyprogesterone acetate 500 mg/day and LNG-IUS. Treatment responses were evaluated every 3 months. EM aspiration biopsy was conducted after LNG-IUS removal followed D&C. The tissue samples were histologically compared. The diagnostic concordance rate of the two tests was examined with κ statistics. Twenty-eight pairs of EM samples were obtained from five patients. The diagnostic concordance rate of D&C and EM aspiration biopsy was 39.3% (κ value=0.26). Of the seven samples diagnosed as normal with D&C, three (42.8%) were diagnosed as normal by using EM aspiration biopsy. Of the eight samples diagnosed with endometrioid adenocarcinoma by using D&C, three (37.5%) were diagnosed with endometrioid adenocarcinoma by using EM aspiration biopsy. Of the 13 complex EM hyperplasia samples diagnosed with the D&C, five (38.5%) were diagnosed with EM hyperplasia by using EM aspiration biopsy. Of the samples obtained through EM aspiration, 46.4% were insufficient for histological evaluation. To evaluate the treatment responses of patients with early-stage EC treated with high dose oral progestin and LNG-IUS, D&C should be conducted after LNG-IUS removal.

Ifosfamide and cisplatin as neoadjuvant chemotherapy for advanced cervical carcinoma.

PubMed

Leone, B; Vallejo, C; Perez, J; Cuevas, M A; Machiavelli, M; Lacava, J; Focaccia, G; Ferreyra, R; Suttora, G; Romero, A; Castaldi, J; Arroyo, A; Rabinovich, M

1996-04-01

A phase II trial was performed to evaluate the efficacy and toxicity of a combination of cisplatin (CDDP) and ifosfamide (IFX) as neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between August 1991 and September 1993, 57 untreated patients with stages IIB to IVA were entered into this study. Median age was 44 years (range, 25 to 74 years). The distribution by stages (International Federation of Gynecology and Obstetrics) was as follows: IIB, 31 patients; IIIB, 21 patients; and IVA, 5 patients. Therapy consisted of IFX 2000 mg/m(2) 1-h i.v. infusion days 1 to 3; mesna 400 mg/m(2) i.v. bolus at hours 0 and 4, and 800 mg p.o. at hour 8; and CDDP 100 mg/m(2) on day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response assessment were performed by a multidisciplinary team. An objective response was observed in 30 of 56 patients (54%; 95% confidence interval, 41 to 67%). Four patients (7%) had a complete response (CR) and 26(46%) had a partial response (PR). Patients with CR or operable PR underwent surgery, otherwise received definitive radiotherapy. Toxicity was mild to moderate. There were no toxicity related deaths. These results indicate that IFX/CDDP is an active combination for ACC with mild toxicity. The results of phase III studies that evaluate the real impact of neoadjuvant chemotherapy are awaited.

Quantifying the effects of research band resighting activities on staging terns in comparison to other disturbances

USGS Publications Warehouse

Althouse, Melissa; Cohen, Jonathan B.; Spendelow, Jeffrey A.; Karpanty, Sarah M.; Davis, Kayla L.; Parsons, Katharine C.; Luttazi, Cristin F.

2016-01-01

Avian research that involves potential disturbance to the study species may have unintended fitness consequences and could lead to biases in measurements of interest. The effects of band resighting on the behavior of mixed-species flocks of staging waterbirds were evaluated against recreational pedestrian activity that was expected to cause flushing. We found a model with additive effects of distance (near, 0-50 m, or far, 50-200 m) and disturbance type (researcher or pedestrian) best explained flock behaviors. The proportion of staging flocks that flushed in response to pedestrians was greatest when pedestrians were within 50 m of the flock. Virtually no flushes were observed in response to researchers, regardless of distance. These results could assist in alleviating concerns that accepted protocols used for intensive band resighting studies on staging seabirds of special conservation status, such as Roseate (Sterna dougallii) and Common (S. hirundo) terns, may have adverse effects. Our framework could be used by others to test the effects of similar research on sensitive species.

Brassinosteroid and gibberellin control of seedling traits in maize (Zea mays L.).

PubMed

Hu, Songlin; Sanchez, Darlene L; Wang, Cuiling; Lipka, Alexander E; Yin, Yanhai; Gardner, Candice A C; Lübberstedt, Thomas

2017-10-01

In this study, we established two doubled haploid (DH) libraries with a total of 207 DH lines. We applied BR and GA inhibitors to all DH lines at seedling stage and measured seedling BR and GA inhibitor responses. Moreover, we evaluated field traits for each DH line (untreated). We conducted genome-wide association studies (GWAS) with 62,049 genome wide SNPs to explore the genetic control of seedling traits by BR and GA. In addition, we correlate seedling stage hormone inhibitor response with field traits. Large variation for BR and GA inhibitor response and field traits was observed across these DH lines. Seedling stage BR and GA inhibitor response was significantly correlate with yield and flowering time. Using three different GWAS approaches to balance false positive/negatives, multiple SNPs were discovered to be significantly associated with BR/GA inhibitor responses with some localized within gene models. SNPs from gene model GRMZM2G013391 were associated with GA inhibitor response across all three GWAS models. This gene is expressed in roots and shoots and was shown to regulate GA signaling. These results show that BRs and GAs have a great impact for controlling seedling growth. Gene models from GWAS results could be targets for seeding traits improvement. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects and safety of mechanical bathing as a complementary therapy for terminal stage cancer patients from the physiological and psychological perspective: a pilot study.

PubMed

Fujimoto, Sawako; Iwawaki, Yoko; Takishita, Yukie; Yamamoto, Yoko; Murota, Masako; Yoshioka, Saori; Hayano, Azusa; Hosokawa, Toyoshi; Yamanaka, Ryuya

2017-11-01

In palliative care hospitals in Japan, mechanical bathing is conducted to maintain cleanliness. However, the physiological and psychological influence of mechanical bathing on patients has not been sufficiently studied. The objective of this study was to assess, using physiological and psychological indices, the effects of mechanical bathing care for patients in the terminal stage of cancer. Mechanical bathing was performed using a Marine Court SB7000 in a supine or semi-seated position. The heart rate variability analysis method was used to measure autonomic nervous system function. The patients' state of anxiety was assessed using the State-Trait Anxiety Inventory (STAI), a psychological index, and patients' verbal responses were also collected after mechanical bathing. Twenty-four patients were enrolled in this study. Their sympathetic and parasympathetic nervous activity did not differ before and after bathing. A significant difference was found between pre- and post-bathing anxiety, as evaluated by STAI (P < 0.0001). In the patient's verbal responses that was collected, the most frequently mentioned descriptors were 'comfortable' and 'relaxed'. Patients were more relaxed after mechanical bathing according to STAI evaluation and their verbal responses. The findings suggest that the method of bathing used in this study is safe and pain-relieving for terminal stage cancer patients. It is thus possible to provide safe and comfortable care for terminal stage cancer patients using mechanical baths. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Imaging Prostate Cancer With Prostate-Specific Membrane Antigen PET/CT and PET/MRI: Current and Future Applications.

PubMed

Hope, Thomas A; Afshar-Oromieh, Ali; Eiber, Matthias; Emmett, Louise; Fendler, Wolfgang P; Lawhn-Heath, Courtney; Rowe, Steven P

2018-06-27

The purpose of this article is to describe the large number of radiotracers being evaluated for prostate-specific membrane antigen (PSMA) PET, which is becoming a central tool in the staging of prostate cancer. PSMA PET is a highly promising modality for the staging of prostate cancer because of its higher detection rate compared with that of conventional imaging. Both PET/CT and PET/MRI offer benefits with PSMA radiotracers, and PSMA PET findings frequently lead to changes in management. It is imperative that subsequent treatment changes be evaluated to show improved outcomes. PSMA PET also has potential applications, including patient selection for PSMA-based radioligand therapy and evaluation of treatment response.

Docetaxel as neoadjuvant chemotherapy in patients with advanced cervical carcinoma.

PubMed

Vallejo, Carlos T; Machiavelli, Mario R; Pérez, Juan E; Romero, Alberto O; Bologna, Fabrina; Vicente, Hernán; Lacava, Juan A; Ortiz, Eduardo H; Cubero, Alberto; Focaccia, Guillermo; Suttora, Guillermo; Scenna, Mirna; Boughen, José M; Leone, Bernardo A

2003-10-01

The purpose of this study was to evaluate the efficacy and toxicity of docetaxel as single-agent neoadjuvant chemotherapy in locoregionally advanced cervical carcinoma. Between April 1998 and August 2000, 38 untreated patients with International Federation of Gynecology and Obstetrics stages IIB to IVA were entered onto this study. The median age was 44 years (range: 25-66 years). Stages: IIB 22 patients, IIIB 15 patients, and IVA 1 pt. Treatment consisted of docetaxel 100 mg/m2 IV infusion during 1 hour. Standard premedication with dexamethasone, diphenhydramine, and ranitidine was used. Cycles were repeated every 3 weeks for three courses, followed by radical surgery when it was judged appropriate, or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. 106 cycles of therapy were administered; all patients were evaluable for TX, whereas 35 were evaluable for response (3 patients refused further treatment after the first cycle of therapy). Complete response (CR): 1 patient (3%); partial response: 11 patients (31%), for an overall objective response rate of 34% (95% CI: 15-53%); no change (NC): 16 patients (46%); and progressive disease: 7 patients (20%). Six patients (17%) underwent surgery and a pathologic CR was confirmed in 1 of them. The median time to treatment failure and the median survival have not been reached yet. The limiting toxicity was leukopenia in 25 patients (69%) (G1-G2: 14 patients, G3: 10 patients, and G4: 1 patient). Neutropenia: 28 patients (78%) (G1-G2: 10 patients, G3: 8 and G4: 10). Myalgias: 17 patients (47%) (G1-G2: 15 patients and G3: 2 patients). Emesis: 21 patients (55%) (G1-G2: 19 patients and G3: 2 patients). Alopecia G3: 13 patients (36%); rash cutaneous 26 patients (68%) (G1-G2: 22 patients and G3: 4 patients). There were no hypersensitivity reactions or fluid-retention syndrome. The received dose intensity was 91% of that projected. Docetaxel is an active drug against advanced cervical carcinoma with moderate toxicity. Further evaluation in association with other agents is clearly justified.

Design requirements for SRB production control system. Volume 3: Package evaluation, modification and hardware

NASA Technical Reports Server (NTRS)

1981-01-01

The software package evaluation was designed to analyze commercially available, field-proven, production control or manufacturing resource planning management technology and software package. The analysis was conducted by comparing SRB production control software requirements and conceptual system design to software package capabilities. The methodology of evaluation and the findings at each stage of evaluation are described. Topics covered include: vendor listing; request for information (RFI) document; RFI response rate and quality; RFI evaluation process; and capabilities versus requirements.

Protein extraction and gel-based separation methods to analyze responses to pathogens in carnation (Dianthus caryophyllus L).

PubMed

Ardila, Harold Duban; Fernández, Raquel González; Higuera, Blanca Ligia; Redondo, Inmaculada; Martínez, Sixta Tulia

2014-01-01

We are currently using a 2-DE-based proteomics approach to study plant responses to pathogenic fungi by using the carnation (Dianthus caryophyllus L)-Fusarium oxysporum f. sp. dianthi pathosystem. It is clear that the protocols for the first stages of a standard proteomics workflow must be optimized to each biological system and objectives of the research. The optimization procedure for the extraction and separation of proteins by 1-DE and 2-DE in the indicated system is reported. This strategy can be extrapolated to other plant-pathogen interaction systems in order to perform an evaluation of the changes in the host protein profile caused by the pathogen and to identify proteins which, at early stages, are involved or implicated in the plant defense response.

Evacuation behavior and Three Mile Island.

PubMed

Cutter, S; Barnes, K

1982-06-01

The responses of the residents to the nuclear power plant arcident at Three Mile Island, Pennsylvania illustrate the factors influencing pre-impact coping responses of populations exposed to technological hazards. Confusion itnd ambiguous information influenced both the decision to evaluate and to remain in place. Proximity to the facility, stage in life cycle and the actions of friends and neighbors influenced the decision to evacuate.

Genotypic variation in response to salinity in a new sexual germplasm of Cenchrus ciliaris L.

PubMed

Quiroga, Mariana; Tommasino, Exequiel; Griffa, Sabrina; Ribotta, Andrea; Colomba, Eliana López; Carloni, Edgardo; Grunberg, Karina

2016-05-01

As part of a breeding program for new salt-tolerant sexual genotypes of Cenchrus ciliaris L., here we evaluated the salt-stress response of two new sexual hybrids, obtained by controlled crosses, at seedling and germination stages. A seedling hydroponic experiment with 300 mM NaCl was performed and physiological variables and growth components were evaluated. While salt-treated sexual material did not show a decrease in productivity with respect to control plants, a differential response in some physiological characteristics was observed. Sexual hybrid 1-9-1 did not suffer oxidative damage and its proline content did not differ from that of control treatment. By contrast, sexual hybrid 1-7-11 suffered oxidative damage and accumulated proline, maintaining its growth under saline stress. At the germination stage, sexual hybrid 1-9-1 presented the highest Germination Rate Index at the maximum NaCl concentration assayed, suggesting an ecological advantage in this genotype. These new sexual resources are promising maternal parental with differential response to salt and could be incorporated in a breeding program of C. ciliaris in the search of new genotypes tolerant to salinity. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Do the conventional clinicopathologic parameters predict for response and survival in head and neck cancer patients undergoing neoadjuvant chemotherapy?

PubMed

Fonseca, E; Cruz, J J; Dueñas, A; Gómez, A; Sánchez, P; Martín, G; Nieto, A; Soria, P; Muñoz, A; Gómez, J L; Pardal, J L

1996-01-01

Neoadjuvant chemotherapy for head and neck carcinoma is still an important treatment modality. The prognostic value of patient and tumor parameters has been extensively evaluated in several trials, yielding mixed results. We report the prognostic factors emerging from a group of patients undergoing neoadjuvant chemotherapy. From April 1986 to June 1992, 149 consecutive patients received cisplatin-5-fluorouracil-based neoadjuvant chemotherapy. After four courses of chemotherapy, patients underwent local-regional treatment with surgery, radiation or both. A variety of patient and tumor characteristics were evaluated as predictors for response to chemotherapy and survival. The complete response, partial response and no response rates to NAC were 52%, 33% and 15%, respectively. No parameters predicted response to chemotherapy. At a maximum follow-up of 87 months, overall survival was 39% and disease-free survival was 49%. Variables shown to be predictors of survival in univariate analyses were age, performance status, histology, site, T, N, stage, and response to chemotherapy. Using the Cox regression analysis, only complete response to induction chemotherapy (P = 0.0006), performance status (P = 0.03), stage (P = 0.01), age (P = 0.03) and primary tumor site (P = 0.04) emerged as independent prognostic factors for survival. Complete response to chemotherapy was confirmed as the strongest prognostic factor influencing survival. However, conventional clinicopathologic factors did not predict response, hence, potential prognostic biologic and molecular factors for response must be sought. At present, much effort must be made for the improvement of the complete response rate, which seems to be a requisite to prolong survival.

Role of endoscopic ultrasonography in the staging and follow-up of esophageal cancer.

PubMed

Lightdale, Charles J; Kulkarni, Ketan G

2005-07-10

To evaluate the role of endoscopic ultrasonography (EUS) in the initial staging and follow-up of esophageal cancer on the basis of a review of the published literature. Articles published from 1985 to 2005 were searched and reviewed using the following keywords: "esophageal cancer staging," "endoscopic ultrasound," and "endoscopic ultrasonography." For initial anatomic staging, EUS results have consistently shown more than 80% accuracy compared with surgical pathology for depth of tumor invasion (T). Accuracy increased with higher stage, and was >90% for T3 cancer. EUS results have shown accuracy in the range of 75% for initial staging of regional lymph nodes (N). EUS has been invariably more accurate than computed tomography for T and N staging. EUS is limited for staging distant metastases (M), and therefore EUS is usually performed after a body imaging modality such as computed tomography or positron emission tomography. Pathologic staging can be achieved at EUS using fine-needle aspiration (FNA) to obtain cytology from suspect Ns. FNA has had greatest efficacy in confirming celiac axis lymph node metastases with more than 90% accuracy. EUS is inaccurate for staging after radiation and chemotherapy because of inability to distinguish inflammation and fibrosis from residual cancer, but a more than 50% decrease in tumor cross-sectional area or diameter has been found to correlate with treatment response. EUS has a central role in the initial anatomic staging of esophageal cancer because of its high accuracy in determining the extent of locoregional disease. EUS is inaccurate for staging after radiation therapy and chemotherapy, but can be useful in assessing treatment response.

An evaluation of corn earworm damage and thresholds in soybean

NASA Astrophysics Data System (ADS)

Adams, Brian Patrick

Interactions between corn earworm, Helicoverpa zea (Boddie), and soybean, Glycine max L. (Merrill), were investigated in the Mid-South to evaluate thresholds and damage levels. Field studies were conducted in both indeterminate and determinate modern cultivars to evaluate damage, critical injury levels, and soybean response to simulated corn earworm injury. Field studies were also conducted to evaluate the response of indeterminate cultivars to infestations of corn earworm. Field studies were also conducted to investigate the relationship between pyrethroid insecticide application and corn earworm oviposition in soybean. Results of field studies involving simulated corn earworm damage indicated the need for a dynamic threshold that becomes more conservative as soybean phenology progressed through the reproductive growth stages. This suggested that soybean was more tolerant to fruit loss during the earlier reproductive stages and was able to compensate for fruit loss better during this time than at later growth stages. Results of field studies involving infestations of corn earworm indicated that current thresholds are likely too liberal. This resulted in economic injury level tables being constructed based upon a range of crop values and control costs, however, a general action threshold was also recommended for indeterminate soybean in the Mid-South. Field study results investigating the relationship of pyrethroid application and corn earworm oviposition indicated that even in the presence of an insecticide, corn earworm prefers to oviposit in the upper portion of the canopy, as well as on the leaves as opposed to all other plant parts, consistent with all previous literature.

Outcome Study of Cobalt Based Stereotactic Body Radiation Therapy for Patients with Inoperable Stage III Non-small Cell Lung Cancer.

PubMed

Wang, Yingjie; Lan, Fengming; Kang, Xiaoli; Shao, Yinjian; Li, Hongqi; Li, Ping; Wu, Weizhang; Wang, Jidong; Chang, Dongshu; Wang, Yong; Xia, Tingyi

2015-10-01

Aim of this paper is to retrospectively evaluate the efficacy and toxicity of specialized Body Cobalt based system (BCBS) treatment in the senior patients group (.65 years) with Stage III non-small cell lung carcinoma (NSCLC). A total of 49 patients (41 males and 8 females) with Stage III NSCLC according to UICC TNM classification (6(th) edition) were treated using OUR-QGD™ BCBS which was designed and manufactured in China. Post treatment evaluation with follow-up information was collected from April 2001 to December 2006 in our department. Median age of enrolled patients was 71 years old (65-85). Among those patients, 36 patients were pathologically identified with squamous cell carcinoma, and the other 13 patients were confirmed as adenocarcinoma. All patients were immobilized by vacuum based immobilization mold and then performed slow CT scan without any respiration gating devices. The daily radiation prescription dose was defined at 50% isodose line covering primary lesions and metastatic lymph nodes with doses from 2.5 to 6 Gy in 5 fractions per week according to the tumor stage and internally approved treatment protocols by the Institutional Review Board (IRB). Median daily dose and total delivery dose of 50% isodose line were 4 Gy and 41 Gy, respectively. In this study group, total of 3 patients received neoadjuvant cisplatin-based chemotherapy. Tumor response evaluated 12 weeks after radiation has demonstrated 13 complete responses (26.5%), 21 partial responses (42.9%). The overall survival (OS) rate of 1-year, 2-year and 3-year was 63.3%, 40.8% and 20.4%, respectively. The median and mean survival time was 22 and 24 months. All 49 patients tolerated the treatment well and have completed the planned therapy regiment. Body Cobalt based system treatment of those over 65 years old patients with Stage III NSCLC had reasonable and superior curative effect as well as local control, and at the same time without severe radiation side effects. © The Author(s) 2014.

The Role of Epigenomics in Aquatic Toxicology

EPA Science Inventory

Over the past decade, the field of molecular biology has rapidly incorporated epigenetic studies to evaluate organism–environment interactions that can result in chronic effects. Such responses arise from early life stage stress, the utilization of genetic information over ...

77 FR 34047 - Medicare Program; Proposal Evaluation Criteria and Standards for End Stage Renal Disease (ESRD...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-08

... by section 1881(c)(2) of the Act. These functions are to: Encourage participation in vocational... strives to promote health care that is respectful of and responsive to individual patient preferences...

Phase II study of everolimus in children and adults with neurofibromatosis type 2 and progressive vestibular schwannomas

PubMed Central

Karajannis, Matthias A.; Legault, Geneviève; Hagiwara, Mari; Giancotti, Filippo G.; Filatov, Alexander; Derman, Anna; Hochman, Tsivia; Goldberg, Judith D.; Vega, Emilio; Wisoff, Jeffrey H.; Golfinos, John G.; Merkelson, Amanda; Roland, J. Thomas; Allen, Jeffrey C.

2014-01-01

Background Activation of the mammalian target of rapamycin (mTOR) signaling pathway is thought to be a key driver of tumor growth in Merlin (NF2)-deficient tumors. Everolimus is an oral inhibitor of mTOR complex 1 (mTORC1) with antitumor activity in a variety of cancers. Methods We conducted a single-institution, prospective, 2-stage, open-label phase II study to estimate the response rate to everolimus in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannoma (VS). Ten eligible patients were enrolled, including 2 pediatric patients. Everolimus was administered at a daily dose of 10 mg (adults) or 5 mg/m2/day (children <18 y) orally in continuous 28-day courses, for up to 12 courses. Response was assessed every 3 months with MRI, using 3-dimensional volumetric tumor analysis, and audiograms. Nine patients were evaluable for the primary response, defined as ≥15% decrease in VS volume. Hearing response was evaluable as a secondary endpoint in 8 patients. Results None of the 9 patients with evaluable disease experienced a clinical or MRI response. No objective imaging or hearing responses were observed in stage 1 of the trial, and the study was closed according to predefined stopping rules. Conclusion Everolimus is ineffective for the treatment of progressive VS in NF2 patients. We are currently conducting a pharmacokinetic/pharmacodynamic (“phase 0”) study of everolimus in presurgical VS patients to elucidate the biological basis for apparent treatment resistance to mTORC1 inhibition in these tumors. PMID:24311643

Online two-stage association method for robust multiple people tracking

NASA Astrophysics Data System (ADS)

Lv, Jingqin; Fang, Jiangxiong; Yang, Jie

2011-07-01

Robust multiple people tracking is very important for many applications. It is a challenging problem due to occlusion and interaction in crowded scenarios. This paper proposes an online two-stage association method for robust multiple people tracking. In the first stage, short tracklets generated by linking people detection responses grow longer by particle filter based tracking, with detection confidence embedded into the observation model. And, an examining scheme runs at each frame for the reliability of tracking. In the second stage, multiple people tracking is achieved by linking tracklets to generate trajectories. An online tracklet association method is proposed to solve the linking problem, which allows applications in time-critical scenarios. This method is evaluated on the popular CAVIAR dataset. The experimental results show that our two-stage method is robust.

Estimation of Supersonic Stage Separation Aerodynamics of Winged-Body Launch Vehicles Using Response Surface Methods

NASA Technical Reports Server (NTRS)

Erickson, Gary E.; Deloach, Richard

2008-01-01

A collection of statistical and mathematical techniques referred to as response surface methodology was used to estimate the longitudinal stage separation aerodynamic characteristics of a generic, bimese, winged multi-stage launch vehicle configuration using data obtained on small-scale models at supersonic speeds in the NASA Langley Research Center Unitary Plan Wind Tunnel. The simulated Mach 3 staging was dominated by multiple shock wave interactions between the orbiter and booster vehicles throughout the relative spatial locations of interest. This motivated a partitioning of the overall inference space into several contiguous regions within which the separation aerodynamics were presumed to be well-behaved and estimable using cuboidal and spherical central composite designs capable of fitting full second-order response functions. The primary goal was to approximate the underlying overall aerodynamic response surfaces of the booster vehicle in belly-to-belly proximity to the orbiter vehicle using relatively simple, lower-order polynomial functions that were piecewise-continuous across the full independent variable ranges of interest. The quality of fit and prediction capabilities of the empirical models were assessed in detail, and the issue of subspace boundary discontinuities was addressed. The potential benefits of augmenting the central composite designs to full third order using computer-generated D-optimality criteria were also evaluated. The usefulness of central composite designs, the subspace sizing, and the practicality of fitting low-order response functions over a partitioned inference space dominated by highly nonlinear and possibly discontinuous shock-induced aerodynamics are discussed.

Comparison of prehatch C-start responses in rainbow trout and lake trout embryos by means of a tactile stimulus test

USGS Publications Warehouse

Wright, P.J.; Noltie, Douglas B.; Tillitt, D.E.

2003-01-01

The C-start in teleost fishes, a type of startle response, mediates the ability to respond to abrupt, unexpected stimuli and is characterized by a short-latency, C-type fast start acceleration. In prehatch fish embryos, the C-start appears necessary for mechanical breakdown of the egg chorion and successful hatching by way of increased embryo movement and distribution of the hatching enzymes. In later stages, the C-start plays an important role in predator avoidance. Using tactile stimulation, we evaluated the C-start response in rainbow trout Oncorhynchus mykiss at 170 degree-days, when 6.6% of embryos exhibited C-starts, and lake trout Salvelinus namaycush embryos at 320 degree-days, when 23% of embryos exhibited C-starts. Triplicate groups of embryos were later tested at three developmental stages: early (220 and 360 degree-days for rainbow trout and lake trout, respectively), middle (260 and 480 degree-days, respectively), and late (320 and 560 degree-days, respectively). The proportion of trout embryos exhibiting C-start increased through time, such that 100% had responded by the late stage, just prior to hatching. C-starts could be obtained by repeated stimulation, and the relative activity of the embryos (based on the number of flexures per stimulus) also increased over time. Rainbow trout and lake trout showed very similar C-start responses at parallel developmental stages, and these patterns of response were similar to those reported in other fish species.

Reactive oxygen species initiate a protective response in plant roots to stress induced by environmental bisphenol A.

PubMed

Zhang, Jiazhi; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

2018-06-15

Bisphenol A (BPA), a contaminant of emerging concern, can affect plant growth and development at high concentrations. Reactive oxygen species (ROS) production is a general primary response in plants to stress. Here, the aim is to investigate whether ROS in plants play protective roles for stress induced by BPA exposure at environmental concentrations. In this study, soybean roots (seedling, flowering and podding stages) were exposed to 1.5 and 3.0 mg L -1 BPA, and ROS response was measured. The relationship between ROS levels and residual BPA content in soybean roots was evaluated. The results showed that exposure (9 h) to 1.5 mg L -1 BPA elicited changes in ROS production. ROS then gradually accumulated in soybean roots (seedling stage). Exposure to 3.0 mg L -1 BPA elicited a stronger and earlier ROS responses at the flowering and podding stage, but did not lead to membrane lipid peroxidation. Residual BPA content in soybean roots reached peak concentrations after 9 h of exposure, and then gradually decreased at the flowering and podding stage. These results indicate that ROS in soybean roots might be involved in the oxidative metabolism of BPA, which could prevent BPA from damaging exposed plants. In conclusion, the observed ROS metabolic effects may be self-protection responses of plants to stress induced by BPA exposure. Copyright © 2018 Elsevier Inc. All rights reserved.

TLR and IMD signaling pathways from Caligus rogercresseyi (Crustacea: Copepoda): in silico gene expression and SNPs discovery.

PubMed

Valenzuela-Muñoz, V; Gallardo-Escárate, C

2014-02-01

The Toll and IMD signaling pathways represent one of the first lines of innate immune defense in invertebrates like Drosophila. However, for crustaceans like Caligus rogercresseyi, there is very little genomic information and, consequently, understanding of immune mechanisms. Massive sequencing data obtained for three developmental stages of C. rogercresseyi were used to evaluate in silico the expression patterns and presence of SNPs variants in genes involved in the Toll and IMD pathways. Through RNA-seq analysis, which used 20 contigs corresponding to relevant genes of the Toll and IMD pathways, an overexpression of genes linked to the Toll pathway, such as toll3 and Dorsal, were observed in the copepod stage. For the chalimus and adult stages, overexpression of genes in both pathways, such as Akirin and Tollip and IAP and Toll9, respectively, were observed. On the other hand, PCA statistical analysis inferred that in the chalimus and adult stages, the immune response mechanism was more developed, as evidenced by a relation between these two stages and the genes of both pathways. Moreover, 136 SNPs were identified for 20 contigs in genes of the Toll and IMD pathways. This study provides transcriptomic information about the immune response mechanisms of Caligus, thus providing a foundation for the development of new control strategies through blocking the innate immune response. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prioritizing guideline topics: development and evaluation of a practical tool.

PubMed

Ketola, Eeva; Toropainen, Erja; Kaila, Minna; Luoto, Riitta; Mäkelä, Marjukka

2007-08-01

A clear process for selecting and adopting clinical practice guidelines in the new topic areas is needed. The aim of this study is to design and develop a practical tool to assess guideline topics that have been suggested to the organization responsible for producing guidelines. We carried out an iterative development, feasibility and validation study of a guideline topic prioritization tool. The setting included the guideline producer organization and the tax-funded health care system. In the first stage of the tool development, participants were researchers, members of the Current Care Board and experts from health care organizations. In the second stage, the evaluation was done internally within the project by three independent reviewers. The main outcome measures were responses to an evaluation questionnaire, qualitative process feedback and analysis of the performance of the instrument on a random set of guidelines. Evaluations by three independent reviewers revealed good agreement and face validity with respect to its feasibility as a planning tool at the guideline board level. Feedback from board members suggested that the instrument is useful in prioritizing guideline topics. This instrument was accepted for use by the Board. Further developments are needed to ensure feedback and acceptability of the instrument by those proposing topics.

Evaluation of a Web-Based App Demonstrating an Exclusionary Algorithmic Approach to TNM Cancer Staging

PubMed Central

2015-01-01

Background TNM staging plays a critical role in the evaluation and management of a range of different types of cancers. The conventional combinatorial approach to the determination of an anatomic stage relies on the identification of distinct tumor (T), node (N), and metastasis (M) classifications to generate a TNM grouping. This process is inherently inefficient due to the need for scrupulous review of the criteria specified for each classification to ensure accurate assignment. An exclusionary approach to TNM staging based on sequential constraint of options may serve to minimize the number of classifications that need to be reviewed to accurately determine an anatomic stage. Objective Our aim was to evaluate the usability and utility of a Web-based app configured to demonstrate an exclusionary approach to TNM staging. Methods Internal medicine residents, surgery residents, and oncology fellows engaged in clinical training were asked to evaluate a Web-based app developed as an instructional aid incorporating (1) an exclusionary algorithm that polls tabulated classifications and sorts them into ranked order based on frequency counts, (2) reconfiguration of classification criteria to generate disambiguated yes/no questions that function as selection and exclusion prompts, and (3) a selectable grid of TNM groupings that provides dynamic graphic demonstration of the effects of sequentially selecting or excluding specific classifications. Subjects were asked to evaluate the performance of this app after completing exercises simulating the staging of different types of cancers encountered during training. Results Survey responses indicated high levels of agreement with statements supporting the usability and utility of this app. Subjects reported that its user interface provided a clear display with intuitive controls and that the exclusionary approach to TNM staging it demonstrated represented an efficient process of assignment that helped to clarify distinctions between tumor, node, and metastasis classifications. High overall usefulness ratings were bolstered by supplementary comments suggesting that this app might be readily adopted for use in clinical practice. Conclusions A Web-based app that utilizes an exclusionary algorithm to prompt the assignment of tumor, node, and metastasis classifications may serve as an effective instructional aid demonstrating an efficient and informative approach to TNM staging. PMID:28410163

Effect of low-level copper and pentachlorophenol exposure on various early life stages of Xenopus laevis

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

Fort, D.J.; Stover, E.L.

1996-12-31

An evaluation of the effects of low-level copper and pentachlorophenol exposure on various early life stages of the South African clawed frog, Xenopus laevis, was performed using stage-specific and long-term continuous exposures. Stage-specific exposure experiments were conducted such that separate subsets of embryos and larvae from the same clutch were exposed to two toxicants, copper and pentachlorphenol, from 0 d to 4 d (standard Frog Embryo Teratogenesis Assay--Xenopus [FETAX]), 4 d to 8 d, 8 d to 12 d, and 12 d to 16 d. Results from two separate concentration-response experiments indicated that sensitivity to either toxicant increased in eachmore » successive time period. Longer-term exposure studies conducted for 60 to 75 days indicated that copper, but not pentachlorophenol induced reduction deficiency malformations of the hind limb at concentrations as low as 0.05 mg/L. Pentachlorophenol concentrations as low as 0.5 {micro}g/L inhibited tail resorption. However, copper did not adversely affect the process of tail resorption. These results indicated that studies evaluating longer-term developmental processes are important in ecological hazard evaluation.« less

Effect of chronic copper and pentachlorophenol exposure to early life stages of Xenopus laevis

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

Fort, D.J.; Stover, E.L.

1995-12-31

An evaluation of the effects of low-level copper and pentachlorophenol exposure on various early life stages of the South African clawed frog, Xenopus laevis was performed using stage-specific and long-term continuous exposures. Stage-specific exposure experiments were conducted such that separate subsets of embryos and larvae from the same clutch were exposed to two toxicants, copper and pentachlorophenol, from 0 d to 4 d (standard Frog Embryo Teratagenesis Assay Xenopus [FETAX]), 4 d to 8 d, 8 d to 12 d, and 12 d to 16 d. Results from two separate concentration-response experiments indicated that sensitivity to either toxicant increased inmore » each successive time period. Continuous exposure studies conducted for 60 to 75 days indicated that copper, but not pentachlorophenol induced reduction deficiency malformations of the hind limb at concentrations as low as 0.05 mg/L. Pentachlorophenol concentrations as low as 0.5/{micro}g/L inhibited tail resorption. However, copper did not adversely affect the process of tail resorption. These results indicated that studies evaluating longer-term developmental processes are important in ecological hazard evaluation.« less

The Trophic Life Cycle Stage of the Opportunistic Fungal Pathogen Pneumocystis murina Hinders the Ability of Dendritic Cells To Stimulate CD4+ T Cell Responses

PubMed Central

Evans, Heather M.; Simpson, Andrew; Shen, Shu; Stromberg, Arnold J.; Pickett, Carol L.

2017-01-01

ABSTRACT The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists of a trophic stage and an ascus-like cystic stage. Infection with the cyst stage induces proinflammatory immune responses, while trophic forms suppress the cytokine response to multiple pathogen-associated molecular patterns (PAMPs), including β-glucan. A targeted gene expression assay was used to evaluate the dendritic cell response following stimulation with trophic forms alone, with a normal mixture of trophic forms and cysts, or with β-glucan. We demonstrate that stimulation with trophic forms downregulated the expression of multiple genes normally associated with the response to infection, including genes encoding transcription factors. Trophic forms also suppressed the expression of genes related to antigen processing and presentation, including the gene encoding the major histocompatibility complex (MHC) class II transactivator, CIITA. Stimulation of dendritic cells with trophic forms, but not a mixture of trophic forms and cysts, reduced the expression of MHC class II and the costimulatory molecule CD40 on the surface of the cells. These defects in the expression of MHC class II and costimulatory molecules corresponded with a reduced capacity for trophic form-loaded dendritic cells to stimulate CD4+ T cell proliferation and polarization. These data are consistent with the delayed innate and adaptive responses previously observed in immunocompetent mice inoculated with trophic forms compared to responses in mice inoculated with a mixture of trophic forms and cysts. We propose that trophic forms broadly inhibit the ability of dendritic cells to fulfill their role as antigen-presenting cells. PMID:28694293

Auditorium acoustics evaluation based on simulated impulse response

NASA Astrophysics Data System (ADS)

Wu, Shuoxian; Wang, Hongwei; Zhao, Yuezhe

2004-05-01

The impulse responses and other acoustical parameters of Huangpu Teenager Palace in Guangzhou were measured. Meanwhile, the acoustical simulation and auralization based on software ODEON were also made. The comparison between the parameters based on computer simulation and measuring is given. This case study shows that auralization technique based on computer simulation can be used for predicting the acoustical quality of a hall at its design stage.

Apply radiomics approach for early stage prognostic evaluation of ovarian cancer patients: a preliminary study

NASA Astrophysics Data System (ADS)

Danala, Gopichandh; Wang, Yunzhi; Thai, Theresa; Gunderson, Camille; Moxley, Katherine; Moore, Kathleen; Mannel, Robert; Liu, Hong; Zheng, Bin; Qiu, Yuchen

2017-03-01

Predicting metastatic tumor response to chemotherapy at early stage is critically important for improving efficacy of clinical trials of testing new chemotherapy drugs. However, using current response evaluation criteria in solid tumors (RECIST) guidelines only yields a limited accuracy to predict tumor response. In order to address this clinical challenge, we applied Radiomics approach to develop a new quantitative image analysis scheme, aiming to accurately assess the tumor response to new chemotherapy treatment, for the advanced ovarian cancer patients. During the experiment, a retrospective dataset containing 57 patients was assembled, each of which has two sets of CT images: pre-therapy and 4-6 week follow up CT images. A Radiomics based image analysis scheme was then applied on these images, which is composed of three steps. First, the tumors depicted on the CT images were segmented by a hybrid tumor segmentation scheme. Then, a total of 115 features were computed from the segmented tumors, which can be grouped as 1) volume based features; 2) density based features; and 3) wavelet features. Finally, an optimal feature cluster was selected based on the single feature performance and an equal-weighed fusion rule was applied to generate the final predicting score. The results demonstrated that the single feature achieved an area under the receiver operating characteristic curve (AUC) of 0.838+/-0.053. This investigation demonstrates that the Radiomic approach may have the potential in the development of high accuracy predicting model for early stage prognostic assessment of ovarian cancer patients.

Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide a for cancer of the oral cavity.

PubMed

Rigual, Nestor; Shafirstein, Gal; Cooper, Michele T; Baumann, Heinz; Bellnier, David A; Sunar, Ulas; Tracy, Erin C; Rohrbach, Daniel J; Wilding, Gregory; Tan, Wei; Sullivan, Maureen; Merzianu, Mihai; Henderson, Barbara W

2013-12-01

The primary objective was to evaluate safety of 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction. Patients with histologically proven oral dysplasia, carcinoma in situ, or early-stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies used an HPPH dose of 4 mg/m(2) and light doses from 50 to 140 J/cm(2). Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of STAT3 were assessed as potential indicators of PDT effective reaction. Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and carcinoma in situ and 82% for squamous cell carcinomas (SCC) lesions at 140 J/cm(2). The responses in the carcinoma in situ/dysplasia cohort are not durable. The PDT-induced STAT3 cross-links is significantly higher (P = 0.0033) in SCC than in carcinoma in situ/dysplasia for all light doses. HPPH-PDT is safe for the treatment of carcinoma in situ/dysplasia and early-stage cancer of the oral cavity. Early-stage oral HNSCC seems to respond better to HPPH-PDT in comparison with premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT-mediated photoreaction. ©2013 AACR.

Single- versus dual-process models of lexical decision performance: insights from response time distributional analysis.

PubMed

Yap, Melvin J; Balota, David A; Cortese, Michael J; Watson, Jason M

2006-12-01

This article evaluates 2 competing models that address the decision-making processes mediating word recognition and lexical decision performance: a hybrid 2-stage model of lexical decision performance and a random-walk model. In 2 experiments, nonword type and word frequency were manipulated across 2 contrasts (pseudohomophone-legal nonword and legal-illegal nonword). When nonwords became more wordlike (i.e., BRNTA vs. BRANT vs. BRANE), response latencies to nonwords were slowed and the word frequency effect increased. More important, distributional analyses revealed that the Nonword Type = Word Frequency interaction was modulated by different components of the response time distribution, depending on the specific nonword contrast. A single-process random-walk model was able to account for this particular set of findings more successfully than the hybrid 2-stage model. (c) 2006 APA, all rights reserved.

Efficacy of Icotinib treatment in patients with stage IIIb/IV non-small cell lung cancer.

PubMed

Qin, Na; Yang, Xinjie; Zhang, Quan; Li, Xi; Zhang, Hui; Lv, Jialin; Wu, Yuhua; Wang, Jinghui; Zhang, Shucai

2014-05-01

To evaluate the efficacy and safety of Icotinib - an orally administered, highly potent selective inhibitor of epidermal growth factor receptor (EGFR) and its active mutations, in the treatment of patients with advanced non-small cell lung cancer (NSCLC). A total of 101 patients with stage IIIb/IV NSCLC were treated with 125 mg Icotinib three times a day until disease progression or intolerable toxicity. Response rate was evaluated using response evaluation criteria in solid tumors and progression-free survival (PFS) was collected. The overall response rate (ORR) and disease control rate (DCR) were 37.6% (38/101) and 79.2% (80/101), respectively. The median PFS was 6.5 months. Multivariate analysis showed that female gender (P= 0.048, 95% confidence interval [CI] 1.010-6.016) and occurrence of rash (P= 0.002, 95% CI 1.667-9.809) were the independent predictive factors for ORR, while a performance status (PS) score of 0-1 (P= 0.001, 95% CI 0.024-0.402) and rash (P= 0.042, 95% CI 1.089-76.557) were the independent predictive factors for DCR. In addition, PS scores of 0-1 (P <0.001, 95% CI 0.135-0.509), and non-smoking (P= 0.017, 95% CI 0.342-0.900) were found to be independent influencing factors for PFS. Moreover, patients with EGFR mutations had better PFS than patients with wild type EGFR, while patients with EGFR exon 19 deletion had better survival than those with EGFR exon 21 mutation. The most common adverse effects of Icotinib were rash (35.6%) and diarrhea (17.8%), which was tolerable. Treatment of stage IIIb/IV NSCLC patients with Icotinib was effective and tolerable, specifically in patients with EGFR mutation.

Real-life Experience for Integration of PET-CT in the Treatment of Hodgkin Lymphoma in Lebanon.

PubMed

Sakr, Riwa; Massoud, Marcel; Kerbage, Fouad; Rached, Layale; Zeghondy, Jean; Akoury, Elie; Nasr, Fady; Chahine, Georges

2017-07-01

Hodgkin lymphoma (HL) is a highly curable disease; < 80% of patients will achieve long-term survival. Positron emission tomography-computed tomography (PET-CT) has played a major role in the evaluation of both disease staging and response and has become an essential component in tailoring patients' treatment. We report the effect of integrating PET-CT into the management of HL in Lebanon. We analyzed the data regarding the usage of PET-CT at diagnosis, during treatment (interim PET), and at the end of treatment. We also analyzed the PET-CT findings from 2009 to 2015. The first PET-CT system was introduced in Lebanon in April 2002 but was not used for the evaluation of HL. Early in 2009, we started to incorporate PET-CT into the treatment of HL. By the end of 2009, 70% of patients were undergoing PET-CT at diagnosis and at the end of treatment. This proportion remained constant until 2013, when an increase occurred, with ≤ 94% of patients undergoing PET-CT at diagnosis. The usage of CT at diagnosis decreased significantly from 70% before 2009 to 52% after 2015. In contrast, CT usage at the end of treatment has fluctuated from 10% in 2009 to 0% in 2012, 2013, and 2014 and 11.76% in 2015. Functional imaging techniques are increasing in popularity compared with anatomic imaging. The usage of PET-CT has emerged as a highly valuable staging and follow-up method in the treatment of HL 8 years after the introduction of PET in Lebanon. PET was used first to improve the staging, then to evaluate the treatment response, and, recently, to tailor therapy according to the response. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative histological evaluation of new tyrosine-derived polymers and poly (L-lactic acid) as a function of polymer degradation.

PubMed

Hooper, K A; Macon, N D; Kohn, J

1998-09-05

Previous studies demonstrated that poly(DTE carbonate) and poly (DTE adipate), two tyrosine-derived polymers, have suitable properties for use in biomedical applications. This study reports the evaluation of the in vivo tissue response to these polymers in comparison to poly(L-lactic acid) (PLLA). Typically, the biocompatibility of a material is determined through histological evaluations as a function of implantation time in a suitable animal model. However, due to changes that can occur in the tissue response at different stages of the degradation process, a fixed set of time points is not ideal for comparative evaluations of materials having different rates of degradation. Therefore the tissue response elicited by poly(DTE carbonate), poly(DTE adipate), and PLLA was evaluated as a function of molecular weight. This allowed the tissue response to be compared at corresponding stages of degradation. Poly(DTE adipate) consistently elicited the mildest tissue response, as judged by the width and lack of cellularity of the fibrous capsule formed around the implant. The tissue response to poly(DTE carbonate) was mild throughout the 570 day study. However, the response to PLLA fluctuated as a function of the degree of degradation, exhibiting an increase in the intensity of inflammation as the implant began to lose mass. At the completion of the study, tissue ingrowth into the degrading and disintegrating poly(DTE adipate) implant was evident while no comparative ingrowth of tissue was seen for PLLA. The similarity of the in vivo and in vitro degradation rates of each polymer confirmed the absence of enzymatic involvement in the degradation process. A comparison of molecular weight retention, water uptake, and mass loss in vivo with two commonly used in vitro systems [phosphate-buffered saline (PBS) and simulated body fluid (SBF)] demonstrated that for the two tyrosine-derived polymers the in vivo results were equally well simulated in vitro with PBS and SBF. However, for PLLA the in vivo results were better simulated in vitro using PBS.

An Experimental Study of High Intensity Focused Ultrasound on Pig's Pancreas and the Early Clinical Experience on Pancreatic Cancer

NASA Astrophysics Data System (ADS)

Xiong, LiuLin; Huang, XiaoBo; Yao, SongSen; Yu, JinSheng; Hwang, JooHa; Fei, XingBo; Yu, QiuHong; Xue, WeiCheng; Zheng, ZhuYing; Wang, XiaoFeng

2007-05-01

Objective: To investigate the feasibility and safety of high intensity focused ultrasound (HIFU) treatment of in vivo pig pancreases, and to evaluate the safety and efficacy of HIFU in the clinical treatment of pancreatic cancer in humans. Methods: HIFU was performed in 12 domestic pig pancreases in vivo with varying acoustic energies. The safety of HIFU treatments was assessed by necropsy. The pathology and microstructure of the treated pancreases were evaluated using standard histology and transmission electron microscopy. Following the animal studies 62 patients with advanced pancreas cancer were treated with 250 - 420 W of acoustic power. There were 3 patients with stage II, 23 patients with stage III, and 36 patients with stage IV disease. Results: In animal studies, precise regions of coagulation necrosis were identified on pathology in 8 specimens that were treated with 420 W or 645 W acoustic power. Treatment effects were unable to be identified in 4 specimens treated with 300˜340 W acoustic power; however, damages to the cells microstructure and apoptosis were identified on electron microscopy. Damage to the stomach and colon were seen in some animals treated with 645 W. In the clinical treatments in humans the following were seen: local tumor control: complete response (CR) 0%, partial response (PR) 17.7%, no change (NC) 54.8%, progressive disease (PD) 27.5%. Pain relief was achieved in 87.1% of patients. The median survival for stage II and III patients was 11.2 months and median survival for stage IV patients was 5.6 months. The total median survival was 8.6 months. The survival rate at 1 year was as follows: stage II and III 42.3%, stage IV 5.6%. The survival rate at 2 years was as follows: stage II and III 15.4%, stage IV 0%. There were no severe complications or adverse events related to HIFU therapy seen in any of the patients treated. Conclusions: This study supports the feasibility of HIFU in the treatment of pancreatic cancer. The clinical application of HIFU to pancreas cancer was safe and effective especially in palliating pain.

Optimization and field use of a bioassay to monitor sea lice Lepeophtheirus salmonis sensitivity to emamectin benzoate.

PubMed

Westcott, Jillian D; Stryhn, Henrik; Burka, John F; Hammell, K Larry

2008-04-01

A bioassay for sea lice Lepeophtheirus salmonis sensitivity towards emamectin benzoate (EMB) was validated for field use. A probit regression model with natural responsiveness was used for the number of affected (moribund or dead) sea lice in bioassays involving different concentrations of EMB. Bioassay optimization included an evaluation of the inter-rater reliability of sea lice responsiveness to EMB and an evaluation of gender-related differences in susceptibility. Adoption of a set of bioassay response criteria improved the concordance (evaluated using the concordance correlation coefficient) between raters' assessments and the model estimation of EC50 values (the 'effective concentration' leading to a response of 50% of the lice not prone to natural response). An evaluation of gender-related differences in EMB susceptibility indicated that preadult stage female sea lice exhibited a significantly larger sensitivity towards EMB in 12 of 19 bioassays compared to preadult males. In order to evaluate sea lice sensitivity to EMB in eastern Canada, the intensive salmon farming area in the Bay of Fundy in southwestern New Brunswick was divided into 4 distinct regions based on industry health management practices and hydrographics. A total of 38 bioassays were completed from 2002 to 2005 using populations of preadult stage sea lice collected from Atlantic salmon Salmo salar farms within the 4 described regions. There was no significant overall effect of region or year on EC50 values; however, analysis of variance indicated a significant effect of time of year on EC50 values in 2002 and a potential effect in 2004 to 2005. Although the range of EC50 values obtained in this 3 yr study did not appear sufficient to affect current clinical success in the control of sea lice, the results suggest a seasonal- or temperature-associated variation in sensitivity to EMB. This will need to be considered if changes in EMB efficacy occur in the future.

Contraceptive social marketing: a continuous cycle of planning, testing and evaluating.

PubMed

1985-01-01

This article outlines the contraceptive marketing process used by the Social Marketing for Change (SOMARC) project. The 1st stage of the process involves analysis of the market, the consumer, and the social marketing organization's capabilities. In the 2nd stage, planning, data collected in the analysis stage are used to define objectives, segment target markets, and devise strategies for each element in the marketing mix. In the 3rd stage, all the elements in the marketing mix are developed and tested (e.g. product concepts, pricing, packaging, communication messages) and refined on the basis of test results. In stage 4, the action plan is implemented and marketing progress and institutional performance are monitored. Stage 5 includes an assessment of in-market effectiveness in terms of responses from consumers, retailers, and health professionals. The last stage feeds back to the 1st. All the reviewed data are recycled into analysis to begin again the continuous process of refinement and improvement.

7 CFR 1940.309 - Responsibilities of the prospective applicant.

Code of Federal Regulations, 2013 CFR

2013-01-01

... and transferees) to consider the potential environmental impacts of their requests at the earliest planning stages and to develop proposals that minimize the potential to adversely impact the environment... successor agency under Public Law 103-354 to evaluate their proposal's potential environmental impacts and...

7 CFR 1940.309 - Responsibilities of the prospective applicant.

Code of Federal Regulations, 2011 CFR

2011-01-01

... and transferees) to consider the potential environmental impacts of their requests at the earliest planning stages and to develop proposals that minimize the potential to adversely impact the environment... successor agency under Public Law 103-354 to evaluate their proposal's potential environmental impacts and...

7 CFR 1940.309 - Responsibilities of the prospective applicant.

Code of Federal Regulations, 2012 CFR

2012-01-01

... and transferees) to consider the potential environmental impacts of their requests at the earliest planning stages and to develop proposals that minimize the potential to adversely impact the environment... successor agency under Public Law 103-354 to evaluate their proposal's potential environmental impacts and...

7 CFR 1940.309 - Responsibilities of the prospective applicant.

Code of Federal Regulations, 2010 CFR

2010-01-01

... and transferees) to consider the potential environmental impacts of their requests at the earliest planning stages and to develop proposals that minimize the potential to adversely impact the environment... successor agency under Public Law 103-354 to evaluate their proposal's potential environmental impacts and...

NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors

PubMed Central

Mansky, Patrick J.; Sannes, Timothy S.; Johnson, Laura Lee; Blackman, Marc R.; Grem, Jean L.; Swain, Sandra M.; Monahan, Brian P.

2013-01-01

Purpose. European Mistletoe (Viscum album L.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone. PMID:24285980

Reproducibility, validity, and responsiveness of the hip outcome score in patients with end-stage hip osteoarthritis.

PubMed

Naal, Florian D; Impellizzeri, Franco M; von Eisenhart-Rothe, Rüdiger; Mannion, Anne F; Leunig, Michael

2012-11-01

To evaluate reproducibility, validity, and responsiveness of the Hip Outcome Score (HOS) in patients with end-stage hip osteoarthritis. In a cohort of 157 consecutive patients (mean age 66 years; 79 women) undergoing total hip replacement, the HOS was tested for the following measurement properties: feasibility (percentage of evaluable questionnaires), reproducibility (intraclass correlation coefficient [ICC] and standard error of measurement [SEM]), construct validity (correlation with the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC], Oxford Hip Score [OHS], Short Form 12 health survey, and University of California, Los Angeles activity scale), internal consistency (Cronbach's alpha), factorial validity (factor analysis), floor and ceiling effects, and internal and external responsiveness at 6 months after surgery (standardized response mean and change score correlations). Missing items occurred frequently. Five percent to 6% of the HOS activities of daily living (ADL) subscales and 20-32% of the sport subscales could not be scored. ICCs were 0.92 for both subscales. SEMs were 1.8 points (ADL subscale) and 2.3 points (sport subscale). Highest correlations were found with the OHS (r = 0.81 for ADL subscale and r = 0.58 for sport subscale) and the WOMAC physical function subscale (r = 0.83 for ADL subscale and r = 0.56 for sport subscale). Cronbach's alpha was 0.93 and 0.88 for the ADL and sport subscales, respectively. Neither unidimensionality of the subscales nor the 2-factor structure was supported by factor analysis. Both subscales showed good internal and external responsiveness. The HOS is reproducible and responsive when assessing patients with end-stage hip osteoarthritis in whom the items are relevant. However, based on the large proportion of missing data and the findings of the factor analysis, we cannot recommend this questionnaire for routine use in this target group. Copyright © 2012 by the American College of Rheumatology.

Papaya latex supernatant has a potent effect on the free-living stages of equid cyathostomins in vitro.

PubMed

Peachey, L E; Pinchbeck, G L; Matthews, J B; Burden, F A; Behnke, J M; Hodgkinson, J E

2016-09-15

The control of equid gastrointestinal nematodes in developed countries, in particular the cyathostomins, is threatened by high levels of anthelmintic resistance. In recent years, there has been increasing interest in the evaluation of traditional 'ethnoveterinary' medicines as alternatives to chemical anthelmintics. The cysteine proteinases (CPs), a group of enzymes derived from fruits such as papaya (Carica papaya), pineapple (Ananas comosus) and figs (Ficus spp.), have shown good efficacy against adult stages of a range of parasitic nematodes, in vitro and in vivo. The efficacy of CPs against cyathostomins remains to be explored. In this study, the efficacy of a crude preparation of CPs, papaya latex supernatant (PLS), against the free-living stages of cyathostomins was evaluated using two in vitro tests, the egg hatch test (EHT) and the larval migration inhibition test (LMIT). It was demonstrated that PLS had a potent effect in the EHT, with EC-50 values in the range of 0.12-0.22μM. At concentrations above 6.25μM the eggs did not develop, below this concentration the L1 developed but they lost integrity of the cuticle upon hatching. These effects were inhibited by pre-incubation of PLS with the CP inhibitor L-trans-epoxysuccinyl-l-leucylamido-(4-guanidino butane) (E64), indicating that CPs were responsible for the anti-parasitic activity. A dose-dependent inhibition of migration of third stage larvae (L3) in the LMIT was demonstrated at higher concentrations of PLS, with EC-50 values in the range of 67.35-106.31μM. Incubation of PLS with E64 prior to use in the LMIT did not reverse the anti-migratory effect, suggesting that CPs were not responsible for the reduced migration of cyathostomin L3 and that PLS also contains an additional active compound. This is the first report of PLS and/or CPs showing activity against the free-living stages of a parasitic helminth. In addition, it suggests that cyathostomins are highly sensitive to the effects of CPs and further evaluation of their efficacy against parasitic stages and in vivo are strongly indicated. Copyright © 2016 Elsevier B.V. All rights reserved.

Mismatch negativity as a potential neurobiological marker of early-stage Alzheimer disease and vascular dementia.

PubMed

Jiang, Shixiang; Yan, Chang; Qiao, Zhengxue; Yao, Haiqian; Jiang, Shiquan; Qiu, Xiaohui; Yang, Xiuxian; Fang, Deyu; Yang, Yanjie; Zhang, Limei; Wang, Lina; Zhang, Liming

2017-04-24

Alzheimer's disease (AD) and vascular dementia (VD) are serious, irreversible forms of cognitive impairment, which means that an early diagnosis is essential to slow down their progression. One potential neurophysiological biomarker of these diseases is the mismatch negativity (MMN) event-related potentials (ERP) component, which reflects an automatic detection mechanism at the pre-attentive stages of information processing. We evaluated the auditory MMN response in individuals from two patient groups: those in the prodromal stages of AD (P-AD) and those in the prodromal stages of VD (P-VD). Thirty patients (15 P-AD patients and 15 P-VD patients) and 30 age-matched controls were recruited to undergo electrophysiological recordings during the presentation of an auditory deviant-standard-reverse oddball paradigm that was used to elicit genuine MMN responses. We show that over the frontal-central area, the mean amplitude of the MMN was significantly reduced in both the P-AD (p=0.017) and P-VD groups (p=0.013) compared with controls. The MMN peak latency in P-VD patients was significantly shorter than in controls (p=0.027). No MMN response differences between the P-AD and P-VD were found in either the frontal-central or the temporal areas. These results indicate that P-AD and P-VD patients exhibit impaired pre-attentive information processing mechanisms as revealed by the frontal-central area MMN response, which is associated with sensory memory and cognitive deficits. Copyright © 2017 Elsevier B.V. All rights reserved.

Performance evaluation of a piezoactuator-based single-stage valve system subjected to high temperature

NASA Astrophysics Data System (ADS)

Jeon, Juncheol; Han, Chulhee; Chung, Jye Ung; Choi, Seung-Bok

2015-01-01

In this paper, a novel single-stage valve system activated by a piezostack actuator is proposed and experimentally evaluated at both room temperature (20 °C) and high temperature (100 °C) conditions. A hinge-lever displacement amplifier is adopted in the valve system to magnify the displacement generated from the piezostack actuator. After explaining the operating principle of the proposed piezostack-driven single-stage valve system, the geometric dimensions and mechanical properties of the valve components are discussed in details. An experimental apparatus is then manufactured to evaluate the performances of the valve system such as flow rate. The experimental apparatus consists of a heat chamber, which can regulate the temperature of the valve system and oil, pneumatic-hydraulic cylinders, a hydraulic circuit, a pneumatic circuit, electronic devices, an interface card, and a high voltage amplifier. The pneumatic-hydraulic cylinder transforms the pneumatic pressure into hydraulic pressure. The performances of the valve system regarding spool response, pressure drop, and flow rate are evaluated and presented. In addition, the performance of the valve system under high temperature condition is compared with that under room temperature condition. The experimental results are plotted in both frequency and time domains.

Characteristics of Human Brain Activity during the Evaluation of Service-to-Service Brand Extension

PubMed Central

Yang, Taeyang; Lee, Seungji; Seomoon, Eunbi; Kim, Sung-Phil

2018-01-01

Brand extension is a marketing strategy to apply the previously established brand name into new goods or service. A number of studies have reported the characteristics of human event-related potentials (ERPs) in response to the evaluation of goods-to-goods brand extension. In contrast, human brain responses to the evaluation of service extension are relatively unexplored. The aim of this study was investigating cognitive processes underlying the evaluation of service-to-service brand extension with electroencephalography (EEG). A total of 56 text stimuli composed of service brand name (S1) followed by extended service name (S2) were presented to participants. The EEG of participants was recorded while participants were asked to evaluate whether a given brand extension was acceptable or not. The behavioral results revealed that participants could evaluate brand extension though they had little knowledge about the extended services, indicating the role of brand in the evaluation of the services. Additionally, we developed a method of grouping brand extension stimuli according to the fit levels obtained from behavioral responses, instead of grouping of stimuli a priori. The ERP analysis identified three components during the evaluation of brand extension: N2, P300, and N400. No difference in the N2 amplitude was found among the different levels of a fit between S1 and S2. The P300 amplitude for the low level of fit was greater than those for higher levels (p < 0.05). The N400 amplitude was more negative for the mid- and high-level fits than the low level. The ERP results of P300 and N400 indicate that the early stage of brain extension evaluation might first detect low-fit brand extension as an improbable target followed by the late stage of the integration of S2 into S1. Along with previous findings, our results demonstrate different cognitive evaluation of service-to-service brand extension from goods-to-goods. PMID:29479313

Characteristics of Human Brain Activity during the Evaluation of Service-to-Service Brand Extension.

PubMed

Yang, Taeyang; Lee, Seungji; Seomoon, Eunbi; Kim, Sung-Phil

2018-01-01

Brand extension is a marketing strategy to apply the previously established brand name into new goods or service. A number of studies have reported the characteristics of human event-related potentials (ERPs) in response to the evaluation of goods-to-goods brand extension. In contrast, human brain responses to the evaluation of service extension are relatively unexplored. The aim of this study was investigating cognitive processes underlying the evaluation of service-to-service brand extension with electroencephalography (EEG). A total of 56 text stimuli composed of service brand name (S1) followed by extended service name (S2) were presented to participants. The EEG of participants was recorded while participants were asked to evaluate whether a given brand extension was acceptable or not. The behavioral results revealed that participants could evaluate brand extension though they had little knowledge about the extended services, indicating the role of brand in the evaluation of the services. Additionally, we developed a method of grouping brand extension stimuli according to the fit levels obtained from behavioral responses, instead of grouping of stimuli a priori . The ERP analysis identified three components during the evaluation of brand extension: N2, P300, and N400. No difference in the N2 amplitude was found among the different levels of a fit between S1 and S2. The P300 amplitude for the low level of fit was greater than those for higher levels ( p < 0.05). The N400 amplitude was more negative for the mid- and high-level fits than the low level. The ERP results of P300 and N400 indicate that the early stage of brain extension evaluation might first detect low-fit brand extension as an improbable target followed by the late stage of the integration of S2 into S1. Along with previous findings, our results demonstrate different cognitive evaluation of service-to-service brand extension from goods-to-goods.

Treatment outcomes regarding the addition of targeted agents in the therapeutic portfolio for stage II-III rectal cancer undergoing neoadjuvant chemoradiation.

PubMed

Liang, Jin-Tung; Chen, Tzu-Chun; Huang, John; Jeng, Yung-Ming; Cheng, Jason Chia-Hsien

2017-11-24

To evaluate the impact of targeted agents in stage II-III rectal cancer undergoing neoadjuvant concurrent chemoradiation therapy (CCRT). A retrospective study was performed in 124 consecutive patients with clinically T 3 N 0-2 M 0 -staged rectal cancer incorporating targeted agents in CCRT. Pathologic complete response was detected in 34.2% (n=26) of bevacizumab+FOLFOX-treated patients (n=76), which was significantly higher (p=0.019, post-hoc statistical power =35.87%) than that (n=10, 20.8%) of the cetuximab+FOLFOX-treated patients (n=48). Patients receiving cetuximab+FOLFOX therapy tended to develop severe liver toxicity (91.7%, n=44 versus 17.1%, n=13, p<0.0001), as evaluated by morphologic grading of hepatic steatosis and sinusoidal dilatation in laparoscopy. In the 57 patients with morphologically severe liver toxicity, 36 (63.2%) retained a normal liver function; for the remaining 21 patients with an abnormal liver function, the abnormality was self-limited in 19 patients, whereas 2 cetuximab-treated patients progressed to hepatic failure and mortality. A subset analysis within bevacizumab+FOLFOX-treated patients with either wild-type (n=36) or mutant (n=40) K-ras status indicated K-ras status did not significantly influence the treatment outcomes. The addition of bevacizumab instead of cetuximab to FOLFOX in the neoadjuvant settings for T 3 N 0-2 M 0 -staged rectal cancer could induce a promising rate of pathologic complete response and lesser hepatotoxicity.

An assigned responsibility system for robotic teleoperation control.

PubMed

Small, Nicolas; Lee, Kevin; Mann, Graham

2018-01-01

This paper proposes an architecture that explores a gap in the spectrum of existing strategies for robot control mode switching in adjustable autonomy. In situations where the environment is reasonably known and/or predictable, pre-planning these control changes could relieve robot operators of the additional task of deciding when and how to switch. Such a strategy provides a clear division of labour between the automation and the human operator(s) before the job even begins, allowing for individual responsibilities to be known ahead of time, limiting confusion and allowing rest breaks to be planned. Assigned Responsibility is a new form of adjustable autonomy-based teleoperation that allows the selective inclusion of automated control elements at key stages of a robot operation plan's execution. Progression through these stages is controlled by automatic goal accomplishment tracking. An implementation is evaluated through engineering tests and a usability study, demonstrating the viability of this approach and offering insight into its potential applications.

The Emotional Dimensions of the Problem-Solving Process.

ERIC Educational Resources Information Center

Hill, Barbara; And Others

1979-01-01

Predictable affective responses are evoked during each phase of a group or organizational problem-solving process. With the needs assessment phase come hope and energy; with goal-setting, confusion and dissatisfaction; with action planning, involvement and accomplishment; with implementation, "stage fright" and joy; with evaluation, pride or…

Survival Advantage Associated with Decrease in Stage at Detection from Stage IIIC to Stage IIIA Epithelial Ovarian Cancer

PubMed Central

Lefringhouse, Jason; Pavlik, Edward; Miller, Rachel; DeSimone, Christopher; Ueland, Frederick; Kryscio, Richard; van Nagell, J. R.

2014-01-01

Objective. The aim of this study was to document the survival advantage of lowering stage at detection from Stage IIIC to Stage IIIA epithelial ovarian cancer. Methods. Treatment outcomes and survival were evaluated in patients with Stage IIIA and Stage IIIC epithelial ovarian cancer treated from 2000 to 2009 at the University of Kentucky Markey Cancer Center (UKMCC) and SEER institutions. Results. Cytoreduction to no visible disease (P < 0.0001) and complete response to platinum-based chemotherapy (P < 0.025) occurred more frequently in Stage IIIA than in Stage IIIC cases. Time to progression was shorter in patients with Stage IIIC ovarian cancer (17 ± 1 months) than in those with Stage II1A disease (36 ± 8 months). Five-year overall survival (OS) improved from 41% in Stage IIIC patients to 60% in Stage IIIA patients treated at UKMCC and from 37% to 56% in patients treated at SEER institutions for a survival advantage of 19% in both data sets. 53% of Stage IIIA and 14% of Stage IIIC patients had NED at last followup. Conclusions. Decreasing stage at detection from Stage IIIC to stage IIIA epithelial ovarian cancer is associated with a 5-year survival advantage of nearly 20% in patients treated by surgical tumor cytoreduction and platinum-based chemotherapy. PMID:25254047

Explosively driven hypervelocity launcher: Second-stage augmentation techniques

NASA Technical Reports Server (NTRS)

Baum, D. W.

1973-01-01

The results are described of a continuing study aimed at developing a two-stage explosively driven hypervelocity launcher capable of achieving projectile velocities between 15 and 20 km/sec. The testing and evaluation of a new cylindrical impact technique for collapsing the barrel of two-stage launcher are reported. Previous two-stage launchers have been limited in ultimate performance by incomplete barrel collapse behind the projectile. The cylindrical impact technique explosively collapses a steel tube concentric with and surrounding the barrel of the launcher. The impact of the tube on the barrel produces extremely high stresses which cause the barrel to collapse. The collapse rate can be adjusted by appropriate variation of the explosive charge and tubing parameters. Launcher experiments demonstrated that the technique did achieve complete barrel collapse and form a second-stage piston. However, jetting occurred in the barrel collapse process and was responsible for severe projectile damage.

US Intergroup Trial of Response-Adapted Therapy for Stage III to IV Hodgkin Lymphoma Using Early Interim Fluorodeoxyglucose–Positron Emission Tomography Imaging: Southwest Oncology Group S0816

PubMed Central

Li, Hongli; Schöder, Heiko; Straus, David J.; Moskowitz, Craig H.; LeBlanc, Michael; Rimsza, Lisa M.; Bartlett, Nancy L.; Evens, Andrew M.; Mittra, Erik S.; LaCasce, Ann S.; Sweetenham, John W.; Barr, Paul M.; Fanale, Michelle A.; Knopp, Michael V.; Noy, Ariela; Hsi, Eric D.; Cook, James R.; Lechowicz, Mary Jo; Gascoyne, Randy D.; Leonard, John P.; Kahl, Brad S.; Cheson, Bruce D.; Fisher, Richard I.; Friedberg, Jonathan W.

2016-01-01

Purpose Four US National Clinical Trials Network components (Southwest Oncology Group, Cancer and Leukemia Group B/Alliance, Eastern Cooperative Oncology Group, and the AIDS Malignancy Consortium) conducted a phase II Intergroup clinical trial that used early interim fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to determine the utility of response-adapted therapy for stage III to IV classic Hodgkin lymphoma. Patients and Methods The Southwest Oncology Group S0816 (Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma) trial enrolled 358 HIV-negative patients between July 1, 2009, and December 2, 2012. A PET scan was performed after two initial cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and was labeled PET2. PET2-negative patients (Deauville score 1 to 3) received an additional four cycles of ABVD, whereas PET2-positive patients (Deauville score 4 to 5) were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for six cycles. Among 336 eligible and evaluable patients, the median age was 32 years (range, 18 to 60 years), with 52% stage III, 48% stage IV, 49% International Prognostic Score 0 to 2, and 51% score 3 to 7. Results Three hundred thirty-six of the enrolled patients were evaluable. Central review of the interim PET2 scan was performed in 331 evaluable patients, with 271 (82%) PET2-negative and 60 (18%) PET2-positive. Of 60 eligible PET2-positive patients, 49 switched to eBEACOPP as planned and 11 declined. With a median follow-up of 39.7 months, the Kaplan-Meier estimate for 2-year overall survival was 98% (95% CI, 95% to 99%), and the 2-year estimate for progression-free survival (PFS) was 79% (95% CI, 74% to 83%). The 2-year estimate for PFS in the subset of patients who were PET2-positive after two cycles of ABVD was 64% (95% CI, 50% to 75%). Both nonhematologic and hematologic toxicities were greater in the eBEACOPP arm than in the continued ABVD arm. Conclusion Response-adapted therapy based on interim PET imaging after two cycles of ABVD seems promising with a 2-year PFS of 64% for PET2-positive patients, which is much higher than the expected 2-year PFS of 15% to 30%. PMID:27069074

Ifosfamide and vinorelbine as first-line chemotherapy for advanced non-small cell lung carcinoma.

PubMed

Vallejo, C; Romero, A; Perez, J; Cuevas, M; Lacava, J; Sabatini, C; Dominguez, M; Rodriguez, R; Barbieri, M; Romero Acuña, L; Romero Acuña, J; Langhi, M; Amato, S; Salvadori, M; Ortiz, E; Machiavelli, M; Leone, B

1996-12-01

We evaluated the efficacy and toxicity of the novel combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in patients with stage IIIB and IV non-small cell lung cancer (NSCLC). Between March 1993 and November 1994, 44 patients (17 stage IIIB; 27 stage IV) received a regimen consisting of IFX, 2 g/m2 in a 1-h infusion, days 1-3; mesna, 400 mg/m2 in an i.v. bolus at hours 0 and 4 and 800 mg orally at hour 8, days 1-3; and VNB, 35 mg/ m2 in a 20-min infusion, days 1 and 15. During the first course only, a half dose of VNB (17.5 mg/m2) was administered on days 8 and 22. Courses were repeated every 28 days. Forty patients were fully evaluable for response, and 44 were assessable for toxicity. Objective regression was recorded in 13 of 40 patients (33%). No patient achieved a complete response. Thirteen patients presented a partial response (33%); 17 (42%) had no change; and progressive disease was observed in 10 (25%). The median duration of response was 10 months, and the median time to treatment failure for the whole group was 4 months. Median survival was 11 months. The dose-limiting toxic effect was myelosuppression. Leukopenia occurred in 25 patients (57%) and was grade 3 or 4 in 8 patients (18%). Twelve patients (27%) developed peripheral neurotoxicity, while five had mild IFX-induced CNS toxicity. Phlebitis was observed in 15 of 30 patients (50%) who did not have central implantable venous systems. The IFX-VNB combination exhibited an activity against NSCLC that was among the highest reported for non-cisplatin-containing regimens, with a toxicity profile that was easily managed.

Photodynamic Therapy with 3-(1’-hexyloxyethyl) pyropheophorbide a (HPPH) for Cancer of the Oral Cavity

PubMed Central

Rigual, Nestor; Shafirstein, Gal; Cooper, Michele T.; Baumann, Heinz; Bellnier, David A.; Sunar, Ulas; Tracy, Erin C.; Rohrbach, Daniel J.; Wilding, Gregory; Tan, Wei; Sullivan, Maureen; Merzianu, Mihai; Henderson, Barbara W.

2013-01-01

Purpose The primary objective was to evaluate safety of 3-(1’-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction. Experimental Design Patients with histologically proven oral dysplasia, carcinoma in situ (CiS ) or early stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies employed an HPPH dose of 4 mg/m2 and light doses from 50 to 140 J/cm2. Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of signal transducer and activator of transcription 3 (STAT3) were assessed as potential indicators of PDT effective reaction. Results Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and CiS, and 82% for SCCs lesions at 140 J/cm2. The responses in the CiS/dysplasia cohort are not durable. The PDT induced STAT3 cross-links is significantly higher (P=0.0033) in SCC than in CiS/dysplasia for all light-doses. Conclusion HPPH-PDT is safe for the treatment of CiS/dysplasia and early stage cancer of the oral cavity. Early stage oral HNSCC appears to respond better to HPPH-PDT in comparison to premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT mediated photoreaction. PMID:24088736

A Gynecologic Oncology Group phase II trial of the protein kinase C-beta inhibitor, enzastaurin and evaluation of markers with potential predictive and prognostic value in persistent or recurrent epithelial ovarian and primary peritoneal malignancies

PubMed Central

Usha, Lydia; Sill, Michael W.; Darcy, Kathleen M.; Benbrook, Doris M.; Hurteau, Jean A; Michelin, David P.; Mannel, Robert S.; Hanjani, Parviz; De Geest, Koen; Godwin, Andrew K.

2011-01-01

Purpose Protein kinase C (PKC) activation contributes to proliferation and angiogenesis in epithelial ovarian or primary peritoneal carcinoma (EOC/PPC). A multi-institutional phase II trial was conducted to evaluate the efficacy and safety of PKCβ inhibitor enzastaurin in persistent or recurrent EOC/PPC and to explore potential prognostic and predictive biomarkers. Methods Eligible women with measurable platinum-sensitive and resistant EOC/PPC were treated with continuous administration of oral enzastaurin until disease progression or unacceptable toxicity. A two-stage sequential design was used to evaluate progression-free survival (PFS) ≥ 6-months, tumor response, and toxicity. Translational studies included sequencing of the TP53, PTEN, PIK3CA and PKCβII genes for somatic mutations, quantitative PCR assays for AKT2 and PTEN copy number alterations, and measurement of circulating VEGF-A plasma levels. Results Among 27 eligible and evaluable patients, 3 women with PFS ≥ 6-months (11%) and 2 women with partial responses (7%) were observed. One of them achieved a durable response and remains on the study. No grade 4 adverse events were observed. Most common grade 3 adverse events were constitutional (4) and gastrointestinal (3). Mutations in the TP53 gene and abnormal copy number in the PTEN gene were common (56% and 48% of cases, respectively). Conclusions Enzastaurin was tolerable but had insufficient activity to proceed with the second stage of accrual. However, 1 patient has been progression-free for 44 months. No association between a biomarker and response to enzastaurin has been found. Exploratory analysis suggested an association between survival and PTEN copy number losses. PMID:21414654

Radiotherapy dose–response analysis for diffuse large B-cell lymphoma with a complete response to chemotherapy

PubMed Central

2012-01-01

Objective To examine the efficacy of different radiation doses after achievement of a complete response to chemotherapy in diffuse large B-cell lymphoma (DLBCL). Methods Patients with stage I-IV DLBCL treated from 1995–2009 at Duke Cancer Institute who achieved a complete response to chemotherapy were reviewed. In-field control, event-free survival, and overall survival were calculated using the Kaplan-Meier method. Dose response was evaluated by grouping treated sites by delivered radiation dose. Results 105 patients were treated with RT to 214 disease sites. Chemotherapy (median 6 cycles) was R-CHOP (65%), CHOP (26%), R-CNOP (2%), or other (7%). Post-chemotherapy imaging was PET/CT (88%), gallium with CT (1%), or CT only (11%). The median RT dose was 30 Gy (range, 12–40 Gy). The median radiation dose was higher for patients with stage I-II disease compared with patients with stage III-IV disease (30 versus 24.5 Gy, p < 0.001). Five-year in-field control, event-free survival, and overall survival for all patients was 94% (95% CI: 89-99%), 84% (95% CI: 77-92%), and 91% (95% CI: 85-97%), respectively. Six patients developed an in-field recurrence at 10 sites, without a clear dose response. In-field failure was higher at sites ≥ 10 cm (14% versus 4%, p = 0.06). Conclusion In-field control was excellent with a combined modality approach when a complete response was achieved after chemotherapy without a clear radiation dose response. PMID:22720801

A phase II safety and efficacy study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor pazopanib in patients with metastatic urothelial cancer.

PubMed

Pili, Roberto; Qin, Rui; Flynn, P J; Picus, Joel; Millward, Michael; Ho, Wing Ming; Pitot, Henry; Tan, Winston; Miles, Kiersten M; Erlichman, Charles; Vaishampayan, Ulka

2013-12-01

Vascular endothelial growth factor (VEGF) is produced by bladder cancer cell lines in vitro and expressed in human bladder tumor tissues. Pazopanib is a vascular endothelial receptor tyrosine kinase inhibitor with anti-angiogenesis and anti-tumor activity in several preclinical models. A 2-stage phase II study was conducted to assess the activity and toxicity profile of pazopanib in patients with metastatic, urothelial carcinoma. Patients with one prior systemic therapy for metastatic urothelial carcinoma were eligible. Patients received pazopanib at a dose of 800 mg orally for a 4-week cycle. Nineteen patients were enrolled. No grade 4 or 5 events were experienced. Nine patients experienced 11 grade 3 adverse events. Most common toxicities were anemia, thrombocytopenia, leucopenia, and fatigue. For stage I, none of the first 16 evaluable patients were deemed a success (complete response or partial response) by the Response Evaluation Criteria In Solid Tumors criteria during the first four 4-week cycles of treatment. Median progression-free survival was 1.9 months. This met the futility stopping rule of interim analysis, and therefore the trial was recommended to be permanently closed. Pazopanib did not show significant activity in patients with urothelial carcinoma. The role of anti-VEGF therapies in urothelial carcinoma may need further evaluation in rational combination strategies. Copyright © 2013 Elsevier Inc. All rights reserved.

Checkpoint inhibition for advanced mucosal melanoma.

PubMed

Thierauf, Julia; Veit, Johannes A; Hess, Jochen; Treiber, Nicolai; Lisson, Catharina; Weissinger, Stephanie E; Bommer, Martin; Hoffmann, Thomas K

2017-04-01

Whereas anti-PD-1 therapy has demonstrated a significant and durable response against advanced cutaneous melanoma, conventional chemotherapies have shown only minor benefit against advanced mucosal melanoma. To investigate the efficacy of anti-PD-1 therapy in a small cohort of patients with mucosal melanoma of the head and neck. We analysed five patients with mucosal melanoma of the head and neck who received nivolumab or pembrolizumab, at an advanced stage. Expression of PD-L1 and PD-1 in all tumour samples was evaluated immunohistochemically. All patients received at least two cycles of nivolumab or pembrolizumab. The most severe adverse events were categorised as CTCAE (common terminology criteria for adverse events) Grade 2. All patients showed progressive disease after restaging at three and six months, and no partial or complete response was observed. Immunohistochemical staining demonstrated PD-L1 expression in less than 5% of tumour cells. Systemic therapy with either nivolumab or pembrolizumab showed no clinical response, however, tumour progression was identified in all patients using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 and immune-related response criteria (irRC) to evaluate tumour response.

[Search for protective antigens in Ixodes persulcatus (ixodidae) salivary gland extracts].

PubMed

Shtannikov, A V; Reshetniak, T V; Repolovskaia, T V; Panfertsev, E A; Perovskaia, O N; Gutova, V P; Vasil'eva, I S; Ershova, A S; Prilipov, A G; Biketov, S F; Zeidner, N

2010-01-01

RT-PCR evaluation of the activity of eight Ixodes persulcatus salivary gland genes shows clear distinctions in their expression depending of the stage of tick feeding. Out of them, only Salp 10 and Salp 15 proteins may be regarded as candidates for protective antigens to develop anti-tick and anti-Borrelia vaccines. Firstly they play an important role in feeding a tick and modifying a host's immune response. Secondly, the increasing expression of the salp 10 and salp 10 genes begins at early tick feeding stages. Thirdly, the activity of these genes increases with the beginning of feeding by tens and hundreds times and keeps at this level until the third tick feeding stage is over.

Stagewise cognitive development: an application of catastrophe theory.

PubMed

van der Maas, H L; Molenaar, P C

1992-07-01

In this article an overview is given of traditional methodological approaches to stagewise cognitive developmental research. These approaches are evaluated and integrated on the basis of catastrophe theory. In particular, catastrophe theory specifies a set of common criteria for testing the discontinuity hypothesis proposed by Piaget. Separate criteria correspond to distinct methods used in cognitive developmental research. Such criteria are, for instance, the detection of spurts in development, bimodality of test scores, and increased variability of responses during transitional periods. When a genuine stage transition is present, these criteria are expected to be satisfied. A revised catastrophe model accommodating these criteria is proposed for the stage transition in cognitive development from the preoperational to the concrete operational stage.

Developing Memory Reconsolidation Blockers as Novel PTSD Treatments

DTIC Science & Technology

2012-06-01

freezing in a Pavlovian cue- conditioned fear task in rats. In Stage II, we will evaluate the ability of candidate drugs to reverse fear conditioning ...disorder (PTSD). The underlying theory is that candidate drugs , when given following the reactivation of a conditioned fear response in animals, or a...traumatic memory in humans, will reduce the strength of the conditioned response or traumatic memory. We plan to test such drugs , either alone or in

Glutathione-s-transferase-pi expression in early breast cancer: association with outcome and response to chemotherapy.

PubMed

Arun, Banu K; Granville, Laura A; Yin, Guosheng; Middleton, Lavinia P; Dawood, Shaheenah; Kau, Shu-Wan; Kamal, Arif; Hsu, Limin; Hortobagyi, Gabriel N; Sahin, Aysegul A

2010-06-01

Glutathione-S-transferase-pi (GST-pi) is a detoxification enzyme expressed in breast cancer; however its involvement in chemotherapy sensitivity and prognosis is not well understood. We evaluated the expression of GSTpi and its predictive role of chemotherapy response. Breast tumor samples from 166 patients at stage I/II of the disease were immunostained for GST-pi, and the expression was 96 %. There was a trend toward improved disease-free survival with high GST-pi expression (p =.09). There was a statistically non-significant association between high GST-pi expression and improved outcome with adjuvant chemotherapy (p =.055). Further studies should evaluate the role of GST-pi expression in relation to response to different chemotherapies.

Novel linear piezoelectric motor for precision position stage

NASA Astrophysics Data System (ADS)

Chen, Chao; Shi, Yunlai; Zhang, Jun; Wang, Junshan

2016-03-01

Conventional servomotor and stepping motor face challenges in nanometer positioning stages due to the complex structure, motion transformation mechanism, and slow dynamic response, especially directly driven by linear motor. A new butterfly-shaped linear piezoelectric motor for linear motion is presented. A two-degree precision position stage driven by the proposed linear ultrasonic motor possesses a simple and compact configuration, which makes the system obtain shorter driving chain. Firstly, the working principle of the linear ultrasonic motor is analyzed. The oscillation orbits of two driving feet on the stator are produced successively by using the anti-symmetric and symmetric vibration modes of the piezoelectric composite structure, and the slider pressed on the driving feet can be propelled twice in only one vibration cycle. Then with the derivation of the dynamic equation of the piezoelectric actuator and transient response model, start-upstart-up and settling state characteristics of the proposed linear actuator is investigated theoretically and experimentally, and is applicable to evaluate step resolution of the precision platform driven by the actuator. Moreover the structure of the two-degree position stage system is described and a special precision displacement measurement system is built. Finally, the characteristics of the two-degree position stage are studied. In the closed-loop condition the positioning accuracy of plus or minus <0.5 μm is experimentally obtained for the stage propelled by the piezoelectric motor. A precision position stage based the proposed butterfly-shaped linear piezoelectric is theoretically and experimentally investigated.

Spermidine affects the transcriptome responses to high temperature stress in ripening tomato fruit.

PubMed

Cheng, Lin; Sun, Rong-rong; Wang, Fei-yan; Peng, Zhen; Kong, Fu-ling; Wu, Jian; Cao, Jia-shu; Lu, Gang

2012-04-01

High temperature adversely affects quality and yield of tomato fruit. Polyamine can alleviate heat injury in plants. This study is aimed to investigate the effects of polyamine and high temperature on transcriptional profiles in ripening tomato fruit. An Affymetrix tomato microarray was used to evaluate changes in gene expression in response to exogenous spermidine (Spd, 1 mmol/L) and high temperature (33/27 °C) treatments in tomato fruits at mature green stage. Of the 10101 tomato probe sets represented on the array, 127 loci were differentially expressed in high temperature-treated fruits, compared with those under normal conditions, functionally characterized by their involvement in signal transduction, defense responses, oxidation reduction, and hormone responses. However, only 34 genes were up-regulated in Spd-treated fruits as compared with non-treated fruits, which were involved in primary metabolism, signal transduction, hormone responses, transcription factors, and stress responses. Meanwhile, 55 genes involved in energy metabolism, cell wall metabolism, and photosynthesis were down-regulated in Spd-treated fruits. Our results demonstrated that Spd might play an important role in regulation of tomato fruit response to high temperature during ripening stage.

Matrix metalloproteinase-9 expression correlated with tumor response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy

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

Unsal, Diclehan; Uner, Aytug; Akyurek, Nalan

2007-01-01

Purpose: To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients. Methods and Materials: Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primarymore » endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression. Results: Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p < 0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive. Conclusions: Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.« less

Proteome changes in the initial bacterial colonist during ecological succession in an acid mine drainage biofilm community

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

Mueller, Ryan; Dill, Brian; Pan, Chongle

2011-01-01

Proteomes of acid mine drainage biofilms at different stages of ecological succession were examined to understand microbial responses to changing community membership. We evaluated the degree of reproducibility of the community proteomes between samples of the same growth stage and found stable and predictable protein abundance patterns across time and sampling space, allowing for a set of 50 classifier proteins to be identified for use in predicting growth stages of undefined communities. Additionally, physiological changes in the dominant species, Leptospirillum Group II, were analysed as biofilms mature. During early growth stages, this population responds to abiotic stresses related to growthmore » on the acid mine drainage solution. Enzymes involved in protein synthesis, cell division and utilization of 1- and 2-carbon compounds were more abundant in early growth stages, suggesting rapid growth and a reorganization of metabolism during biofilm initiation. As biofilms thicken and diversify, external stresses arise from competition for dwindling resources, which may inhibit cell division of Leptospirillum Group II through the SOS response. This population also represses translation and synthesizes more complex carbohydrates and amino acids in mature biofilms. These findings provide unprecedented insight into the physiological changes that may result from competitive interactions within communities in natural environments.« less

Predictors of outcome in patients with advanced nonseminomatous germ cell testicular tumors.

PubMed

Yetisyigit, Tarkan; Babacan, Nalan; Urun, Yuksel; Seber, Erdogan Selcuk; Cihan, Sener; Arpaci, Erkan; Yildirim, Nuriye; Aksoy, Sercan; Budakoglu, Burcin; Zengin, Nurullah; Oksuzoglu, Berna; Yalcin, Banu Cicek; Alkis, Necati

2014-01-01

Predictor factors determining complete response to treatment are still not clearly defined. We aimed to evaluate clinicopathological features, risk factors, treatment responses, and survival analysis of patient with advanced nonseminomatous GCTs (NSGCTs). Between November 1999 and September 2011, 140 patients with stage II and III NSGCTs were referred to our institutions and 125 patients with complete clinical data were included in this retrospective study. Four cycles of BEP regimen were applied as a first-line treatment. Salvage chemotherapy and/or high-dose chemotherapy (HDCT) with autologous stem cell transplantation were given in patients who progressed after BEP chemotherapy. Post-chemotherapy surgery was performed in selected patients with incomplete radiographic response and normal tumor markers. The median age was 28 years. For the good, intermediate and poor risk groups, compete response rates (CRR) were, 84.6%, 67.9% and 59.4%, respectively. Extragonadal tumors, stage 3 disease, intermediate and poor risk factors, rete testis invasion were associated with worse outcomes. There were 32 patients (25.6%) with non-CR who were treated with salvage treatment. Thirty-one patients died from GCTs and 94% of them had stage III disease. Even though response rates are high, some patients with GCTs still need salvage treatment and cure cannot be achieved. Non-complete response to platinium-based first-line treatment is a negative prognostic factor. Our study confirmed the need for a prognostic and predictive model and more effective salvage approaches.

Advantage of FMISO-PET over FDG-PET for predicting histological response to preoperative chemotherapy in patients with oral squamous cell carcinoma.

PubMed

Sato, Jun; Kitagawa, Yoshimasa; Yamazaki, Yutaka; Hata, Hironobu; Asaka, Takuya; Miyakoshi, Masaaki; Okamoto, Shozo; Shiga, Tohru; Shindoh, Masanobu; Kuge, Yuji; Tamaki, Nagara

2014-11-01

Hypoxia, a prognostic factor in many types of cancer, can be detected by (18)F-fluoromisonidazole (FMISO) positron emission tomography (PET). It is unclear whether hypoxia reflects the response to chemotherapy in patients with oral squamous cell carcinoma (OSCC). The correlations of FMISO-PET and FDG-PET with histological response to preoperative chemotherapy were therefore assessed in patients with OSCC. This study enrolled 22 patients with OSCC undergoing preoperative chemotherapy. The T-stages were T2 in 6 patients, T3 in 3, and T4a in 13, and the N-stages were N0 in 14 patients, N1 in 3, and N2 in 5. Each patient was evaluated by both FMISO-PET and FDG-PET before surgery, and the maximum standardized uptake value (SUVmax) of FDG- and FMISO-PET and tumor-muscle ratio (TMR) of FMISO-PET were measured. The threshold for the hypoxic volume based on TMR was set at 1.25. The histological response to preoperative chemotherapy was evaluated using operative materials. FMISO-PET and FDG-PET detected uptake by primary OSCCs in 15 (68%) and 21 (95%) patients, respectively, and median SUVmaxs of FMISO- and FDG-PET in the primary site were 2.0 (range, 1.3-3.5) and 16.0 (range, 1.0-32.2), respectively. The median of FMISO TMR was 1.5 (range, 0.99-2.96). There were five cases whose FMISO TMR was less than 1.25. Histological evaluation showed good response to preoperative chemotherapy in 7 patients (32%) and poor response in 15 (68%). Good response was significantly more prevalent in patients with negative than positive FMISO uptake (P < 0.001) and without the hypoxic area evaluated by FMISO-PET TMR (P = 0.04), whereas FDG uptake was not significantly correlated with response to chemotherapy response. Multivariate logistic regression analysis showed that FMISO uptake was an independent significant predictor of response to preoperative chemotherapy (P = 0.03, odds ratio = 0.06, 95% confidence interval = 0.004-0.759). An advantage of FMISO-PET over FDG-PET for predicting histological response to preoperative chemotherapy in patients with OSCC was observed.

Evaluation of Sex-specific Responses to Trenbolone Acetate Metabolites in Early Life-stage Fathead Minnows (Pimephales promelas) Using Molecular Tools

EPA Science Inventory

The occurrence of endocrine disrupting chemicals (EDCs) in concentrated animal feed operation (CAFO) waste, and the potential effects of these chemicals on aquatic ecosystems have been of recent concern, especially in large agricultural regions. Currently, little is known concer...

An Evaluation of Hierarchical Bayes Estimation for the Two- Parameter Logistic Model.

ERIC Educational Resources Information Center

Kim, Seock-Ho

Hierarchical Bayes procedures for the two-parameter logistic item response model were compared for estimating item parameters. Simulated data sets were analyzed using two different Bayes estimation procedures, the two-stage hierarchical Bayes estimation (HB2) and the marginal Bayesian with known hyperparameters (MB), and marginal maximum…

Lung cancer treatment costs, including patient responsibility, by disease stage and treatment modality, 1992 to 2003.

PubMed

Cipriano, Lauren E; Romanus, Dorothy; Earle, Craig C; Neville, Bridget A; Halpern, Elkan F; Gazelle, G Scott; McMahon, Pamela M

2011-01-01

The objective of this analysis was to estimate costs for lung cancer care and evaluate trends in the share of treatment costs that are the responsibility of Medicare beneficiaries. The Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 1991-2003 for 60,231 patients with lung cancer were used to estimate monthly and patient-liability costs for clinical phases of lung cancer (prediagnosis, staging, initial, continuing, and terminal), stratified by treatment, stage, and non-small- versus small-cell lung cancer. Lung cancer-attributable costs were estimated by subtracting each patient's own prediagnosis costs. Costs were estimated as the sum of Medicare reimbursements (payments from Medicare to the service provider), co-insurance reimbursements, and patient-liability costs (deductibles and "co-payments" that are the patient's responsibility). Costs and patient-liability costs were fit with regression models to compare trends by calendar year, adjusting for age at diagnosis. The monthly treatment costs for a 72-year-old patient, diagnosed with lung cancer in 2000, in the first 6 months ranged from $2687 (no active treatment) to $9360 (chemo-radiotherapy); costs varied by stage at diagnosis and histologic type. Patient liability represented up to 21.6% of care costs and increased over the period 1992-2003 for most stage and treatment categories, even when care costs decreased or remained unchanged. The greatest monthly patient liability was incurred by chemo-radiotherapy patients, which ranged from $1617 to $2004 per month across cancer stages. Costs for lung cancer care are substantial, and Medicare is paying a smaller proportion of the total cost over time. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Assessment of stage of change, decisional balance, self-efficacy, and use of processes of change of low-income parents for increasing servings of fruits and vegetables to preschool-aged children.

PubMed

Hildebrand, Deana A; Betts, Nancy M

2009-01-01

Use the Transtheoretical Model of Behavior Change (TTM) to determine the proportionate stage of change of low-income parents and primary caregivers (PPC) for increasing accessibility, measured as servings served, of fruits and vegetables (FV) to their preschool-aged children and evaluate response differences for theoretical constructs. Cross-sectional, quantitative survey design consisting of staging algorithm, construct scales, and food frequency questionnaire. Rural and urban communities in a southwestern state of the United States. 238 low-income PPC enrolled in federal nutrition education programs were recruited from group nutrition education sessions. Stage of change using a staging algorithm, TTM constructs of processes of change, decisional balance, and self-efficacy measured by multiple-item scales using Likert response, and fruit and vegetable servings served using a food frequency questionnaire. Descriptive analysis, Pearson's chi-square, analyses of variance with Tukey's Honestly Significant Difference post hoc test, and principal component function analysis. Of the surveyed PPC, 43% were in precontemplation/contemplation stages, and 29% were in the preparation stage for increasing FV accessibility (measured by servings served) to their preschool-aged children. PPC in the action/maintenance stages evidenced greater use of behavioral processes and had higher self-efficacy scores compared to PPC in precontemplation/contemplation and preparation stages. Interventions aimed at increasing FV accessibility for preschool-aged children should be tailored to meet PPCs' stage of change. Interventions targeting PPC in precontemplation/contemplation stages should use methods to share ideas for planning meals and snacks to include FV. Interventions for PPC in the preparation stage should aim to build skills in quick preparation of economical FV, address parental role modeling of FV consumption, and encourage goal setting. Learning formats providing social support may prove effective in prevention of behavior relapse for PPC in action/maintenance stages.

Modelling and temporal performances evaluation of networked control systems using (max, +) algebra

NASA Astrophysics Data System (ADS)

Ammour, R.; Amari, S.

2015-01-01

In this paper, we address the problem of temporal performances evaluation of producer/consumer networked control systems. The aim is to develop a formal method for evaluating the response time of this type of control systems. Our approach consists on modelling, using Petri nets classes, the behaviour of the whole architecture including the switches that support multicast communications used by this protocol. (max, +) algebra formalism is then exploited to obtain analytical formulas of the response time and the maximal and minimal bounds. The main novelty is that our approach takes into account all delays experienced at the different stages of networked automation systems. Finally, we show how to apply the obtained results through an example of networked control system.

Chemometric optimization of the robustness of the near infrared spectroscopic method in wheat quality control.

PubMed

Pojić, Milica; Rakić, Dušan; Lazić, Zivorad

2015-01-01

A chemometric approach was applied for the optimization of the robustness of the NIRS method for wheat quality control. Due to the high number of experimental (n=6) and response variables to be studied (n=7) the optimization experiment was divided into two stages: screening stage in order to evaluate which of the considered variables were significant, and optimization stage to optimize the identified factors in the previously selected experimental domain. The significant variables were identified by using fractional factorial experimental design, whilst Box-Wilson rotatable central composite design (CCRD) was run to obtain the optimal values for the significant variables. The measured responses included: moisture, protein and wet gluten content, Zeleny sedimentation value and deformation energy. In order to achieve the minimal variation in responses, the optimal factor settings were found by minimizing the propagation of error (POE). The simultaneous optimization of factors was conducted by desirability function. The highest desirability of 87.63% was accomplished by setting up experimental conditions as follows: 19.9°C for sample temperature, 19.3°C for ambient temperature and 240V for instrument voltage. Copyright © 2014 Elsevier B.V. All rights reserved.

Identification of putative QTLs for seedling stage phosphorus starvation response in finger millet (Eleusine coracana L. Gaertn.) by association mapping and cross species synteny analysis

PubMed Central

Ramakrishnan, M.; Ceasar, S. Antony; Vinod, K. K.; Duraipandiyan, V.; Ajeesh Krishna, T. P.; Upadhyaya, Hari D.; Al-Dhabi, N. A.

2017-01-01

A germplasm assembly of 128 finger millet genotypes from 18 countries was evaluated for seedling-stage phosphorus (P) responses by growing them in P sufficient (Psuf) and P deficient (Pdef) treatments. Majority of the genotypes showed adaptive responses to low P condition. Based on phenotype behaviour using the best linear unbiased predictors for each trait, genotypes were classified into, P responsive, low P tolerant and P non-responsive types. Based on the overall phenotype performance under Pdef, 10 genotypes were identified as low P tolerants. The low P tolerant genotypes were characterised by increased shoot and root length and increased root hair induction with longer root hairs under Pdef, than under Psuf. Association mapping of P response traits using mixed linear models revealed four quantitative trait loci (QTLs). Two QTLs (qLRDW.1 and qLRDW.2) for low P response affecting root dry weight explained over 10% phenotypic variation. In silico synteny analysis across grass genomes for these QTLs identified putative candidate genes such as Ser-Thr kinase and transcription factors such as WRKY and basic helix-loop-helix (bHLH). The QTLs for response under Psuf were mapped for traits such as shoot dry weight (qHSDW.1) and root length (qHRL.1). Putative associations of these QTLs over the syntenous regions on the grass genomes revealed proximity to cytochrome P450, phosphate transporter and pectin methylesterase inhibitor (PMEI) genes. This is the first report of the extent of phenotypic variability for P response in finger millet genotypes during seedling-stage, along with the QTLs and putative candidate genes associated with P starvation tolerance. PMID:28820887

Identification of putative QTLs for seedling stage phosphorus starvation response in finger millet (Eleusine coracana L. Gaertn.) by association mapping and cross species synteny analysis.

PubMed

Ramakrishnan, M; Ceasar, S Antony; Vinod, K K; Duraipandiyan, V; Ajeesh Krishna, T P; Upadhyaya, Hari D; Al-Dhabi, N A; Ignacimuthu, S

2017-01-01

A germplasm assembly of 128 finger millet genotypes from 18 countries was evaluated for seedling-stage phosphorus (P) responses by growing them in P sufficient (Psuf) and P deficient (Pdef) treatments. Majority of the genotypes showed adaptive responses to low P condition. Based on phenotype behaviour using the best linear unbiased predictors for each trait, genotypes were classified into, P responsive, low P tolerant and P non-responsive types. Based on the overall phenotype performance under Pdef, 10 genotypes were identified as low P tolerants. The low P tolerant genotypes were characterised by increased shoot and root length and increased root hair induction with longer root hairs under Pdef, than under Psuf. Association mapping of P response traits using mixed linear models revealed four quantitative trait loci (QTLs). Two QTLs (qLRDW.1 and qLRDW.2) for low P response affecting root dry weight explained over 10% phenotypic variation. In silico synteny analysis across grass genomes for these QTLs identified putative candidate genes such as Ser-Thr kinase and transcription factors such as WRKY and basic helix-loop-helix (bHLH). The QTLs for response under Psuf were mapped for traits such as shoot dry weight (qHSDW.1) and root length (qHRL.1). Putative associations of these QTLs over the syntenous regions on the grass genomes revealed proximity to cytochrome P450, phosphate transporter and pectin methylesterase inhibitor (PMEI) genes. This is the first report of the extent of phenotypic variability for P response in finger millet genotypes during seedling-stage, along with the QTLs and putative candidate genes associated with P starvation tolerance.

The Effects of Caffeine Supplementation on Physiological Responses to Submaximal Exercise in Endurance-Trained Men.

PubMed

Glaister, Mark; Williams, Benjamin Henley; Muniz-Pumares, Daniel; Balsalobre-Fernández, Carlos; Foley, Paul

2016-01-01

The aim of this study was to evaluate the effects of caffeine on physiological responses to submaximal exercise, with a focus on blood lactate concentration ([BLa]). Using a randomised, single-blind, crossover design; 16 endurance-trained, male cyclists (age: 38 ± 8 years; height: 1.80 ± 0.05 m; body mass: 76.6 ± 7.8 kg; [Formula: see text]: 4.3 ± 0.6 L∙min-1) completed four trials on an electromagnetically-braked cycle ergometer. Each trial consisted of a six-stage incremental test (3 minute stages) followed by 30 minutes of passive recovery. One hour before trials 2-4, participants ingested a capsule containing 5 mg∙kg-1 of either caffeine or placebo (maltodextrin). Trials 2 and 3 were designed to evaluate the effects of caffeine on various physiological responses during exercise and recovery. In contrast, Trial 4 was designed to evaluate the effects of caffeine on [BLa] during passive recovery from an end-exercise concentration of 4 mmol∙L-1. Relative to placebo, caffeine increased [BLa] during exercise, independent of exercise intensity (mean difference: 0.33 ± 0.41 mmol∙L-1; 95% likely range: 0.11 to 0.55 mmol∙L-1), but did not affect the time-course of [BLa] during recovery (p = 0.604). Caffeine reduced ratings of perceived exertion (mean difference: 0.5 ± 0.7; 95% likely range: 0.1 to 0.9) and heart rate (mean difference: 3.6 ± 4.2 b∙min-1; 95% likely range: 1.3 to 5.8 b∙min-1) during exercise, with the effect on the latter dissipating as exercise intensity increased. Supplement × exercise intensity interactions were observed for respiratory exchange ratio (p = 0.004) and minute ventilation (p = 0.034). The results of the present study illustrate the clear, though often subtle, effects of caffeine on physiological responses to submaximal exercise. Researchers should be aware of these responses, particularly when evaluating the physiological effects of various experimental interventions.

Suitability of frequency modulated thermal wave imaging for skin cancer detection-A theoretical prediction.

PubMed

Bhowmik, Arka; Repaka, Ramjee; Mulaveesala, Ravibabu; Mishra, Subhash C

2015-07-01

A theoretical study on the quantification of surface thermal response of cancerous human skin using the frequency modulated thermal wave imaging (FMTWI) technique has been presented in this article. For the first time, the use of the FMTWI technique for the detection and the differentiation of skin cancer has been demonstrated in this article. A three dimensional multilayered skin has been considered with the counter-current blood vessels in individual skin layers along with different stages of cancerous lesions based on geometrical, thermal and physical parameters available in the literature. Transient surface thermal responses of melanoma during FMTWI of skin cancer have been obtained by integrating the heat transfer model for biological tissue along with the flow model for blood vessels. It has been observed from the numerical results that, flow of blood in the subsurface region leads to a substantial alteration on the surface thermal response of the human skin. The alteration due to blood flow further causes a reduction in the performance of the thermal imaging technique during the thermal evaluation of earliest melanoma stages (small volume) compared to relatively large volume. Based on theoretical study, it has been predicted that the method is suitable for detection and differentiation of melanoma with comparatively large volume than the earliest development stages (small volume). The study has also performed phase based image analysis of the raw thermograms to resolve the different stages of melanoma volume. The phase images have been found to be clearly individuate the different development stages of melanoma compared to raw thermograms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Induction chemotherapy in head and neck squamous cell carcinoma of the paranasal sinus and nasal cavity: a role in organ preservation

PubMed Central

Ock, Chan-Young; Keam, Bhumsuk; Kim, Tae Min; Han, Doo Hee; Won, Tae-Bin; Lee, Se-Hoon; Hah, J. Hun; Kwon, Tack-Kyun; Kim, Dong-Wan; Kim, Dong-Young; Rhee, Chae-Seo; Wu, Hong-Gyun; Sung, Myung-Whun; Heo, Dae Seog

2016-01-01

Background/Aims: The role of induction chemotherapy (IC) for eyeball preservation has not been established in head and neck squamous cell carcinoma (HNSCC) of the paranasal sinus and nasal cavity (PNSNC). Periorbital involvement frequently leads to eyeball exenteration with a margin of safety. We evaluated the treatment outcomes, including survival and eyeball preservation, of patients who received IC for HNSCC of the PNSNC. Methods: We reviewed 21 patients diagnosed with HNSCC of the PNSNC who were treated with IC. We analyzed response, eyeball preservation rate, and overall survival. Results: Tumors were located in the paranasal sinus (n = 14) or nasal cavity (n = 7). Most patients had stage T4a (n = 10) or T4b (n = 7) disease. More than half of the patients received a chemotherapy regimen of docetaxel, fluorouracil, and cisplatin (n = 11). Thirteen patients (61.9%) achieved a partial response after IC and 15 patients (71.4%) achieved T down-staging. Among 17 patients with stage T4 disease, which confers a high risk of orbital exenteration, 14 (82.4%) achieved preservation of the involved eye. The 3-year overall survival (OS) rate of patients who achieved a partial response to IC was 84.6%. The 3-year OS rate of patients with stable disease or disease progression after IC was 25.0% (p = 0.038). Conclusions: IC could be considered for down-staging patients with advanced T-stage disease. It could also be a reasonable option for eyeball preservation in locally advanced HNSCC of the PNSNC. PMID:26976150

Complete Neoadjuvant Treatment for Rectal Cancer: The Brown University Oncology Group CONTRE Study.

PubMed

Perez, Kimberly; Safran, Howard; Sikov, William; Vrees, Matthew; Klipfel, Adam; Shah, Nishit; Schechter, Steven; Oldenburg, Nicklas; Pricolo, Victor; Rosati, Kayla; Dipetrillo, Thomas

2017-06-01

Following preoperative chemoradiation and surgery, many patients with stage II to III rectal cancer are unable to tolerate full-dose adjuvant chemotherapy. BrUOG R-224 was designed to assess the impact of COmplete Neoadjuvant Treatment for REctal cancer (CONTRE), primary chemotherapy followed by chemoradiation and surgery, on treatment delivery, toxicities, and pathologic response at surgery. Patients with clinical stage II to III (T3 to T4 and/or N1 to N2) rectal cancer received 8 cycles of modified FOLFOX6 followed by capecitabine 825 mg/m bid concurrent with 50.4 Gy intensity-modulated radiation therapy. Surgery was performed 6 to 10 weeks after chemoradiation. Thirty-nine patients were enrolled between August 2010 and June 2013. Median age was 61 years (30 to 79 y); 7 patients (18%) were clinical stage II and 32 (82%) stage III. Thirty-six patients (92%) received all 8 cycles of mFOLFOX6, of whom 35 completed subsequent chemoradiation; thus 89% of patients received CONTRE as planned. No unexpected toxicities were reported. All patients had resolution of bleeding and improvement of obstructive symptoms, with no complications requiring surgical intervention. Pathologic complete response (ypT0N0) was demonstrated in 13 patients (33%; 95% CI, 18.24%-47.76%). CONTRE seems to be a well-tolerated alternative to the current standard treatment sequence. Evaluating its impact on long-term outcomes would require a large randomized trial, but using pathologic response as an endpoint, it could serve as a platform for assessing the addition of novel agents to preoperative treatment in stage II to III rectal cancer.

Influence of environmental factors on biotic responses to nutrient enrichment in agricultural streams

USGS Publications Warehouse

Maret, Terry R.; Konrad, Christopher P.; Tranmer, Andrew W.

2010-01-01

The influence of environmental factors on biotic responses to nutrients was examined in three diverse agricultural regions of the United States. Seventy wadeable sites were selected along an agricultural land use gradient while minimizing natural variation within each region. Nutrients, habitat, algae, macroinvertebrates, and macrophyte cover were sampled during a single summer low-flow period in 2006 or 2007. Continuous stream stage and water temperature were collected at each site for 30 days prior to sampling. Wide ranges of concentrations were found for total nitrogen (TN) (0.07-9.61 mg/l) and total phosphorus (TP) (R2) for nutrients and biotic measures across all sites ranged from 0.08 to 0.32 and generally were not higher within each region. The biotic measures (RCHL, SCHL, and AQM) were combined in an index to evaluate eutrophic status across sites that could have different biotic responses to nutrient enrichment. Stepwise multiple regression identified TN, percent canopy, median riffle depth, and daily percent change in stage as significant factors for the eutrophic index (R2 = 0.50, p < 0.001). A TN threshold of 0.48 mg/l was identified where eutrophic index scores became less responsive to increasing TN concentrations, for all sites. Multiple plant growth indicators should be used when evaluating eutrophication, especially when streams contain an abundance of macrophytes.

The extent of the uptake of plasmid into the skin determines the immune responses induced by a DNA vaccine applied topically onto the skin

PubMed Central

Yu, Zhen; Chung, Woon-Gye; Sloat, Brian R.; Löhr, Christiane V.; Weiss, Richard; Rodriguez, B. Leticia; Li, Xinran; Cui, Zhengrong

2011-01-01

Objectives Non-invasive immunization by applying plasmid DNA topically onto the skin is an attractive immunization approach. However, the immune responses induced are generally weak. Previously, we showed that the antibody responses induced by topical DNA vaccine were significantly enhanced when hair follicles in the application area were induced into anagen (growth) stage by hair plucking. In the present study, we further investigated the mechanism of immune enhancement. Methods Three different methods, hair plucking or treatment with retinoic acid (RA) or O- tetradecanoylphorbol-13-acetate (TPA), were used to induce hair follicles into anagen stage before mice were dosed with a β-galactosidase-encoding plasmid, and the specific antibody responses induced were evaluated. Key findings The hair plucking method was more effective at enhancing the resultant antibody responses. Treatment with RA or TPA caused more damages to the skin and induced more severe local inflammations than hair plucking. However, hair plucking was most effective at enhancing the uptake or retention of the DNA in the application area. Conclusions The uptake of plasmid DNA in the application area correlated with the antibody responses induced by a topically applied DNA. PMID:21235583

Effort provides its own reward: endeavors reinforce subjective expectation and evaluation of task performance.

PubMed

Wang, Lei; Zheng, Jiehui; Meng, Liang

2017-04-01

Although many studies have investigated the relationship between the amount of effort invested in a certain task and one's attitude towards the subsequent reward, whether exerted effort would impact one's expectation and evaluation of performance feedback itself still remains to be examined. In the present study, two types of calculation tasks that varied in the required effort were adopted, and we resorted to electroencephalography to probe the temporal dynamics of how exerted effort would affect one's anticipation and evaluation of performance feedback. In the high-effort condition, a more salient stimulus-preceding negativity was detected during the anticipation stage, which was accompanied with a more salient FRN/P300 complex (a more positive P300 and a less negative feedback-related negativity) in response to positive outcomes in the evaluation stage. These results suggested that when more effort was invested, an enhanced anticipatory attention would be paid toward one's task performance feedback and that positive outcomes would be subjectively valued to a greater extent.

Challenges in Pathologic Staging of Renal Cell Carcinoma: A Study of Interobserver Variability Among Urologic Pathologists.

PubMed

Williamson, Sean R; Rao, Priya; Hes, Ondrej; Epstein, Jonathan I; Smith, Steven C; Picken, Maria M; Zhou, Ming; Tretiakova, Maria S; Tickoo, Satish K; Chen, Ying-Bei; Reuter, Victor E; Fleming, Stewart; Maclean, Fiona M; Gupta, Nilesh S; Kuroda, Naoto; Delahunt, Brett; Mehra, Rohit; Przybycin, Christopher G; Cheng, Liang; Eble, John N; Grignon, David J; Moch, Holger; Lopez, Jose I; Kunju, Lakshmi P; Tamboli, Pheroze; Srigley, John R; Amin, Mahul B; Martignoni, Guido; Hirsch, Michelle S; Bonsib, Stephen M; Trpkov, Kiril

2018-06-06

Staging criteria for renal cell carcinoma differ from many other cancers, in that renal tumors are often spherical with subtle, finger-like extensions into veins, renal sinus, or perinephric tissue. We sought to study interobserver agreement in pathologic stage categories for challenging cases. An online survey was circulated to urologic pathologists interested in kidney tumors, yielding 89% response (31/35). Most questions included 1 to 4 images, focusing on: vascular and renal sinus invasion (n=24), perinephric invasion (n=9), and gross pathology/specimen handling (n=17). Responses were collapsed for analysis into positive and negative/equivocal for upstaging. Consensus was regarded as an agreement of 67% (2/3) of participants, which was reached in 20/33 (61%) evaluable scenarios regarding renal sinus, perinephric, or vein invasion, of which 13/33 (39%) had ≥80% consensus. Lack of agreement was especially encountered regarding small tumor protrusions into a possible vascular lumen, close to the tumor leading edge. For gross photographs, most were interpreted as suspicious but requiring histologic confirmation. Most participants (61%) rarely used special stains to evaluate vascular invasion, usually endothelial markers (81%). Most agreed that a spherical mass bulging well beyond the kidney parenchyma into the renal sinus (71%) or perinephric fat (90%) did not necessarily indicate invasion. Interobserver agreement in pathologic staging of renal cancer is relatively good among urologic pathologists interested in kidney tumors, even when selecting cases that test the earliest and borderline thresholds for extrarenal extension. Disagreements remain, however, particularly for tumors with small, finger-like protrusions, closely juxtaposed to the main mass.

Clinical evaluation of the vector algorithm for neonatal hearing screening using automated auditory brainstem response.

PubMed

Keohane, Bernie M; Mason, Steve M; Baguley, David M

2004-02-01

A novel auditory brainstem response (ABR) detection and scoring algorithm, entitled the Vector algorithm is described. An independent clinical evaluation of the algorithm using 464 tests (120 non-stimulated and 344 stimulated tests) on 60 infants, with a mean age of approximately 6.5 weeks, estimated test sensitivity greater than 0.99 and test specificity at 0.87 for one test. Specificity was estimated to be greater than 0.95 for a two stage screen. Test times were of the order of 1.5 minutes per ear for detection of an ABR and 4.5 minutes per ear in the absence of a clear response. The Vector algorithm is commercially available for both automated screening and threshold estimation in hearing screening devices.

Survival outcome of intermediate risk neuroblastoma at Children Cancer Hospital Egypt.

PubMed

Elzomor, Hossam; Ahmed, Gehad; Elmenawi, Salma; Elkinaai, Naglaa; Refaat, Amal; Soliman, Sonya; Abdelwahab, Mai Amr; Zaghloul, Mohamed Saad; Fawzy, Mohamed

2018-03-01

The study aims to evaluate survival outcome in newly diagnosed pediatric intermediate risk neuroblastoma patients treated at the Children Cancer Hospital - Egypt and their relation to various clinical and pathological factors. The study included stage 3 patients <1.5 years, children 1.5 years or older with stage 3 disease and favorable histopathological features, infants (<1 year) with International Neuroblastoma Staging System (INSS) stage 4 disease, stage 4 children 1-1.5 years with favorable biology, and infants stage 4 s (with unfavorable biologic features). Patients received systemic chemotherapy, in the form of etoposide and carboplatin alternating with cyclophosphamide, doxorubicin and vincristine, administered at 3-week intervals, with a total of 6 or 8 cycles guided by reaching objective overall response (complete/very good partial/partial response). The study included 136 patients, 67 males and 69 females. 101 patients had abdominal primary tumors, 28 had mediastinal masss and 7 with masses in the neck; 68% were stage 3 and the remaining (n = 44) had metastatic disease. The three-year overall survival (OS) and event-free survival (EFS) estimates were 94% ± 2% and 90.9% ± 2.5%, respectively. OS and EFS by gender, age, pathology and INPC were all statistically not significantly different. Moreover, OS for patients having surgery versus no surgery (inoperable residual only) was statistically significant (98.4% ± 1.6% & 88.7% ± 5.3%, respectively, p = .034). A very high rate of survival is currently achievable in patients with intermediate risk neuroblastoma by chemotherapy or chemotherapy and surgery. In addition to response, our plan is to adopt biologically-based treatment to reduce treatment-induced complications among survivors. Copyright © 2018 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

The role of fluorine-18-fluorodeoxyglucose positron emission tomography in evaluating the response to tyrosine-kinase inhibitors in patients with metastatic primary renal cell carcinoma.

PubMed

Caldarella, Carmelo; Muoio, Barbara; Isgrò, Maria Antonietta; Porfiri, Emilio; Treglia, Giorgio; Giovanella, Luca

2014-09-01

Positron emission tomography-computed tomography (PET-CT) using fluorodeoxyglucose (FDG) is increasingly used in the evaluation of patients with advanced renal cell carcinoma (RCC), primarily for staging purposes. The aim of this paper is to perform a systematic review about the usefulness of PET-CT using FDG in response assessment after treatment with tyrosine-kinase inhibitors (TKIs) in patients with advanced RCC. The scientific literature about the role of PET-CT using FDG in the assessment of response to treatment with TKIs in patients affected by advanced RCC was systematically reviewed. Seven studies about the role of PET-CT using FDG in the response assessment after treatment with TKIs (essentially sunitinib and sorafenib) in advanced RCC were retrieved in full-text and analysed, to determine the predictive role of this morpho-functional imaging method on patient outcome. To date, the role of PET-CT using FDG in evaluating the response to TKIs in metastatic RCC patients is still not well defined, partly due to heterogeneity of available studies; however, PET-CT reveals potential role for the selection of patients undergoing therapy with TKIs. The use of contrast-enhanced PET-CT appears to be promising for a "multi-dimensional" evaluation of treatment response in these patients.

Prevalence and strength of density-dependent tree recruitment

Treesearch

Kai Zhu; Christopher W. Woodall; Joao V.D. Monteiro; James S. Clark

2015-01-01

Density dependence could maintain diversity in forests, but studies continue to disagree on its role. Part of the disagreement results from the fact that different studies have evaluated different responses (survival, recruitment, or growth) of different stages (seeds, seedlings, or adults) to different inputs (density of seedlings, density or distance to adults). Most...

Positron emission tomography/computerized tomography in lung cancer

PubMed Central

Vural, Gulin Ucmak

2014-01-01

Positron emission tomography (PET) using 2-(18F)-flouro-2-deoxy-D-glucose (FDG) has emerged as a useful tool in the clinical work-up of lung cancer. This review article provides an overview of applications of PET in diagnosis, staging, treatment response evaluation, radiotherapy planning, recurrence assessment and prognostication of lung cancer. PMID:24914421

HYPOXIC EFFECT ON GROWTH OF PALEOMENETES VULGARIS LARVAE AND OTHER SPECIES: USING CONSTANT EXPOSURE DATA TO PREDICT CYCLIC EXPOSURE RESPONSE

EPA Science Inventory

First stage larval marsh grass shrimp, Palaemonetes vulgaris, were exposed to patterns of diurnal, semidiurnal, and constant hypoxia to evaluate effects on growth and to determine if there was a consistent relationship between exposures. A comparison of growth with cyclic exposur...

Interpreting Visual Texts: Use of an Analytic Rubric to Evaluate Student Responses to Writing Prompts

ERIC Educational Resources Information Center

Sundeen, Todd H.; O'Neil, Kathleen; Fanselow, Stephanie A.

2017-01-01

Younger students' visual texts are statements and stories conveyed through drawings or other artwork and often convey meaning beyond the child's capability to communicate with written expression. Although opportunities for expression through drawing are routinely offered to children in the initial and middle stages of early childhood literacy…

Evaluating Mesorectal Lymph Nodes in Rectal Cancer Before and After Neoadjuvant Chemoradiation Using Thin-Section T2-Weighted Magnetic Resonance Imaging

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

Koh, Dow-Mu; Chau, Ian; Tait, Diana

2008-06-01

Purpose: To apply thin-section T2-weighted magnetic resoance imaging (MRI) to evaluate the number, size, distribution, and morphology of benign and malignant mesorectal lymph nodes before and after chemoradiation treatment compared with histopathologic findings. Methods and Materials: Twenty-five patients with poor-risk adenocarcinoma of the rectum treated with neoadjuvant chemoradiation were evaluated prospectively. Thin-section T2-weighted MR images obtained before and after chemoradiation treatment were independently reviewed in consensus by 2 expert radiologists to determine the tumor stage, nodal size, nodal distribution, and nodal stage. Total mesorectal excision surgery after chemoradiation allowed MR nodal stage to be compared with histopathology using {kappa} statistics.more » Nodal downstaging was compared using the Chi-square test. Results: Before chemoradiation, 152 mesorectal nodes were visible (mean, 6.2 mm; 100 benign, 52 malignant) and 4 of 52 malignant nodes were in contact with the mesorectal fascia. The nodal staging was 7/25 N0, 10/25 N1, and 7/25 N2. After chemoradiation, only 29 nodes (mean, 4.1 mm; 24 benign, 5 malignant) were visible, and none were in contact with the mesorectal fascia. Nodal downstaging was observed: 20/25 N0 and 5/25 N1 (p < 0.01, Chi-square test). There was good agreement between MRI and pathologic T-staging ({kappa} = 0.64) and N-staging ({kappa} = 0.65) after chemoradiation. Conclusions: Neoadjuvant chemoradiation treatment resulted in a decrease in size and number of malignant- and benign-appearing mesorectal nodes on MRI. Nodal downstaging and nodal regression from the mesorectal fascia were observed after treatment. MRI is a useful tool for assessing nodal response to neoadjuvant treatment.« less

Influence of acute progressive hypoxia on cardiovascular variability in conscious spontaneously hypertensive rats

PubMed Central

Sugimura, Mitsutaka; Hirose, Yohsuke; Hanamoto, Hiroshi; Okada, Kenji; Boku, Aiji; Morimoto, Yoshinari; Taki, Kunitaka; Niwa, Hitoshi

2008-01-01

The purpose of this study is to examine the influence of acute progressive hypoxia on cardiovascular variability and striatal dopamine (DA) levels in conscious, spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). After preparation for measurement, the inspired oxygen concentration of rats was decreased to 10% within 5 min (descent stage), maintained at 10% for 10 min (fixed stage), and then elevated back to 20% over 5 min (recovery stage). The systolic blood pressure (SBP) and heart rate (HR) variability at each stage was calculated to evaluate the autonomic nervous system response using the wavelet method. Striatal DA during each stage was measured using in vivo microdialysis. We found that SHR showed a more profound hemodynamic response to progressive hypoxia as compared to WKY. Cardiac parasympathetic activity in SHR was significantly inhibited by acute progressive hypoxia during all stages, as shown by the decrease in the high frequency band of HR variability (HR-HF), along with transient increase in sympathetic activity during the early hypoxic phase. This decrease in the HR-HF continued even when SBP was elevated. Striatal DA levels showed the transient similar elevation in both groups. These findings suggest that acute progressive hypoxic stress in SHR inhibits cardiac parasympathetic activity through reduction of baroreceptor reflex sensitivity, with potentially severe deleterious effects on circulation, in particular on HR and circulatory control. Furthermore, it is thought that the influence of acute progressive hypoxia on striatal DA levels is similar in SHR and WKY. PMID:18599365

A phase II study of sunitinib in patients with recurrent epithelial ovarian and primary peritoneal carcinoma: an NCIC Clinical Trials Group Study.

PubMed

Biagi, J J; Oza, A M; Chalchal, H I; Grimshaw, R; Ellard, S L; Lee, U; Hirte, H; Sederias, J; Ivy, S P; Eisenhauer, E A

2011-02-01

Sunitinib is a multitargeted receptor tyrosine kinase inhibitor. We conducted a two-stage phase II study to evaluate the objective response rate of oral sunitinib in recurrent epithelial ovarian cancer. Eligibility required measurable disease and one or two prior chemotherapies, at least one platinum based. Platinum-sensitive or -resistant disease was allowed. Initial dose schedule was sunitinib 50 mg daily, 4 of 6 weeks. Observation of fluid accumulations during off-treatment periods resulted in adoption of continuous 37.5 mg daily dosing in the second stage of accrual. Of 30 eligible patients, most had serous histology (67%), were platinum sensitive (73%) and had two prior chemotherapies (60%). One partial response (3.3%) and three CA125 responses (10%) were observed, all in platinum-sensitive patients using intermittent dosing. Sixteen (53%) had stable disease. Five had >30% decrease in measurable disease. Overall median progression-free survival was 4.1 months. Common adverse events included fatigue, gastrointestinal symptoms, hand-foot syndrome and hypertension. No gastrointestinal perforation occurred. Single-agent sunitinib has modest activity in recurrent platinum-sensitive ovarian cancer, but only at the 50 mg intermittent dose schedule, suggesting that dose and schedule may be vital considerations in further evaluation of sunitinib in this cancer setting.

Hypopituitarism after irradiation in children

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

Wara, W.M.; Richards, G.E.; Grumbach, M.M. Kaplan, S.L.

1977-01-01

Nine children were referred to the University of California Medical Center, San Francisco, for growth evaluation. Each had received conventional radiation doses to the head for tumors not involving the hypothalamus or pituitary, and demonstrated clinical and laboratory evidence of hormonal deficiencies several years after treatment. Six had significant height retardation. Growth hormone deficiency was documented in all by lack of response to provocative insulin, arginine, and/or L-dopa stimulation. ACTH function was evaluated by plasma cortisol response to insulin hypoglycemia in 7; one had a subnormal response. Plasma gonadotropins were measured after lutenizing hormone releasing factor (LRF) in 7 patients;more » only one had an abnormal response for age and stage of sexual maturation. Foresight in treatment planning and careful follow-up of patients receiving irradiation to the head is critical, since hypothalamic-pituitary deficiencies which may occur insidiously over many years, can largely be compensated.« less

Efficacy of TACE in TIPS Patients: Comparison of Treatment Response to Chemoembolization for Hepatocellular Carcinoma in Patients With and Without a Transjugular Intrahepatic Portosystemic Shunt

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

Kuo, Yuo-Chen, E-mail: yuo-chen.kuo@ucsf.edu; Kohi, Maureen P., E-mail: maureen.kohi@ucsf.edu; Naeger, David M., E-mail: david.naeger@ucsf.edu

Purpose: To compare treatment response after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) in patients with and without a transjugular intrahepatic portosystemic shunt (TIPS). Materials and Methods: A retrospective review of patients who underwent conventional TACE for HCC between January 2005 and December 2009 identified 10 patients with patent TIPS. From the same time period, 23 patients without TIPS were selected to control for comparable Model for End-Stage Liver Disease and Child-Pugh-Turcotte scores. The two groups showed similar distribution of Barcelona Clinic Liver Cancer and United Network of Organ Sharing stages. Target HCC lesions were evaluated according to the modifiedmore » response evaluation criteria in solid tumors (mRECIST) guidelines. Transplantation rate, time to tumor progression, and overall survival (OS) were documented. Results: After TACE, the rate of complete response was significantly greater in non-TIPS patients compared with TIPS patients (74 vs. 30 %, p = 0.03). Objective response rate (complete and partial response) trended greater in the non-TIPS group (83 vs. 50 %, p = 0.09). The liver transplantation rate was 80 and 74 % in the TIPS and non-TIPS groups, respectively (p = 1.0). Time to tumor progression was similar (p = 0.47) between the two groups. OS favored the non-TIPS group (p = 0.01) when censored for liver transplantation. Conclusion: TACE is less effective in achieving complete or partial response using mRECIST criteria in TIPS patients compared with those without a TIPS. Nevertheless, similar clinical outcomes may be achieved, particularly in TIPS patients who are liver-transplantation candidates.« less

Genetic Architecture of Flooding Tolerance in the Dry Bean Middle-American Diversity Panel

PubMed Central

Soltani, Ali; MafiMoghaddam, Samira; Walter, Katelynn; Restrepo-Montoya, Daniel; Mamidi, Sujan; Schroder, Stephan; Lee, Rian; McClean, Phillip E.; Osorno, Juan M.

2017-01-01

Flooding is a devastating abiotic stress that endangers crop production in the twenty-first century. Because of the severe susceptibility of common bean (Phaseolus vulgaris L.) to flooding, an understanding of the genetic architecture and physiological responses of this crop will set the stage for further improvement. However, challenging phenotyping methods hinder a large-scale genetic study of flooding tolerance in common bean and other economically important crops. A greenhouse phenotyping protocol was developed to evaluate the flooding conditions at early stages. The Middle-American diversity panel (n = 272) of common bean was developed to capture most of the diversity exits in North American germplasm. This panel was evaluated for seven traits under both flooded and non-flooded conditions at two early developmental stages. A subset of contrasting genotypes was further evaluated in the field to assess the relationship between greenhouse and field data under flooding condition. A genome-wide association study using ~150 K SNPs was performed to discover genomic regions associated with multiple physiological responses. The results indicate a significant strong correlation (r > 0.77) between greenhouse and field data, highlighting the reliability of greenhouse phenotyping method. Black and small red beans were the least affected by excess water at germination stage. At the seedling stage, pinto and great northern genotypes were the most tolerant. Root weight reduction due to flooding was greatest in pink and small red cultivars. Flooding reduced the chlorophyll content to the greatest extent in the navy bean cultivars compared with other market classes. Races of Durango/Jalisco and Mesoamerica were separated by both genotypic and phenotypic data indicating the potential effect of eco-geographical variations. Furthermore, several loci were identified that potentially represent the antagonistic pleiotropy. The GWAS analysis revealed peaks at Pv08/1.6 Mb and Pv02/41 Mb that are associated with root weight and germination rate, respectively. These regions are syntenic with two QTL reported in soybean (Glycine max L.) that contribute to flooding tolerance, suggesting a conserved evolutionary pathway involved in flooding tolerance for these related legumes. PMID:28729876

Genetic Architecture of Flooding Tolerance in the Dry Bean Middle-American Diversity Panel.

PubMed

Soltani, Ali; MafiMoghaddam, Samira; Walter, Katelynn; Restrepo-Montoya, Daniel; Mamidi, Sujan; Schroder, Stephan; Lee, Rian; McClean, Phillip E; Osorno, Juan M

2017-01-01

Flooding is a devastating abiotic stress that endangers crop production in the twenty-first century. Because of the severe susceptibility of common bean ( Phaseolus vulgaris L.) to flooding, an understanding of the genetic architecture and physiological responses of this crop will set the stage for further improvement. However, challenging phenotyping methods hinder a large-scale genetic study of flooding tolerance in common bean and other economically important crops. A greenhouse phenotyping protocol was developed to evaluate the flooding conditions at early stages. The Middle-American diversity panel ( n = 272) of common bean was developed to capture most of the diversity exits in North American germplasm. This panel was evaluated for seven traits under both flooded and non-flooded conditions at two early developmental stages. A subset of contrasting genotypes was further evaluated in the field to assess the relationship between greenhouse and field data under flooding condition. A genome-wide association study using ~150 K SNPs was performed to discover genomic regions associated with multiple physiological responses. The results indicate a significant strong correlation ( r > 0.77) between greenhouse and field data, highlighting the reliability of greenhouse phenotyping method. Black and small red beans were the least affected by excess water at germination stage. At the seedling stage, pinto and great northern genotypes were the most tolerant. Root weight reduction due to flooding was greatest in pink and small red cultivars. Flooding reduced the chlorophyll content to the greatest extent in the navy bean cultivars compared with other market classes. Races of Durango/Jalisco and Mesoamerica were separated by both genotypic and phenotypic data indicating the potential effect of eco-geographical variations. Furthermore, several loci were identified that potentially represent the antagonistic pleiotropy. The GWAS analysis revealed peaks at Pv08/1.6 Mb and Pv02/41 Mb that are associated with root weight and germination rate, respectively. These regions are syntenic with two QTL reported in soybean ( Glycine max L.) that contribute to flooding tolerance, suggesting a conserved evolutionary pathway involved in flooding tolerance for these related legumes.

The evaluation of distributed damage in concrete based on sinusoidal modeling of the ultrasonic response.

PubMed

Sepehrinezhad, Alireza; Toufigh, Vahab

2018-05-25

Ultrasonic wave attenuation is an effective descriptor of distributed damage in inhomogeneous materials. Methods developed to measure wave attenuation have the potential to provide an in-site evaluation of existing concrete structures insofar as they are accurate and time-efficient. In this study, material classification and distributed damage evaluation were investigated based on the sinusoidal modeling of the response from the through-transmission ultrasonic tests on polymer concrete specimens. The response signal was modeled as single or the sum of damping sinusoids. Due to the inhomogeneous nature of concrete materials, model parameters may vary from one specimen to another. Therefore, these parameters are not known in advance and should be estimated while the response signal is being received. The modeling procedure used in this study involves a data-adaptive algorithm to estimate the parameters online. Data-adaptive algorithms are used due to a lack of knowledge of the model parameters. The damping factor was estimated as a descriptor of the distributed damage. The results were compared in two different cases as follows: (1) constant excitation frequency with varying concrete mixtures and (2) constant mixture with varying excitation frequencies. The specimens were also loaded up to their ultimate compressive strength to investigate the effect of distributed damage in the response signal. The results of the estimation indicated that the damping was highly sensitive to the change in material inhomogeneity, even in comparable mixtures. In addition to the proposed method, three methods were employed to compare the results based on their accuracy in the classification of materials and the evaluation of the distributed damage. It is shown that the estimated damping factor is not only sensitive to damage in the final stages of loading, but it is also applicable in evaluating micro damages in the earlier stages providing a reliable descriptor of damage. In addition, the modified amplitude ratio method is introduced as an improvement of the classical method. The proposed methods were validated to be effective descriptors of distributed damage. The presented models were also in good agreement with the experimental data. Copyright © 2018 Elsevier B.V. All rights reserved.

Skin denervation and its clinical significance in late-stage chronic kidney disease.

PubMed

Chao, Chi-Chao; Wu, Vin-Cent; Tan, Chun-Hsiang; Wang, Yi-Mei; Tseng, Ming-Tsung; Wu, Pei-Chen; Lin, Yea-Huey; Lin, Whei-Min; Wu, Kwan-Dun; Hsieh, Sung-Tsang

2011-02-01

To investigate the skin innervation and its clinical significance in late-stage chronic kidney disease (CKD). Case series. National Taiwan University Hospital, Taipei, Taiwan. Forty consecutive nondiabetic patients with late-stage CKD (14 female and 26 male; mean [SD] age, 60.7 [12.3] years), including 2 cases with stage 3 CKD, 6 with stage 4 CKD, and 32 with stage 5 CKD, ie, end-stage kidney disease. Clinical evaluation of neurological deficits, nerve conduction study, autonomic function tests, and a 3-mm-diameter skin biopsy specimen taken from the distal leg. Quantitation of epidermal innervation, parameters of nerve conduction study, R-R interval variability, and sympathetic skin response. Clinically, 21 patients (52.5%) were symptomatic with paresthesia over the limbs or autonomic symptoms. The intraepidermal nerve fiber (IENF) density was markedly reduced in patients with CKD compared with age- and sex-matched controls (mean [SD], 2.8 [2.0] vs 8.6 [2.8] fibers/mm; P < .001). Skin denervation was observed in 27 patients (67.5%). Fifteen patients (37.5%) had abnormalities on nerve conduction studies, and 29 patients (72.5%) had abnormal results on autonomic function tests. By analysis with multiple regression models, the IENF density was negatively correlated with the duration of renal disease (P = .02). Additionally, the R-R interval variability at rest was linearly correlated with the IENF density (P = .02) and the absence of sympathetic skin responses at the soles was associated with reduced IENF density (P = .03). Small-fiber sensory and autonomic neuropathies constitute the major form of neuropathy in late-stage CKD. Furthermore, skin denervation was associated with the duration of renal disease.

Efficacy of Icotinib treatment in patients with stage IIIb/IV non-small cell lung cancer

PubMed Central

Qin, Na; Yang, Xinjie; Zhang, Quan; Li, Xi; Zhang, Hui; Lv, Jialin; Wu, Yuhua; Wang, Jinghui; Zhang, Shucai

2014-01-01

Background To evaluate the efficacy and safety of Icotinib – an orally administered, highly potent selective inhibitor of epidermal growth factor receptor (EGFR) and its active mutations, in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Methods A total of 101 patients with stage IIIb/IV NSCLC were treated with 125 mg Icotinib three times a day until disease progression or intolerable toxicity. Response rate was evaluated using response evaluation criteria in solid tumors and progression-free survival (PFS) was collected. Results The overall response rate (ORR) and disease control rate (DCR) were 37.6% (38/101) and 79.2% (80/101), respectively. The median PFS was 6.5 months. Multivariate analysis showed that female gender (P= 0.048, 95% confidence interval [CI] 1.010–6.016) and occurrence of rash (P= 0.002, 95% CI 1.667–9.809) were the independent predictive factors for ORR, while a performance status (PS) score of 0–1 (P= 0.001, 95% CI 0.024–0.402) and rash (P= 0.042, 95% CI 1.089–76.557) were the independent predictive factors for DCR. In addition, PS scores of 0–1 (P <0.001, 95% CI 0.135–0.509), and non-smoking (P= 0.017, 95% CI 0.342–0.900) were found to be independent influencing factors for PFS. Moreover, patients with EGFR mutations had better PFS than patients with wild type EGFR, while patients with EGFR exon 19 deletion had better survival than those with EGFR exon 21 mutation. The most common adverse effects of Icotinib were rash (35.6%) and diarrhea (17.8%), which was tolerable. Conclusion Treatment of stage IIIb/IV NSCLC patients with Icotinib was effective and tolerable, specifically in patients with EGFR mutation. PMID:26767007

Interim Positron Emission Tomography Response-Adapted Therapy in Advanced-Stage Hodgkin Lymphoma: Final Results of the Phase II Part of the HD0801 Study.

PubMed

Zinzani, Pier Luigi; Broccoli, Alessandro; Gioia, Daniela Maria; Castagnoli, Antonio; Ciccone, Giovannino; Evangelista, Andrea; Santoro, Armando; Ricardi, Umberto; Bonfichi, Maurizio; Brusamolino, Ercole; Rossi, Giuseppe; Anastasia, Antonella; Zaja, Francesco; Vitolo, Umberto; Pavone, Vincenzo; Pulsoni, Alessandro; Rigacci, Luigi; Gaidano, Gianluca; Stelitano, Caterina; Salvi, Flavia; Rusconi, Chiara; Tani, Monica; Freilone, Roberto; Pregno, Patrizia; Borsatti, Eugenio; Sacchetti, Gian Mauro; Argnani, Lisa; Levis, Alessandro

2016-04-20

The clinical impact of positron emission tomography (PET) evaluation performed early during first-line therapy in patients with advanced-stage Hodgkin lymphoma, in terms of providing a rationale to shift patients who respond poorly onto a more intensive regimen (PET response-adapted therapy), remains to be confirmed. The phase II part of the multicenter HD0801 study involved 519 patients with advanced-stage de novo Hodgkin lymphoma who received an initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and who underwent an early ifosfamide-containing salvage treatment followed by stem-cell transplantation if they showed a positive PET evaluation after two cycles of chemotherapy (PET2). The primary end point was 2-year progression-free survival calculated for both PET2-negative patients (who completed a full six cycles of ABVD treatment) and PET2-positive patients. Overall survival was a secondary end point. In all, 103 of the 512 evaluable patients were PET2 positive. Among them, 81 received the scheduled salvage regimen with transplantation, 15 remained on ABVD (physician's decision, mostly because of minimally positive PET2), five received an alternative treatment, and two were excluded because of diagnostic error. On intention-to-treat analysis, the 2-year progression-free survival was 76% for PET2-positive patients (regardless of the salvage treatment they received) and 81% for PET2-negative patients. Patients with advanced-stage Hodgkin lymphoma for whom treatment was at high risk of failing appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70% of PET2-positive patients through obtaining the same 2-year progression-free survival as the PET2-negative subgroup. © 2016 by American Society of Clinical Oncology.

Immune Responses and Protection of Aotus Monkeys Immunized with Irradiated Plasmodium vivax Sporozoites

PubMed Central

Jordán-Villegas, Alejandro; Perdomo, Anilza Bonelo; Epstein, Judith E.; López, Jesús; Castellanos, Alejandro; Manzano, María R.; Hernández, Miguel A.; Soto, Liliana; Méndez, Fabián; Richie, Thomas L.; Hoffman, Stephen L.; Arévalo-Herrera, Myriam; Herrera, Sócrates

2011-01-01

A non-human primate model for the induction of protective immunity against the pre-erythrocytic stages of Plasmodium vivax malaria using radiation-attenuated P. vivax sporozoites may help to characterize protective immune mechanisms and identify novel malaria vaccine candidates. Immune responses and protective efficacy induced by vaccination with irradiated P. vivax sporozoites were evaluated in malaria-naive Aotus monkeys. Three groups of six monkeys received two, five, or ten intravenous inoculations, respectively, of 100,000 irradiated P. vivax sporozoites; control groups received either 10 doses of uninfected salivary gland extract or no inoculations. Immunization resulted in the production low levels of antibodies that specifically recognized P. vivax sporozoites and the circumsporozoite protein. Additionally, immunization induced low levels of antigen-specific IFN-γ responses. Intravenous challenge with viable sporozoites resulted in partial protection in a dose-dependent manner. These findings suggest that the Aotus monkey model may be able to play a role in preclinical development of P. vivax pre-erythrocytic stage vaccines. PMID:21292877

The Prognostic Influence of BRAF Mutation and other Molecular, Clinical and Laboratory Parameters in Stage IV Colorectal Cancer.

PubMed

Karadima, Maria L; Saetta, Angelica A; Chatziandreou, Ilenia; Lazaris, Andreas C; Patsouris, Efstratios; Tsavaris, Nikolaos

2016-10-01

Our aim was to evaluate the predictive and prognostic influence of BRAF mutation and other molecular, clinical and laboratory parameters in stage IV colorectal cancer (CRC). 60 patients were included in this retrospective analysis, and 17 variables were examined for their relation with treatment response and survival. KRAS mutation was identified in 40.3 % of cases, BRAF and PIK3CA in 8.8 % and 10.5 % respectively. 29.8 % of patients responded to treatment. Median survival time was 14.3 months. Weight loss, fever, abdominal metastases, blood transfusion, hypoalbuminaimia, BRAF and PIK3CA mutations, CRP and DNA Index were associated with survival. In multivariate analysis, male patients had 3.8 times higher probability of response, increased DNA Index was inversely correlated with response and one unit raise of DNA Index augmented 6 times the probability of death. Our findings potentiate the prognostic role of BRAF, PIK3CA mutations and ploidy in advanced CRC.

Vinorelbine as neoadjuvant chemotherapy in advanced cervical carcinoma.

PubMed

Lacava, J A; Leone, B A; Machiavelli, M; Romero, A O; Perez, J E; Elem, Y L; Ferreyra, R; Focaccia, G; Suttora, G; Salvadori, M A; Cuevas, M A; Acuña, L R; Acuña, J R; Langhi, M; Amato, S; Castaldi, J; Arroyo, A; Vallejo, C T

1997-02-01

To evaluate the efficacy and toxicity of vinorelbine (VNB) as single-agent neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between December 1993 and October 1995, 43 untreated patients with stages IIB to IVA squamous cell cervical cancer were entered onto this study. Forty-two patients are assessable for response and 43 for toxicity. The median age was 46 years (range, 28 to 65). Distribution by stages (International Federation of Gynecology and Obstetrics [FIGO]) was as follows: IIB, 18 patients; IIIA, one; IIIB, 19; and IVA, five. Therapy consisted of VNB 30 mg/m2 by 20-minute intravenous (IV) infusion repeated weekly for 12 injections and followed by radical surgery if feasible or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. One patient was considered not assessable for response. A total of 493 cycles of therapy were administered and objective remissions were observed in 19 of 42 patients (45%; 95% confidence interval, 30% to 60%). Two patients (5%) had a complete response (CR) and 17 (40%) a partial response (PR); no change (NC) was observed in 16 (38%) and progressive disease (PD) in seven (17%). Six of 19 patients (32%) who achieved objective responses (ORs) underwent surgery. The median time to failure and median survival time have not been reached yet. There were no therapy-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (81%) and was grade 3 or 4 in seven (17%). Twelve patients (28%) developed peripheral neuropathy, while myalgias occurred in 10 (23%). Constipation was observed in nine patients (21%), one with a prolonged ileum. Phlebitis was recorded in 18 patients (41%). In contrast, emesis and mucositis were rarely observed. No patient developed alopecia grade 3. By the end of the twelfth course of treatment, the average received dose-intensity was 85.4% of that projected. VNB is an active drug against ACC with moderate toxicity. Its activity is among the highest reported for single agents. Further evaluation in association with other agents is clearly justified.

Inter-Observer Agreement of Whole-Body Computed Tomography in Staging and Response Assessment in Lymphoma: The Lugano Classification.

PubMed

Razek, Ahmed Abdel Khalek Abdel; Shamaa, Sameh; Lattif, Mahmoud Abdel; Yousef, Hanan Hamid

2017-01-01

To assess inter-observer agreement of whole-body computed tomography (WBCT) in staging and response assessment in lymphoma according to the Lugano classification. Retrospective analysis was conducted of 115 consecutive patients with lymphomas (45 females, 70 males; mean age of 46 years). Patients underwent WBCT with a 64 multi-detector CT device for staging and response assessment after a complete course of chemotherapy. Image analysis was performed by 2 reviewers according to the Lugano classification for staging and response assessment. The overall inter-observer agreement of WBCT in staging of lymphoma was excellent ( k =0.90, percent agreement=94.9%). There was an excellent inter-observer agreement for stage I ( k =0.93, percent agreement=96.4%), stage II ( k =0.90, percent agreement=94.8%), stage III ( k =0.89, percent agreement=94.6%) and stage IV ( k =0.88, percent agreement=94%). The overall inter-observer agreement in response assessment after a completer course of treatment was excellent ( k =0.91, percent agreement=95.8%). There was an excellent inter-observer agreement in progressive disease ( k =0.94, percent agreement=97.1%), stable disease ( k =0.90, percent agreement=95%), partial response ( k =0.96, percent agreement=98.1%) and complete response ( k =0.87, Percent agreement=93.3%). We concluded that WBCT is a reliable and reproducible imaging modality for staging and treatment assessment in lymphoma according to the Lugano classification.

An adaptive two-stage dose-response design method for establishing proof of concept.

PubMed

Franchetti, Yoko; Anderson, Stewart J; Sampson, Allan R

2013-01-01

We propose an adaptive two-stage dose-response design where a prespecified adaptation rule is used to add and/or drop treatment arms between the stages. We extend the multiple comparison procedures-modeling (MCP-Mod) approach into a two-stage design. In each stage, we use the same set of candidate dose-response models and test for a dose-response relationship or proof of concept (PoC) via model-associated statistics. The stage-wise test results are then combined to establish "global" PoC using a conditional error function. Our simulation studies showed good and more robust power in our design method compared to conventional and fixed designs.

Carryover effect of postpartum inflammatory diseases on developmental biology and fertility in lactating dairy cows.

PubMed

Ribeiro, E S; Gomes, G; Greco, L F; Cerri, R L A; Vieira-Neto, A; Monteiro, P L J; Lima, F S; Bisinotto, R S; Thatcher, W W; Santos, J E P

2016-03-01

The objective of this series of studies was to investigate the effects of inflammatory diseases occurring before breeding on the developmental biology and reproductive responses in dairy cows. Data from 5 studies were used to investigate different questions associating health status before breeding and reproductive responses. Health information for all studies was composed of the incidence of retained fetal membranes, metritis, mastitis, lameness, and respiratory and digestive problems from parturition until the day of breeding. Retained placenta and metritis were grouped as uterine disease (UTD). Mastitis, lameness, digestive and respiratory problems were grouped as nonuterine diseases (NUTD). Study 1 evaluated the effect of disease before artificial insemination (AI), anovulation before synchronization of the estrous cycle, and low body condition score at AI on pregnancy per AI, as well as their potential interactions or additive effects. Study 2 investigated the effect of site of inflammation (UTD vs. NUTD) and time of occurrence relative to preantral or antral stages of ovulatory follicle development, and the effect of UTD and NUTD on fertility responses of cows bred by AI or by embryo transfer. Study 3 evaluated the effect of disease on fertilization and embryonic development to the morula stage. Study 4 evaluated the effect of disease on preimplantation conceptus development as well as secretion of IFN-τ and transcriptome. Study 5 investigated the effect of diseases before AI on the transcript expression of interferon-stimulated genes in peripheral blood leukocytes during peri-implantation stages of conceptus development after first AI postpartum. Altogether, these studies demonstrated that inflammatory disease before breeding reduced fertilization of oocytes and development to morula, and impaired early conceptus development to elongation stages and secretion of IFN-τ in the uterine lumen. Diseases caused inflammation-like changes in transcriptome of conceptus cells, increased risk of pregnancy loss, and reduced pregnancy or calving per breeding. Moreover, the effects on reproduction were independent of cyclic status before synchronization of the estrous cycle and body condition score at breeding, which all had additive negative effects on fertility of dairy cows. Occurrence of disease at preantral or at antral stages of ovulatory follicle development had similar detrimental effects on pregnancy results. The carryover effects of diseases on developmental biology might last longer than 4 mo. Reduced oocyte competence is a likely reason for carryover effects of diseases on developmental biology, but impaired uterine environment was also shown to be involved. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Reaching the Surveillance-Response Stage of Schistosomiasis Control in The People's Republic of China: A Modelling Approach.

PubMed

Feng, Y; Liu, L; Xia, S; Xu, J-F; Bergquist, R; Yang, G-J

2016-01-01

With the goal set to eliminate schistosomiasis nationwide by 2020, The People's Republic of China has initiated the surveillance-response stage to identify remaining sources of infection and potential pockets from where the disease could reemerge. Shifting the focus from classical monitoring and evaluation to rapid detection and immediate response, this approach requires modelling to bridge the surveillance and response components. We review here studies relevant to schistosomiasis modelling in a Chinese surveillance-response system with the expectation to achieve a practically useful understanding of the current situation and potential future study directions. We also present useful experience that could tentatively be applied in other endemic regions in the world. Modelling is discussed at length as it plays an essential role, both with regard to the intermediate snail host and in the definitive, mammal hosts. Research gaps with respect to snail infection, animal hosts and sectoral research cooperation are identified and examined against the prevailing background of ecosystem and socioeconomic changes with a focus on coexisting challenges and opportunities in a situation with increasing financial constraints. Copyright © 2016 Elsevier Ltd. All rights reserved.

High environmental ammonia exposure has developmental-stage specific and long-term consequences on the cortisol stress response in zebrafish.

PubMed

Williams, Tegan A; Bonham, Luke A; Bernier, Nicholas J

2017-12-01

The capacity for early life environmental stressors to induce programming effects on the endocrine stress response in fish is largely unknown. In this study we determined the effects of high environmental ammonia (HEA) exposure on the stress response in larval zebrafish, assessed the tolerance of embryonic and larval stages to HEA, and evaluated whether early life HEA exposure has long-term consequences on the cortisol response to a novel stressor. Exposure to 500-2000μM NH 4 Cl for 16h did not affect the gene expression of corticotropin-releasing factor (CRF) system components in 1day post-fertilization (dpf) embryos, but differentially increased crfa, crfb and CRF binding protein (crfbp) expression and stimulated both dose- and time-dependent increases in the whole body cortisol of 5dpf larvae. Pre-acclimation to HEA at 1dpf did not affect the cortisol response to a subsequent NH 4 Cl exposure at 5dpf. In contrast, pre-acclimation to HEA at 5dpf caused a small but significant reduction in the cortisol response to a second NH 4 Cl exposure at 10dpf. While continuous exposure to 500-2000μM NH 4 Cl between 0 and 5dpf had a modest effect on mean survival time, exposure to 400-1000μM NH 4 Cl between 10 and 14dpf decreased mean survival time in a dose-dependent manner. Moreover, pre-acclimation to HEA at 5dpf significantly decreased the risk of mortality to continuous NH 4 Cl exposure between 10 and 14dpf. Finally, while HEA at 1dpf did not affect the cortisol stress response to a novel vortex stressor at 5dpf, the same HEA treatment at 5dpf abolished vortex stressor-induced increases in whole body cortisol at 10 and 60dpf. Together these results show that the impact of HEA on the cortisol stress response during development is life-stage specific and closely linked to ammonia tolerance. Further, we demonstrate that HEA exposure at the larval stage can have persistent effects on the capacity to respond to stressors in later life. Copyright © 2017 Elsevier Inc. All rights reserved.

A Phase II Safety and Efficacy Study of the Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor Pazopanib in Patients With Metastatic Urothelial Cancer

PubMed Central

Pili, Roberto; Qin, Rui; Flynn, P.J.; Picus, Joel; Millward, Michael; Ho, Wing Ming; Pitot, Henry; Tan, Winston; Miles, Kiersten M.; Erlichman, Charles; Vaishampayan, Ulka

2013-01-01

Vascular endothelial growth factor (VEGF) is expressed in human bladder tumors. A phase II study was conducted to assess the VEGF inhibitor pazopanib in patients with metastatic, urothelial carcinoma. Nineteen patients with one prior systemic therapy were enrolled. No objective responses were observed and median progression-free survival was 1.9 months. The role of anti-VEGF therapies in urothelial carcinoma remains to be determined. Background Vascular endothelial growth factor (VEGF) is produced by bladder cancer cell lines in vitro and expressed in human bladder tumor tissues. Pazopanib is a vascular endothelial receptor tyrosine kinase inhibitor with anti-angiogenesis and anti-tumor activity in several preclinical models. A 2-stage phase II study was conducted to assess the activity and toxicity profile of pazopanib in patients with metastatic, urothelial carcinoma. Methods Patients with one prior systemic therapy for metastatic urothelial carcinoma were eligible. Patients received pazopanib at a dose of 800 mg orally for a 4-week cycle. Results Nineteen patients were enrolled. No grade 4 or 5 events were experienced. Nine patients experienced 11 grade 3 adverse events. Most common toxicities were anemia, thrombocytopenia, leucopenia, and fatigue. For stage I, none of the first 16 evaluable patients were deemed a success (complete response or partial response) by the Response Evaluation Criteria In Solid Tumors criteria during the first four 4-week cycles of treatment. Median progression-free survival was 1.9 months. This met the futility stopping rule of interim analysis, and therefore the trial was recommended to be permanently closed. Conclusions Pazopanib did not show significant activity in patients with urothelial carcinoma. The role of anti-VEGF therapies in urothelial carcinoma may need further evaluation in rational combination strategies. PMID:23891158

A CRITICAL ASSESSMENT OF BIODOSIMETRY METHODS FOR LARGE-SCALE INCIDENTS

PubMed Central

Swartz, Harold M.; Flood, Ann Barry; Gougelet, Robert M.; Rea, Michael E.; Nicolalde, Roberto J.; Williams, Benjamin B.

2014-01-01

Recognition is growing regarding the possibility that terrorism or large-scale accidents could result in potential radiation exposure of hundreds of thousands of people and that the present guidelines for evaluation after such an event are seriously deficient. Therefore, there is a great and urgent need for after-the-fact biodosimetric methods to estimate radiation dose. To accomplish this goal, the dose estimates must be at the individual level, timely, accurate, and plausibly obtained in large-scale disasters. This paper evaluates current biodosimetry methods, focusing on their strengths and weaknesses in estimating human radiation exposure in large-scale disasters at three stages. First, the authors evaluate biodosimetry’s ability to determine which individuals did not receive a significant exposure so they can be removed from the acute response system. Second, biodosimetry’s capacity to classify those initially assessed as needing further evaluation into treatment-level categories is assessed. Third, we review biodosimetry’s ability to guide treatment, both short- and long-term, is reviewed. The authors compare biodosimetric methods that are based on physical vs. biological parameters and evaluate the features of current dosimeters (capacity, speed and ease of getting information, and accuracy) to determine which are most useful in meeting patients’ needs at each of the different stages. Results indicate that the biodosimetry methods differ in their applicability to the three different stages, and that combining physical and biological techniques may sometimes be most effective. In conclusion, biodosimetry techniques have different properties, and knowledge of their properties for meeting the different needs for different stages will result in their most effective use in a nuclear disaster mass-casualty event. PMID:20065671

Evaluation of aqueous and ethanol extract of bioactive medicinal plant, Cassia didymobotrya (Fresenius) Irwin & Barneby against immature stages of filarial vector, Culex quinquefasciatus Say (Diptera: Culicidae).

PubMed

Nagappan, Raja

2012-09-01

To evaluate aqueous and ethanol extract of Cassia didymobotrya leaves against immature stages of Culex quinquefasciatus. The mortality rate of immature mosquitoes was tested in wide and narrow range concentration of the plant extract based on WHO standard protocol. The wide range concentration tested in the present study was 10 000, 1 000, 100, 10 and 1 mg/L and narrow range concentration was 50, 100, 150, 200 and 250 mg/L. 2nd instar larvae exposed to 100 mg/L and above concentration of ethanol extract showed 100% mortality. Remaining stages such as 3rd, 4th and pupa, 100% mortality was observed at 1 000 mg/L and above concentration after 24 h exposure period. In aqueous extract all the stages 100% mortality was recorded at 1 000 mg/L and above concentration. In narrow range concentration 2nd instar larvae 100% mortality was observed at 150 mg/L and above concentration of ethanol extract. The remaining stages 100% mortality was recorded at 250 mg/L. In aqueous extract all the tested immature stages 100% mortality was observed at 250 mg/L concentration after 24 h exposure period. The results clearly indicate that the rate of mortality was based dose of the plant extract and stage of the mosquitoes. From this study it is confirmed and concluded that Cassia didymobotrya is having active principle which is responsible for controlling Culex quinquefasciatus. The isolation of bioactive molecules and development of simple formulation technique is important for large scale implementation.

Development of the Biological Experimental Design Concept Inventory (BEDCI)

PubMed Central

Deane, Thomas; Jeffery, Erica; Pollock, Carol; Birol, Gülnur

2014-01-01

Interest in student conception of experimentation inspired the development of a fully validated 14-question inventory on experimental design in biology (BEDCI) by following established best practices in concept inventory (CI) design. This CI can be used to diagnose specific examples of non–expert-like thinking in students and to evaluate the success of teaching strategies that target conceptual changes. We used BEDCI to diagnose non–expert-like student thinking in experimental design at the pre- and posttest stage in five courses (total n = 580 students) at a large research university in western Canada. Calculated difficulty and discrimination metrics indicated that BEDCI questions are able to effectively capture learning changes at the undergraduate level. A high correlation (r = 0.84) between responses by students in similar courses and at the same stage of their academic career, also suggests that the test is reliable. Students showed significant positive learning changes by the posttest stage, but some non–expert-like responses were widespread and persistent. BEDCI is a reliable and valid diagnostic tool that can be used in a variety of life sciences disciplines. PMID:25185236

Landscape ecological security response to land use change in the tidal flat reclamation zone, China.

PubMed

Zhang, Runsen; Pu, Lijie; Li, Jianguo; Zhang, Jing; Xu, Yan

2016-01-01

As coastal development becomes a national strategy in Eastern China, land use and landscape patterns have been affected by reclamation projects. In this study, taking Rudong County, China as a typical area, we analyzed land use change and its landscape ecological security responses in the tidal flat reclamation zone. The results show that land use change in the tidal flat reclamation zone is characterized by the replacement of natural tidal flat with agricultural and construction land, which has also led to a big change in landscape patterns. We built a landscape ecological security evaluation system, which consists of landscape interference degree and landscape fragile degree, and then calculated the landscape ecological security change in the tidal flat reclamation zone from 1990 to 2008 to depict the life cycle in tidal flat reclamation. Landscape ecological security exhibited a W-shaped periodicity, including the juvenile stage, growth stage, and maturation stage. Life-cycle analysis demonstrates that 37 years is required for the land use system to transform from a natural ecosystem to an artificial ecosystem in the tidal flat reclamation zone.

An evaluation of silver-stage American Eel conspecific chemical cueing during outmigration

USGS Publications Warehouse

Schmucker, Andrew K.; Johnson, Nicholas S.; Galbraith, Heather S.; Li, Weiming

2017-01-01

American Eel Anguilla rostrata abundance has declined in recent decades, in part because sexually maturing, silver-stage adults, outmigrating from freshwater to oceanic spawning grounds, encounter migratory blockades or perish when passing through active hydroelectric turbines. To help improve downstream passage effectiveness and increase survival rates, the role of silver-stage American Eel conspecific chemical cueing during outmigration was investigated using a new type of bioassay. Inside a laboratory flume, downstream-swimming eels were exposed to both live (putative attractant) and dead (putative repellent) conspecific washings to determine whether their trajectory of downstream movement, level of activity, or time spent inside targeted areas of the arena changed after exposure. Silver eels were not attracted to or repulsed by either odor, as none of five scoring metrics indicated a behavioral response. Results did not support the hypothesis that conspecific chemical cueing is a mechanism for downstream migration coordination or danger avoidance; however responses may not have been readily apparent in this type of assay. Fisheries managers may opt to focus future research on more feasible restoration efforts using alternate experimental designs to remedy this ecological issue.

Comprehensive Structural Dynamic Analysis of the SSME/AT Fuel Pump First-Stage Turbine Blade

NASA Technical Reports Server (NTRS)

Brown, A. M.

1998-01-01

A detailed structural dynamic analysis of the Pratt & Whitney high-pressure fuel pump first-stage turbine blades has been performed to identify the cause of the tip cracking found in the turbomachinery in November 1997. The analysis was also used to help evaluate potential fixes for the problem. Many of the methods available in structural dynamics were applied, including modal displacement and stress analysis, frequency and transient response to tip loading from the first-stage Blade Outer Gas Seals (BOGS), fourier analysis, and shock spectra analysis of the transient response. The primary findings were that the BOGS tip loading is impulsive in nature, thereby exciting many modes of the blade that exhibit high stress at the tip cracking location. Therefore, a proposed BOGS count change would not help the situation because a clearly identifiable resonance situation does not exist. The recommendations for the resolution of the problem are to maintain the existing BOGS count, eliminate the stress concentration in the blade due to its geometric design, and reduce the applied load on the blade by adding shiplaps in the BOGS.

Stage-dependent toxicity of bisphenol a on Rhinella arenarum (anura, bufonidae) embryos and larvae.

PubMed

Wolkowicz, Ianina R Hutler; Herkovits, Jorge; Pérez Coll, Cristina S

2014-02-01

The acute and chronic toxicity of bisphenol A (BPA) was evaluated on the common South American toad Rhinella arenarum embryos and larvae by means of continuous and pulse exposure treatments. Embryos were treated continuously from early blastula (S.4) up to complete operculum (S.25), during early larval stages and by means of 24 h pulse exposures of BPA in concentrations ranging between 1.25 and 40 mg L(-1) , in order to evaluate the susceptibility to this compound in different developmental stages. For lethal effects, S.25 was the most sensitive and gastrula was the most resistant to BPA. The Teratogenic Index for neurula, the most sensitive embryonic stage for sublethal effects was 4.7. The main morphological alterations during early stages were: delayed or arrested development, reduced body size, persistent yolk plug, microcephaly, axial/tail flexures, edemas, blisters, waving fin, underdeveloped gills, mouth malformations, and cellular dissociation. BPA caused a remarkable narcotic effect from gill circulation stage (S.20) onwards in all the organisms exposed after 3 h of treatment with 10 mg L(-1) BPA. After recovering, the embryos exhibited scarce response to stimuli, erratic or circular swimming, and spasmodic contractions from 5 mg L(-1) onwards. Our results highlight the lethal and sublethal effectsof BPA on R. arenarum embryos and larvae, in the last case both at structural and functional levels. Copyright © 2011 Wiley Periodicals, Inc., A Wiley Company.

High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group.

PubMed

Pritchard, Jon; Cotterill, Simon J; Germond, Shirley M; Imeson, John; de Kraker, Jan; Jones, David R

2005-04-01

High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative "megatherapy" was evaluated in a randomised, multi-centre trial. Between 1982 and 1985, 167 children with stages IV and III neuroblastoma (123 stage IV > 1 year old at diagnosis and 44 stage III and stage IV from 6 to 12 months old at diagnosis) were treated with oncovin, cisplatin, epipodophyllotoxin, and cyclophosphamide (OPEC) induction chemotherapy every 3 weeks. After surgical excision of primary tumour, the 90 patients (69% of the total) who achieved complete response (CR) or good partial response (GPR) were eligible for randomisation either to high dose melphalan (180 mg per square meter) with autologous bone marrow support or to no further treatment. Sixty-five (72%) of eligible children were actually randomised and 21 of these patients were surviving at time of this analysis, with median follow-up from randomisation of 14.3 years. Five year event-free survival (EFS) was 38% (95% confidence interval (CI) 21-54%) in the melphalan-treated group and 27% (95% CI 12-42%) in the "no-melphalan" group. This difference was not statistically significant (P = 0.08, log rank test) but for the 48 randomised stage IV patients aged >1 year at diagnosis outcome was significantly better in the melphalan-treated group-5 year EFS 33% versus 17% (P = 0.01, log rank test). In this trial, high dose melphalan improved the length of EFS and overall survival of children with stage IV neuroblastoma >1 year of age who achieved CR or GPR after OPEC induction therapy and surgery. Multi-agent myeloablative regimens are now widely used as consolidation therapy for children with stage IV disease and in those with other disease stages when the MYCN gene copy number in tumour cells is amplified. Because they are more toxic, complex, and costly these combination megatherapy regimens should be compared with single agent melphalan in randomised clinical trials.

Response, Emergency Staging, Communications, Uniform Management, and Evacuation (R.E.S.C.U.M.E.) : report on functional and performance requirements, and high-level data and communication needs.

DOT National Transportation Integrated Search

1995-06-01

INTELLIGENT VEHICLE INITIATIVE OR IVI ABSTRACT THE GOAL OF THE TRAVTEK CAMERA CAR STUDY WAS TO FURNISH A DETAILED EVALUATION OF DRIVING AND NAVIGATION PERFORMANCE, SYSTEM USABILITY, AND SAFETY FOR THE TRAVTEK SYSTEM. TO ACHIEVE THIS GOAL, AN INSTRUME...

Local Dependence in an Operational CAT: Diagnosis and Implications

ERIC Educational Resources Information Center

Pommerich, Mary; Segall, Daniel O.

2008-01-01

The accuracy of CAT scores can be negatively affected by local dependence if the CAT utilizes parameters that are misspecified due to the presence of local dependence and/or fails to control for local dependence in responses during the administration stage. This article evaluates the existence and effect of local dependence in a test of…

Functional responses and prey-stage preferences of a predatory gall midge and two predacious mites wtih twospotted spider mites, Tetranychus urticae as host

USDA-ARS?s Scientific Manuscript database

The twospotted spider mite, Tetranychus urticae (Acari: Tetranychidae), is an important pest of vegetables and other crops. This study was conducted to evaluate and compare the potential role of three commercially available predators, predatory gall midge, Feltiella acarisuga (Vallot) (Diptera: Ceci...

Site factor variations and responses in temporary forest types in northern Idaho

Treesearch

J. A. Larsen

1940-01-01

The object of the study was to analyze and evaluate the environmental factors which govern the progressional stages of the secondary forest succession in northern Idaho. \\When this study began much uncertainty existed regarding the distribution of trees and forest types in relation to temperature, precipitation, and evaporation and regarding their soil moisture and...

Predictors of Androgen Deprivation Therapy Efficacy Combined With Prostatic Irradiation: The Central Role of Tumor Stage and Radiation Dose

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

Williams, Scott, E-mail: scott.williams@petermac.or; Buyyounouski, Mark; Kestin, Larry

2011-03-01

Purpose: To evaluate the response of clinically localized prostate cancer to various durations of planned androgen deprivation therapy (ADT) and to investigate subgroups predicting response. Methods and Materials: Data of 3,666 prostate cancer patients treated with either combined ADT and external beam radiotherapy (EBRT) or EBRT alone at four institutions were examined. ADT consisted of neoadjuvant, concurrent, or adjuvant ADT or combinations of these regimens. The primary endpoint was time to biochemical failure (nadir plus 2 ng/ml), assessed from the end of therapy. Factors predictive for the need for ADT were examined with interaction analyses. Results: The impact of increasingmore » ADT duration was nonlinear with, on average, 6 months of adjuvant ADT resulting in a reduction of the risk of biochemical failure by 38% (95% confidence interval [CI], 29%-46%), while 12, 24, and 36 months of ADT resulted in a 58% (95% CI, 47%-67%), 66% (95% CI, 55%-75%), and 66% (95% CI, 51%-77%) relative failure reduction, respectively. Patients with higher T stage cancers and those treated with lower radiation doses had a significantly greater benefit for increasing ADT duration (interaction, p = 0.016 and p = 0.007, respectively). Pretreatment prostate-specific antigen values, Gleason score, age, and risk group did not modify the response to ADT. Conclusions: The known ADT efficacy derived from randomized studies can be generalized to patients with different features, and individual predictions of potential benefit from ADT use and duration may be calculated to aid patient and physician decision making. Tumor stage and radiation dose variations were related to significantly different ADT duration effects. The validity of these predictive factors requires prospective evaluation.« less

Histological evaluations and inflammatory responses of different dental implant abutment materials: A human histology pilot study.

PubMed

Sampatanukul, Teeratida; Serichetaphongse, Pravej; Pimkhaokham, Atiphan

2018-04-01

Improvements of soft tissue to the abutment surface results in more stable peri-implant conditions, however, few human histological studies have compared soft tissue responses around different abutment materials. To describe the peri-implant tissue around 3 abutment materials; titanium, zirconia, and gold alloy, over an 8-week healing period. Fifteen edentulous sites were treated with implants. Eight weeks later, peri-implant tissue was harvested and processed using a nonseparation resin embedded technique. The tissue attachment characteristics were assessed at clinical stages using the gingival index (GI) score, surgical stage (surgical score), and histological stage (histological attachment percentage). Additionally, the inflammatory responses were evaluated using inflammatory extent and inflammatory cellularity grades. Nonparametrical statistics were used to describe the GI and surgical scores, and analytical statistics were used to analyze the histological attachment percentages as well as the inflammatory extent and cellularity grades amongst the 3 groups. There were no statistically significant differences among the groups for GI score (P = .071) and surgical score (P = .262). Titanium and zirconia exhibited nearly similar mean histological attachment percentages while gold alloy had a significantly lower percentage (P = .004). For the inflammatory extent and cellularity grades, the odds of being one grade higher for gold alloy abutment was 5.18 and 17.8 times that of titanium abutment, respectively. However, for the zirconia abutment, the odds were 0.87 and 7.5 times higher than the titanium group. The tissue around the gold alloy abutments resulted in worse attachment conditions compared with the titanium and zirconia abutments. Inflammation tended to be higher in the tissue around the gold alloy abutments than the titanium and zirconia abutments. © 2017 Wiley Periodicals, Inc.

Ovarian function during puberty in girls with type 1 diabetes mellitus: response to leuprolide.

PubMed

Codner, Ethel; Mook-Kanamori, Dennis; Bazaes, Rodrigo A; Unanue, Nancy; Sovino, Hugo; Ugarte, Francisca; Avila, Alejandra; Iñiguez, German; Cassorla, Fernando

2005-07-01

An increased prevalence of polycystic ovary syndrome (PCOS) has been reported in adult women with type 1 diabetes mellitus (DM1). We investigated whether these hormonal abnormalities begin during puberty by evaluating the ovarian steroidogenic response to leuprolide acetate. We studied 56 adolescent girls with DM1 (aged 12.3 +/- 0.2 yr) and 64 healthy girls (C) (aged 11.9 +/- 0.2 yr) up to 2 yr post menarche, matched by age, body mass index, and pubertal development. We evaluated anthropometrical data and Ferriman-Gallway score and performed a leuprolide test (500 microg sc) to study ovarian function. Ovarian volume was determined by transabdominal ultrasonography. We found five DM1 but no C girls with abnormally located terminal hair (Fisher's exact, P < 0.05). Free androgen index increased throughout puberty in girls with DM1 (ANOVA, P < 0.0001), which was associated with a decrease in SHBG levels in girls with DM1 (ANOVA, P < 0.0001). Stimulated 17OH progesterone (17OHProg) increased throughout puberty only in girls with DM1 (ANOVA, P < 0.01). Girls with DM1 at Tanner stage 5 had higher stimulated LH to FSH ratio, testosterone, and 17OHProg levels than girls at Tanner stage 4. In contrast, in C girls the stimulated testosterone, 17OHProg, and LH to FSH ratio were similar at Tanner stages 4 and 5. Ovarian volumes and uterine length were larger in girls with DM1 (analysis of covariance, P < 0.05). These data suggest that patients with DM1 have differences in ovarian steroidogenic response to leuprolide, compared with C girls during puberty. Future studies in young women should clarify whether these findings are related to the pathogenesis of hyperandrogenism later in life.

The Effect of High Energy Ball Milling on the Dynamic Response of Aluminum Powders

NASA Astrophysics Data System (ADS)

Beason, Matthew T.; Justice, Andrew W.; Gunduz, Ibrahim E.; Son, Steven F.

2017-06-01

Ball milling is an effective method to enhance the reactivity of intermetallic reactives by reducing characteristic diffusions distances. During this process, ductile reactants are mixed into a lamellar material with nanoscale features, resulting in significant strain hardening. Plate impact experiments using a single stage light gas gun have been performed to evaluate the effect of high energy ball milling (HEBM) on the mechanical properties and dynamic response of cold pressed aluminum compacts. The average grain size of the milled material is evaluate and suggested as a method of correlating the measured response to the properties of milled composites. This material is based upon work supported by the Department of Energy, National Nuclear Security Administration, under Award Number(s) DE-NA0002377, as well as individual funding (Beason) by the Department of Defense through the NDSEG.

High-throughput screening of chemical effects on ...

EPA Pesticide Factsheets

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2,060 chemical samples on steroidogenesis via HPLC-MS/MS quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a three stage screening strategy. The first stage established the maximum tolerated concentration (MTC; >70% viability) per sample. The second stage quantified changes in hormone levels at the MTC while the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were pre-stimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2,060 chemical samples evaluated, 524 samples were selected for six-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into five distinct profiles generally representing putative mechanisms of action, including CYP17A1 and HSD3B inhibition. A d

High-throughput screening of chemical effects on steroidogenesis using H295R human adrenocortical carcinoma cells

EPA Pesticide Factsheets

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ? 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 00b5M forskolin for 48??h to induce steroidogenesis followed by chemical treatment for 48??h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 1703b2-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into 5 distinct profiles generally representing putative mec

Tin-tungsten mineralizing processes in tungsten vein deposits: Panasqueira, Portugal

NASA Astrophysics Data System (ADS)

Lecumberri-Sanchez, P.; Pinto, F.; Vieira, R.; Wälle, M.; Heinrich, C. A.

2015-12-01

Tungsten has a high heat resistance, density and hardness, which makes it widely applied in industry (e.g. steel, tungsten carbides). Tungsten deposits are typically magmatic-hydrothermal systems. Despite the economic significance of tungsten, there are no modern quantitative analytical studies of the fluids responsible for the formation of its highest-grade deposit type (tungsten vein deposits). Panasqueira (Portugal) is a tungsten vein deposit, one of the leading tungsten producers in Europe and one of the best geologically characterized tungsten vein deposits. In this study, compositions of the mineralizing fluids at Panasqueira have been determined through combination of detailed petrography, microthermometric measurements and LA-ICPMS analyses, and geochemical modeling has been used to determine the processes that lead to tungsten mineralization. We characterized the fluids related to the various mineralizing stages in the system: the oxide stage (tin and tungsten mineralization), the sulfide stage (chalcopyrite and sphalerite mineralization) and the carbonate stage. Thus, our results provide information on the properties of fluids related with specific paragenetic stages. Furthermore we used those fluid compositions in combination with host rock mineralogy and chemistry to evaluate which are the controlling factors in the mineralizing process. This study provides the first quantitative analytical data on fluid composition for tungsten vein deposits and evaluates the controlling mineralization processes helping to determine the mechanisms of formation of the Panasqueira tin-tungsten deposit and providing additional geochemical constraints on the local distribution of mineralization.

Cancer-specific Relationship Awareness, Relationship Communication, and Intimacy Among Couples Coping with Early Stage Breast Cancer

PubMed Central

Manne, Sharon L.; Siegel, Scott; Kashy, Deborah; Heckman, Carolyn J.

2013-01-01

If couples can maintain normalcy and quality in their relationship during the cancer experience, they may experience greater relational intimacy. Cancer-specific relationship awareness, which is an attitude defined as partners focusing on the relationship and thinking about how they might maintain normalcy and cope with cancer as a couple or “team”, is one factor that may help couples achieve this goal. The main aim of this study was to evaluate the associations between cancer-specific relationship awareness, cancer-specific communication (i.e., talking about cancer’s impact on the relationship, disclosure, and responsiveness to partner disclosure), and relationship intimacy and evaluate whether relationship communication mediated the association between relationship awareness and intimacy. Two hundred fifty four women diagnosed with early stage breast cancer and their partners completed measures of cancer-specific relationship awareness, relationship talk, self-and perceived partner disclosure, perceived partner responsiveness, and relationship intimacy. Results indicated that patients and spouses who were higher in cancer-specific relationship awareness engaged in more relationship talk, reported higher levels of self-disclosure, and perceived that their partner disclosed more. Their partners reported that they were more responsive to disclosures. Relationship talk and perceived partner responsiveness mediated the association between cancer–specific relationship awareness and intimacy. Helping couples consider ways they can maintain normalcy and quality during the cancer experience and framing coping with cancer as a “team” effort may facilitate better communication and ultimately enhance relationship intimacy. PMID:25242854

Sarcomatoid Carcinoma of the Lung: The Mayo Clinic Experience in 127 Patients.

PubMed

Maneenil, Kunlatida; Xue, Zhiqiang; Liu, Ming; Boland, Jennifer; Wu, Fengying; Stoddard, Shawn M; Molina, Julian; Yang, Ping

2018-05-01

Pulmonary sarcomatoid carcinoma (PSC) is an unusual form of non-small-cell lung cancer (NSCLC). Because of its rarity and heterogeneity, the treatment and prognosis of PSC have not been clearly described. We retrospectively evaluated all patients with a diagnosis of PSC from 1997 to 2015 at the Mayo Clinic (Rochester, MN). The clinical characteristics, treatment details, and outcomes were collected. The survival rates of the PSC patients were compared with those for other subtypes of NSCLC. We used propensity score matching to minimize the bias resulting from to imbalanced comparison groups. The study included 127 PSC patients. The median age at diagnosis was 68 years (range, 32-89 years), most of whom were men (61%) and smokers (82%). The clinical stage was I, II, III, and IV in 15.9%, 20.6%, 22.2%, and 41.3%, respectively. The median survival time was 9.9 months (95% confidence interval [CI], 7.6-12.6 months). The 1-, 2-, and 5-year survival rates were 42%, 23%, and 15%, respectively. Most patients received multimodality treatment. Of the 3 patients who received neoadjuvant chemotherapy, a partial response was demonstrated in 2. Twenty-five patients who underwent palliative chemotherapy were evaluated for tumor response: 52% experienced progression, 40% stable disease, 8.0% a partial response, and 0% a complete response. Multivariate analysis showed T stage, M stage, and treatment with surgery plus neoadjuvant chemotherapy or surgery plus adjuvant therapy were independent prognostic factors (P < .05). In matched analysis, multivariate models revealed worse overall survival for PSC compared with adenocarcinoma (hazard ratio, 2.38; 95% CI, 1.61-2.53) and squamous cell carcinoma (hazard ratio, 2.20; 95% CI, 1.44-2.34). We found the outcome of PSC to be significantly worse than that of adenocarcinoma and squamous cell carcinoma. Neoadjuvant or adjuvant chemotherapy, in addition to surgical resection, should be considered. Copyright © 2017 Elsevier Inc. All rights reserved.

Intensity Modulated Radiation Therapy for Early-Stage Primary Gastric Diffuse Large B-Cell Lymphoma: Dosimetric Analysis, Clinical Outcome, and Quality of Life

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

Liu, Xin; Fang, Hui; Tian, Yuan

Purpose: To evaluate the dosimetric superiority, efficacy, toxicity, and quality of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods and Materials: Forty-six consecutive patients with early-stage PG-DLBCL underwent IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as the non-germinal center B cell–like subtype. Dosimetric parameters of the planning target volume (PTV) and organs at risk were assessed. Survival rates were depicted with the Kaplan-Meier method and compared with the log-rank test. Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last follow-up contact. Results: Themore » median PTV mean dose was 41.6 Gy. Only 0.73% of the PTV received <95% of the prescribed dose, indicating excellent target coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively. The 5-year overall survival (OS), progression-free survival, and locoregional control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage, lactate dehydrogenase level, and immunophenotype were significant prognostic factors for OS, and only stage was a significant factor for locoregional control. Consolidation IMRT in patients with complete response after chemotherapy resulted in significantly better OS and progression-free survival than salvage IMRT in patients with non-complete response. Two of 8 patients who had chronic liver disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late toxicity was observed. The long-term global and functional QOL scales were excellent, with negligible symptom scales. Conclusions: Intensity modulated radiation therapy yielded excellent target coverage and critical tissue sparing and achieved favorable outcomes with acceptable toxicity and good long-term QOL in early-stage PG-DLBCL.« less

Is elevated CO2 in space really harmful to growth and development? A case study of Chufa (Cyperus esculentus L.) in Lunar Palace-1

NASA Astrophysics Data System (ADS)

Liu, Guanghui; Dong, Chen; Fu, Yuming; Wang, Minjuan; Shao, Lingzhi; Yu, Juan; Liu, Hong

2018-05-01

CO2 concentration [CO2] level in artificial ecosystems such as greenhouse agriculture and space farming can easily exceed 1000 μmol mol-1 (or ppm). In order to understand how the growth and development in crop plants may respond to elevated CO2, it is necessary to determine if crop leaves in the closed artificial ecosystem have a fully developed photosynthetic apparatus, and whether or not photosynthesis in these leaves is more responsive to elevated CO2 concentration. To address this issue, we evaluated the response of photosynthetic characteristics, leaf water status and antioxidant capacity of Chufa (Cyperus esculentus L.), which is a sedge-like plant with 1-2 cm small sweet tubers in length, under elevated CO2 concentrations in an artificial closed ecosystem. The results showed that Chufa plants cultivated in the elevated CO2 environment from the seedling stage to the maturity stage were characterized by more appropriate chlorophyll content and photosynthetic rate. The photosynthetic rate of Chufa plants in the 1000 and 3000 ppm treatments was no significant difference with that in 500 ppm CO2 condition both at seedling stage and rapid growth stage. All the treatments had a high relative water content (RWC) about 60% at the maturity stage. However, there was no significant difference in membrane stability index (MSI) at the rapid growth stage. The antioxidase enzymes activities experienced a rise and a drop and reached the peak at the rapid growth stage. Elevated CO2, especially more than 1000 ppm conditions, may accelerant Chufa plants aging process.

Systematic review and meta-analysis of the accuracy of MRI and endorectal ultrasound in the restaging and response assessment of rectal cancer following neoadjuvant therapy.

PubMed

Memon, S; Lynch, A C; Bressel, M; Wise, A G; Heriot, A G

2015-09-01

Restaging imaging by MRI or endorectal ultrasound (ERUS) following neoadjuvant chemoradiotherapy is not routinely performed, but the assessment of response is becoming increasingly important to facilitate individualization of management. A search of the MEDLINE and Scopus databases was performed for studies that evaluated the accuracy of restaging of rectal cancer following neoadjuvant chemoradiotherapy with MRI or ERUS against the histopathological outcome. A systematic review of selected studies was performed. The methodological quality of studies that qualified for meta-analysis was critically assessed to identify studies suitable for inclusion in the meta-analysis. Sixty-three articles were included in the systematic review. Twelve restaging MRI studies and 18 restaging ERUS studies were eligible for meta-analysis of T-stage restaging accuracy. Overall, ERUS T-stage restaging accuracy (mean [95% CI]: 65% [56-72%]) was nonsignificantly higher than MRI T-stage accuracy (52% [44-59%]). Restaging MRI is accurate at excluding circumferential resection margin involvement. Restaging MRI and ERUS were equivalent for prediction of nodal status: the accuracy of both investigations was 72% with over-staging and under-staging occurring in 10-15%. The heterogeneity amongst restaging studies is high, limiting conclusive findings regarding their accuracies. The accuracy of restaging imaging is different for different pathological T stages and highest for T3 tumours. Morphological assessment of T- or N-stage by MRI or ERUS is currently not accurate or consistent enough for clinical application. Restaging MRI appears to have a role in excluding circumferential resection margin involvement. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

[Use of positron-emission tomography with F18-fluorodeoxyglucose for the assessment of lung lesions suspicious of malignancy].

PubMed

Jofré, M Josefina; Massardo, Teresa; González, Patricio; Canessa, José; Sierralta, Paulina; Humeres, Pamela; Galaz, Rodrigo; Valdebenito, Robert

2005-05-01

Positron-emission tomography (PET) with F18-fluorodeoxyglucose (FDG) is very helpful in the evaluation and management of lung lesions. It is specially useful for the characterization of solitary nodules, for the staging, evaluation of recurrence and therapeutic response in non-small cell lung cancer, for the evaluation of small cell lung cancer and for the assessment of pulmonary metastases. This article is a literature review on PET with FDG in lung cancer. A preliminary analysis of PET results at the Military Hospital in Santiago, Chile, is also presented.

Flehmen response in bull: role of vaginal mucus and other body fluids of bovine with special reference to estrus.

PubMed

Sankar, R; Archunan, G

2004-07-30

The present investigation was carried out with a view to evaluate the frequency of Flehmen behaviour in bull in response to body fluids of cows in various stages of the estrous cycle, in the context of estrus detection. The study was performed on free moving bulls under natural conditions. Samples of vaginal mucus, saliva, faeces and milk of pro-estrus, estrus and di-estrus stages collected from donor cows were rubbed individually onto the genital regions of non-estrus animals (dummy cows) and the bulls were observed for 30 min for assessment of Flehmen behaviour. The duration of Flehmen behaviour shown by bulls was maximum towards the dummy cows receiving estrus sample. Such Flehmen behaviour, however, did not occur in bulls in response to the cows receiving samples of other stages. The statistical significance was higher (P < 0.001) in exhibiting repeated Flehmen behaviour towards estrus as compared to those of pro-estrus and di-estrus. Among the various body fluids tested, the exhibition of Flehmen behaviour was significantly higher (P < 0.01) in response to estrus vaginal fluid. No response was observed on dummy cows (control) to which only water was applied on the genital region. The results suggest that vaginal mucus may act as an additional/secondary source along with urine in eliciting copulatary behaviour and executing coitus in bulls during estrus. The results further suggest that in addition to vaginal mucus, other body fluids like saliva, faeces and milk have estrus-related odours and are probably involved in bovine bio-communication.

Relations Among River Stage, Rainfall, Ground-Water Levels, and Stage at Two Missouri River Flood-Plain Wetlands

USGS Publications Warehouse

Kelly, Brian P.

2001-01-01

The source of water is important to the ecological function of Missouri River flood-plain wetlands. There are four potential sources of water to flood-plain wetlands: direct flow from the river channel during high river stage, ground-water movement into the wetlands in response to river-stage changes and aquifer recharge, direct precipitation, and runoff from surrounding uplands. Concurrent measurements of river stage, rainfall, ground-water level, and wetland stage were compared for two Missouri River flood-plain wetlands located near Rocheport, Missouri, to characterize the spatial and temporal relations between river stage, rainfall, ground-water levels and wetland stage, determine the source of water to each wetland, and compare measured and estimated stage and ground-water levels at each site. The two sites chosen for this study were wetland NC-5, a non-connected, 50 feet deep scour constantly filled with water, formed during the flood of 1993, and wetland TC-1, a shallow, temporary wetland intermittently filled with water. Because these two wetlands bracket a range of wetland types of the Missouri River flood plain, the responses of other Missouri River wetlands to changes in river stage, rainfall, and runoff should be similar to the responses exhibited by wetlands NC-5 and TC-1. For wetlands deep enough to intersect the ground-water table in the alluvial aquifer, such as wetland NC-5, the ground-water response factor can estimate flood-plain wetland stage changes in response to known river-stage changes. Measured maximum stage and ground-water-level changes at NC-5 fall within the range of estimated changes using the ground-water response factor. Measured maximum ground-water-level changes at TC-1 are similar to, but consistently greater than the estimated values, and are most likely the result of alluvial deposits with higher than average hydraulic conductivity located between wetland TC-1 and the Missouri River. Similarity between ground-water level and stage hydrography at wetland NC-5 indicate that ground-water-level fluctuations caused by river-stage changes control the stage of wetland NC-5. A 2-day lag time exists between river-stage changes and ground water and stage changes at wetland NC-5. The lack of a measurable response of wetland NC-5 stage to rainfall indicate that rainfall is not a large source of water to wetland NC-5. Stage in wetland TC-1 only increased at high river stage in June and July 1999, and from runoff caused by local rainfall during the winter. The 2-day lag time between peak stages at wetland TC-1 and peak Missouri River stages compared to the 1-day lag time between Missouri River stage and ground-water peaks at wetland TC-1 indicates ground-water flow does not directly affect wetland stage at TC-1, but surface-water flow does affect wetland stage at TC-1 during high river stage. Comparing wetland TC-1 stage to potential water sources indicates the most likely explanation for the rise in stage at wetland TC-1 is surface runoff supplied via seepage through the levees and upward flow of ground water through alluvial deposits of higher hydraulic conductivity during high river stage. The rate of decrease in wetland TC-1 stage was limited by the rate at which ground-water level decreased. Stage response to rainfall at wetland TC-1 during the winter months and no response to greater rainfall amounts during spring and summer months indicate that evapotranspiration may limit the affect of rainfall on stage at wetland TC-1 during the growing season.

Survival of patients with intermediate stage hepatocellular carcinoma treated with superselective transarterial chemoembolization using doxorubicin-loaded DC Bead under cone-beam computed tomography control

PubMed Central

Stabuc, Borut; Jansa, Rado; Garbajs, Manca

2016-01-01

Abstract Background The purpose of this retrospective study was to evaluate treatment response, adverse events and survival rates of patients with intermediate stage HCC treated with superselective doxorubicin-loaded DC Bead transarterial chemoembolization (DEBDOX) under cone beam computed tomography (CBCT) control. Patients and methods Between October 2010 and June 2012, 35 consecutive patients with intermediate stage HCC (32 male, 3 female; average age, 67.5 ± 7.8 years; 22 patients Child-Pugh class A, 8 class B, 5 without cirrhosis) were treated with DEBDOX TACE. Portal vein thrombosis was observed in 6 (17.1%) patients. DEBDOX TACE was performed by superselective catheterization of feeding vessels followed by embolization with 100-300 μm microspheres loaded with 50-100 mg of doxorubicin. In all cases, CBCT was used during chemoembolization. Tumor response rates were defined according to mRECIST criteria. Results Overall, 120 procedures were performed (mean, 3.2 per patients). We treated 97 lesions with an average diameter of 4.9 ± 1.9 cm. There were 32 minor and 2 (1.6%) major complications (one liver abscess and one cerebrovascular insult). After a mean follow-up of 27.7 ± 10.5 months, 94.3% of patients achieved an objective response to treatment (42.4% complete response and 57.6% partial response). Mean time to progression was 10.9 ± 5.3 months. Mean overall survival was 33.9 months (95% CI; 28.9 – 38.9 months), with 1- and 2- year survival of 97.1% and 65.7%, respectively. Conclusions Superselective DEBDOX TACE performed under CBCT control is a safe and effective method with high rates of tumor response and overall survival. PMID:27904450

Developing an inventor support service which performs early stage market and manufacturing evaluations. Final report

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

Not Available

1991-10-01

American businesses are learning the difficult high cost lesson of ignoring production and market factors (producibility, unit product cost (UPC), marketability, etc) during the engineering design phase of product development. Studies have shown that the Japanese spend three times as long as Americans in the design feasibility and decision process of new product introductions and one third the amount of time in the implementation of those products. There is a 20 to 1 cost benefit on effort applied in the design phase versus the production phase of the product life cycle. The number one goal of this project was tomore » establish an organization that has, as one of its purposes, the providing of services responsive to the needs of independent inventors. The number two goal was to demonstrate the value of providing marketing and manufacturing counsel at an early stage in the product development process. The first study goal was met by providing the materials and information necessary to establish an evaluation team and an organization to handle such evaluations. The second study goal was met by demonstrating the impact of early market analysis and manufacturing considerations on product design and therefore on the description of the invention for four different inventions. These inventions were selected at various stages of development. Regardless of stage of development, the marketing and manufacturing reviews resulted in significant changes in design and/or market positioning.« less

Developing an inventor support service which performs early stage market and manufacturing evaluations. [Final Report

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

Not Available

1991-10-01

American businesses are learning the difficult high cost lesson of ignoring production and market factors (producibility, unit product cost (UPC), marketability, etc) during the engineering design phase of product development. Studies have shown that the Japanese spend three times as long as Americans in the design feasibility and decision process of new product introductions and one third the amount of time in the implementation of those products. There is a 20 to 1 cost benefit on effort applied in the design phase versus the production phase of the product life cycle. The number one goal of this project was tomore » establish an organization that has, as one of its purposes, the providing of services responsive to the needs of independent inventors. The number two goal was to demonstrate the value of providing marketing and manufacturing counsel at an early stage in the product development process. The first study goal was met by providing the materials and information necessary to establish an evaluation team and an organization to handle such evaluations. The second study goal was met by demonstrating the impact of early market analysis and manufacturing considerations on product design and therefore on the description of the invention for four different inventions. These inventions were selected at various stages of development. Regardless of stage of development, the marketing and manufacturing reviews resulted in significant changes in design and/or market positioning.« less

Effect of low-dose ionizing radiation on luminous marine bacteria: radiation hormesis and toxicity.

PubMed

Kudryasheva, N S; Rozhko, T V

2015-04-01

The paper summarizes studies of effects of alpha- and beta-emitting radionuclides (americium-241, uranium-235+238, and tritium) on marine microorganisms under conditions of chronic low-dose irradiation in aqueous media. Luminous marine bacteria were chosen as an example of these microorganisms; bioluminescent intensity was used as a tested physiological parameter. Non-linear dose-effect dependence was demonstrated. Three successive stages in the bioluminescent response to americium-241 and tritium were found: 1--absence of effects (stress recognition), 2--activation (adaptive response), and 3--inhibition (suppression of physiological function, i.e. radiation toxicity). The effects were attributed to radiation hormesis phenomenon. Biological role of reactive oxygen species, secondary products of the radioactive decay, is discussed. The study suggests an approach to evaluation of non-toxic and toxic stages under conditions of chronic radioactive exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Complete pathological response (ypT0N0M0) after preoperative chemotherapy alone for stage IV rectal cancer.

PubMed

Naiken, Surennaidoo P; Toso, Christian; Rubbia-Brandt, Laura; Thomopoulos, Theodoros; Roth, Arnaud; Mentha, Gilles; Morel, Philippe; Gervaz, Pascal

2014-01-17

Complete pathological response occurs in 10-20% of patients with rectal cancer who are treated with neoadjuvant chemoradiation therapy prior to pelvic surgery. The possibility that complete pathological response of rectal cancer can also occur with neoadjuvant chemotherapy alone (without radiation) is an intriguing hypothesis. A 66-year old man presented an adenocarcinoma of the rectum with nine liver metastases (T3N1M1). He was included in a reverse treatment, aiming at first downsizing the liver metastases by chemotherapy, and subsequently performing the liver surgery prior to the rectum resection. The neoadjuvant chemotherapy consisted in a combination of oxaliplatin, 5-FU, irinotecan, leucovorin and bevacizumab (OCFL-B). After a right portal embolization, an extended right liver lobectomy was performed. On the final histopathological analysis, all lesions were fibrotic, devoid of any viable cancer cells. One month after liver surgery, the rectoscopic examination showed a near-total response of the primary rectal adenocarcinoma, which convinced the colorectal surgeon to perform the low anterior resection without preoperative radiation therapy. Macroscopically, a fibrous scar was observed at the level of the previously documented tumour, and the histological examination of the surgical specimen did not reveal any malignant cells in the rectal wall as well as in the mesorectum. All 15 resected lymph nodes were free of tumour, and the final tumour stage was ypT0N0M0. Clinical outcome was excellent, and the patient is currently alive 5 years after the first surgery without evidence of recurrence. The presented patient with stage IV rectal cancer and liver metastases was in a unique situation linked to its inclusion in a reversed treatment and the use of neoadjuvant chemotherapy alone. The observed achievement of a complete pathological response after chemotherapy should promote the design of prospective randomized studies to evaluate the benefits of chemotherapy alone in patients with stages II-III rectal adenocarcinoma (without metastasis).

Standardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group.

PubMed

Provenzano, Elena; Bossuyt, Veerle; Viale, Giuseppe; Cameron, David; Badve, Sunil; Denkert, Carsten; MacGrogan, Gaëtan; Penault-Llorca, Frédérique; Boughey, Judy; Curigliano, Giuseppe; Dixon, J Michael; Esserman, Laura; Fastner, Gerd; Kuehn, Thorsten; Peintinger, Florentia; von Minckwitz, Gunter; White, Julia; Yang, Wei; Symmans, W Fraser

2015-09-01

Neoadjuvant systemic therapy is being used increasingly in the treatment of early-stage breast cancer. Response, in the form of pathological complete response, is a validated and evaluable surrogate end point of survival after neoadjuvant therapy. Thus, pathological complete response has become a primary end point for clinical trials. However, there is a current lack of uniformity in the definition of pathological complete response. A review of standard operating procedures used by 28 major neoadjuvant breast cancer trials and/or 25 sites involved in such trials identified marked variability in specimen handling and histologic reporting. An international working group was convened to develop practical recommendations for the pathologic assessment of residual disease in neoadjuvant clinical trials of breast cancer and information expected from pathology reports. Systematic sampling of areas identified by informed mapping of the specimen and close correlation with radiological findings is preferable to overly exhaustive sampling, and permits taking tissue samples for translational research. Controversial areas are discussed, including measurement of lesion size, reporting of lymphovascular space invasion and the presence of isolated tumor cells in lymph nodes after neoadjuvant therapy, and retesting of markers after treatment. If there has been a pathological complete response, this must be clearly stated, and the presence/absence of residual ductal carcinoma in situ must be described. When there is residual invasive carcinoma, a comment must be made as to the presence/absence of chemotherapy effect in the breast and lymph nodes. The Residual Cancer Burden is the preferred method for quantifying residual disease in neoadjuvant clinical trials in breast cancer; other methods can be included per trial protocols and regional preference. Posttreatment tumor staging using the Tumor-Node-Metastasis system should be included. These recommendations for standardized pathological evaluation and reporting of neoadjuvant breast cancer specimens should improve prognostication for individual patients and allow comparison of treatment outcomes within and across clinical trials.

Intrinsic cardiac nervous system in tachycardia induced heart failure.

PubMed

Arora, Rakesh C; Cardinal, Rene; Smith, Frank M; Ardell, Jeffrey L; Dell'Italia, Louis J; Armour, J Andrew

2003-11-01

The purpose of this study was to test the hypothesis that early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiac function. After 2 wk of rapid ventricular pacing in nine anesthetized canines, cardiac and right atrial neuronal function were evaluated in situ in response to enhanced cardiac sensory inputs, stimulation of extracardiac autonomic efferent neuronal inputs, and close coronary arterial administration of neurochemicals that included nicotine. Right atrial neuronal intracellular electrophysiological properties were then evaluated in vitro in response to synaptic activation and nicotine. Intrinsic cardiac nicotine-sensitive, neuronally induced cardiac responses were also evaluated in eight sham-operated, unpaced animals. Two weeks of rapid ventricular pacing reduced the cardiac index by 54%. Intrinsic cardiac neurons of paced hearts maintained their cardiac mechano- and chemosensory transduction properties in vivo. They also responded normally to sympathetic and parasympathetic preganglionic efferent neuronal inputs, as well as to locally administered alpha-or beta-adrenergic agonists or angiotensin II. The dose of nicotine needed to modify intrinsic cardiac neurons was 50 times greater in failure compared with normal preparations. That dose failed to alter monitored cardiovascular indexes in failing preparations. Phasic and accommodating neurons identified in vitro displayed altered intracellular membrane properties compared with control, including decreased membrane resistance, indicative of reduced excitability. Early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiodynamics. While maintaining its capacity to transduce cardiac mechano- and chemosensory inputs, as well as inputs from extracardiac autonomic efferent neurons, intrinsic cardiac nicotine-sensitive, local-circuit neurons differentially remodel such that their capacity to influence cardiodynamics becomes obtunded.

Thermal behaviour and kinetics of coal/biomass blends during co-combustion.

PubMed

Gil, M V; Casal, D; Pevida, C; Pis, J J; Rubiera, F

2010-07-01

The thermal characteristics and kinetics of coal, biomass (pine sawdust) and their blends were evaluated under combustion conditions using a non-isothermal thermogravimetric method (TGA). Biomass was blended with coal in the range of 5-80 wt.% to evaluate their co-combustion behaviour. No significant interactions were detected between the coal and biomass, since no deviations from their expected behaviour were observed in these experiments. Biomass combustion takes place in two steps: between 200 and 360 degrees C the volatiles are released and burned, and at 360-490 degrees C char combustion takes place. In contrast, coal is characterized by only one combustion stage at 315-615 degrees C. The coal/biomass blends presented three combustion steps, corresponding to the sum of the biomass and coal individual stages. Several solid-state mechanisms were tested by the Coats-Redfern method in order to find out the mechanisms responsible for the oxidation of the samples. The kinetic parameters were determined assuming single separate reactions for each stage of thermal conversion. The combustion process of coal consists of one reaction, whereas, in the case of the biomass and coal/biomass blends, this process consists of two or three independent reactions, respectively. The results showed that the chemical first order reaction is the most effective mechanism for the first step of biomass oxidation and for coal combustion. However, diffusion mechanisms were found to be responsible for the second step of biomass combustion. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Investigation of an optical sensor for small tilt angle detection of a precision linear stage

NASA Astrophysics Data System (ADS)

Saito, Yusuke; Arai, Yoshikazu; Gao, Wei

2010-05-01

This paper presents evaluation results of the characteristics of the angle sensor based on the laser autocollimation method for small tilt angle detection of a precision linear stage. The sensor consists of a laser diode (LD) as the light source, and a quadrant photodiode (QPD) as the position-sensing detector. A small plane mirror is mounted on the moving table of the stage as a target mirror for the sensor. This optical system has advantages of high sensitivity, fast response speed and the ability for two-axis angle detection. On the other hand, the sensitivity of the sensor is determined by the size of the optical spot focused on the QPD, which is a function of the diameter of the laser beam projected onto the target mirror. Because the diameter is influenced by the divergence of the laser beam, this paper focuses on the relationship between the sensor sensitivity and the moving position of the target mirror (sensor working distance) over the moving stroke of the stage. The main error components that influence the sensor sensitivity are discussed and the optimal conditions of the optical system of the sensor are analyzed. The experimental result about evaluation of the effective working distance is also presented.

Laboratory test methods for evaluating the fire response of aerospace materials

NASA Technical Reports Server (NTRS)

Hilado, C. J.

1979-01-01

The test methods which were developed or evaluated were intended to serve as means of comparing materials on the basis of specific responses under specific sets of test conditions, using apparatus, facilities, and personnel that would be within the capabilities of perhaps the majority of laboratories. Priority was given to test methods which showed promise of addressing the pre-ignition state of a potential fire. These test methods were intended to indicate which materials may present more hazard than others under specific test conditions. These test methods are discussed and arranged according to the stage of a fire to which they are most relevant. Some observations of material performance which resulted from this work are also discussed.

Developing a pain management program through continuous improvement strategies.

PubMed

Woodward, Dora

2005-01-01

Pain affects more than one third of cancer patients in the early stages of their disease, dramatically rising above 70% in the advanced stages. Numerous studies have been conducted in the pursuit of cancer pain relief, yet the prevalence of pain persists. This article focuses on a pain management program, developed by a performance improvement team, which addressed the inadequacies of current pain management. Performance improvement activities are described through the process of assessment, planning, implementation, and evaluation of the pain management program. This pain management program is uniquely derived from a unit core value that all staff is responsible and accountable for pain management.

Evaluating the fate of mercury and other metals across the life-cycle stages from the use of FGD gypsum for wallboard production

EPA Science Inventory

In 2007, 12.3 million tons of flue gas desulfurization (FGD) gypsum was produced due to air emission controls at coal-fired power plants. With increasing use of wet scrubbers in response to more stringent air pollution control requirements, FGD gypsum production is expected to in...

An Experience Oriented-Convergence Improved Gravitational Search Algorithm for Minimum Variance Distortionless Response Beamforming Optimum.

PubMed

Darzi, Soodabeh; Tiong, Sieh Kiong; Tariqul Islam, Mohammad; Rezai Soleymanpour, Hassan; Kibria, Salehin

2016-01-01

An experience oriented-convergence improved gravitational search algorithm (ECGSA) based on two new modifications, searching through the best experiments and using of a dynamic gravitational damping coefficient (α), is introduced in this paper. ECGSA saves its best fitness function evaluations and uses those as the agents' positions in searching process. In this way, the optimal found trajectories are retained and the search starts from these trajectories, which allow the algorithm to avoid the local optimums. Also, the agents can move faster in search space to obtain better exploration during the first stage of the searching process and they can converge rapidly to the optimal solution at the final stage of the search process by means of the proposed dynamic gravitational damping coefficient. The performance of ECGSA has been evaluated by applying it to eight standard benchmark functions along with six complicated composite test functions. It is also applied to adaptive beamforming problem as a practical issue to improve the weight vectors computed by minimum variance distortionless response (MVDR) beamforming technique. The results of implementation of the proposed algorithm are compared with some well-known heuristic methods and verified the proposed method in both reaching to optimal solutions and robustness.

[Emotional intelligence and oscillatory responses on the emotional facial expressions].

PubMed

Kniazev, G G; Mitrofanova, L G; Bocharov, A V

2013-01-01

Emotional intelligence-related differences in oscillatory responses to emotional facial expressions were investigated in 48 subjects (26 men and 22 women) in age 18-30 years. Participants were instructed to evaluate emotional expression (angry, happy and neutral) of each presented face on an analog scale ranging from -100 (very hostile) to + 100 (very friendly). High emotional intelligence (EI) participants were found to be more sensitive to the emotional content of the stimuli. It showed up both in their subjective evaluation of the stimuli and in a stronger EEG theta synchronization at an earlier (between 100 and 500 ms after face presentation) processing stage. Source localization using sLORETA showed that this effect was localized in the fusiform gyrus upon the presentation of angry faces and in the posterior cingulate gyrus upon the presentation of happy faces. At a later processing stage (500-870 ms) event-related theta synchronization in high emotional intelligence subject was higher in the left prefrontal cortex upon the presentation of happy faces, but it was lower in the anterior cingulate cortex upon presentation of angry faces. This suggests the existence of a mechanism that can be selectively increase the positive emotions and reduce negative emotions.

Telomere Length in Leukocyte DNA in Gastric Cancer Patients and its Association with Clinicopathological Features and Prognosis.

PubMed

Tahara, Tomomitsu; Tahara, Sayumi; Horiguchi, Noriyuki; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Yamada, Hyuga; Yoshida, Dai; Ohmori, Takafumi; Maeda, Kohei; Komura, Naruomi; Ikuno, Hirokazu; Jodai, Yasutaka; Kamano, Toshiaki; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Tuskamoto, Tetsuya; Urano, Makoto; Shibata, Tomoyuki; Kuroda, Makoto; Ohmiya, Naoki

2017-04-01

Telomere shortening in leukocytes has been thought to be associated with reduced immune response capacity and increased chromosome instability. Several studies indicate that telomere length in the peripheral blood leukocyte DNA can predict clinical outcome of several cancers. We evaluated the potential association between telomere shortening in the leukocyte DNA and clinicopathological features and prognosis of gastric cancer (GC) in Japanese patients. Telomere length in leukocyte DNA was measured using quantitative real-time polymerase chain reaction (PCR) in 207 GC patients. The association between telomere length and clinicopathological features and prognosis was evaluated. These short-telomere group was significantly associated with advanced stage (p=0.015), worse overall survival (OS) and progression-free survival (PFS) (p=0.046 and 0.026, respectively). The same group was also weakly associated with overall and peritoneal recurrences (p=0.052 and 0.059, respectively). Telomere shortening in leukocyte DNA is associated with advanced stage and poor prognosis of GC, which may reflect their reduced immune response capacity or increased chromosome instability. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Environment-dependent microevolution in a Mediterranean pine (Pinus pinaster Aiton).

PubMed

Alía, Ricardo; Chambel, Regina; Notivol, Eduardo; Climent, José; González-Martínez, Santiago C

2014-09-23

A central question for understanding the evolutionary responses of plant species to rapidly changing environments is the assessment of their potential for short-term (in one or a few generations) genetic change. In our study, we consider the case of Pinus pinaster Aiton (maritime pine), a widespread Mediterranean tree, and (i) test, under different experimental conditions (growth chamber and semi-natural), whether higher recruitment in the wild from the most successful mothers is due to better performance of their offspring; and (ii) evaluate genetic change in quantitative traits across generations at two different life stages (mature trees and seedlings) that are known to be under strong selection pressure in forest trees. Genetic control was high for most traits (h2 = 0.137-0.876) under the milder conditions of the growth chamber, but only for ontogenetic change (0.276), total height (0.415) and survival (0.719) under the more stressful semi-natural conditions. Significant phenotypic selection gradients were found in mature trees for traits related to seed quality (germination rate and number of empty seeds). Moreover, female relative reproductive success was significantly correlated with offspring performance for specific leaf area (SLA) in the growth chamber experiment, and stem mass fraction (SMF) in the experiment under semi-natural conditions, two adaptive traits related to abiotic stress-response in pines. Selection gradients based on genetic covariance of seedling traits and responses to selection at this stage involved traits related to biomass allocation (SMF) and growth (as decomposed by a Gompertz model) or delayed ontogenetic change, depending also on the testing environment. Despite the evidence of microevolutionary change in adaptive traits in maritime pine, directional or disruptive changes are difficult to predict due to variable selection at different life stages and environments. At mature-tree stages, higher female effective reproductive success can be explained by differences in their production of offspring (due to seed quality) and, to a lesser extent, by seemingly better adapted seedlings. Selection gradients and responses to selection for seedlings also differed across experimental conditions. The distinct processes involved at the two life stages (mature trees or seedlings) together with environment-specific responses advice caution when predicting likely evolutionary responses to environmental change in Mediterranean forest trees.

Development of the Flu-PRO: a patient-reported outcome (PRO) instrument to evaluate symptoms of influenza.

PubMed

Powers, John H; Guerrero, M Lourdes; Leidy, Nancy Kline; Fairchok, Mary P; Rosenberg, Alice; Hernández, Andrés; Stringer, Sonja; Schofield, Christina; Rodríguez-Zulueta, Patricia; Kim, Katherine; Danaher, Patrick J; Ortega-Gallegos, Hilda; Bacci, Elizabeth Dansie; Stepp, Nathaniel; Galindo-Fraga, Arturo; St Clair, Kristina; Rajnik, Michael; McDonough, Erin A; Ridoré, Michelande; Arnold, John C; Millar, Eugene V; Ruiz-Palacios, Guillermo M

2016-01-05

To develop content validity of a comprehensive patient-reported outcome (PRO) measure following current best scientific methodology to standardize assessment of influenza (flu) symptoms in clinical research. Stage I (Concept Elicitation): 1:1 telephone interviews with influenza-positive adults (≥18 years) in the US and Mexico within 7 days of diagnosis. Participants described symptom type, character, severity, and duration. Content analysis identified themes and developed the draft Flu-PRO instrument. Stage II (Cognitive Interviewing): The Flu-PRO was administered to a unique set of influenza-positive adults within 14 days of diagnosis; telephone interviews addressed completeness, respondent interpretation of items and ease of use. Samples: Stage I: N = 46 adults (16 US, 30 Mexico); mean (SD) age: 38 (19), 39 (14) years; % female: 56%, 73%; race: 69% White, 97% Mestizo. Stage II: N = 34 adults (12 US, 22 Mexico); age: 37 (14), 39 (11) years; % female: 50%, 50%; race: 58% White, 100% Mestizo. Symptoms identified by >50%: coughing, weak or tired, throat symptoms, congestion, headache, weakness, sweating, chills, general discomfort, runny nose, chest (trouble breathing), difficulty sleeping, and body aches or pains. No new content was uncovered during Stage II; participants easily understood the instrument. Results show the 37-item Flu-PRO is a content valid measure of influenza symptoms in adults with a confirmed diagnosis of influenza. Research is underway to evaluate the suitability of the instrument for children and adolescents. This work can form the basis for future quantitative tests of reliability, validity, and responsiveness to evaluate the measurement properties of Flu-PRO for use in clinical trials and epidemiology studies.

Patients' and family caregivers' understanding of the cancer stage, treatment goal, and chance of cure: A study with patient-caregiver-physician triad.

PubMed

Shin, Dong Wook; Cho, Juhee; Kim, So Young; Yang, Hyung Kook; Park, Keeho; Kweon, Sun-Seog; Koh, Dai Ha; Nam, Hae-Sung; Park, Jong-Hyock

2018-01-01

Accurate understanding of the extent of disease, treatment goal, and prognosis is a prerequisite for patients with cancer and their caregivers to make informed decision. We sought to evaluate patients' and family caregivers' understanding of the cancer stage, treatment goal, and chance of cure taking their own physician's evaluation as reference. A national survey was performed with 750 patient-caregiver dyads (75.5% participation rate) recruited by 134 oncologists in 13 cancer centers (93% participation rate) in South Korea. Both patients and caregivers were asked to report their knowledge of patient's cancer stage, treatment goal, and chance of cure. Concordance was evaluated with percentage agreement and weighted κ, and predictors of discordance of patient and caregiver's response with that of physician's were explored by multivariate regression analyses with mixed effect model. The agreement rates between patient-physician and caregiver-physician were 63.0% and 65.9% for disease stage, 69.0% and 70.0% for treatment goal, and 41.4% and 45.1% for chance of cure. When discordance occurs, patients and caregivers often had an optimistic view. Distant stage, older age, female sex, and absence of depression were associated with optimistic view of patients, and there was significant between-physician variance for all 3 outcomes. The discordance revealed that our study suggests the need for better communication between physician and patients, as well as the caregivers. Research is needed to develop a comprehensive strategy to improve the understanding of the patients and family so that treatment decisions are made based on realistic estimation. Copyright © 2017 John Wiley & Sons, Ltd.

Conceptual framework for development of comprehensive e-health evaluation tool.

PubMed

Khoja, Shariq; Durrani, Hammad; Scott, Richard E; Sajwani, Afroz; Piryani, Usha

2013-01-01

The main objective of this study was to develop an e-health evaluation tool based on a conceptual framework including relevant theories for evaluating use of technology in health programs. This article presents the development of an evaluation framework for e-health programs. The study was divided into three stages: Stage 1 involved a detailed literature search of different theories and concepts on evaluation of e-health, Stage 2 plotted e-health theories to identify relevant themes, and Stage 3 developed a matrix of evaluation themes and stages of e-health programs. The framework identifies and defines different stages of e-health programs and then applies evaluation theories to each of these stages for development of the evaluation tool. This framework builds on existing theories of health and technology evaluation and presents a conceptual framework for developing an e-health evaluation tool to examine and measure different factors that play a definite role in the success of e-health programs. The framework on the horizontal axis divides e-health into different stages of program implementation, while the vertical axis identifies different themes and areas of consideration for e-health evaluation. The framework helps understand various aspects of e-health programs and their impact that require evaluation at different stages of the life cycle. The study led to the development of a new and comprehensive e-health evaluation tool, named the Khoja-Durrani-Scott Framework for e-Health Evaluation.

Dose-Response Relationship between Radiation Dose and Loco-regional Control in Patients with Stage II-III Esophageal Cancer Treated with Definitive Chemoradiotherapy.

PubMed

Kim, Hyun Ju; Suh, Yang-Gun; Lee, Yong Chan; Lee, Sang Kil; Shin, Sung Kwan; Cho, Byung Chul; Lee, Chang Geol

2017-07-01

The correlation between radiation dose and loco-regional control (LRC) was evaluated in patients with stage II-III esophageal cancer treated with definitive concurrent chemoradiotherapy (CRT). Medical records of 236 stage II-III esophageal cancer patients treated with definitive CRT at Yonsei Cancer Center between 1994 and 2013 were retrospectively reviewed. Among these, 120 received a radiation dose of < 60 Gy (standard-dose group), while 116 received ≥ 60 Gy (high-dose group). The median doses of radiation in the standard- and high-dose groups were 50.4 and 63 Gy, respectively. Concurrent 5-fluorouracil/cisplatin chemotherapy was administered to most patients. There were no differences in patient characteristics between the two groups except for high Karnofsky performance status and lower-thoracic lesions being more prevalent in the standard-dose group. The median progression-free survival (PFS) and overall survival (OS) times were 13.2 months and 26.2 months, respectively. Patients in the high-dose group had significantly better 2-year LRC (69.1% vs. 50.3%, p=0.002), median PFS (16.7 months vs. 11.7 months, p=0.029), and median OS (35.1 months vs. 22.3 months, p=0.043). Additionally, LRC exhibited a dose-response relationship and the complete response rate was significantly higher in the high-dose group (p=0.006). There were no significant differences in treatment-related toxicities between the groups. A higher radiation dose (> 60 Gy) is associated with increased LRC, PFS, and OS in patients with stage II-III esophageal cancer treated with definitive CRT.

Nuclear grade and DNA ploidy in stage IV breast cancer with only visceral metastases at initial diagnosis.

PubMed

De Lena, M; Barletta, A; Marzullo, F; Rabinovich, M; Leone, B; Vallejo, C; Machiavelli, M; Romero, A; Perez, J; Lacava, J; Cuevas, M A; Rodriguez, R; Schittulli, F; Paradisco, A

1996-01-01

The presence of early metastases to distant sites in breast cancer patients is an infrequent event whose mechanisms are still not clear. The aim of this study was to evaluate the biologic and clinical role of DNA ploidy and cell nuclear grade of primary tumors in the metastatic process of a series of stage IV previously untreated breast cancer patients with only visceral metastases. DNA flow cytometry analysis on paraffin-embedded material and cell nuclear grading of primary tumors was performed on a series of 50 breast cancer patients with only visceral metastases at the time of initial diagnosis. Aneuploidy was found in 28/46 (61%) of evaluable cases and was independent of site of involvement, clinical response, time of progression and overall survival of patients. Of the 46 cases evaluable for nuclear grade, 5 (11%), 16 (35%) and 25 (54%) were classified as G1 (well-differentiated) G2 and G3, respectively. Nuclear grade also was unrelated to response to therapy and overall survival, whereas time to progression was significantly longer in G1-2 than G3 tumors with the logrank test (P < 0.03) and multivariate analysis. Our results seem to stress the difficulty to individualize different prognostic subsets from a series of breast cancer patients with only visceral metastases at initial diagnosis according to DNA flow cytometry and nuclear grade.

Development, implementation, and evaluation of an energy and power unit of instruction for junior high school industrial arts/technology education programs

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

Litowitz, L.S.

The unit of instruction was developed and refined in three stages. In the first stage, potential objectives for the unit of instruction were identified from appropriate literature. The objectives were mailed to a group primarily consisting of IA/TE state supervisors for critiquing. Upon receiving responses from the critique group, a revised list of objectives was created. From this revised list a content framework was developed. The content framework was then submitted for critiquing to a second group primarily consisting of energy and power curriculum developers. The responses from the second critique group were summarized, and a refined content framework wasmore » produced. A series of twelve hand-on learning activities for junior high school students were then developed to fulfill the unit objectives and concepts identified in the content framework. These activities were critiqued by a final group of experts representing in-service junior high school IA/TE teachers. Revisions to the unit of instruction were made based on feedback from the final critique group. The unit of instruction was then implemented in a junior high school setting as a final means of obtaining formative evaluation. Results of the formative evaluation indicated that the students who participated in the field test had met many of the unit objectives. Recommendations as to the use of the unit of instruction were made.« less

Slump test: sensory responses in asymptomatic subjects.

PubMed

Walsh, Jeremy; Flatley, Miriam; Johnston, Niall; Bennett, Kathleen

2007-01-01

The Slump Test is used as a fast, low-cost diagnostic tool in the evaluation of leg and back pain disorders. The purpose of this study was to identify the normative sensory responses to the Slump Test in asymptomatic subjects. Eighty-four subjects were tested using a standardized procedure by the same examiner to ensure consistency. Prevalence, intensity, location, and nature of responses at each stage of the Slump Test [Slumped Sitting (SS), Knee Extension (KE), Ankle Dorsiflexion (AD), and Cervical Extension (CE)] were recorded. Of the subjects, 97.6% reported a sensory response during the Slump Test. Prevalence of responses increased significantly from 29.8% at SS to 94% at KE and decreased significantly from 97.6% at AD to 65.5% at CE. Median intensity of responses increased significantly from 0/10 at SS, through 4/10 at KE, to 6/10 at AD, and then decreased significantly to 2/10 at CE. At SS, responses were located at the back or neck, but during the subsequent stages, responses were located most commonly in the posterior thigh, knee, and calf. In terms of nature, a number of different descriptors were used, the most common being "stretch," "tight," and "pull." Approximately 80% of subjects reporting a response had complete or partial relief of this response following cervical extension, indicating that the normal response to the Slump Test may be considered a neurogenic response. This normative data may be used as a reference point when using the Slump Test in the examination of leg and back pain disorders.

Slump Test: Sensory Responses in Asymptomatic Subjects

PubMed Central

Walsh, Jeremy; Flatley, Miriam; Johnston, Niall; Bennett, Kathleen

2007-01-01

The Slump Test is used as a fast, low-cost diagnostic tool in the evaluation of leg and back pain disorders. The purpose of this study was to identify the normative sensory responses to the Slump Test in asymptomatic subjects. Eighty-four subjects were tested using a standardized procedure by the same examiner to ensure consistency. Prevalence, intensity, location, and nature of responses at each stage of the Slump Test [Slumped Sitting (SS), Knee Extension (KE), Ankle Dorsiflexion (AD), and Cervical Extension (CE)] were recorded. Of the subjects, 97.6% reported a sensory response during the Slump Test. Prevalence of responses increased significantly from 29.8% at SS to 94% at KE and decreased significantly from 97.6% at AD to 65.5% at CE. Median intensity of responses increased significantly from 0/10 at SS, through 4/10 at KE, to 6/10 at AD, and then decreased significantly to 2/10 at CE. At SS, responses were located at the back or neck, but during the subsequent stages, responses were located most commonly in the posterior thigh, knee, and calf. In terms of nature, a number of different descriptors were used, the most common being “stretch,” “tight,” and “pull.” Approximately 80% of subjects reporting a response had complete or partial relief of this response following cervical extension, indicating that the normal response to the Slump Test may be considered a neurogenic response. This normative data may be used as a reference point when using the Slump Test in the examination of leg and back pain disorders. PMID:19066672

The role of cytokines in the pathogenesis and staging of Trypanosoma brucei rhodesiense sleeping sickness.

PubMed

Kato, Charles D; Matovu, Enock; Mugasa, Claire M; Nanteza, Ann; Alibu, Vincent P

2016-01-01

Human African trypanosomiasis due to Trypanosoma brucei rhodesiense is invariably fatal if untreated with up to 12.3 million people at a risk of developing the disease in Sub-Saharan Africa. The disease is characterized by a wide spectrum of clinical presentation coupled with differences in disease progression and severity. While the factors determining this varied response have not been clearly characterized, inflammatory cytokines have been partially implicated as key players. In this review, we consolidate available literature on the role of specific cytokines in the pathogenesis of T. b. rhodesiense sleeping sickness and further discuss their potential as stage biomarkers. Such information would guide upcoming research on the immunology of sleeping sickness and further assist in the selection and evaluation of cytokines as disease stage or diagnostic biomarkers.

Randomized phase 2/3 trial of CpG oligodeoxynucleotide PF-3512676 alone or with dacarbazine for patients with unresectable stage III and IV melanoma.

PubMed

Weber, Jeffrey S; Zarour, Hassan; Redman, Bruce; Trefzer, Uwe; O'Day, Steven; van den Eertwegh, Alfons J M; Marshall, Ernest; Wagner, Stefan

2009-09-01

The primary objective of this phase 2 study was to assess the objective response rate (complete response [CR] + partial responses [PR]), by Response Evaluation Criteria in Solid Tumors, of PF-3512676, a CpG oligodeoxynucleotide, alone in 2 doses or in combination with dacarbazine (DTIC) in patients with unresectable stage IIIB/C or stage IV malignant melanoma, with the aim of selecting an arm to take forward to a phase 3 portion of the study. A total of 184 patients were randomized to 1 of 4 treatments: PF-3512676 10 mg (low dose), at 40 mg (high dose), 40 mg plus DTIC (850 mg/m(2)), or DTIC (850 mg/m(2)) alone. Patients received PF-3512676 subcutaneously weekly in a 3-week cycle and received DTIC intravenously on the first week of the cycle. The objective response rate (PR or CR, confirmed or unconfirmed) in the 40 mg + DTIC arm was 16% (7 patients) compared with 8% (3 patients) with DTIC alone. One (2%) patient in the 10-mg and 0 patients in the 40-mg arms achieved an objective response. Best response of CR or PR or stable disease (SD), with no minimum duration defined for SD, was achieved by 15 (33%) patients in the 40 mg + DTIC arm, 15 (38%) patients in the DTIC-only arm, 8 (17%) patients in the 10-mg arm, and 9 (20%) patients in the 40-mg arm. The most frequently reported adverse events were classified as local injection site reactions or systemic flu-like symptoms, specifically fatigue, rigors, and pyrexia. PF-3512676 at the doses used was generally well tolerated. The modest objective response rates observed in all arms did not warrant continuation to the phase 3 portion of the study.

Evaluation of acoustic testing techniques for spacecraft systems

NASA Technical Reports Server (NTRS)

Cockburn, J. A.

1971-01-01

External acoustic environments, structural responses, noise reductions, and the internal acoustic environments have been predicted for a typical shroud/spacecraft system during lift-off and various critical stages of flight. Spacecraft responses caused by energy transmission from the shroud via mechanical and acoustic paths have been compared and the importance of the mechanical path has been evaluated. Theoretical predictions have been compared extensively with available laboratory and in-flight measurements. Equivalent laboratory acoustic fields for simulation of shroud response during the various phases of flight have been derived and compared in detail. Techniques for varying the time-space correlations of laboratory acoustic fields have been examined, together with methods for varying the time and spatial distribution of acoustic amplitudes. Possible acoustic testing configurations for shroud/spacecraft systems have been suggested and trade-off considerations have been reviewed. The problem of simulating the acoustic environments versus simulating the structural responses has been considered and techniques for testing without the shroud installed have been discussed.

[Evaluation of breast cancer treatment at a tertiary-level institution with Popular Health Insurance in Mexico].

PubMed

Arce-Salinas, Claudia; Lara-Medina, Fernando Ulises; Alvarado-Miranda, Alberto; Castañeda-Soto, Noel; Bargalló-Rocha, Enrique; Ramírez-Ugalde, María Teresa; Pérez-Sánchez, Víctor; Rivera, Lesbia; Gambo-Vignole, Carlos; Santamaría-Galicia, Julieta; Nieves-Casas, Rosa Isela; Morán-Muñoz, Héctor; Mohar-Betancourt, Alejandro

2012-01-01

In our country breast cancer represents a major health problem. Only 45% of all population has access to health services, the consequence is delay in diagnosis and treatment. In Mexico, 66% of all new cases of breast cancer are diagnosed in locally advanced stages. From May 2007 the Health System Protection Against Catastrophic Expenses, called Seguro Popular (SP), breast cancer was included in covering the treatment of this neoplasm in any patient without access to social security. To evaluate the results and impact of SP in the adjuvant and neoadjuvant treatment of a group of patients diagnosed with breast cancer at an institution of national reference. We analyzed a group of 259 patients in stages (I-IIIC). The clinical stages I and II (55 patients) were treated with adjuvant chemotherapy FAC -T (fluorouracil 500 mg/m2, adriamycin 50 mg/m2 and cyclophosphamide 500 mg/m2 (FAC) followed by 12 weeks of paclitaxel 80 mg/m2 +/- trastuzumab loading dose of 4 mg/kg followed by 2 mg/kg); 204 patients in locally advanced stages (IIB-IIIC) received FAC-T +/- trastuzumab followed by surgery. Adjuvant treatment consisted of endocrine therapy for hormone-sensitive patients and radiotherapy 50 cGy according to international standards. The age at diagnosis was 47 years (range 23-68). 80% of them were locally advanced stages (IIB-IIIC) and were treated in a neoadjuvant setting, 20% was in early stages, treated with surgery and adjuvant chemotherapy The disease-free survival and overall survival at 30 months was 85.7 and 90% respectively. Overall pathologic complete response was obtained in 15% of cases. In the subgroup analysis showed that 41% of patients HER2 (+), 29% of triple-negative patients and 9% of hormone-sensitive tumors achieved complete pathological response (p = 0.0001). This is the first analysis of efficacy of adjuvant and neoadjuvant treatment in breast cancer since the introduction of popular secure non-entitled population. It is clear that treatment efficacy is similar to that reported in the literature, with 15% of pRC and survival to 30 months in 94-80%. The coverage of health expenditures treats a larger number of patients optimally. Along with this, efforts should be made to reduce the high frequency of diagnosis at advanced stage.

Nonlinear electro-optic tuning of plasmonic nano-filter

NASA Astrophysics Data System (ADS)

Kotb, Rehab; Ismail, Yehea; Swillam, Mohamed A.

2015-03-01

Efficient, easy and accurate tuning techniques to a plasmonic nano-filter are investigated. The proposed filter supports both blue and red shift in the resonance wavelength. By varying the refractive index with a very small change (in the order of 10-3), the resonance wavelength can be controlled efficiently. Using Pockels material, an electrical tuning to the response of the filter is demonstrated. In addition, the behavior of the proposed filter can be controlled optically using Kerr material. A new approach of multi-stage electro-optic controlling is introduced. By cascading two stages and filling the first stage with pockels material and the second stage with kerr material, the output response of the second stage can be controlled by controlling the output response of the first stage electrically. Due to the sharp response of the proposed filter, 60nm shift in the resonance wavelength per 10 voltages is achieved. This nano-filter has compact size, low loss, sharp response and wide range of tunabilty which is highly demandable in many biological and sensing applications.

[Intraarterial chemotherapy for uterine cervical adenocarcinoma: evaluation of its efficacy as neoadjuvant therapy].

PubMed

Usuki, N; Hirokawa, K; Tashiro, T; Saiwai, S; Miyamoto, T

1999-10-01

We performed preoperative intraarterial chemotherapy in twenty cases of uterine cervical adenocarcinoma (stage Ib: 2, II: 15, III: 3) and evaluated the efficacy of this therapy. The dosages used were 75-120 mg of CDDP, 10-20 mg of MMC and 30-60 mg of EPIR. These drugs were administered by intraarterial one-shot infusion twice every three weeks. In five cases, complete response (CR) of the primary lesion was confirmed by histologic examination. There were no cases of CR inpatients with well differentiated adenocarcinoma. Stage reduction was achieved in all cases except three. In all but one case, more than 50% volume reduction was recognized on MR images. These results were not significantly different from those in cases of uterine cervical squamous cell carcinoma in which we performed this therapy. Therefore, we concluded that intraarterial chemotherapy is highly effective and should be carried out as neoadjuvant therapy for advanced uterine cervical adenocarcinoma.

The interaction between state and dispositional emotions in decision making: An ERP study.

PubMed

Wang, Yingying; Gu, Ruolei; Luo, Yue-Jia; Zhou, Chenglin

2017-02-01

In this study, to investigate the influence of incidental emotions on decision making in high-anxious individuals, participants were required to perform a monetary gambling task. Behavioral and electroencephalography responses were recorded to explore the stages of option assessment and outcome evaluation during decision making, respectively. Incidental emotions were elicited by facial expression pictures presented on the background, which included four conditions (control, neutral, fearful, and happy). Results showed smaller feedback-related negativity (FRN) amplitudes in high-anxious participants than low-anxious participants in the control, neutral, and fearful conditions, but not in the happy condition, for small outcomes. The P3 amplitudes were larger in high-anxious participants compared to their counterparts in the fearful and happy conditions, but not in the other conditions. In short, the interaction effects between trait anxiety and facial emotions manifested on the outcome evaluation stage of decision making. Copyright © 2016 Elsevier B.V. All rights reserved.

Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection

PubMed Central

Muir, Roshell; Metcalf, Talibah; Tardif, Virginie; Takata, Hiroshi; Phanuphak, Nittaya; Kroon, Eugene; Colby, Donn J.; Trichavaroj, Rapee; Valcour, Victor; Robb, Merlin L.; Michael, Nelson L.; Ananworanich, Jintanat; Trautmann, Lydie; Haddad, Elias K.

2016-01-01

The RV254 cohort of HIV-infected very early acute (4thG stage 1 and 2) (stage 1/2) and late acute (4thG stage 3) (stage 3) individuals was used to study T helper- B cell responses in acute HIV infection and the impact of early antiretroviral treatment (ART) on T and B cell function. To investigate this, the function of circulating T follicular helper cells (cTfh) from this cohort was examined, and cTfh and memory B cell populations were phenotyped. Impaired cTfh cell function was observed in individuals treated in stage 3 when compared to stage 1/2. The cTfh/B cell cocultures showed lower B cell survival and IgG secretion at stage 3 compared to stage 1/2. This coincided with lower IL-10 and increased RANTES and TNF-α suggesting a role for inflammation in altering cTfh and B cell responses. Elevated plasma viral load in stage 3 was found to correlate with decreased cTfh-mediated B cell IgG production indicating a role for increased viremia in cTfh impairment and dysfunctional humoral response. Phenotypic perturbations were also evident in the mature B cell compartment, most notably a decrease in resting memory B cells in stage 3 compared to stage 1/2, coinciding with higher viremia. Our coculture assay also suggested that intrinsic memory B cell defects could contribute to the impaired response despite at a lower level. Overall, cTfh-mediated B cell responses are significantly altered in stage 3 compared to stage 1/2, coinciding with increased inflammation and a reduction in memory B cells. These data suggest that early ART for acutely HIV infected individuals could prevent immune dysregulation while preserving cTfh function and B cell memory. PMID:27463374

Influence of Environmental Factors on Biotic Responses to Nutrient Enrichment in Agricultural Streams1

PubMed Central

Maret, Terry R; Konrad, Christopher P; Tranmer, Andrew W

2010-01-01

The influence of environmental factors on biotic responses to nutrients was examined in three diverse agricultural regions of the United States. Seventy wadeable sites were selected along an agricultural land use gradient while minimizing natural variation within each region. Nutrients, habitat, algae, macroinvertebrates, and macrophyte cover were sampled during a single summer low-flow period in 2006 or 2007. Continuous stream stage and water temperature were collected at each site for 30 days prior to sampling. Wide ranges of concentrations were found for total nitrogen (TN) (0.07-9.61 mg/l) and total phosphorus (TP) (<0.004-0.361 mg/l), but biotic responses including periphytic and sestonic chlorophyll a (RCHL and SCHL, respectively), and percent of stream bed with aquatic macrophyte (AQM) growth were not strongly related to concentrations of TN or TP. Pearson’s coefficient of determination (R2) for nutrients and biotic measures across all sites ranged from 0.08 to 0.32 and generally were not higher within each region. The biotic measures (RCHL, SCHL, and AQM) were combined in an index to evaluate eutrophic status across sites that could have different biotic responses to nutrient enrichment. Stepwise multiple regression identified TN, percent canopy, median riffle depth, and daily percent change in stage as significant factors for the eutrophic index (R2 = 0.50, p < 0.001). A TN threshold of 0.48 mg/l was identified where eutrophic index scores became less responsive to increasing TN concentrations, for all sites. Multiple plant growth indicators should be used when evaluating eutrophication, especially when streams contain an abundance of macrophytes. PMID:22457568

Relationship between aflatoxin contamination and physiological responses of corn plants under drought and heat stress.

PubMed

Kebede, Hirut; Abbas, Hamed K; Fisher, Daniel K; Bellaloui, Nacer

2012-11-20

Increased aflatoxin contamination in corn by the fungus Aspergillus flavus is associated with frequent periods of drought and heat stress during the reproductive stages of the plants. The objective of this study was to evaluate the relationship between aflatoxin contamination and physiological responses of corn plants under drought and heat stress. The study was conducted in Stoneville, MS, USA under irrigated and non-irrigated conditions. Five commercial hybrids, P31G70, P33F87, P32B34, P31B13 and DKC63-42 and two inbred germplasm lines, PI 639055 and PI 489361, were evaluated. The plants were inoculated with Aspergillus flavus (K-54) at mid-silk stage, and aflatoxin contamination was determined on the kernels at harvest. Several physiological measurements which are indicators of stress response were determined. The results suggested that PI 639055, PI 489361 and hybrid DKC63-42 were more sensitive to drought and high temperature stress in the non-irrigated plots and P31G70 was the most tolerant among all the genotypes. Aflatoxin contamination was the highest in DKC63-42 and PI 489361 but significantly lower in P31G70. However, PI 639055, which is an aflatoxin resistant germplasm, had the lowest aflatoxin contamination, even though it was one of the most stressed genotypes. Possible reasons for these differences are discussed. These results suggested that the physiological responses were associated with the level of aflatoxin contamination in all the genotypes, except PI 639055. These and other physiological responses related to stress may help examine differences among corn genotypes in aflatoxin contamination.

Epigenetic Alteration by DNA Methylation of ESR1, MYOD1 and hTERT Gene Promoters is Useful for Prediction of Response in Patients of Locally Advanced Invasive Cervical Carcinoma Treated by Chemoradiation.

PubMed

Sood, S; Patel, F D; Ghosh, S; Arora, A; Dhaliwal, L K; Srinivasan, R

2015-12-01

Locally advanced invasive cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) IIB/III] is treated by chemoradiation. The response to treatment is variable within a given FIGO stage. Therefore, the aim of the present study was to evaluate the gene promoter methylation profile and corresponding transcript expression of a panel of six genes to identify genes which could predict the response of patients treated by chemoradiation. In total, 100 patients with invasive cervical cancer in FIGO stage IIB/III who underwent chemoradiation treatment were evaluated. Ten patients developed systemic metastases during therapy and were excluded. On the basis of patient follow-up, 69 patients were chemoradiation-sensitive, whereas 21 were chemoradiation-resistant. Gene promoter methylation and gene expression was determined by TaqMan assay and quantitative real-time PCR, respectively, in tissue samples. The methylation frequency of ESR1, BRCA1, RASSF1A, MLH1, MYOD1 and hTERT genes ranged from 40 to 70%. Univariate and hierarchical cluster analysis revealed that gene promoter methylation of MYOD1, ESR1 and hTERT could predict for chemoradiation response. A pattern of unmethylated MYOD1, unmethylated ESR1 and methylated hTERT promoter as well as lower ESR1 transcript levels predicted for chemoradiation resistance. Methylation profiling of a panel of three genes that includes MYOD1, ESR1 and hTERT may be useful to predict the response of invasive cervical carcinoma patients treated with standard chemoradiation therapy. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Integrated bioconversion of syngas into bioethanol and biopolymers.

PubMed

Lagoa-Costa, Borja; Abubackar, Haris Nalakath; Fernández-Romasanta, María; Kennes, Christian; Veiga, María C

2017-09-01

Syngas bioconversion is a promising method for bioethanol production, but some VFA remains at the end of fermentation. A two-stage process was set-up, including syngas fermentation as first stage under strict anaerobic conditions using C. autoethanogenum as inoculum, with syngas (CO/CO 2 /H 2 /N 2 , 30/10/20/40) as gaseous substrate. The second stage consisted in various fed-batch assays using a highly enriched PHA accumulating biomass as inoculum, where the potential for biopolymer production from the remaining acetic acid at the end of the syngas fermentation was evaluated. All of the acetic acid was consumed and accumulated as biopolymer, while ethanol and 2,3-butanediol remained basically unused. It can be concluded that a high C/N ratio in the effluent from the syngas fermentation stage was responsible for non-consumption of alcohols. A maximum PHA content of 24% was reached at the end of the assay. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immunopathological Patterns from EAE and Theiler’s Virus Infection: Is Multiple Sclerosis a Homogenous 1-stage or Heterogenous 2-stage Disease?

PubMed Central

Martinez, Nicholas E.; Sato, Fumitaka; Omura, Seiichi; Minagar, Alireza; Alexander, J. Steven; Tsunoda, Ikuo

2012-01-01

Multiple sclerosis (MS) is a disease which can present in different clinical courses. The most common form of MS is the relapsing-remitting (RR) course, which in many cases evolves into secondary progressive (SP) disease. Autoimmune models such as experimental autoimmune encephalomyelitis (EAE) have been developed to represent the various clinical forms of MS. These models along with clinico-pathological evidence obtained from MS patients have allowed us to propose ‘1-stage’ and ‘2-stage’ disease theories to explain the transition in the clinical course of MS from RR to SP. Relapses in MS are associated with pro-inflammatory T helper (Th) 1/Th17 immune responses, while remissions are associated with anti-inflammatory Th2/regulatory T (Treg) immune responses. Based on the ‘1-stage disease’ theory, the transition from RR to SP disease occurs when the inflammatory immune response overwhelms the anti-inflammatory immune response. The ‘2-stage disease’ theory proposes that the transition from RR to SP-MS occurs when the Th2 response or some other responses overwhelm the inflammatory response resulting in the sustained production of anti-myelin antibodies, which cause continuing demyelination, neurodegeneration, and axonal loss. The Theiler’s virus model is also a 2-stage disease, where axonal degeneration precedes demyelination during the first stage, followed by inflammatory demyelination during the second stage. PMID:22633747

Evaluating the aquatic toxicity of complex organic chemical mixtures: lessons learned from polycyclic aromatic hydrocarbon and petroleum hydrocarbon case studies.

PubMed

Landrum, Peter F; Chapman, Peter M; Neff, Jerry; Page, David S

2012-04-01

Experimental designs for evaluating complex mixture toxicity in aquatic environments can be highly variable and, if not appropriate, can produce and have produced data that are difficult or impossible to interpret accurately. We build on and synthesize recent critical reviews of mixture toxicity using lessons learned from 4 case studies, ranging from binary to more complex mixtures of primarily polycyclic aromatic hydrocarbons and petroleum hydrocarbons, to provide guidance for evaluating the aquatic toxicity of complex mixtures of organic chemicals. Two fundamental requirements include establishing a dose-response relationship and determining the causative agent (or agents) of any observed toxicity. Meeting these 2 requirements involves ensuring appropriate exposure conditions and measurement endpoints, considering modifying factors (e.g., test conditions, test organism life stages and feeding behavior, chemical transformations, mixture dilutions, sorbing phases), and correctly interpreting dose-response relationships. Specific recommendations are provided. Copyright © 2011 SETAC.

Prognostic value of neoadjuvant treatment response in locally advanced rectal cancer.

PubMed

Sada, Yvonne H; Tran Cao, Hop S; Chang, George J; Artinyan, Avo; Musher, Benjamin L; Smaglo, Brandon G; Massarweh, Nader N

2018-06-01

For locally advanced rectal cancer, response to neoadjuvant radiation has been associated with improved outcomes but has not been well characterized in general practice. The goals of this study were to describe disease response rates after neoadjuvant treatment and to evaluate the association between disease response and survival. Retrospective cohort study of patients aged 18-80 y with clinical stage II and III rectal adenocarcinoma in the National Cancer Database (2006-2012). All patients underwent radical resection after neoadjuvant treatment. Treatment responses were defined as follows: no tumor response; intermediate-T and/or N downstaging with residual disease; and complete-ypT0N0. Multivariable, multinomial regression was used to evaluate the association between neoadjuvant radiation use and disease response. Multivariable Cox regression was used to evaluate the association between disease response and overall risk of death. Among 12,024 patients, 12% had a complete and 30% an intermediate response. Neoadjuvant chemotherapy alone was less likely to achieve an intermediate (relative risk ratio: 0.70 [0.56-0.88]) or a complete response (relative risk ratio: 0.59 [0.41-0.84]) relative to neoadjuvant radiation. Tumor response was associated with improved 5-y overall survival (complete = 90.2%, intermediate = 82.0%, no response = 70.5%; log-rank, P < 0.001). Complete and intermediate pathologic responses were associated with decreases in risk of death (hazard ratio: 0.40 [0.34-0.48] and 0.63 [0.57-0.69], respectively) compared to no response. Primary tumor and nodal response were independently associated with decreased risk of death. Neoadjuvant radiation is associated with treatment response, and pathologic response is associated with improved survival. Pathologic response may be an early benchmark for the oncologic effectiveness of neoadjuvant treatment. Published by Elsevier Inc.

Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer.

PubMed

Kawamura, Junichiro; Sugiura, Fumiaki; Sukegawa, Yasushi; Yoshioka, Yasumasa; Hida, Jin-Ichi; Hazama, Shoichi; Okuno, Kiyotaka

2018-02-23

We previously reported a phase I clinical trial of a peptide vaccine ring finger protein 43 (RNF43) and 34-kDa translocase of the outer mitochondrial membrane (TOMM34) combined with uracil-tegafur (UFT)/LV for patients with metastatic colorectal cancer (CRC), and demonstrated the safety and immunological responsiveness of this combination therapy. In this study, we evaluated vaccination-induced immune responses to clarify the survival benefit of the combination therapy as adjuvant treatment. We enrolled 44 patients initially in an HLA-masked fashion. After the disclosure of HLA, 28 patients were in the HLA-A*2402-matched and 16 were in the unmatched group. In the HLA-matched group, 14 patients had positive CTL responses specific for the RNF43 and/or TOMM34 peptides after 2 cycles of treatment and 9 had negative responses; in the HLA-unmatched group, 10 CTL responses were positive and 2 negative. In the HLA-matched group, 3-year relapse-free survival (RFS) was significantly better in the positive CTL subgroup than in the negative-response subgroup. Patients with negative vaccination-induced CTL responses showed a significant trend towards shorter RFS than those with positive responses. Moreover, in the HLA-unmatched group, the positive CTL response subgroup showed an equally good 3-year RFS as in the HLA-matched group. In conclusion, vaccination-induced CTL response to peptide vaccination could predict survival in the adjuvant setting for stage III CRC. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Blue light-induced immunosuppression in Bactrocera dorsalis adults, as a carryover effect of larval exposure.

PubMed

Tariq, K; Noor, M; Hori, M; Ali, A; Hussain, A; Peng, W; Chang, C-J; Zhang, H

2017-12-01

Detrimental effects of ultraviolet (UV) light on living organisms are well understood, little is known about the effects of blue light irradiation. Although a recent study revealed that blue light caused more harmful effects on insects than UV light and blue light irradiation killed insect pests of various orders including Diptera, the effects of blue light on physiology of insects are still largely unknown. Here we studied the effects of blue light irradiation on cuticular melanin in larval and the immune response in adult stage of Bactrocera dorsalis. We also evaluated the effects of blue light exposure in larval stage on various age and mass at metamorphosis and the mediatory role of cuticular melanin in carryover effects of larval stressors across metamorphosis. We found that larvae exposed to blue light decreased melanin contents in their exoskeleton with smaller mass and delayed metamorphosis than insects reared without blue light exposure. Across metamorphosis, lower melanotic encapsulation response and higher susceptibility to Beauveria bassiana was detected in adults that had been exposed to blue light at their larval stage, thereby constituting the first evidence that blue light impaired adult immune function in B. dorsalis as a carryover effect of larval exposure.

Melanoma.

PubMed

Gershenwald, J E

2001-01-01

The presentations at the American Society of Clinical Oncology 2001 meeting reported or updated the results of phase I, II, and III randomized trials and also reported important meta-analyses and retrospective studies impacting on the management of patients with melanoma. In the treatment of early stage melanoma, the prognostic significance of pathologic status of sentinel lymph nodes was affirmed. With respect to regional nodal involvement (American Joint Committee on Cancer [AJCC] stage III), investigators presented the interim results of the United Kingdom randomized low-dose interferon (IFN) trial, and up-to-date meta-analyses of several IFN trials including a pooled analysis of the Eastern Cooperative Oncology Group trials evaluating interferon in the adjuvant setting. In the advanced disease setting (AJCC stage IV), several studies elucidated the pros and cons of biochemotherapy in patients with metastatic melanoma, with an emphasis on seeking to improve response in the central nervous system and durability of response in general. Thought provoking was new data regarding the potential for lovastatin to act as a chemopreventive agent for melanoma. Translational studies were presented, one supporting the importance of HLA-typing in developing targeted vaccine therapy. Finally, the results of a novel experimental melanoma vaccine were presented using autologous tumor-derived heat-shock protein peptide complex-96 (HSPPC-96).

Taking one’s time in feeling other-race pain: an event-related potential investigation on the time-course of cross-racial empathy

PubMed Central

Meconi, Federica; Castelli, Luigi; Dell’Acqua, Roberto

2014-01-01

Using the event-related potential (ERP) approach, we tracked the time-course of white participants’ empathic reactions to white (own-race) and black (other-race) faces displayed in a painful condition (i.e. with a needle penetrating the skin) and in a nonpainful condition (i.e. with Q-tip touching the skin). In a 280–340 ms time-window, neural responses to the pain of own-race individuals under needle penetration conditions were amplified relative to neural responses to the pain of other-race individuals displayed under analogous conditions. This ERP reaction to pain, whose source was localized in the inferior frontal gyrus, correlated with the empathic concern ratings of the Interpersonal Reactivity Index questionnaire. In a 400–750 ms time-window, the difference between neural reactions to the pain of own-race individuals, localized in the middle frontal gyrus and other-race individuals, localized in the temporoparietal junction was reduced to nil. These findings support a functional, neural and temporal distinction between two sequential processing stages underlying empathy, namely, a race-biased stage of pain sharing/mirroring followed by a race-unbiased stage of cognitive evaluation of pain. PMID:23314008

Study on the application of ambient vibration tests to evaluate the effectiveness of seismic retrofitting

NASA Astrophysics Data System (ADS)

Liang, Li; Takaaki, Ohkubo; Guang-hui, Li

2018-03-01

In recent years, earthquakes have occurred frequently, and the seismic performance of existing school buildings has become particularly important. The main method for improving the seismic resistance of existing buildings is reinforcement. However, there are few effective methods to evaluate the effect of reinforcement. Ambient vibration measurement experiments were conducted before and after seismic retrofitting using wireless measurement system and the changes of vibration characteristics were compared. The changes of acceleration response spectrum, natural periods and vibration modes indicate that the wireless vibration measurement system can be effectively applied to evaluate the effect of seismic retrofitting. The method can evaluate the effect of seismic retrofitting qualitatively, it is difficult to evaluate the effect of seismic retrofitting quantitatively at this stage.

Use of Oncept melanoma vaccine in 69 canine oral malignant melanomas in the UK.

PubMed

Verganti, S; Berlato, D; Blackwood, L; Amores-Fuster, I; Polton, G A; Elders, R; Doyle, R; Taylor, A; Murphy, S

2017-01-01

Oral malignant melanomas carry a poor-to-guarded prognosis because of their local invasiveness and high metastatic propensity. The Oncept melanoma vaccine is licensed to treat dogs with stage II or III locally-controlled oral malignant melanoma and this retrospective study aimed to assess survival of affected dogs treated with the vaccine in the UK. Medical records of dogs with histopathologically-confirmed oral malignant melanoma that received the vaccine as part of their treatment were evaluated. Survival analyses for potential prognostic factors were performed. Sixty-nine dogs were included; 56 dogs, staged I to III, and with previous locoregional therapy, had a median survival time of 455 days (95% CI: 324 to 586 days). Based on Kaplan-Meier survival analysis with associated log-rank testing, no significant prognostic factors were identified for this population. Of the 13 patients with macroscopic disease treated with vaccine alone or in combination therapy, eight showed clinical response. Three patients with stage IV oral malignant melanoma survived 171, 178 and 288 days from diagnosis. Patients treated with the melanoma vaccine in our study had survival times similar to their counterparts receiving the vaccine in the USA. There were observed responses in patients with macroscopic disease and so the vaccine could be considered as palliative treatment in dogs with stage IV disease. © 2017 British Small Animal Veterinary Association.

Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus.

PubMed

Macías, Juan; Berenguer, Juan; Japón, Miguel A; Girón, José A; Rivero, Antonio; López-Cortés, Luis F; Moreno, Ana; González-Serrano, Mercedes; Iribarren, José A; Ortega, Enrique; Miralles, Pilar; Mira, José A; Pineda, Juan A

2009-10-01

A few studies have assessed the observed fibrosis progression between serial liver biopsies (LB) in human immunodeficiency virus (HIV) / hepatitis C virus (HCV)-coinfected patients. Approximately half of the patients progressed at least one fibrosis stage over a short period of time. The risk factors for this fast progression need clarification. Because of this, we evaluated the observed fibrosis progression rates of HIV/HCV-coinfected patients and the risk factors for accelerated progression. Overall, 135 HIV-infected patients with positive serum HCV RNA, without other possible causes of liver disease, who underwent two LB, separated at least by 1 year, were included in this retrospective cohort study. The median (Q1-Q3) time between both LBs was 3.3 (2.0-5.2) years. Patients showed the following changes in fibrosis stage: regression >or =1 stage: 23 (17%), no change: 52 (39%), progression 1 stage: 38 (28%), and progression > or =2 stages: 22 (16%). Seventeen (13%) patients had cirrhosis in the second biopsy. Factors independently associated with progression > or =1 stage were undetectable plasma HIV RNA during the follow-up (relative risk [RR] [95% confidence interval, 95% CI] 0.61 [0.39-0.93], P = 0.03), moderate-to-severe lobular necroinflammation (1.77 [1.16-2.7], P = 0.009), time between biopsies (1.11 [1.08-1.2], P = 0.01), and end of treatment response to anti-HCV therapy (0.41 [0.19-0.88], P = 0.02). Fibrosis progresses with high frequency in HIV/HCV-coinfected patients over a period of time of 3 years. Absent-to-mild lobular necroinflammation at baseline, achievement of response with anti-HCV treatment, and effective antiretroviral therapy are associated with slower fibrosis progression.

A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole

PubMed Central

2010-01-01

Background Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of CYP19A1 and their effect on response to neoadjuvant letrozole in early BC. Methods We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4th month by World Health Organization (WHO) criteria. Three polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood. Results Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009). Conclusions Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients. PMID:20144226

Phase II clinical study of valproic acid plus cisplatin and cetuximab in recurrent and/or metastatic squamous cell carcinoma of Head and Neck-V-CHANCE trial.

PubMed

Caponigro, Francesco; Di Gennaro, Elena; Ionna, Franco; Longo, Francesco; Aversa, Corrado; Pavone, Ettore; Maglione, Maria Grazia; Di Marzo, Massimiliano; Muto, Paolo; Cavalcanti, Ernesta; Petrillo, Antonella; Sandomenico, Fabio; Maiolino, Piera; D'Aniello, Roberta; Botti, Gerardo; De Cecio, Rossella; Losito, Nunzia Simona; Scala, Stefania; Trotta, Annamaria; Zotti, Andrea Ilaria; Bruzzese, Francesca; Daponte, Antonio; Calogero, Ester; Montano, Massimo; Pontone, Monica; De Feo, Gianfranco; Perri, Francesco; Budillon, Alfredo

2016-11-25

Recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) has a poor prognosis and the combination of cisplatin and cetuximab, with or without 5-fluorouracil, is the gold standard treatment in this stage. Thus, the concomitant use of novel compounds represents a critical strategy to improve treatment results. Histone deacetylase inhibitors (HDACi) enhance the activity of several anticancer drugs including cisplatin and anti-Epidermal Growth Factor Receptor (anti-EGFR) compounds. Preclinical studies in models have shown that vorinostat is able to down regulate Epidermal Growth Factor Receptor (EGFR) expression and to revert epithelial to mesenchimal transition (EMT). Due to its histone deacetylase (HDAC) inhibiting activity and its safe use as a chronic therapy for epileptic disorders, valproic acid (VPA) has been considered a good candidate for anticancer therapy. A reasonable option may be to employ the combination of cisplatin, cetuximab and VPA in recurrent/metastatic SCCHN taking advantage of the possible positive interaction between histone deacetylase inhibitors, cisplatin and/or anti-EGFR. V-CHANCE is a phase 2 clinical trial evaluating, in patients with recurrent/metastatic squamous cell carcinoma of the head and neck never treated with first-line chemotherapy, the concomitant standard administration of cisplatin (on day 1, every 3 weeks) and cetuximab (on day 1, weekly), in combination with oral VPA given daily from day -14 with a titration strategy in each patient (target serum level of 50-100 μg/ml). Primary end point is the objective response rate measured according to Response Evaluation Criteria in Solid Tumors (RECIST). Sample size, calculated according to Simon 2 stage minimax design will include 21 patients in the first stage with upper limit for rejection being 8 responses, and 39 patients in the second stage, with upper limit for rejection being 18 responses. Secondary endpoints are time to progression, duration of response, overall survival, safety. Objectives of the translational study are the evaluation on tumor samples of markers of treatment efficacy/resistance (i.e. γH2AX, p21/WAF, RAD51, XRCC1, EGFR, p-EGFR, Ki-67) and specific markers of VPA HDAC inhibitory activity (histones and proteins acetylation, Histone deacetylase isoforms) as well as valproate test, histones and proteins acetylation of peripheral blood mononuclear cell, tested on blood samples at baseline and at different time points during treatment. Overall, this study could provide a less toxic and more effective first-line chemotherapy regimen in patients with recurrent/metastatic squamous cell carcinoma of the head and neck by demonstrating the feasibility and efficacy of cisplatin/cetuximab plus valproic acid. Moreover, correlative studies could help to identify responder patients, and will add insights in the mechanism of the synergistic interaction between these agents. 2014-001523-69 TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02624128.

A Method for Writing Open-Ended Curved Arrow Notation Questions for Multiple-Choice Exams and Electronic-Response Systems

ERIC Educational Resources Information Center

Ruder, Suzanne M.; Straumanis, Andrei R.

2009-01-01

A critical stage in the process of developing a conceptual understanding of organic chemistry is learning to use curved arrow notation. From this stems the ability to predict reaction products and mechanisms beyond the realm of memorization. Since evaluation (i.e., testing) is known to be a key driver of student learning, it follows that a new…

Performance of Automated Speech Scoring on Different Low- to Medium-Entropy Item Types for Low-Proficiency English Learners. Research Report. ETS RR-17-12

ERIC Educational Resources Information Center

Loukina, Anastassia; Zechner, Klaus; Yoon, Su-Youn; Zhang, Mo; Tao, Jidong; Wang, Xinhao; Lee, Chong Min; Mulholland, Matthew

2017-01-01

This report presents an overview of the "SpeechRater"? automated scoring engine model building and evaluation process for several item types with a focus on a low-English-proficiency test-taker population. We discuss each stage of speech scoring, including automatic speech recognition, filtering models for nonscorable responses, and…

The Role of Affect and Cognition in Processing Messages about Early Diagnosis for Alzheimer’s Disease by Older People

PubMed Central

De Pelsmacker, Patrick; Lewi, Martine; Cauberghe, Veroline

2017-01-01

Through early diagnosis of symptoms, the Alzheimer’s disease process can be decelerated. The main concern is to encourage the population at risk to take responsible actions at the earliest stage of the onset of the disease. Persuasive communication is essential to achieve this. In an experimental study, the evaluation of awareness messages for early diagnosis containing weak and strong arguments and negative and positive images was performed on a sample of older Belgians. The mediating role of affective responses and message thoughts was explored. Strong arguments led to a more positive evaluation of the message than weak arguments directly and indirectly via the positive effect they had on message affect and thoughts, which, in turn, positively affected message evaluation. A negative message image led to a more positive message evaluation than a positive one. This effect was not mediated by either message affect or message thoughts. PMID:28604627

[Randomized clinical trial of IEP and EP regimens in the treatment of patients with small cell lung cancer].

PubMed

Zhou, Hui; Wang, Anlan; Huang, Zhihua; Zhou, Wenwei

2004-06-20

To observe and compare the efficacy and safety of IEP and EP regimens for small cell lung cancer (SCLC). Sixty-four patients with SCLC pathologically proved were randomly divided into IEP group ( n =32) and EP group ( n =32). All the 64 patients were evaluable for response and toxicity. In IEP group, the total responsive rate, responsive rates of limited-stage patients and extensive-stage patients were 84.4%(27/32), 100.0%(15/15) and 70.6%(12/17) respectively; while in EP group, those were 75.0%(24/32), 85.7%(12/14) and 66.7% (12/18) respectively. The median duration of remission was 6 months and 1-year survival rate was 62.5% in IEP group, and 5 months and 56.2% in EP group. There was no significant difference in response rate, median duration of remission and 1-year survival between the two groups ( P > 0.05). The main toxicity was myelosuppression. Incidences of leukopenia at grade III-IV, nausea, vomiting and alopecia were significantly higher in the IEP arm than those in the EP arm ( P < 0.01 ). High response rates and tolerable toxicities are attainable for small cell lung cancer treated with IEP and EP. IEP regimen shows a similar response rate compared with EP regimen. They might be considered as relevant regimens in initial patients with small cell lung cancer.

Neoadjuvant Long-Course Chemoradiotherapy for Rectal Cancer: Does Time to Surgery Matter?

PubMed Central

Panagiotopoulou, Ioanna G.; Parashar, Deepak; Qasem, Eyas; Mezher-Sikafi, Rasha; Parmar, Jitesh; Wells, Alan D.; Bajwa, Farrukh M.; Menon, Madhav; Jephcott, Catherine R.

2015-01-01

The objective of this paper was to evaluate whether delaying surgery following long-course chemoradiotherapy for rectal cancer correlates with pathologic complete response. Pre-operative chemoradiotherapy (CRT) is standard practice in the UK for the management of locally advanced rectal cancer. Optimal timing of surgery following CRT is still not clearly defined. All patients with a diagnosis of rectal cancer who had undergone long-course CRT prior to surgery between January 2008 and December 2011 were included. Statistical analysis was performed using Stata 11. Fifty-nine patients received long-course CRT prior to surgery in the selected period. Twenty-seven percent (16/59) of patients showed a complete histopathologic response and 59.3% (35/59) of patients had tumor down-staging from radiologically-assessed node positive to histologically-proven node negative disease. There was no statistically significant delay to surgery after completion of CRT in the 16 patients with complete response (CR) compared with the rest of the group [IR: incomplete response; CR group median: 74.5 days (IQR: 70–87.5) and IR group median: 72 days (IQR: 57–83), P = 0.470]. Although no statistically significant predictors of either complete response or tumor nodal status down-staging were identified in logistic regression analyses, a trend toward complete response was seen with longer delay to surgery following completion of long-course CRT. PMID:26414816

Characterization of necrosis-inducing NLP proteins in Phytophthora capsici

PubMed Central

2014-01-01

Background Effector proteins function not only as toxins to induce plant cell death, but also enable pathogens to suppress or evade plant defense responses. NLP-like proteins are considered to be effector proteins, and they have been isolated from bacteria, fungi, and oomycete plant pathogens. There is increasing evidence that NLPs have the ability to induce cell death and ethylene accumulation in plants. Results We evaluated the expression patterns of 11 targeted PcNLP genes by qRT-PCR at different time points after infection by P. capsici. Several PcNLP genes were strongly expressed at the early stages in the infection process, but the expression of other PcNLP genes gradually increased to a maximum at late stages of infection. The genes PcNLP2, PcNLP6 and PcNLP14 showed the highest expression levels during infection by P. capsici. The necrosis-inducing activity of all targeted PcNLP genes was evaluated using heterologous expression by PVX agroinfection of Capsicum annuum and Nicotiana benthamiana and by Western blot analysis. The members of the PcNLP family can induce chlorosis or necrosis during infection of pepper and tobacco leaves, but the chlorotic or necrotic response caused by PcNLP genes was stronger in pepper leaves than in tobacco leaves. Moreover, PcNLP2, PcNLP6, and PcNLP14 caused the largest chlorotic or necrotic areas in both host plants, indicating that these three genes contribute to strong virulence during infection by P. capsici. This was confirmed through functional evaluation of their silenced transformants. In addition, we further verified that four conserved residues are putatively active sites in PcNLP1 by site-directed mutagenesis. Conclusions Each targeted PcNLP gene affects cells or tissues differently depending upon the stage of infection. Most PcNLP genes could trigger necrotic or chlorotic responses when expressed in the host C. annuum and the non-host N. benthamiana. Individual PcNLP genes have different phytotoxic effects, and PcNLP2, PcNLP6, and PcNLP14 may play important roles in symptom development and may be crucial for virulence, necrosis-inducing activity, or cell death during infection by P. capsici. PMID:24886309

Characterization of necrosis-inducing NLP proteins in Phytophthora capsici.

PubMed

Feng, Bao-Zhen; Zhu, Xiao-Ping; Fu, Li; Lv, Rong-Fei; Storey, Dylan; Tooley, Paul; Zhang, Xiu-Guo

2014-05-08

Effector proteins function not only as toxins to induce plant cell death, but also enable pathogens to suppress or evade plant defense responses. NLP-like proteins are considered to be effector proteins, and they have been isolated from bacteria, fungi, and oomycete plant pathogens. There is increasing evidence that NLPs have the ability to induce cell death and ethylene accumulation in plants. We evaluated the expression patterns of 11 targeted PcNLP genes by qRT-PCR at different time points after infection by P. capsici. Several PcNLP genes were strongly expressed at the early stages in the infection process, but the expression of other PcNLP genes gradually increased to a maximum at late stages of infection. The genes PcNLP2, PcNLP6 and PcNLP14 showed the highest expression levels during infection by P. capsici. The necrosis-inducing activity of all targeted PcNLP genes was evaluated using heterologous expression by PVX agroinfection of Capsicum annuum and Nicotiana benthamiana and by Western blot analysis. The members of the PcNLP family can induce chlorosis or necrosis during infection of pepper and tobacco leaves, but the chlorotic or necrotic response caused by PcNLP genes was stronger in pepper leaves than in tobacco leaves. Moreover, PcNLP2, PcNLP6, and PcNLP14 caused the largest chlorotic or necrotic areas in both host plants, indicating that these three genes contribute to strong virulence during infection by P. capsici. This was confirmed through functional evaluation of their silenced transformants. In addition, we further verified that four conserved residues are putatively active sites in PcNLP1 by site-directed mutagenesis. Each targeted PcNLP gene affects cells or tissues differently depending upon the stage of infection. Most PcNLP genes could trigger necrotic or chlorotic responses when expressed in the host C. annuum and the non-host N. benthamiana. Individual PcNLP genes have different phytotoxic effects, and PcNLP2, PcNLP6, and PcNLP14 may play important roles in symptom development and may be crucial for virulence, necrosis-inducing activity, or cell death during infection by P. capsici.

Treatment of advanced refractory sarcomas with ifosfamide and etoposide combination chemotherapy.

PubMed

Yalçin, S; Güllü, I; Barişta, I; Tekuzman, G; Ozişik, Y; Celik, I; Kars, A

1998-01-01

Chemotherapy options for resistant advanced-stage sarcomas are limited and in most cases disappointing. In a phase II study, we treated 26 consecutive patients with refractory advanced sarcoma with ifosfamide and etoposide combination chemotherapy. All patients had received prior doxorubicin- and/or cyclophosphamide-based chemotherapies. Seventeen patients were male and 9 were female. The patients' median age was 35 years (range: 19-67 years). A total of 24 patients were eligible for evaluation of responses. Seven patients had a complete response (CR) (29.1%), 3 had a partial response (PR) (12.5%), 3 had stable disease (SD) (12.5%), and 11 had progressive disease (PD) (45.9%). An overall 41.6% objective response was achieved. Median time to treatment failure was 13.3 months. A total of 108 cycles of therapy were evaluable for evaluation of toxicity. Myelosuppression, observed in 55.5% of the treatment courses, was the major dose-limiting toxicity. Nausea and vomiting, seen in 64% of the courses, were the most important nonhematological side effects. Alopecia was almost universal. Hemorrhagic cystitis was observed in only 1 patient. We have concluded that the combination of ifosfamide, mesna, and etoposide is effective in advanced refractory sarcomas, and has acceptable toxicity.

A progressive 5-week exercise therapy program leads to significant improvement in knee function early after anterior cruciate ligament injury.

PubMed

Eitzen, Ingrid; Moksnes, Håvard; Snyder-Mackler, Lynn; Risberg, May Arna

2010-11-01

Prospective cohort study without a control group. Firstly, to present our 5-week progressive exercise therapy program in the early stage after anterior cruciate ligament (ACL) injury. Secondly, to evaluate changes in knee function after completion of the program for patients with ACL injury in general and also when classified as potential copers or noncopers, and, finally, to examine potential adverse events. Few studies concerning early-stage ACL rehabilitation protocols exist. Consequently, little is known about the tolerance for, and outcomes from, short-term exercise therapy programs in the early stage after injury. One-hundred patients were included in a 5-week progressive exercise therapy program, within 3 months after injury. Knee function before and after completion of the program was evaluated from isokinetic quadriceps and hamstrings muscle strength tests, 4 single-leg hop tests, 2 different self-assessment questionnaires, and a global rating of knee function. A 2-way mixed-model analysis of variance was conducted to evaluate changes from pretest to posttest for the limb symmetry index for muscle strength and single-leg hop tests, and the change in scores for the patient-reported questionnaires. In addition, absolute values and the standardized response mean for muscle strength and single-leg hop tests were calculated at pretest and posttest for the injured and uninjured limb. Adverse events during the 5-week period were recorded. The progressive 5-week exercise therapy program led to significant improvements (P<.05) in knee function from pretest to posttest both for patients classified as potential copers and noncopers. Standardized response mean values for changes in muscle strength and single-leg hop performance from pretest to posttest for the injured limb were moderate to strong (0.49-0.84), indicating the observed improvements to be clinically relevant. Adverse events occurred in 3.9% of the patients. Short-term progressive exercise therapy programs are well tolerated and should be incorporated in early-stage ACL rehabilitation, either to improve knee function before ACL reconstruction or as a first step in further nonoperative management. Therapy, level 2b.

A Multi-Stage Longitudinal Comparative Design Stage II Evaluation of the Changing Lives Program: The Life Course Interview (RDA-LCI)

ERIC Educational Resources Information Center

Arango, Lisa Lewis; Kurtines, William M.; Montgomery, Marilyn J.; Ritchie, Rachel

2008-01-01

The study reported in this article, a Multi-Stage Longitudinal Comparative Design Stage II evaluation conducted as a planned preliminary efficacy evaluation (psychometric evaluation of measures, short-term controlled outcome studies, etc.) of the Changing Lives Program (CLP), provided evidence for the reliability and validity of the qualitative…

Molecular Phenotyping in Predicting Response in Patients With Stage IB-III Esophageal Cancer Receiving Combination Chemotherapy

ClinicalTrials.gov

2018-01-16

Stage IB Esophageal Adenocarcinoma; Stage IIA Esophageal Adenocarcinoma; Stage IIB Esophageal Adenocarcinoma; Stage IIIA Esophageal Adenocarcinoma; Stage IIIB Esophageal Adenocarcinoma; Stage IIIC Esophageal Adenocarcinoma

[Factors associated with advanced thyroid cancer in pediatric patients in a high specialty medical unit in Northeast Mexico].

PubMed

García-Castillo, Lizbeth Ariana; Bahena-García, Ana Laura; Sánchez-Sánchez, Luz María; del Carmen Palacios-Saucedo, Gerardo

2015-01-01

Thyroid cancer represents 2% of all childhood malignances. Its incidence rises 1.1% per year. In comparison with adults, childhood thyroid cancer is detected in a more advanced stage, but with a survival rate above 95%. The objective of this study was to evaluate whether there are factors associated with advanced stages of thyroid cancer in pediatric patients. Nineteen patients were included, 13 (68.4%) were female and six male, all between 7-15 years, with a median of 11 years. Fifteen in advanced and four in early stage. The median age of patients in advanced stage at time of diagnosis was 10.6 years (7-15) and 13.2 (12-14) were in early stage (p=0.075). There was a delay of nine months to get a diagnosis in advanced stage, and 7.2 in early stage (p=0.931). Three of the patients with advanced stage and two with early stage were from Nuevo León (Mexico) and the rest were foreign (p=0.567). In the group with advanced stage, two had thyroid cancer familiar history, and none in the early stage group (p=0.452). Nine patients in advanced stage and three in early stage presented thyroid nodule as the first sign of illness. Six patients in advanced stage and one in early stage presented goiter (p=0.590). None of the studied patients had radiation history. Six patients in advanced stage and one in early stage suffered from Hashimoto's Thyroiditis (p=0.590). Eleven in advanced stage and one in early stage had papillary histologic variety. Four in advanced stage and three in early stage had papillary histologic variety with a follicular patter (p=0.083). Eight patients presented lung metastasis at time of diagnosis (p=0.061). There are no factors associated with advanced stage thyroid cancer in pediatric populations. Although half of studied patients presented lung metastasis, treatment response and survival is satisfactory.

Evolution of Monitoring and Evaluation of AIDS Response in Ukraine: Laying the Groundwork for Evidence-Based Health Care.

PubMed

Dumchev, Kostyantyn; Varetska, Olga; Kuzin, Ihor

2017-07-01

Once facing the most severe HIV epidemic in Eastern Europe, Ukraine has built an elaborate Monitoring and Evaluation (M&E) system to track the response to AIDS. This system was developed using recommendations and input from multiple international expert organizations and donors and, at the current stage, serves as a best practice model in many areas. The present paper aims to provide a comprehensive overview of the evolution of the M&E system in Ukraine since its inception. Notable achievements and challenges are described and illustrated by epidemiological data and the recommendations for future development are discussed. Unique experiences and advances in M&E in Ukraine may be useful to other countries facing similar epidemiological, structural or methodological issues.

Improving the hospital 'soundscape': a framework to measure individual perceptual response to hospital sounds.

PubMed

Mackrill, J B; Jennings, P A; Cain, R

2013-01-01

Work on the perception of urban soundscapes has generated a number of perceptual models which are proposed as tools to test and evaluate soundscape interventions. However, despite the excessive sound levels and noise within hospital environments, perceptual models have not been developed for these spaces. To address this, a two-stage approach was developed by the authors to create such a model. First, semantics were obtained from listening evaluations which captured the feelings of individuals from hearing hospital sounds. Then, 30 participants rated a range of sound clips representative of a ward soundscape based on these semantics. Principal component analysis extracted a two-dimensional space representing an emotional-cognitive response. The framework enables soundscape interventions to be tested which may improve the perception of these hospital environments.

Concordance of Carcinoembryonic Antigen Ratio and Response Evaluation Criteria in Solid Tumors as Prognostic Surrogate Indicators of Metastatic Colorectal Cancer Patients Treated with Chemotherapy.

PubMed

Huang, Sheng-Chieh; Lin, Jen-Kou; Lin, Tzu-Chen; Chen, Wei-Shone; Yang, Shung-Haur; Wang, Huann-Sheng; Lan, Yuan-Tzu; Lin, Chun-Chi; Jiang, Jeng-Kai; Chang, Shih-Ching

2015-07-01

Carcinoembryonic antigen (CEA) is widely used as a tumor marker in colorectal cancer (CRC). This study aimed to evaluate the role of the degree of change in CEA levels during the treatment period and found that the degree of change highly correlated with disease survival and Response Evaluation Criteria in Solid Tumors (RECIST) criteria in evaluating therapy response. A total of 447 metastatic CRC patients treated with surgery of the primary tumor followed by systemic therapy at a single center from the year 2000 through 2011 were reviewed. The degree of change in CEA levels was expressed as the CEA ratio (post-CEA/pre-CEA) and classified into four groups during the treatment period for further evaluation. The imaging change of the same population was also compared with the CEA ratio during the treatment period. The CEA ratio was significantly correlated with different chemotherapy regimens (p < 0.001), pre-treatment CEA level (p < 0.001), lymphovascular invasion (p = 0.006), and tumor differentiation (p = 0.018). CEA ratio and imaging change according to RECIST criteria were both correlated with overall survival (p < 0.001). These two methods for evaluating treatment response were highly correlated (p < 0.001). CEA ratio was found to be a reliable prognostic factor in stage IV CRC, and was highly correlated with the imaging survey according to RECIST criteria. Further prospective studies are essential to validate these findings.

Tracking bed bugs (Cimex lectularius): a study of the effect of physiological and extrinsic factors on the response to bed bug-derived volatiles.

PubMed

Weeks, E N I; Logan, J G; Birkett, M A; Pickett, J A; Cameron, M M

2013-02-01

The common bed bug, Cimex lectularius, feeds on the blood of mammal and bird hosts, and is a pest of global importance. Semiochemicals are chemicals involved in animal communication that may affect behaviour and/or physiology. Attractive semiochemicals that play a role in mediating bed bug behaviour could be exploited for the development of a highly effective novel monitoring device. Tracking software was used to record the response of bed bugs to volatiles from paper previously exposed to conspecific bugs in a still-air olfactometer illuminated by infrared lights, through a variety of activity variables. The effect of time of day as an extrinsic factor, and sex, stage, mating status and nutritional status as physiological factors on the response of bed bugs to the volatiles was examined. Bed bugs of both sexes and all stages responded to the volatiles from bed bug-exposed papers, showing significant attraction and orientation towards the volatile source whether they were starved or engorged. Confirmation that the physiological factors examined do not affect the response of bed bugs to the volatiles from bed bug-exposed papers provides evidence that these bed bug-derived volatiles contain aggregation cues, as semiochemicals that promote aggregation should by definition be detected by both sexes and all life stages. A device baited with such semiochemicals could play a major role in limiting the impact of the current bed bug resurgence by enabling timely detection of infestations, along with quantitative evaluation of control and effective surveillance of the geographical distribution of the pest species.

The linear transformation model with frailties for the analysis of item response times.

PubMed

Wang, Chun; Chang, Hua-Hua; Douglas, Jeffrey A

2013-02-01

The item response times (RTs) collected from computerized testing represent an underutilized source of information about items and examinees. In addition to knowing the examinees' responses to each item, we can investigate the amount of time examinees spend on each item. In this paper, we propose a semi-parametric model for RTs, the linear transformation model with a latent speed covariate, which combines the flexibility of non-parametric modelling and the brevity as well as interpretability of parametric modelling. In this new model, the RTs, after some non-parametric monotone transformation, become a linear model with latent speed as covariate plus an error term. The distribution of the error term implicitly defines the relationship between the RT and examinees' latent speeds; whereas the non-parametric transformation is able to describe various shapes of RT distributions. The linear transformation model represents a rich family of models that includes the Cox proportional hazards model, the Box-Cox normal model, and many other models as special cases. This new model is embedded in a hierarchical framework so that both RTs and responses are modelled simultaneously. A two-stage estimation method is proposed. In the first stage, the Markov chain Monte Carlo method is employed to estimate the parametric part of the model. In the second stage, an estimating equation method with a recursive algorithm is adopted to estimate the non-parametric transformation. Applicability of the new model is demonstrated with a simulation study and a real data application. Finally, methods to evaluate the model fit are suggested. © 2012 The British Psychological Society.

Role of Immune Checkpoint Inhibitors in Small Cell Lung Cancer.

PubMed

Cooper, Maryann R; Alrajhi, Abdullah M; Durand, Cheryl R

Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancer diagnoses each year. SCLC is characterized by a rapid doubling time, early metastatic spread, and an unfavorable prognosis overall. Most patients with SCLC will respond to initial treatment; however, the majority will experience a disease recurrence and response to second-line therapies is poor. Immune checkpoint inhibitors may be an option given the success in other diseases. A literature search was conducted using Medline (1946-July week 1, 2017) and Embase (1996-2017 week 28) with the search terms small cell lung cancer combined with nivolumab or ipilimumab or pembrolizumab or atezolizumab or tremelimumab or durvalumab. Five clinical trials, including extended follow-up for 2, that evaluated immune checkpoint inhibitors in limited stage or extensive stage SCLC were included. In 2 phase 2 trials, ipilimumab was added to upfront chemotherapy. In both trials, an improvement in progression-free survival was seen. Toxicity, when combined with a platinum and etoposide, was significant. In a confirmatory phase 3 trial, ipilimumab did not prolong overall survival when added to first-line chemotherapy. Overall, response rates were similar between the placebo and ipilimumab groups. A phase 1/2 trial evaluated nivolumab alone or in combination with ipilimumab in recurrent SCLC. Results revealed that nivolumab monotherapy and the combination of nivolumab and ipilimumab were relatively safe and had antitumor activity. Pembrolizumab has been evaluated in a multicohort, phase 1b trial. Preliminary data showed a durable response in the second-line setting. Given the lack of overall survival data and significant toxicity associated with the combination of ipilimumab with first-line chemotherapy, this treatment is not a reasonable option at this time. Nivolumab alone or in combination with ipilimumab is a valid option for recurrent SCLC.

Predictive Factor Analysis of Response-Adapted Radiation Therapy for Chemotherapy-Sensitive Pediatric Hodgkin Lymphoma: Analysis of the Children's Oncology Group AHOD 0031 Trial

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

Charpentier, Anne-Marie; Friedman, Debra L.; Wolden, Suzanne

Purpose: To evaluate whether clinical risk factors could further distinguish children with intermediate-risk Hodgkin lymphoma (HL) with rapid early and complete anatomic response (RER/CR) who benefit significantly from involved-field RT (IFRT) from those who do not, and thereby aid refinement of treatment selection. Methods and Materials: Children with intermediate-risk HL treated on the Children's Oncology Group AHOD 0031 trial who achieved RER/CR with 4 cycles of chemotherapy, and who were randomized to 21-Gy IFRT or no additional therapy (n=716) were the subject of this study. Recursive partitioning analysis was used to identify factors associated with clinically and statistically significant improvement inmore » event-free survival (EFS) after randomization to IFRT. Bootstrap sampling was used to evaluate the robustness of the findings. Result: Although most RER/CR patients did not benefit significantly from IFRT, those with a combination of anemia and bulky limited-stage disease (n=190) had significantly better 4-year EFS with the addition of IFRT (89.3% vs 77.9% without IFRT; P=.019); this benefit was consistently reproduced in bootstrap analyses and after adjusting for other prognostic factors. Conclusion: Although most patients achieving RER/CR had favorable outcomes with 4 cycles of chemotherapy alone, those children with initial bulky stage I/II disease and anemia had significantly better EFS with the addition of IFRT as part of combined-modality therapy. Further work evaluating the interaction of clinical and biologic factors and imaging response is needed to further optimize and refine treatment selection.« less

Experimental study of cyclic creep and high-cycle fatigue of welded joints of St3 steel by the DIC technique

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

Kibitkin, Vladimir V., E-mail: vvk@ispms.tsc.ru; Solodushkin, Andrey I., E-mail: s.ai@sibmail.com; Pleshanov, Vasily S., E-mail: vsp@ispms.tsc.ru

In the paper the mechanisms of plastic deformation and fracture of welded joints of steel St3 were investigated at high-cycle fatigue and cyclic creep by the digital image correlation (DIC) technique. The evolution of strain rate is studied for the following regions: base metal, HAZ, and fusion zone. This strain rate evolution can be considered as a mechanical response of material. Three stages of deformation evolution are shown: deformation hardening (I), fatigue crack initiation (II), and the last stage is related to main crack (III). Two criteria are offered to evaluate the current mechanical state of welded joints.

Benefits and Disadvantages of Neoadjuvant Radiochemotherapy (RCT) in the Multimodal Therapy of Squamous Esophageal Cancer (ESC).

PubMed

Hanna, Adrian; Birla, Rodica; Iosif, Cristina; Boeriu, Marius; Constantinoiu, Silviu

2016-01-01

The purpose of this paper is to present the advantages and disadvantages of neoadjuvant RCT in multimodal therapyof ESC. Between 1998-2014 221 patients were treated with ESC, 85 of whom received neoadjuvant RCT. For these we have made imaging and pathologic assessment of response using RECIST and MANDARD criteria and statistical data were interpreted in terms of the factors that influence the response. Also, they were evaluated statistical correlations between RCT and resectability, postoperative morbidity, mortality and long-term survival. 45 patients were imagistic responders and 34 underwent surgery, 40 non-responders of which 14 underwent surgery. Of the 48 surgical patients with preoperative RCT, histopathological evaluation showed that 32 were pathological responders and 16 non responders. There were performed statistical analyzes of correlations between RCT and resectability, stage, location of ESC, morbidity, mortality and survival. RCT increase resectability, improves survival and maximum duration of survival, more in responders than in nonresponders and does not affect postoperative complications and postoperative mortality, nor among the responders or nonresponders. Imaging evaluation result of the response to RCT overestimate responders. Celsius.

Twenty-Five-Year Experience With Radical Chemoradiation for Anal Cancer

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

Tomaszewski, Jonathan M., E-mail: jonathan.tomaszewski@petermac.org; Link, Emma; Leong, Trevor

2012-06-01

Purpose: To evaluate the prognostic factors, patterns of failure, and late toxicity in patients treated with chemoradiation (CRT) for anal cancer. Methods and Materials: Consecutive patients with nonmetastatic squamous cell carcinoma of the anus treated by CRT with curative intent between February 1983 and March 2008 were identified through the institutional database. Chart review and telephone follow-up were undertaken to collect demographic data and outcome. Results: Two hundred eighty-four patients (34% male; median age 62 years) were identified. The stages at diagnosis were 23% Stage I, 48% Stage II, 10% Stage IIIA, and 18% Stage IIIB. The median radiotherapy dosemore » to the primary site was 54 Gy. A complete clinical response to CRT was achieved in 89% of patients. With a median follow-up time of 5.3 years, the 5-year rates of locoregional control, distant control, colostomy-free survival, and overall survival were 83% (95% confidence interval [CI] 78-88), 92% (95% CI, 89-96), 73% (95% CI, 68-79), and 82% (95% CI, 77-87), respectively. Higher T stage and male sex predicted for locoregional failure, and higher N stage predicted for distant metastases. Locoregional failure occurred most commonly at the primary site. Omission of elective inguinal irradiation resulted in inguinal failure rates of 1.9% and 12.5% in T1N0 and T2N0 patients, respectively. Pelvic nodal failures were very uncommon. Late vaginal and bone toxicity was observed in addition to gastrointestinal toxicity. Conclusions: CRT is a highly effective approach in anal cancer. However, subgroups of patients fare relatively poorly, and novel approaches are needed. Elective inguinal irradiation can be safely omitted only in patients with Stage I disease. Vaginal toxicity and insufficiency fractures of the hip and pelvis are important late effects that require prospective evaluation.« less

Twenty-five-year experience with radical chemoradiation for anal cancer.

PubMed

Tomaszewski, Jonathan M; Link, Emma; Leong, Trevor; Heriot, Alexander; Vazquez, Melisa; Chander, Sarat; Chu, Julie; Foo, Marcus; Lee, Mark T; Lynch, Craig A; Mackay, John; Michael, Michael; Tran, Phillip; Ngan, Samuel Y

2012-06-01

To evaluate the prognostic factors, patterns of failure, and late toxicity in patients treated with chemoradiation (CRT) for anal cancer. Consecutive patients with nonmetastatic squamous cell carcinoma of the anus treated by CRT with curative intent between February 1983 and March 2008 were identified through the institutional database. Chart review and telephone follow-up were undertaken to collect demographic data and outcome. Two hundred eighty-four patients (34% male; median age 62 years) were identified. The stages at diagnosis were 23% Stage I, 48% Stage II, 10% Stage IIIA, and 18% Stage IIIB. The median radiotherapy dose to the primary site was 54 Gy. A complete clinical response to CRT was achieved in 89% of patients. With a median follow-up time of 5.3 years, the 5-year rates of locoregional control, distant control, colostomy-free survival, and overall survival were 83% (95% confidence interval [CI] 78-88), 92% (95% CI, 89-96), 73% (95% CI, 68-79), and 82% (95% CI, 77-87), respectively. Higher T stage and male sex predicted for locoregional failure, and higher N stage predicted for distant metastases. Locoregional failure occurred most commonly at the primary site. Omission of elective inguinal irradiation resulted in inguinal failure rates of 1.9% and 12.5% in T1N0 and T2N0 patients, respectively. Pelvic nodal failures were very uncommon. Late vaginal and bone toxicity was observed in addition to gastrointestinal toxicity. CRT is a highly effective approach in anal cancer. However, subgroups of patients fare relatively poorly, and novel approaches are needed. Elective inguinal irradiation can be safely omitted only in patients with Stage I disease. Vaginal toxicity and insufficiency fractures of the hip and pelvis are important late effects that require prospective evaluation. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

High-intensity focused ultrasound (HIFU) for pancreatic carcinoma: evaluation of feasibility, reduction of tumour volume and pain intensity.

PubMed

Marinova, Milka; Rauch, Maximilian; Mücke, Martin; Rolke, Roman; Gonzalez-Carmona, Maria A; Henseler, Jana; Cuhls, Henning; Radbruch, Lukas; Strassburg, Christian P; Zhang, Lian; Schild, Hans H; Strunk, Holger M

2016-11-01

Prognosis of patients with locally advanced pancreatic adenocarcinoma is extremely poor. They often suffer from cancer-related pain reducing their quality of life. This prospective observational study aimed to evaluate feasibility, local tumour response, and changes in quality of life and symptoms in Caucasian patients with locally advanced pancreatic cancer treated by ultrasound-guided high-intensity focused ultrasound (HIFU). Thirteen patients underwent HIFU, five with stage III, eight with stage IV UICC disease. Ten patients received simultaneous palliative chemotherapy. Postinterventional clinical assessment included evaluation of quality of life and symptom changes using standardized questionnaires. CT and MRI follow-up evaluated the local tumour response. HIFU was successfully performed in all patients. Average tumour reduction was 34.2 % at 6 weeks and 63.9 % at 3 months. Complete or partial relief of cancer-related pain was achieved in 10 patients (77 %), five of whom required less analgesics for pain control. Quality of life was improved revealing increased global health status and alleviated symptoms. HIFU treatment was well tolerated. Eight patients experienced transient abdominal pain directly after HIFU. HIFU ablation of pancreatic carcinoma is a feasible, safe and effective treatment with a crucial benefit in terms of reduction of tumour volume and pain intensity. • US-guided HIFU is feasible and safe for patients with unresectable pancreatic cancer. • HIFU can considerably reduce tumour volume and cancer-related pain. • Patients treated with HIFU experienced significant and lasting reduction of pain intensity. • HIFU has a crucial clinical benefit for patients with pancreatic cancer.

Characteristic morphological and frictional changes in sputtered MoS/sub 2 films

NASA Technical Reports Server (NTRS)

Spalvins, T.

1984-01-01

Three microstructural growth stages of sputtered MoS2 films were identified with respect to film thickness: (1) ridge formation during nucleation, (2) an equiaxed transition zone, and (3) a columnar-fiber-like structure. Each of these growth stages are characterized in terms of microcrystallite size, shape, and orientation. The effective lubricating film thickness is established in terms of the microstructural growth stages during sliding experiments. The film has a tendency to break up within the columnar zone. Actual lubrication is performed by the remaining film which is 0.18 to 0.22 microns thick. Also a visual screening is proposed to evaluate the integrity of the as-sputtered MoS2 film. The lubricating properties are identified with respect to optical changes before and after wiping. The orientation of the microcrystallites are responsible for the optical reflective changes observed.

Expression of Plasmodium vivax crt-o Is Related to Parasite Stage but Not Ex Vivo Chloroquine Susceptibility.

PubMed

Pava, Zuleima; Handayuni, Irene; Wirjanata, Grennady; To, Sheren; Trianty, Leily; Noviyanti, Rintis; Poespoprodjo, Jeanne Rini; Auburn, Sarah; Price, Ric N; Marfurt, Jutta

2016-01-01

Chloroquine (CQ)-resistant Plasmodium vivax is present in most countries where P. vivax infection is endemic, but the underlying molecular mechanisms responsible remain unknown. Increased expression of P. vivax crt-o (pvcrt-o) has been correlated with in vivo CQ resistance in an area with low-grade resistance. We assessed pvcrt-o expression in isolates from Papua (Indonesia), where P. vivax is highly CQ resistant. Ex vivo drug susceptibilities to CQ, amodiaquine, piperaquine, mefloquine, and artesunate were determined using a modified schizont maturation assay. Expression levels of pvcrt-o were measured using a novel real-time quantitative reverse transcription-PCR method. Large variations in pvcrt-o expression were observed across the 51 isolates evaluated, with the fold change in expression level ranging from 0.01 to 59 relative to that seen with the P. vivax β-tubulin gene and from 0.01 to 24 relative to that seen with the P. vivax aldolase gene. Expression was significantly higher in isolates with the majority of parasites at the ring stage of development (median fold change, 1.7) compared to those at the trophozoite stage (median fold change, 0.5; P < 0.001). Twenty-nine isolates fulfilled the criteria for ex vivo drug susceptibility testing and showed high variability in CQ responses (median, 107.9 [range, 6.5 to 345.7] nM). After controlling for the parasite stage, we found that pvcrt-o expression levels did not correlate with the ex vivo response to CQ or with that to any of the other antimalarials tested. Our results highlight the importance of development-stage composition for measuring pvcrt-o expression and suggest that pvcrt-o transcription is not a primary determinant of ex vivo drug susceptibility. A comprehensive transcriptomic approach is warranted for an in-depth investigation of the role of gene expression levels and P. vivax drug resistance. Copyright © 2015 Pava et al.

Comparative analysis of cerebrospinal fluid from the meningo-encephalitic stage of T. b. gambiense and rhodesiense sleeping sickness patients using TMT quantitative proteomics.

PubMed

Tiberti, Natalia; Sanchez, Jean-Charles

2015-09-01

The quantitative proteomics data here reported are part of a research article entitled "Increased acute immune response during the meningo-encephalitic stage of Trypanosoma brucei rhodesiense sleeping sickness compared to Trypanosoma brucei gambiense", published by Tiberti et al., 2015. Transl. Proteomics 6, 1-9. Sleeping sickness (human African trypanosomiasis - HAT) is a deadly neglected tropical disease affecting mainly rural communities in sub-Saharan Africa. This parasitic disease is caused by the Trypanosoma brucei (T. b.) parasite, which is transmitted to the human host through the bite of the tse-tse fly. Two parasite sub-species, T. b. rhodesiense and T. b. gambiense, are responsible for two clinically different and geographically separated forms of sleeping sickness. The objective of the present study was to characterise and compare the cerebrospinal fluid (CSF) proteome of stage 2 (meningo-encephalitic stage) HAT patients suffering from T. b. gambiense or T. b. rhodesiense disease using high-throughput quantitative proteomics and the Tandem Mass Tag (TMT(®)) isobaric labelling. In order to evaluate the CSF proteome in the context of HAT pathophysiology, the protein dataset was then submitted to gene ontology and pathway analysis. Two significantly differentially expressed proteins (C-reactive protein and orosomucoid 1) were further verified on a larger population of patients (n=185) by ELISA, confirming the mass spectrometry results. By showing a predominant involvement of the acute immune response in rhodesiense HAT, the proteomics results obtained in this work will contribute to further understand the mechanisms of pathology occurring in HAT and to propose new biomarkers of potential clinical utility. The mass spectrometry raw data are available in the Pride Archive via ProteomeXchange through the identifier PXD001082.

Use of sequential endorectal US to predict the tumor response of preoperative chemoradiotherapy in rectal cancer.

PubMed

Li, Ning; Dou, Lizhou; Zhang, Yueming; Jin, Jing; Wang, Guiqi; Xiao, Qin; Li, Yexiong; Wang, Xin; Ren, Hua; Fang, Hui; Wang, Weihu; Wang, Shulian; Liu, Yueping; Song, Yongwen

2017-03-01

Accurate prediction of the response to preoperative chemoradiotherapy (CRT) potentially assists in the individualized selection of treatment. Endorectal US (ERUS) is widely used for the pretreatment staging of rectal cancer, but its use for preoperatively predicting the effects of CRT is not well evaluated because of the inflammation, necrosis, and fibrosis induced by CRT. This study assessed the value of sequential ERUS in predicting the efficacy of preoperative CRT for locally advanced rectal cancer. Forty-one patients with clinical stage II/III rectal adenocarcinoma were enrolled prospectively. Radiotherapy was delivered to the pelvis with concurrent chemotherapy of capecitabine and oxaliplatin. Total mesorectal excision was performed 6 to 8 weeks later. EUS measurements of primary tumor maximum diameter were performed before (ERUS1), during (ERUS2), and 6 to 8 weeks after (ERUS3) CRT, and the ratios of these were calculated. Correlations between ERUS values, tumor regression grade (TRG), T down-staging rate, and pathologic complete response (pCR) rate were assessed, and survival was analyzed. There was no significant correlation between ERUS2/ERUS1 and TRG. The value of ERUS3/ERUS1 correlated with pCR rate and TRG but not T down-staging rate. An ERUS3 value of 6.3 mm and ERUS3/ERUS1 of 52% were used as the cut-off for predicting pCR, and patients were divided into good and poor prognosis groups. Although not statistically significant, 3-year recurrence and survival rates of the good prognosis group were better than those of the poor prognosis group. Sequential ERUS may predict therapeutic efficacy of preoperative CRT for locally advanced rectal cancer. (Clinical trial registration number: NCT01582750.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Autonomic nervous function in patients with Meniere's disease evaluated by power spectral analysis of heart rate variability.

PubMed

Yamada, M; Mizuta, K; Ito, Y; Furuta, M; Sawai, S; Miyata, H

1999-10-01

A hypothesis has been advanced that the autonomic nervous dysfunction (AND) relates to the development of vertigo in Meniere's disease (MD). We also studied the causal relationship between AND and vertigo in MD. We evaluated autonomic nervous function in 17 patients with MD (five men and 12 women ranging in age from 16 to 70 years) by classifying them by their stages of attack and interval of vertigo and with power spectral analysis (PSA) of heart rate variability. Fourteen healthy volunteers were also tested as controls. At the interval stage, parasympathetic nervous hypofunction and significant depression of sympathetic response due to postural changes from the supine to the standing position were observed in many of those patients. At the attack stage, sympathetic nervous hypofunction was observed in some of the patients. These findings lead us to the conclusion that AND relates to vertigo in MD as a predisposing factor. However, the question of whether AND relates as a trigger or as a consequence of vertigo in MD has not been adequately solved in this study. We will make further studies on circadian variation of autonomic nervous function.

Evaluation of the Removal of Indicator Bacteria from Domestic Sludge Processed by Autothermal Thermophilic Aerobic Digestion (ATAD)

PubMed Central

Piterina, Anna V.; Bartlett, John; Pembroke, Tony J.

2010-01-01

The degradation of sludge solids in an insulated reactor during Autothermal Thermophilic Aerobic Digestion (ATAD) processing results in auto-heating, thermal treatment and total solids reduction, however, the ability to eliminate pathogenic organisms has not been analysed under large scale process conditions. We evaluated the ATAD process over a period of one year in a two stage, full scale Irish ATAD plant established in Killarney and treating mixed primary and secondary sludge, by examining the sludge microbiologically at various stages during and following ATAD processing to determine its ability to eliminate indicator organisms. Salmonella spp. (pathogen) and fecal-coliform (indicator) densities were well below the limits used to validate class A biosolids in the final product. Enteric pathogens present at inlet were deactivated during the ATAD process and were not detected in the final product using both traditional microbial culture and molecular phylogenetic techniques. A high DNase activity was detected in the bulk sludge during the thermophilic digestion stage which may be responsible for the rapid turn over of DNA from lysed cells and the removal of mobile DNA. These results offer assurance for the safe use of ATAD sludge as a soil supplement following processing. PMID:20948933

Evaluation of the removal of indicator bacteria from domestic sludge processed by Autothermal Thermophilic Aerobic Digestion (ATAD).

PubMed

Piterina, Anna V; Bartlett, John; Pembroke, Tony J

2010-09-01

The degradation of sludge solids in an insulated reactor during Autothermal Thermophilic Aerobic Digestion (ATAD) processing results in auto-heating, thermal treatment and total solids reduction, however, the ability to eliminate pathogenic organisms has not been analysed under large scale process conditions. We evaluated the ATAD process over a period of one year in a two stage, full scale Irish ATAD plant established in Killarney and treating mixed primary and secondary sludge, by examining the sludge microbiologically at various stages during and following ATAD processing to determine its ability to eliminate indicator organisms. Salmonella spp. (pathogen) and fecal-coliform (indicator) densities were well below the limits used to validate class A biosolids in the final product. Enteric pathogens present at inlet were deactivated during the ATAD process and were not detected in the final product using both traditional microbial culture and molecular phylogenetic techniques. A high DNase activity was detected in the bulk sludge during the thermophilic digestion stage which may be responsible for the rapid turn over of DNA from lysed cells and the removal of mobile DNA. These results offer assurance for the safe use of ATAD sludge as a soil supplement following processing.

Development of 70 MW class superconducting generator with quick-response excitation

NASA Astrophysics Data System (ADS)

Miyaike, Kiyoshi; Kitajima, Toshio; Ito, Tetsuo

2002-03-01

The development of a superconducting generator had been carried out for 12 years under the first stage of a Super GM project. The 70 MW class model machine with quick response excitation was manufactured and evaluated in the project. This type of superconducting generator improves power system stability against rapid load fluctuations at the power system faults. This model machine achieved all development targets including high stability during rapid excitation control. It was also connected to the actual 77 kV electrical power grid as a synchronous condenser and proved advantages and high-operation reliability of the superconducting generator.

Exploring the universal ecological responses to climate change in a univoltine butterfly.

PubMed

Fenberg, Phillip B; Self, Angela; Stewart, John R; Wilson, Rebecca J; Brooks, Stephen J

2016-05-01

Animals with distinct life stages are often exposed to different temperatures during each stage. Thus, how temperature affects these life stages should be considered for broadly understanding the ecological consequences of climate warming on such species. For example, temperature variation during particular life stages may affect respective change in body size, phenology and geographic range, which have been identified as the "universal" ecological responses to climate change. While each of these responses has been separately documented across a number of species, it is not known whether each response occurs together within a species. The influence of temperature during particular life stages may help explain each of these ecological responses to climate change. Our goal was to determine if monthly temperature variation during particular life stages of a butterfly species can predict respective changes in body size and phenology. We also refer to the literature to assess if temperature variability during the adult stage influences range change over time. Using historical museum collections paired with monthly temperature records, we show that changes in body size and phenology of the univoltine butterfly, Hesperia comma, are partly dependent upon temporal variation in summer temperatures during key stages of their life cycle. June temperatures, which are likely to affect growth rate of the final larval instar, are important for predicting adult body size (for males only; showing a positive relationship with temperature). July temperatures, which are likely to influence the pupal stage, are important for predicting the timing of adult emergence (showing a negative relationship with temperature). Previous studies show that August temperatures, which act on the adult stage, are linked to range change. Our study highlights the importance of considering temperature variation during each life stage over historic time-scales for understanding intraspecific response to climate change. Range edge studies of ectothermic species that have annual life cycles, long time-series occurrence data, and associated temperature records (ideally at monthly resolutions) could be useful model systems for intraspecific tests of the universal ecological responses to climate change and for exploring interactive effects. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

Long term protection after immunization with P. berghei sporozoites correlates with sustained IFNγ responses of hepatic CD8+ memory T cells.

PubMed

Nganou-Makamdop, Krystelle; van Gemert, Geert-Jan; Arens, Theo; Hermsen, Cornelus C; Sauerwein, Robert W

2012-01-01

Protection against P. berghei malaria can successfully be induced in mice by immunization with both radiation attenuated sporozoites (RAS) arresting early during liver stage development, or sporozoites combined with chloroquine chemoprophylaxis (CPS), resulting in complete intra-hepatic parasite development before killing of blood-stages by chloroquine takes place. We assessed the longevity of protective cellular immune responses by RAS and CPS P. berghei immunization of C57BL/6j mice. Strong effector and memory (T(EM)) CD8+ T cell responses were induced predominantly in the liver of both RAS and CPS immunized mice while CD4+ T cells with memory phenotype remained at base line levels. Compared to unprotected naïve mice, we found high sporozoite-specific IFNγ ex vivo responses that associated with induced levels of in vivo CD8+ T(EM) cells in the liver but not spleen. Long term evaluation over a period of 9 months showed a decline of malaria-specific IFNγ responses in RAS and CPS mice that significantly correlated with loss of protection (r(2) = 0.60, p<0.0001). The reducing IFNγ response by hepatic memory CD8+ T cells could be boosted by re-exposure to wild-type sporozoites. Our data show that sustainable protection against malaria associates with distinct intra-hepatic immune responses characterized by strong IFNγ producing CD8+ memory T cells.

Effectiveness of surgical treatment in chronic migraine.

PubMed

Amaya-Blas, Francisco Javier; Mecott, Gabriel A; Marfil-Rivera, Alejandro; Tamayo-Esquivel, María de Lourdes; García-Pérez, Mauricio Manuel; Chacón-Moreno, Hernán; Pérez-Porras, Sergio; Coutiño, Rosa; Castro-Góvea, Yanko

2018-01-01

Migraine affects more than 35 million people in the United States of America, and 10% of the population in the world. The purpose of this study was to evaluate the effectiveness of surgical treatment in chronic migraine with frontal or occipital trigger areas. We designed a pilot, proof of concept, and prospective study to analyze the effectiveness of surgical release of trigger nerves in severe frontal or occipital chronic migraines. The study was approved by the Ethics and Investigation Committee of Hospital Universitario Dr. José Eleuterio González (Monterrey, N.L., Mexico). We included patients diagnosed with chronic migraine by the neurology service of Hospital Universitario Dr. José Eleuterio González that attended our consult from March to December 2012. The patients were assessed by the MIDAS questionnaire and the diagnosis confirmed by injecting 2% lidocaine in the trigger sites. We realized a superior palpebral approach in frontal migraines to resection the glabellar muscles and an occipital approach to free the greater occipital nerve bilaterally. We evaluated complete and partial clinical response measuring the frequency, intensity, and duration of migraine episodes. We included three patients with Stage IV (severe incapacitating) frontal or occipital chronic migraines. Two were occipital trigger sites and one frontal. We obtained complete clinical response in two patients and a partial response in one. Pain intensity decreased in all patients. Surgical treatment is effective in Stage IV (severe incapacitating) frontal or occipital trigger chronic migraines. Copyright: © 2018 Permanyer.

Caspase-3 activity, response to chemotherapy and clinical outcome in patients with colon cancer.

PubMed

de Oca, Javier; Azuara, Daniel; Sanchez-Santos, Raquel; Navarro, Matilde; Capella, Gabriel; Moreno, Victor; Sola, Anna; Hotter, Georgina; Biondo, Sebastiano; Osorio, Alfonso; Martí-Ragué, Joan; Rafecas, Antoni

2008-01-01

The prognostic value of the degree of apoptosis in colorectal cancer is controversial. This study evaluates the putative clinical usefulness of measuring caspase-3 activity as a prognostic factor in colonic cancer patients receiving 5-fluoracil adjuvant chemotherapy. We evaluated caspase-3-like protease activity in tumours and in normal colon tissue. Specimens were studied from 54 patients. These patients had either stage III cancer (Dukes stage C) or high-risk stage II cancer (Dukes stage B2 with invasion of adjacent organs, lymphatic or vascular infiltration or carcinoembryonic antigen [CEA] >5). Median follow-up was 73 months. Univariate analysis was performed previously to explore the relation of different variables (age, sex, preoperative CEA, tumour size, Dukes stage, vascular invasion, lymphatic invasion, caspase-3 activity in tumour and caspase-3 activity in normal mucosa) as prognostic factors of tumour recurrence after chemotherapy treatment. Subsequently, a multivariate Cox regression model was performed. Median values of caspase-3 activity in tumours were more than twice those in normal mucosa (88.1 vs 40.6 U, p=0.001), showing a statistically significant correlation (r=0.34). Significant prognostic factors of recurrence in multivariate analysis were: male sex (odds ratio, OR=3.53 [1.13-10.90], p=0.02), age (OR=1.09 [1.01-1.18], p=0.03), Dukes stage (OR=1.93 [1.01-3.70]), caspase-3 activity in normal mucosa (OR=1.02 [1.01-1.04], p=0.017) and caspase-3 activity in tumour (OR=1.02 [1.01-1.03], p=0.013). Low caspase-3 activity in the normal mucosa and tumour are independent prognostic factors of tumour recurrence in patients receiving adjuvant 5-fluoracil-based treatment in colon cancer, correlating with poor disease-free survival and higher recurrence rate.

Development and psychometric evaluation of a new team effectiveness scale for all types of community adult mental health teams: a mixed-methods approach.

PubMed

El Ansari, Walid; Lyubovnikova, Joanne; Middleton, Hugh; Dawson, Jeremy F; Naylor, Paul B; West, Michael A

2016-05-01

Defining 'effectiveness' in the context of community mental health teams (CMHTs) has become increasingly difficult under the current pattern of provision required in National Health Service mental health services in England. The aim of this study was to establish the characteristics of multi-professional team working effectiveness in adult CMHTs to develop a new measure of CMHT effectiveness. The study was conducted between May and November 2010 and comprised two stages. Stage 1 used a formative evaluative approach based on the Productivity Measurement and Enhancement System to develop the scale with multiple stakeholder groups over a series of qualitative workshops held in various locations across England. Stage 2 analysed responses from a cross-sectional survey of 1500 members in 135 CMHTs from 11 Mental Health Trusts in England to determine the scale's psychometric properties. Based on an analysis of its structural validity and reliability, the resultant 20-item scale demonstrated good psychometric properties and captured one overall latent factor of CMHT effectiveness comprising seven dimensions: improved service user well-being, creative problem-solving, continuous care, inter-team working, respect between professionals, engagement with carers and therapeutic relationships with service users. The scale will be of significant value to CMHTs and healthcare commissioners both nationally and internationally for monitoring, evaluating and improving team functioning in practice. © 2015 John Wiley & Sons Ltd.

Response of Caligus rogercresseyi (Boxshall & Bravo, 2000) to treatment with Hydrogen Peroxide: Recovery of parasites, fish infestation and egg viability under experimental conditions.

PubMed

Marín, S L; González, M P; Madariaga, S T; Mancilla, M; Mancilla, J

2018-06-01

Hydrogen peroxide (HP) is used to remove C. rogercresseyi from fish but little is known about its effect on this species. This study determined EC 50 and concentration immobilizing 100% of specimens, capacity of parasites exposed to HP to recover and infest fish, and effect on survival into the copepodid stage. EC 50 and concentration immobilizing 100% of specimens were estimated by exposing parasites for 20 min to 11 concentrations and evaluating effect at 1 and 24 h post-exposure. Capacity to recover and infest fish, and survival into copepodid were evaluated by exposing parasites and eggs to HP for 20 min. Recovery and fish infestation were evaluated at 25 and 24 h post-exposure, respectively. Eggs were grown until control reached the copepodid stage and survival calculated. EC 50 was 709.8 ppm.100% immobilization was obtained at 825 ppm. Male and female recover 0.5 and 1 h post-exposure, respectively. Percentage of parasites exposed and not exposed to HP that were recovered on fish was not significantly different. Survival to copepodid was lower in those exposed to HP. HP effect is greater on copepodids, but 100% of the mobile stages are immobilized under 825 ppm causing detachment from fish and potentially driven away, reducing infestation risk. © 2017 John Wiley & Sons Ltd.

Lazy gene (la) responsible for both an agravitropism of seedlings and lazy habit of tiller growth in rice (Oryza sativa L.).

PubMed

Abe, K; Takahashi, H; Suge, H

1996-12-01

Using an isogenic line of rice having lazy gene (la), we studied the correlation between the agravitropic response at the young seedling stage and the lazy habit (prostrate growth of tillers) at the more advanced stage of growth. In this study, it was found that both agravitropism and lazy habit were controlled by the single recessive la gene. That is, F2 segregants of Kamenoo x lazy-Kamenoo, which had an agravitropic response at their young seedling stage, showed a lazy habit of growth in the more advanced stage of vegetative growth. On the other hand, seedlings that showed normal gravitropic curvature at their early stage of growth had an upright growth in the mature stage.

The influence of the oestrous cycle on the radiation response of solid tumours

NASA Astrophysics Data System (ADS)

Swann, Patricia R.

Oestrogen increases the transcription of nitric oxide synthase, thus increasing nitric oxide production, which can result in vasodilation of blood vessels. Fluctuating levels of oestrogen throughout the menstrual cycle has the potential to affect tumour blood flow. Variations of blood supply to a solid tumour can influence tumour oxygenation and subsequently the percentage of hypoxic cells. As hypoxic cells are more resistant to radiation than well-oxygenated cells, this could potentially affect the radiation response of the tumour. This project evaluated the impact of the oestrous stage on the radiation response of BCHT, RIF-1 and SCCvii tumours in syngeneic C3H mice. The oestrous cycle consists of the following stages, pro-oestrus, oestrus, metoestrus and dioestrus and each stage can be determined by the cellular composition of vaginal smears. The peak of oestrogen occurs in the ovulatory phase and a second smaller peak occurs in dioestrus. Subcutaneous tumour were treated at a volume of 200 - 250 mm3 with local irradiation of 10 Gy ionising radiation at different stages of the oestrous cycle. Tumours were excised either immediately or 24 hours after irradiation and disaggregated into a single cell suspension. Tumour cell survival was assessed by clonogenic assay of the excised tumour relative to untreated tumours excised at the corresponding oestrous stage. Tumours irradiated in oestrus consistently produced the lowest surviving fraction after immediate and delayed excision. Tumours irradiated in pro-oestrus and excised immediately after irradiation, showed a two-fold increase in surviving fraction compared to tumours irradiated in oestrus. The surviving fractions of tumours excised 24 hours after irradiation were less than for tumours excised immediately after irradiation. Surviving fractions of irradiated, clamped KHT tumours were independent of oestrous stage. To confirm that these oestrous stage dependent changes were due to changes in tumour perfusion, the degree of transient perfusion in the tumours was assessed. This used a fluorescent double-staining technique by intravenous injection of the fluorescent dyes Hoechst 33342 and diheptyloxacarbocyanine with a 20 minute interval between dye administrations. These dyes stain functional blood vessels and can be viewed under the fluorescent microscope. Regions of vasculature stained with both dyes indicate constant perfusion throughout the experiment, whereas only one dye indicates mismatch or transient perfusion. Tumour vasculature that experiences intermittent perfusion will result in areas of acute hypoxia that can impact on the radiation response of the tumour. The results shows that in oestrus, KHT and RIF-1 tumours showed the lowest proportion of transient perfusion, where as this oestrous stage produced the most mismatch perfusion in the SCCvii tumour. The metastatic spread of KHT tumour cells was influenced by the oestrous cycle. Fractionated irradiation of a primary tumour during metoestrus and dioestrus showed less tumour control by radiation when compared to tumours irradiated in oestrus. The intravenous injection of KHT tumour cells in oestrus and dioestrus also produced a less metastatic burden to the lungs than cells injected in pro-oestrus and metoestrus. The results of this project suggest that there are oestrous stage dependent effects that could alter the radiation response of tumours.

The Role of Dual-Time Combined 18-Fluorideoxyglucose Positron Emission Tomography and Computed Tomography in the Staging and Restaging Workup of Locally Advanced Rectal Cancer, Treated With Preoperative Chemoradiation Therapy and Radical Surgery

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

Capirci, Carlo; Rubello, Domenico; Pasini, Felice

2009-08-01

Purpose: In patients with locally advanced rectal cancer (LARC) staging and, after preoperative chemo-radiation therapy (CRT), restaging workup could be useful to tailor therapeutic approaches. Fluorine-18-fluorodeoxyglucose positron emission tomography ([{sup 18}F]FDG-PET) is a promising tool for monitoring the effect of antitumor therapy. This study was aimed to evaluate the possible role of dual time sequential FDG-PET scans in the staging and restaging workup of LARC. Methods and Materials: Eighty-seven consecutive patients with LARC were enrolled. CRT consisted of external-beam intensified radiotherapy (concurrent boost), with concomitant chemotherapy PVI 5-FU (300mg/m{sup 2}/day) followed 8-10 weeks later by surgery. All patients underwent [{supmore » 18}F]FDG-PET/CT before and 5-6 weeks later after the completion of CRT. Measurements of FDG uptake (SUV{sub max}), and percentage of SUV{sub max} difference (Response Index = RI) between pre- and post-CRT [{sup 18}F]FDG-PET scans were evaluated. Results: Six of 87 patients were excluded due to protocol deviation. Following CRT, 40/81 patients (49%) were classified as responders according to Mandard's criteria (TRG1-2). The mean pre-CRT SUV{sub max} was significantly higher than post-CRT (15.8, vs 5.9; p < 0.001). The mean RI was significantly higher in responders than in nonresponder patients (71.3% vs 38%; p = 0.0038). Using a RI cut-off of 65% for defining response to therapy, the following parameters have been obtained: 84.5% sensitivity, 80% specificity, 81.4% positive predictive value, 84.2% negative predictive value, and 81% overall accuracy. Conclusion: These results suggest the potential role of [{sup 18}F]FDG-PET in the restaging workup after preoperative CRT in LARC. RI seems the best predictor to identify CRT response.« less

Uncertainty Analysis of Simulated Hydraulic Fracturing

NASA Astrophysics Data System (ADS)

Chen, M.; Sun, Y.; Fu, P.; Carrigan, C. R.; Lu, Z.

2012-12-01

Artificial hydraulic fracturing is being used widely to stimulate production of oil, natural gas, and geothermal reservoirs with low natural permeability. Optimization of field design and operation is limited by the incomplete characterization of the reservoir, as well as the complexity of hydrological and geomechanical processes that control the fracturing. Thus, there are a variety of uncertainties associated with the pre-existing fracture distribution, rock mechanics, and hydraulic-fracture engineering that require evaluation of their impact on the optimized design. In this study, a multiple-stage scheme was employed to evaluate the uncertainty. We first define the ranges and distributions of 11 input parameters that characterize the natural fracture topology, in situ stress, geomechanical behavior of the rock matrix and joint interfaces, and pumping operation, to cover a wide spectrum of potential conditions expected for a natural reservoir. These parameters were then sampled 1,000 times in an 11-dimensional parameter space constrained by the specified ranges using the Latin-hypercube method. These 1,000 parameter sets were fed into the fracture simulators, and the outputs were used to construct three designed objective functions, i.e. fracture density, opened fracture length and area density. Using PSUADE, three response surfaces (11-dimensional) of the objective functions were developed and global sensitivity was analyzed to identify the most sensitive parameters for the objective functions representing fracture connectivity, which are critical for sweep efficiency of the recovery process. The second-stage high resolution response surfaces were constructed with dimension reduced to the number of the most sensitive parameters. An additional response surface with respect to the objective function of the fractal dimension for fracture distributions was constructed in this stage. Based on these response surfaces, comprehensive uncertainty analyses were conducted among input parameters and objective functions. In addition, reduced-order emulation models resulting from this analysis can be used for optimal control of hydraulic fracturing. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

An Experience Oriented-Convergence Improved Gravitational Search Algorithm for Minimum Variance Distortionless Response Beamforming Optimum

PubMed Central

Darzi, Soodabeh; Tiong, Sieh Kiong; Tariqul Islam, Mohammad; Rezai Soleymanpour, Hassan; Kibria, Salehin

2016-01-01

An experience oriented-convergence improved gravitational search algorithm (ECGSA) based on two new modifications, searching through the best experiments and using of a dynamic gravitational damping coefficient (α), is introduced in this paper. ECGSA saves its best fitness function evaluations and uses those as the agents’ positions in searching process. In this way, the optimal found trajectories are retained and the search starts from these trajectories, which allow the algorithm to avoid the local optimums. Also, the agents can move faster in search space to obtain better exploration during the first stage of the searching process and they can converge rapidly to the optimal solution at the final stage of the search process by means of the proposed dynamic gravitational damping coefficient. The performance of ECGSA has been evaluated by applying it to eight standard benchmark functions along with six complicated composite test functions. It is also applied to adaptive beamforming problem as a practical issue to improve the weight vectors computed by minimum variance distortionless response (MVDR) beamforming technique. The results of implementation of the proposed algorithm are compared with some well-known heuristic methods and verified the proposed method in both reaching to optimal solutions and robustness. PMID:27399904

Role of PET/CT for precision medicine in lung cancer: perspective of the Society of Nuclear Medicine and Molecular Imaging.

PubMed

Greenspan, Bennett S

2017-12-01

This article discusses the role of PET/CT in contributing to precision medicine in lung cancer, and provides the perspective of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) on this process. The mission and vision of SNMMI are listed, along with the guidance provided by SNMMI to promote best practice in precision medicine. Basic principles of PET/CT are presented. An overview of the use of PET/CT imaging in lung cancer is discussed. In lung cancer patients, PET/CT is vitally important for optimal patient management. PET/CT is essential in determining staging and re-staging of disease, detecting recurrent or residual disease, evaluating response to therapy, and providing prognostic information. PET/CT is also critically important in radiation therapy planning by determining the extent of active disease, including an assessment of functional tumor volume. The current approach in tumor imaging is a significant advance over conventional imaging. However, recent advances suggest that therapeutic response criteria in the near future will be based on metabolic characteristics and will include the evaluation of biologic characteristics of tumors to further enhance the effectiveness of precision medicine in lung cancer, producing improved patient outcomes with less morbidity.

Carnivory during Ontogeny of the Plagioscion squamosissimus: A Successful Non-Native Fish in a Lentic Environment of the Upper Paraná River Basin

PubMed Central

Neves, Mayara Pereira; Delariva, Rosilene Luciana; Guimarães, Ana Tereza Bittencourt; Sanches, Paulo Vanderlei

2015-01-01

This study evaluated feeding patterns and ontogenetic variations in a non-native fish species (Plagioscion squamosissimus) in an isolated lake in the Upper Paraná River floodplain. Quarterly samplings were performed from April 2005 to February 2006 using plankton nets to capture larvae, seining nets for juveniles, and gill nets and trammel for adults. Stomach contents (n = 378) were examined according to the volumetric method in which the volume of each food item was estimated using graduated test tubes or a glass counting plate. During early development (larval stage), P. squamosissimus consumed mainly Cladocera and Copepoda. Juveniles showed a more diverse diet, including shrimp (Macrobrachium amazonicum), fish, aquatic insects (Trichoptera, Ephemeroptera, Chironomidae and pupae of Diptera) and plants. It was notable the high proportion of cannibalism (23.3%) in this stage. Adults consumed predominantly shrimp and fish. The use of food resources varied significantly between development stages (ANOSIM; r = 0.458; p<0.005), showing changes in food preferences during ontogeny. The Similarity Percentage Analysis (SIMPER) indicated that Cladocera and Copepoda were responsible for the differences observed between the larval stages of pre-flexion, flexion and post-flexion. M. amazonicum and Chironomidae were responsible for the differences between juvenile and larval stages, while M. amazonicum and other fishes caused the differences between adults and other ontogenetic stages. These results are confirmed by the relationship between standard length and developmental periods (ANCOVA; r2 = 0.94; p<0.0001). In general, there were low values of trophic niche breadth. The essentially carnivorous habit from the early stages of P. squamosissimus and the predominant use of M. amazonicum by adults have important roles in feeding patterns of the species, suggesting a major contribution to its success and establishment, especially in lentic environments. PMID:26524336

Attachment affects social information processing: Specific electrophysiological effects of maternal stimuli.

PubMed

Wu, Lili; Gu, Ruolei; Zhang, Jianxin

2016-01-01

Attachment is critical to each individual. It affects the cognitive-affective processing of social information. The present study examines how attachment affects the processing of social information, specifically maternal information. We assessed the behavioral and electrophysiological responses to maternal information (compared to non-specific others) in a Go/No-go Association Task (GNAT) with 22 participants. The results illustrated that attachment affected maternal information processing during three sequential stages of information processing. First, attachment affected visual perception, reflected by enhanced P100 and N170 elicited by maternal information as compared to others information. Second, compared to others, mother obtained more attentional resources, reflected by faster behavioral response to maternal information and larger P200 and P300. Finally, mother was evaluated positively, reflected by shorter P300 latency in a mother + good condition as compared to a mother + bad condition. These findings indicated that the processing of attachment-relevant information is neurologically differentiated from other types of social information from an early stage of perceptual processing to late high-level processing.

A Multidisciplinary Sepsis Program Enabled by a Two-Stage Clinical Decision Support System: Factors That Influence Patient Outcomes.

PubMed

Amland, Robert C; Haley, James M; Lyons, Jason J

2016-11-01

Sepsis is an inflammatory response triggered by infection, with risk of in-hospital mortality fueled by disease progression. Early recognition and intervention by multidisciplinary sepsis programs may reverse the inflammatory response among at-risk patient populations, potentially improving outcomes. This retrospective study of a sepsis program enabled by a 2-stage sepsis Clinical Decision Support (CDS) system sought to evaluate the program's impact, identify early indicators that may influence outcomes, and uncover opportunities for quality improvement. Data encompassed 16 527 adult hospitalizations from 2014 and 2015. Of 2108 non-intensive care unit patients screened-in by sepsis CDS, 97% patients were stratified by 177 providers. Risk of adverse outcome improved 30% from baseline to year end, with gains materializing and stabilizing at month 7 after sepsis program go-live. Early indicators likely to influence outcomes include patient age, recent hospitalization, electrolyte abnormalities, hypovolemic shock, hypoxemia, patient location when sepsis CDS activated, and specific alert patterns. © The Author(s) 2015.

Attentional bias modulation by reappraisal in patients with generalized anxiety disorder: an event-related potential study

PubMed Central

Han, H.Y.; Gan, T.; Li, P.; Li, Z.J.; Guo, M.; Yao, S.M.

2014-01-01

Affective states influence subsequent attention allocation. We evaluated emotional negativity bias modulation by reappraisal in patients with generalized anxiety disorder (GAD) relative to normal controls. Event-related potential (ERP) recordings were obtained, and changes in P200 and P300 amplitudes in response to negative or neutral words were noted after decreasing negative emotion or establishing a neutral condition. We found that in GAD patients only, the mean P200 amplitude after negative word presentation was much higher than after the presentation of neutral words. In normal controls, after downregulation of negative emotion, the mean P300 amplitude in response to negative words was much lower than after neutral words, and this was significant in both the left and right regions. In GAD patients, the negative bias remained prominent and was not affected by reappraisal at the early stage. Reappraisal was observed to have a lateralized effect at the late stage. PMID:24863650

A review of risk management process in construction projects of developing countries

NASA Astrophysics Data System (ADS)

Bahamid, R. A.; Doh, S. I.

2017-11-01

In the construction industry, risk management concept is a less popular technique. There are three main stages in the systematic approach to risk management in construction industry. These stages include: a) risk response; b) risk analysis and evaluation; and c) risk identification. The high risk related to construction business affects each of its participants; while operational analysis and management of construction related risks remain an enormous task to practitioners of the industry. This paper tends towards reviewing the existing literature on construction project risk managements in developing countries specifically on risk management process. The literature lacks ample risk management process approach capable of capturing risk impact on diverse project objectives. This literature review aims at discovering the frequently used techniques in risk identification and analysis. It also attempts to identify response to clarifying the different classifications of risk sources in the existing literature of developing countries, and to identify the future research directions on project risks in the area of construction in developing countries.

Comparative Digital Gene Expression Analysis of the Arabidopsis Response to Volatiles Emitted by Bacillus amyloliquefaciens

PubMed Central

Hao, Hai-Ting; Zhao, Xia; Shang, Qian-Han; Wang, Yun; Guo, Zhi-Hong; Zhang, Yu-Bao; Xie, Zhong-Kui; Wang, Ruo-Yu

2016-01-01

Some plant growth-promoting rhizobacteria (PGPR) regulated plant growth and elicited plant basal immunity by volatiles. The response mechanism to the Bacillus amyloliquefaciens volatiles in plant has not been well studied. We conducted global gene expression profiling in Arabidopsis after treatment with Bacillus amyloliquefaciens FZB42 volatiles by Illumina Digital Gene Expression (DGE) profiling of different growth stages (seedling and mature) and tissues (leaves and roots). Compared with the control, 1,507 and 820 differentially expressed genes (DEGs) were identified in leaves and roots at the seedling stage, respectively, while 1,512 and 367 DEGs were identified in leaves and roots at the mature stage. Seventeen genes with different regulatory patterns were validated using quantitative RT-PCR. Numerous DEGs were enriched for plant hormones, cell wall modifications, and protection against stress situations, which suggests that volatiles have effects on plant growth and immunity. Moreover, analyzes of transcriptome difference in tissues and growth stage using DGE profiling showed that the plant response might be tissue-specific and/or growth stage-specific. Thus, genes encoding flavonoid biosynthesis were downregulated in leaves and upregulated in roots, thereby indicating tissue-specific responses to volatiles. Genes related to photosynthesis were downregulated at the seedling stage and upregulated at the mature stage, respectively, thereby suggesting growth period-specific responses. In addition, the emission of bacterial volatiles significantly induced killing of cells of other organism pathway with up-regulated genes in leaves and the other three pathways (defense response to nematode, cell morphogenesis involved in differentiation and trichoblast differentiation) with up-regulated genes were significantly enriched in roots. Interestingly, some important alterations in the expression of growth-related genes, metabolic pathways, defense response to biotic stress and hormone-related genes were firstly founded response to FZB42 volatiles. PMID:27513952

Peritumoral stromal remodeling, pattern of invasion and expression of c-met/HGF in advanced squamous cell carcinoma of the cervix uteri, FIGO stages III and IV.

PubMed

Horn, L-C; Hommel, N; Roschlau, U; Bilek, K; Hentschel, B; Einenkel, J

2012-07-01

Different patterns of invasion (PIs) have prognostic impact in several types of cancer and are associated with different grades of peritumoral stromal remodeling, characterized by the desmoplastic stromal response (DSR). One key regulator influencing cellular motility and peritumoral stromal response is c-met/HGF. This study evaluates the association between different PI, peritumoral DSR and its correlation to the expression of c-met/HGF in squamous cell carcinomas of the uterine cervix (CX). 131 advanced stage CX (FIGO III/IV) were re-evaluated histologically regarding PI, using a two-level scoring system. The tumor grows in solid cords/trabeculae in finger-like PI and in very small groups or single cells in spray-like PI. DSR was categorized as none/weak and moderate/strong. The tumors were stained with antibodies against c-met and HGF. The staining of >30% of tumor cells was defined as overexpression. The PI was correlated to the prognostic outcome, different categories of DSR and expression status of c-met and HGF. 66.4% of the tumors showed a finger-like, and 33.6% a spray-like PI. The spray-like PI showed a reduced two-year overall survival when compared to the finger-like PI (14.0% vs. 29.1%, respectively; p=0.012), and was associated with moderate/strong DSR. The majority of the tumors showed overexpression of c-met (85.4%) and HGF (74.8%). There was no correlation between the expression status of c-met/HGF and the FIGO stage, peritumoral DSR or the prognostic outcome. Spray-like PI is of prognostic impact in cervical carcinoma FIGO III/IV and is associated with strong peritumoral stromal remodeling. There is no prognostic impact of the immunohistochemical expression of c-met/HGF in advanced stage cervical carcinomas. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Developing classification criteria for polymyalgia rheumatica: comparison of views from an expert panel and wider survey.

PubMed

Dasgupta, Bhaskar; Salvarani, Carlo; Schirmer, Michael; Crowson, Cynthia S; Maradit-Kremers, Hilal; Hutchings, Andrew; Matteson, Eric L

2008-02-01

This report summarizes the findings from a consensus process to identify potential classification criteria for polymyalgia rheumatica (PMR). A 3-stage hybrid consensus approach was used to develop potential PMR classification criteria. The first stage consisted of a facilitated meeting of 27 international experts who anonymously rated the importance of 68 potential criteria. The second stage involved a meeting of the experts, who were provided with the results of the first round of ratings and were then asked to re-rate the criteria. In the third stage, the wider acceptance of the 43 criteria that received > 50% support at round 2 was evaluated using an extended mailed survey of 111 rheumatologists and 53 nonrheumatologists in the United States, Canada, and Northern and Western Europe. A total of 68 and 50 criteria were identified and rated in round 1 and round 2, respectively. In round 2, 43 of the 50 items achieved at least 50% support, including 10 core criteria achieving 100% support. In round 3, over 70% of survey respondents agreed on the importance of 7 core criteria. These were age >or=50 years, duration >or=2 weeks, bilateral shoulder and/or pelvic girdle aching, duration of morning stiffness > 45 min, elevated erythrocyte sedimentation rate, elevated C-reactive protein, and rapid steroid response (> 75% global response within 1 wk to prednisolone/prednisone 15 20 mg daily). Among physical signs, more than 70% of survey respondents agreed on the importance of assessing pain and limitation of shoulder (84%) and/or hip (76%) on motion, but agreement was low for peripheral signs like carpal tunnel, tenosynovitis, and peripheral arthritis. There are differences in opinion as to what PMR is and how it should be treated. These findings make it important to develop classification criteria for PMR. The next step is to perform an international prospective study to evaluate the utility of candidate classification criteria for PMR in patients presenting with the polymyalgic syndrome.

Characterization of the institutionalization of pharmaceutical services in Brazilian primary health care.

PubMed

Souza, Gisélia Santana; Costa, Ediná Alves; Barros, Rafael Damasceno de; Pereira, Marcelo Tavares; Barreto, Joslene Lacerda; Guerra, Augusto Afonso; Acurcio, Francisco de Assis; Guibu, Ione Aquemi; Álvares, Juliana; Costa, Karen Sarmento; Karnikowski, Margô Gomes de Oliveira; Soeiro, Orlando Mario; Leite, Silvana Nair

2017-11-13

To characterize the current stage of the institutionalization of pharmaceutical services in Brazilian cities. This study is part of the Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines), a cross-sectional, exploratory, and evaluative study composed by an information survey in a representative sample of cities, stratified by Brazilian regions. We interviewed municipal secretaries of health, responsible for pharmaceutical services, and pharmacists responsible for the dispensing of medicines. The variables selected from the interviews were grouped into five dimensions that defined three stages of pharmaceutical services institutionalization: incipient (0%-34.0%), partial (35.0%-69.0%), and advanced (70.0%-100%), estimated based on the interviewees' answers. Frequencies were estimated with 95% confidence intervals. For the statistical association analysis, the Chi-square test was applied, with significance level of p<0.05. Our results show a partial and heterogeneous process of institutionalization of pharmaceutical services in Brazil, and an advanced stage in formal structures, such as the municipal health plans and the existence of a standardized list of medicines. The analysed variables in the "organization, structure, and financing" dimension configured stages that range from partial to advanced. The management presented partial institutionalization, positively showing the existence of computerized system, but also disparate results regarding the autonomy in the management of financial resources. Indispensable items related to the structure expressed disparities between the regions, with statistically significant differences. The study showed a partial and heterogeneous process of institutionalization of pharmaceutical services in Brazilian cities, showing regional disparities. Variables related to the normative aspects of institutionalization were positively highlighted in all dimensions; however, it is necessary to conduct new studies to evaluate the institutionalization of pharmaceutical services' finalistic activities.

Characterization of the institutionalization of pharmaceutical services in Brazilian primary health care

PubMed Central

Souza, Gisélia Santana; Costa, Ediná Alves; de Barros, Rafael Damasceno; Pereira, Marcelo Tavares; Barreto, Joslene Lacerda; Guerra, Augusto Afonso; Acurcio, Francisco de Assis; Guibu, Ione Aquemi; Álvares, Juliana; Costa, Karen Sarmento; Karnikowski, Margô Gomes de Oliveira; Soeiro, Orlando Mario; Leite, Silvana Nair

2017-01-01

ABSTRACT OBJECTIVE To characterize the current stage of the institutionalization of pharmaceutical services in Brazilian cities. METHODS This study is part of the Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM – National Survey on Access, Use and Promotion of Rational Use of Medicines), a cross-sectional, exploratory, and evaluative study composed by an information survey in a representative sample of cities, stratified by Brazilian regions. We interviewed municipal secretaries of health, responsible for pharmaceutical services, and pharmacists responsible for the dispensing of medicines. The variables selected from the interviews were grouped into five dimensions that defined three stages of pharmaceutical services institutionalization: incipient (0%-34.0%), partial (35.0%-69.0%), and advanced (70.0%-100%), estimated based on the interviewees’ answers. Frequencies were estimated with 95% confidence intervals. For the statistical association analysis, the Chi-square test was applied, with significance level of p<0.05. RESULTS Our results show a partial and heterogeneous process of institutionalization of pharmaceutical services in Brazil, and an advanced stage in formal structures, such as the municipal health plans and the existence of a standardized list of medicines. The analysed variables in the “organization, structure, and financing” dimension configured stages that range from partial to advanced. The management presented partial institutionalization, positively showing the existence of computerized system, but also disparate results regarding the autonomy in the management of financial resources. Indispensable items related to the structure expressed disparities between the regions, with statistically significant differences. CONCLUSION The study showed a partial and heterogeneous process of institutionalization of pharmaceutical services in Brazilian cities, showing regional disparities. Variables related to the normative aspects of institutionalization were positively highlighted in all dimensions; however, it is necessary to conduct new studies to evaluate the institutionalization of pharmaceutical services’ finalistic activities. PMID:29160459

Privacy with emergency medical information used in first response.

PubMed

Croll, Peter R; Ambrosoli, Kimberly M

2012-01-01

In an emergency there are many stages of Medical response. This paper focuses on the first response stage of an emergency medical incident, for example, a sporting accident. Today's Information Technology together with mobile devices now permits vital medical information regarding an individual to be available at the scene. Those first in attendance are often not medically trained. The literature shows the importance of appropriate first response in minimising harm and the significant investments being made to educate the public in this regard. It also highlights the privacy concerns that arise from the provision of sensitive health information in electronic form. The method utilised is a Privacy Impact Assessment to ascertain the suitability and compliance of the proposed technology. This approach follows the privacy guidelines specified by the Australian government to include information flow mapping, evaluation, compliance analysis, risk analysis and recommendations to management. The resultant output is a list of specific questions and a set of commendations and recommendations that are matched against the National Privacy Principles. The paper concludes that: the approach is both technical and pragmatically viable; it can meet all the reasonableness tests for privacy concerns; it can adopt standard security measures, and; it discusses its potential to be integrated into Personally Controlled Electronic Health Records.

Inelastic deformation of metal matrix composites: Plasticity and damage mechanisms, part 2

NASA Technical Reports Server (NTRS)

Majumdar, B. S.; Newaz, G. M.

1992-01-01

The inelastic deformation mechanisms for the SiC (SCS-6)/Ti-15-3 system were studied at 538 C (1000 F) using a combination of mechanical measurements and detailed microstructural examinations. The objectives were to evaluate the contributions of plasticity and damage to the overall MMC response, and to compare the room temperature and elevated temperature deformation behaviors. Four different laminates were studied: (0)8, (90)8,(+ or -45)2s, and (0/90)2s, with the primary emphasis on the unidirectional (0)8, and (90)8 systems. The elevated temperature responses were similar to those at room temperature, involving a two-stage elastic-plastic type of response for the (0)8 system, and a characteristic three-stage deformation response for the (90)8 and (+ or -45)2s systems. The primary effects of elevated temperatures included: (1) reduction in the 'yield' and failure strengths; (2) plasticity through diffused slip rather than concentrated planar slip (which occurred at room temperature); and (3) time-dependent deformation. The inelastic deformation mechanism for the (0)8 MMC was dominated by plasticity at both temperatures. For the (90)8 and (+ or -45)2s MMCs, a combination of damage and plasticity contributed to the deformation at both temperatures.

Review of health information technology usability study methodologies

PubMed Central

Bakken, Suzanne

2011-01-01

Usability factors are a major obstacle to health information technology (IT) adoption. The purpose of this paper is to review and categorize health IT usability study methods and to provide practical guidance on health IT usability evaluation. 2025 references were initially retrieved from the Medline database from 2003 to 2009 that evaluated health IT used by clinicians. Titles and abstracts were first reviewed for inclusion. Full-text articles were then examined to identify final eligibility studies. 629 studies were categorized into the five stages of an integrated usability specification and evaluation framework that was based on a usability model and the system development life cycle (SDLC)-associated stages of evaluation. Theoretical and methodological aspects of 319 studies were extracted in greater detail and studies that focused on system validation (SDLC stage 2) were not assessed further. The number of studies by stage was: stage 1, task-based or user–task interaction, n=42; stage 2, system–task interaction, n=310; stage 3, user–task–system interaction, n=69; stage 4, user–task–system–environment interaction, n=54; and stage 5, user–task–system–environment interaction in routine use, n=199. The studies applied a variety of quantitative and qualitative approaches. Methodological issues included lack of theoretical framework/model, lack of details regarding qualitative study approaches, single evaluation focus, environmental factors not evaluated in the early stages, and guideline adherence as the primary outcome for decision support system evaluations. Based on the findings, a three-level stratified view of health IT usability evaluation is proposed and methodological guidance is offered based upon the type of interaction that is of primary interest in the evaluation. PMID:21828224

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

Zhang, Xi-Mei; Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin; Li, Ye-Xiong, E-mail: yexiong@yahoo.com

Purpose: Early stage peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is rare. The purpose of this study was to evaluate the outcome of treatment as well as the potential role of radiation therapy in PTCL-NOS. Methods and Materials: Thirty-five patients with early stage PTCL-NOS were included. There were 13 patients with stage I disease and 22 with stage II. All patients except 1 received doxorubicin-based chemotherapy alone (n=13) or a combination of chemotherapy and radiation therapy (CMT) (n=21). Results: The 3-year overall survival (OS) and progression-free survival (PFS) rates for the entire group were 41.3% and 25.7%, respectively. The additionmore » of radiation therapy to chemotherapy significantly improved OS and PFS in early stage PTCL-NOS. The 3-year OS and PFS rates were 49.7% and 33.3% for CMT, compared with 23.1% (P=.042) and 15.4% (P=.035) for chemotherapy alone, respectively. The prognosis for patients who achieved a complete response (CR) was significantly better than that observed in those who did not achieve a CR. Conclusions: Despite the aggressive clinical course of early stage PTCL-NOS, additional radiation therapy has a significant impact on outcome. The integration of local radiation therapy into more effective systemic therapies may further improve survival.« less

Impact of forest seral stage on use of ant communities for rapid assessment of terrestrial ecosystem health.

PubMed

Wike, Lynn D; Martin, F Douglas; Paller, Michael H; Nelson, Eric A

2010-01-01

Bioassessment evaluates ecosystem health by using the responses of a community of organisms that integrate all aspects of the ecosystem. A variety of bioassessment methods have been applied to aquatic ecosystems; however, terrestrial methods are less advanced. The objective of this study was to examine baseline differences in ant communities at different seral stages from clear cut to mature pine plantation as a precursor to developing a broader terrestrial bioassessment protocol. Comparative sampling was conducted at nine sites having four seral stages: clearcut, 5 year recovery, 15 year recovery, and mature stands. Soil and vegetation data were also collected at each site. Ants were identified to genus. Analysis of the ant data indicated that ants respond strongly to habitat changes that accompany ecological succession in managed pine forests, and both individual genera and ant community structure can be used as indicators of successional change. Ants exhibited relatively high diversity in both early and mature seral stages. High ant diversity in mature seral stages was likely related to conditions on the forest floor favoring litter dwelling and cold climate specialists. While ants may be very useful in identifying environmental stress in managed pine forests, adjustments must be made for seral stage when comparing impacted and unimpacted forests.

Temporal integration at consecutive processing stages in the auditory pathway of the grasshopper.

PubMed

Wirtssohn, Sarah; Ronacher, Bernhard

2015-04-01

Temporal integration in the auditory system of locusts was quantified by presenting single clicks and click pairs while performing intracellular recordings. Auditory neurons were studied at three processing stages, which form a feed-forward network in the metathoracic ganglion. Receptor neurons and most first-order interneurons ("local neurons") encode the signal envelope, while second-order interneurons ("ascending neurons") tend to extract more complex, behaviorally relevant sound features. In different neuron types of the auditory pathway we found three response types: no significant temporal integration (some ascending neurons), leaky energy integration (receptor neurons and some local neurons), and facilitatory processes (some local and ascending neurons). The receptor neurons integrated input over very short time windows (<2 ms). Temporal integration on longer time scales was found at subsequent processing stages, indicative of within-neuron computations and network activity. These different strategies, realized at separate processing stages and in parallel neuronal pathways within one processing stage, could enable the grasshopper's auditory system to evaluate longer time windows and thus to implement temporal filters, while at the same time maintaining a high temporal resolution. Copyright © 2015 the American Physiological Society.

Evaluation of metal ions and surfactants effect on cell growth and exopolysaccharide production in two-stage submerged culture of Cordyceps militaris.

PubMed

Cui, Jian-Dong; Zhang, Ya-Nan

2012-11-01

During the two-stage submerged fermentation of medicinal mushroom Cordyceps militaris, it was found that K(+), Ca(2+), Mg(2+), and Mn(2+) were favorable to the mycelial growth. The EPS production reached the highest levels in the media containing Mg(2+) and Mn(2+). However, Ca(2+) and K(+) almost failed to increase significantly exopolysaccharides (EPS) production. Sodium dodecyl sulfate (SDS) significantly enhanced EPS production compared with that of without adding SDS when SDS was added on static culture stage of two-stage cultivation process. The presence of Tween 80 in the medium not only simulated mycelial growth but also increased EPS production. By response surface methods (RSM), EPS production reached its peak value of 3.28 g/L under optimal combination of 27.6 mM Mg(2+), 11.1 mM Mn(2+), and 0.05 mM SDS, which was 3.76-fold compared with that of without metal ion and surfactant. The results obtained were useful in better understanding the regulation for efficient production of EPS of C. militaris in the two-stage submerged culture.

How to use PET/CT in the evaluation of response to radiotherapy.

PubMed

Decazes, Pierre; Thureau, Sébastien; Dubray, Bernard; Vera, Pierre

2018-06-01

Radiotherapy is a major treatment modality for many cancers. Tumor response after radiotherapy determines the subsequent steps of the patient's management (surveillance, adjuvant or salvage treatment and palliative care). Tumor response assessed during radiotherapy offers a promising opportunity to adapt the treatment plan to reduced or increased target volume, to specifically target sub-volumes with relevant biological characteristics (metabolism, hypoxia, proliferation, etc.) and to further spare the organs at risk. In addition to its role in the diagnosis and the initial staging, Positron Emission Tomography combined with a Computed Tomography (PET/CT) provides functional information and is therefore attractive to evaluate tumor response. The aim of this paper is to review the published data addressing PET/CT as an evaluation tool in irradiated tumors. Reports on PET/CT acquired at various times (during radiotherapy, after initial (chemo-) radiotherapy, after definitive radiotherapy and during posttreatment follow-up) in solid tumors (lung, head-and-neck, cervix, esophagus, prostate and rectum) were collected and reviewed. Various tracers and technical aspects are also discussed. 18F-FDG PET/CT has a well-established role in clinical routine after definitive chemo-radiotherapy for locally advanced head-and-neck cancers. 18F-choline PET/CT is indicated in prostate cancer patients with biochemical failure. 18F-FDG PET/CT is optional in many other circumstances and the clinical benefits of assessing tumor response with PET/CT remain a field of very active research. The combination of PET with Magnetic Resonance Imaging (PET/MRI) may prove to be valuable in irradiated rectal and cervix cancers. Tumor response can be evaluated by PET/CT with clinical consequences in multiple situations, notably in head and neck and prostate cancers, after radiotherapy. Further clinical evaluation for most cancers is still needed, possibly in association to MRI.

Lamellar pro-inflammatory cytokine expression patterns in laminitis at the developmental stage and at the onset of lameness: innate vs. adaptive immune response.

PubMed

Belknap, J K; Giguère, S; Pettigrew, A; Cochran, A M; Van Eps, A W; Pollitt, C C

2007-01-01

Recent research has indicated that inflammation plays a role in the early stages of laminitis and that, similar to organ failure in human sepsis, early inflammatory mechanisms may lead to downstream events resulting in lamellar failure. Characterisation of the type of immune response (i.e. innate vs. adaptive) is essential in order to develop therapeutic strategies to counteract these deleterious events. To quantitate gene expression of pro-inflammatory cytokines known to be important in the innate and adaptive immune response during the early stages of laminitis, using both the black walnut extract (BWE) and oligofructose (OF) models of laminitis. Real-time qPCR was used to assess lamellar mRNA expression of interleukins-1beta, 2, 4, 6, 8, 10, 12 and 18, and tumour necrosis factor alpha and interferon gamma at the developmental stage and at the onset of lameness. Significantly increased lamellar mRNA expression of cytokines important in the innate immune response were present at the developmental stage of the BWE model, and at the onset of acute lameness in both the BWE model and OF model. Of the cytokines characteristic of the Th1 and Th2 arms of the adaptive immune response, a mixed response was noted at the onset of acute lameness in the BWE model, whereas the response was skewed towards a Th1 response at the onset of lameness in the OF model. Lamellar inflammation is characterised by strong innate immune response in the developmental stages of laminitis; and a mixture of innate and adaptive immune responses at the onset of lameness. These results indicate that anti-inflammatory treatment of early stage laminitis (and the horse at risk of laminitis) should include not only therapeutic drugs that address prostanoid activity, but should also address the marked increases in lamellar cytokine expression.

Age-dependent regulation of ERF-VII transcription factor activity in Arabidopsis thaliana.

PubMed

Giuntoli, Beatrice; Shukla, Vinay; Maggiorelli, Federica; Giorgi, Federico M; Lombardi, Lara; Perata, Pierdomenico; Licausi, Francesco

2017-10-01

The Group VII Ethylene Responsive Factors (ERFs-VII) RAP2.2 and RAP2.12 have been mainly characterized with regard to their contribution as activators of fermentation in plants. However, transcriptional changes measured in conditions that stabilize these transcription factors exceed the mere activation of this biochemical pathway, implying additional roles performed by the ERF-VIIs in other processes. We evaluated gene expression in transgenic Arabidopsis lines expressing a stabilized form of RAP2.12, or hampered in ERF-VII activity, and identified genes affected by this transcriptional regulator and its homologs, including some involved in oxidative stress response, which are not universally induced under anaerobic conditions. The contribution of the ERF-VIIs in regulating this set of genes in response to chemically induced or submergence-stimulated mitochondria malfunctioning was found to depend on the plant developmental stage. A similar age-dependent mechanism also restrained ERF-VII activity upon the core-hypoxic genes, independently of the N-end rule pathway, which is accounted for the control of the anaerobic response. To conclude, this study shed new light on a dual role of ERF-VII proteins under submergence: as positive regulators of the hypoxic response and as repressors of oxidative-stress related genes, depending on the developmental stage at which plants are challenged by stress conditions. © 2017 John Wiley & Sons Ltd.

Aluminum nanoparticle exposure in L1 larvae results in more severe lethality toxicity than in L4 larvae or young adults by strengthening the formation of stress response and intestinal lipofuscin accumulation in nematodes.

PubMed

Wu, Si; Lu, Jianhong; Rui, Qi; Yu, Shunhui; Cai, Ting; Wang, Dayong

2011-01-01

Toxicity of Al(2)O(3)-NPs, as compared to that of Al(2)O(3), to L1-larval, L4-larval or young adult nematodes was evaluated. When exposure was performed at L1-larval stage, the significant increases of lethality, stress response, and intestinal lipofuscin autofluorescence were observed in 6.3-203.9 mg/L of Al(2)O(3)-NPs exposed nematodes. In contrast, when exposure was performed at L4-larval or young adult stage, the significant increases of lethality and intestinal lipofuscin autofluorescence were observed in 12.7-203.9 mg/L of Al(2)O(3)-NPs exposed nematodes, and the significant inductions of stress response were detected in 25.5-203.9 mg/L of Al(2)O(3)-NPs exposed nematodes. Moreover, the lethality was significantly correlated with the stress response and the intestinal lipofuscin autofluorescence in Al(2)O(3)-NPs exposed nematodes. These data imply that Al(2)O(3)-NPs exposure in L1 larvae causes more severe lethality toxicity than in L4 larvae or young adults by strengthening the formation of stress response and intestinal lipofuscin accumulation in nematodes. Copyright © 2010 Elsevier B.V. All rights reserved.

Dopamine Inactivation Efficacy Related to Functional DAT1 and COMT Variants Influences Motor Response Evaluation

PubMed Central

Bender, Stephan; Rellum, Thomas; Freitag, Christine; Resch, Franz; Rietschel, Marcella; Treutlein, Jens; Jennen-Steinmetz, Christine; Brandeis, Daniel; Banaschewski, Tobias; Laucht, Manfred

2012-01-01

Background Dopamine plays an important role in orienting, response anticipation and movement evaluation. Thus, we examined the influence of functional variants related to dopamine inactivation in the dopamine transporter (DAT1) and catechol-O-methyltransferase genes (COMT) on the time-course of motor processing in a contingent negative variation (CNV) task. Methods 64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version). Early and late CNV as well as motor postimperative negative variation were assessed. Adolescents were genotyped for the COMT Val158Met and two DAT1 polymorphisms (variable number tandem repeats in the 3′-untranslated region and in intron 8). Results The results revealed a significant interaction between COMT and DAT1, indicating that COMT exerted stronger effects on lateralized motor post-processing (centro-parietal motor postimperative negative variation) in homozygous carriers of a DAT1 haplotype increasing DAT1 expression. Source analysis showed that the time interval 500–1000 ms after the motor response was specifically affected in contrast to preceding movement anticipation and programming stages, which were not altered. Conclusions Motor slow negative waves allow the genomic imaging of dopamine inactivation effects on cortical motor post-processing during response evaluation. This is the first report to point towards epistatic effects in the motor system during response evaluation, i.e. during the post-processing of an already executed movement rather than during movement programming. PMID:22649558

Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

PubMed Central

García-Albéniz, Xabier; Gallego, Rosa; Hofheinz, Ralf Dieter; Fernández-Esparrach, Gloria; Ayuso-Colella, Juan Ramón; Bombí, Josep Antoni; Conill, Carles; Cuatrecasas, Miriam; Delgado, Salvadora; Ginés, Angels; Miquel, Rosa; Pagés, Mario; Pineda, Estela; Pereira, Verónica; Sosa, Aarón; Reig, Oscar; Victoria, Iván; Feliz, Luis; María de Lacy, Antonio; Castells, Antoni; Burkholder, Iris; Hochhaus, Andreas; Maurel, Joan

2014-01-01

AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team. PMID:25400468

MicroRNA biogenesis pathway from the salmon louse (Caligus rogercresseyi): emerging role in delousing drug response.

PubMed

Valenzuela-Miranda, Diego; Nuñez-Acuña, Gustavo; Valenzuela-Muñoz, Valentina; Asgari, Sassan; Gallardo-Escárate, Cristian

2015-01-25

Despite the increasing evidence of the importance of microRNAs (miRNAs) in the regulation of multiple biological processes, the molecular bases supporting this regulation are still barely understood in crustaceans. Therefore, the molecular characterization and transcriptome modulation of the miRNA biogenesis pathway were evaluated in the salmon louse Caligus rogercresseyi, an ectoparasite that constitutes one of the biggest concerns for salmonid aquaculture industry. Hence, RNA-Seq analysis was conducted from six different developmental stages, and also after bioassays with delousing drugs Deltamethrin and Azamethiphos using adult individuals. In silico analysis evidenced 24 putative genes involved in the miRNA pathway such as biogenesis, transport, maturation and miRNA-target interaction. Moreover, 243 putative single nucleotide polymorphisms (SNPs) were identified, 15 of which showed non-synonym mutations. RNA-Seq analysis revealed that CCR4-Not complex subunit 3 (CNOT3) was upregulated at earlier developmental stages (nauplius I-II and copepodid), and also after the exposure to Azamethiphos, but not to Deltamethrin. In contrast, the subunit 7 (CNOT7) showed an inverse expression pattern. Different Argonaute transcripts were associated to chalimus and adult stages, revealing specific expression patterns in response to antiparasitic drugs. Our results suggest novel insights into the regulatory network of the post-transcriptional gene regulation in C. rogercresseyi mediated by miRNAs, evidencing a putative role during the ontogeny and drug response. Copyright © 2014 Elsevier B.V. All rights reserved.

[The therapeutic value and safety of icotinib as first-line therapy for advanced non-small cell lung cancer patients].

PubMed

Chen, H; Wang, H P; Zhang, L; Si, X Y

2017-01-01

Objective: To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%. The median PFS was 14.9 months (95% CI 13.5-16.3) and the OS was 37.0 weeks (95% CI 27.9-46.1). Patients with brain metastases showed higher ORR( P =0.049). Patients with stage ⅢB had longer PFS than those with stage Ⅳ( P =0.007). The most common adverse events were grade 1-2 skin rash (38 patients, 40.9%). Other adverse events included dry skin, oral mucositis, diarrhea and liver function injury. Three patients withdrew because of severe liver injury or skin rash. No treatment related mortality occurred. Conclusions: Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.

Tough Adults, Frail Babies: An Analysis of Stress Sensitivity across Early Life-History Stages of Widely Introduced Marine Invertebrates

PubMed Central

Pineda, M. Carmen; McQuaid, Christopher D.; Turon, Xavier; López-Legentil, Susanna; Ordóñez, Víctor; Rius, Marc

2012-01-01

All ontogenetic stages of a life cycle are exposed to environmental conditions so that population persistence depends on the performance of both adults and offspring. Most studies analysing the influence of abiotic conditions on species performance have focussed on adults, while studies covering early life-history stages remain rare. We investigated the responses of early stages of two widely introduced ascidians, Styela plicata and Microcosmus squamiger, to different abiotic conditions. Stressors mimicked conditions in the habitats where both species can be found in their distributional ranges and responses were related to the selection potential of their populations by analysing their genetic diversity. Four developmental stages (egg fertilisation, larval development, settlement, metamorphosis) were studied after exposure to high temperature (30°C), low salinities (26 and 22‰) and high copper concentrations (25, 50 and 100 µg/L). Although most stressors effectively led to failure of complete development (fertilisation through metamorphosis), fertilisation and larval development were the most sensitive stages. All the studied stressors affected the development of both species, though responses differed with stage and stressor. S. plicata was overall more resistant to copper, and some stages of M. squamiger to low salinities. No relationship was found between parental genetic composition and responses to stressors. We conclude that successful development can be prevented at several life-history stages, and therefore, it is essential to consider multiple stages when assessing species' abilities to tolerate stress. Moreover, we found that early development of these species cannot be completed under conditions prevailing where adults live. These populations must therefore recruit from elsewhere or reproduce during temporal windows of more benign conditions. Alternatively, novel strategies or behaviours that increase overall reproductive success might be responsible for ensuring population survival. PMID:23077518

Influence of Two Acyclic Homoterpenes (Tetranorterpenes) on the Foraging Behavior of Anthonomus grandis Boh.

PubMed

Magalhães, D M; Borges, M; Laumann, R A; Woodcock, C M; Pickett, J A; Birkett, M A; Blassioli-Moraes, Maria Carolina

2016-04-01

Previous studies have shown that the boll weevil, Anthonomus grandis, is attracted to constitutive and conspecific herbivore-induced cotton volatiles, preferring the blend emitted by cotton at the reproductive over the vegetative stage. Moreover, this preference was paralleled by the release of the acyclic homoterpenes (tetranorterpenes) (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT) and (E,E)-4,8,12-trimethyltrideca-1,3,7,11-tetraene (TMTT) in Delta Opal cotton being higher at the vegetative than at the reproductive stage. Here, we evaluated whether this difference in release of acyclic homoterpenes also occurred in other cotton varieties, and if boll weevils could recognize these compounds as indicators of a specific cotton phenological stage. Results showed that cotton genotypes CNPA TB-90, BRS-293 and Delta Opal all produced higher levels of DMNT and TMTT at the vegetative stage than at the reproductive stage and that these homoterpenes allowed for principal component analysis separation of volatiles produced by the two phenological stages. Electroantennograms confirmed boll weevil antennal responses to DMNT and TMTT. Behavioral assays, using Y-tube olfactometers, showed that adding synthetic homoterpenes to reproductive cotton volatiles (mimicking cotton at the vegetative stage in terms of homoterpene levels) resulted in reduced attraction to boll weevils compared to that to unmodified reproductive cotton. Weevils showed no preference when given a choice between plants at the vegetative stage and the vegetative stage-mimicked plant. Altogether, the results show that DMNT and TMTT are used by boll weevils to distinguish between cotton phenological stages.

Parasite Specific Antibody Levels, Interferon-γ and TLR2 and TLR4 Transcripts in Blood from Dogs with Different Clinical Stages of Leishmaniosis

PubMed Central

Montserrat-Sangrà, Sara; Ordeix, Laura; Martínez-Orellana, Pamela; Solano-Gallego, Laia

2018-01-01

Canine leishmaniosis has a wide range of disease severity from mild (stage I), to severe (stages II–III), or very severe disease (stage IV). The objective of the study was to evaluate and compare serum antibody levels, Leishmania infantum specific IFN-γ production and TLR2 and TLR4 transcripts in non-stimulated blood from dogs with different clinical stages at the time of diagnosis as well as blood parasitemia. Enzyme-Linked ImmunoSorbent Assay (ELISAs) were performed to determine serum antibody levels and IFN-γ production and quantitative polymerase chain reaction (qPCRs) in order to determine blood parasite load and TLR2 and TLR4 transcripts. Older dogs were significantly affected by more severe disease with higher antibody levels and blood parasitemia than dogs with mild disease. IFN-γ production was significantly higher in dogs with stage I disease when compared to dogs with more severe disease. Relative quantification of TLR2 in dogs with mild disease was similar to that of control dogs. On the other hand, TLR2 transcripts were significantly higher in dogs with severe disease as compared with that from control healthy dogs. No differences were found in TLR4 relative quantification between groups. This study demonstrates that dogs with different clinical stages of leishmaniosis present different levels of biological markers indicative of different immune responses. PMID:29547503

Design and clinical outcome of a novel 3D-printed prosthetic joint replacement for the human temporomandibular joint.

PubMed

Ackland, David; Robinson, Dale; Lee, Peter Vee Sin; Dimitroulis, George

2018-05-11

Stock prosthetic temporomandibular joint replacements come in limited sizes, and do not always encompass the joint anatomy that presents clinically. The aims of this study were twofold. Firstly, to design a personalized prosthetic total joint replacement for the treatment of a patient's end-stage temporomandibular joint osteoarthritis, to implant the prosthesis into the patient, and assess clinical outcome 12-months post-operatively; and secondly, to evaluate the influence of changes in prosthetic condyle geometry on implant load response during mastication. A 48-year-old female patient with Grade-5 osteoarthritis to the left temporomandibular joint was recruited, and a prosthesis developed to match the native temporomandibular joint anatomy. The prosthesis was 3D printed, sterilized and implanted into the patient, and pain and function measured 12-months post-operatively. The prosthesis load response during a chewing-bite and maximum-force bite was evaluated using a personalized multi-body musculoskeletal model. Simulations were performed after perturbing condyle thickness, neck length and head sphericity. Increases in prosthetic condyle neck length malaligned the mandible and perturbed temporomandibular joint force. Changes in condylar component thickness greatly influenced fixation screw stress response, while a more eccentric condylar head increased prosthetic joint-contact loading. Post-operatively, the prosthetic temporomandibular joint surgery reduced patient pain from 7/10 to 1/10 on a visual analog scale, and increased intercisal opening distance from 22 mm to 38 mm. This study demonstrates effectiveness of a personalized prosthesis that may ultimately be adapted to treat a wide-range of end-stage temporomandibular joint conditions, and highlights sensitivity of prosthesis load response to changes in condylar geometry. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Diagnostic and Prognostic Value of Tumor Markers (CEA, SCC, CYFRA 21-1, TPS) in Head and Neck Cancer Patients.

PubMed

Barak, Vivian; Meirovitz, Amichay; Leibovici, Vera; Rachmut, Jacob; Peretz, Tamar; Eliashar, Ron; Gross, Menachem

2015-10-01

Establishing prognostic factors is very important in the management of cancer patients. Our aim was to evaluate the clinical significance of a panel of tumor markers, including CEA (Carcino Embryonic Antigen), SCC (Squamous Cell Carcinoma Antigen), TPS (Tissue Polypeptide Specific Antigen) and CYFRA 21-1 in head and neck cancer patients, for assessing treatment response and prognosis of patients. We evaluated 312 blood samples from 143 head and neck cancer patients, from several sub-groups: 82 Larynx Carcinoma pre- and 38 post-therapy, 46 Oral Cavity pre and 29 post-therapy, 12 nasopharynx, 16 parotid and other salivary gland patients. Blood tumor markers levels were evaluated by conventional ELISA assays. Correlations of marker levels to stage of disease, lymph node involvement and therapy, were performed. Serum levels of all four tumor markers were higher before therapy and decreased thereafter in all patients. The decrease in TPS level following therapy was significant (p=0.03). Significantly higher levels of TPS and similarly higher levels of the other tumor markers were demonstrated in advanced disease (stages III and IV) patients, as opposed to early disease (stages I and II) patients (p=0.012). Node positive patients had significantly higher TPS levels as compared to node negative (p=0.02). The same trend was shown by the other markers as well, but did not reach statistical significance. TPS was best correlated to survival of patients; those having low levels had the best clinical outcome and longer survival. CEA, SCC, TPS and CYFRA 21-1 can all serve as useful tumor markers in HNC patients. They assessed response to therapy and were prognostic for recurrence. TPS proved to be the most sensitive predictor of advanced disease and poor prognosis. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

High-dose sequential epirubicin and cyclophosphamide with peripheral blood stem cell support for advanced breast cancer: results of a phase II study

PubMed Central

Cottu, P H; Extra, J M; Espie, M; Marolleau, J P; Roquancourt, A de; Makke, J; Miclea, J M; Laurence, V; Mayeur, D; Lerebours, F; Cuvier, C; Marty, M

2001-01-01

The aim of this study was to evaluate the feasibility of a high-dose intensity and high-dose density multicycle epirubicin and cyclophosphamide regimen with peripheral blood stem cells (PBSC) and haematopoietic growth factor (G-CSF) support in advanced breast cancer patients. From August 1994 to September 1999, 56 breast cancer patients (8 stage IIIB and 48 stage IV) received 205 courses of cyclophosphamide 3 g m−2and epirubicin 100 mg m−2every 14 days. G-CSF 5 μg kg−1day−1was administered from day 3 to neutrophil recovery. 4 courses were planned. PBSC were collected after course 1, and reinfused after courses 3 and 4, with ≥ 2 × 106CD34+ PBSC kg−1required for each reinfusion. 48 patients (86%) received all 4 planned courses. Early withdrawal was consecutive to infectious complications (n= 4), severe asthenia (n= 3), haemorrhagic cystitis (n= 1). A median number of 10.8 × 106CD34+ PBSC kg−1(range, 3–80) was harvested with 1 or 2 apheresis in 48 patients (94%). Median relative dose intensity was 91.3% (range, 72–102%). Grade 4 neutrophil toxicity was observed in 100% of patients. Febrile neutropenia was observed in 40% of courses (median duration 2 days). Red blood cells and platelets had to be transfused in 54% and 27% of courses, respectively. There were no toxic deaths. Objective response rate was 69% in stage IV patients (31/45 evaluable pts), with a 16% complete response rate. Their median progression-free and overall survivals were 22.5 and 37 months, respectively. This epirubicine-containing high-dose regimen appeared feasible, albeit with high toxicity. Time-related progression parameters exceed commonly reported ones. Controlled studies of upfront sequential high-dose chemotherapy are still needed to evaluate its real benefit. © 2001 Cancer Research Campaign PMID:11720455

Breeding drought tolerant rice for shallow rainfed ecosystem of eastern India.

PubMed

Swain, Padmini; Raman, Anitha; Singh, S P; Kumar, Arvind

2017-08-01

In shallow rainfed rice agro-ecosystems, drought stress can occur at any growth stage and can cause a significant yield reduction. During recent years, some rice varieties possessing tolerance of reproductive-stage drought stress have recently been developed. Tolerance of vegetative-stage drought stress is also required to improve rice productivity in drought-prone regions. In this study, we evaluated a set of rice breeding lines for their response to a range of different types of vegetative-stage drought stress in order to propose standardized phenotyping protocols for conducting vegetative-stage drought stress screening trials and also to identify genotypes combining tolerance of vegetative- and reproductive-stage drought stress. A soil water potential threshold of -20 kPa during the vegetative stage was identified as the target for effective selection under vegetative stage with grain yield reduction of about 50% compared to irrigated control trials. Genotypes identified as showing high yield under reproductive-stage drought stress were not necessarily the genotypes showing best performance under vegetative-stage drought stress. Genotypes IR72667-16-1-B-B-3, IR78908-126-B-2-B, and IR79970-B-47-1 showed tolerance of both vegetative-stage and reproductive-stage drought stress. For most, the genotypes that were best under vegetative stage drought or even vegetative stage + reproductive stage drought were different from the genotypes that were best under reproductive stage drought. Based on the cultivar superiority measure, IR69515-6-KKN-4-UBN-4-2-1-1-1 and IR78908-126-B-1-B were the stable genotypes (indicated by low P i ) under both irrigated control and severe vegetative stress conditions, genotypes IR83614-203-B and IR78908-80-B-3-B were stable under irrigated control conditions and moderate stress, whereas IR72667-16-1-B-B-3 was stable under both moderate and severe vegetative-stage stress conditions.

Biomechanics of Ergometric Stress Test: regional and local effects on elastic, transitional and muscular human arteries

NASA Astrophysics Data System (ADS)

Valls, G.; Torrado, J.; Farro, I.; Bia, D.; Zócalo, Y.; Lluberas, S.; Craiem, D.; Armentano, Rl

2011-09-01

Ergometric exercise stress tests (EST) give important information about the cardiovascular (CV) response to increased demands. The expected EST-related changes in variables like blood pressure and heart rate are known, but those in the arterial biomechanics are controversial and incompletely characterized. In this context, this work aims were to characterize the regional and local arterial biomechanical behaviour in response to EST; to evaluate its temporal profile in the post-EST recovery phase; and to compare the biomechanical response of different to EST. Methods: In 16 non-trained healthy young subjects the carotid-femoral pulse wave velocity and the carotid, femoral and brachial arterial distensibility were non-invasively evaluated before (Rest) and after EST. Main results: The EST resulted in an early increase in the arterial stiffness, evidenced by both, regional and local parameters (pulse wave velocity increase and distensibility reduction). When analyzing conjunctly the different post-EST recovery stages there were quali-quantitative differences among the arterial local stiffness response to EST. The biomechanical changes could not be explained only by blood pressure variations.

The Role of Epigenomics in Aquatic Toxicology.

PubMed

Brander, Susanne M; Biales, Adam D; Connon, Richard E

2017-10-01

Over the past decade, the field of molecular biology has rapidly incorporated epigenetic studies to evaluate organism-environment interactions that can result in chronic effects. Such responses arise from early life stage stress, the utilization of genetic information over an individual's life time, and transgenerational inheritance. Knowledge of epigenetic mechanisms provides the potential for a comprehensive evaluation of multigenerational and heritable effects from environmental stressors, such as contaminants. Focused studies have provided a greater understanding of how many responses to environmental stressors are driven by epigenetic modifiers. We discuss the promise of epigenetics and suggest future research directions within the field of aquatic toxicology, with a particular focus on the potential for identifying key heritable marks with consequential impacts at the organism and population levels. Environ Toxicol Chem 2017;36:2565-2573. © 2017 SETAC. © 2017 SETAC.

Acute effects of cocaine and cannabis on response inhibition in humans: an ERP investigation.

PubMed

Spronk, Desirée B; De Bruijn, Ellen R A; van Wel, Janelle H P; Ramaekers, Johannes G; Verkes, Robbert J

2016-11-01

Substance abuse has often been associated with alterations in response inhibition in humans. Not much research has examined how the acute effects of drugs modify the neurophysiological correlates of response inhibition, or how these effects interact with individual variation in trait levels of impulsivity and novelty seeking. This study investigated the effects of cocaine and cannabis on behavioural and event-related potential (ERP) correlates of response inhibition in 38 healthy drug using volunteers. A double-blind placebo-controlled randomized three-way crossover design was used. All subjects completed a standard Go/NoGo task after administration of the drugs. Compared with a placebo, cocaine yielded improved accuracy, quicker reaction times and an increased prefrontal NoGo-P3 ERP. Cannabis produced opposing results; slower reaction times, impaired accuracy and a reduction in the amplitude of the prefrontal NoGo-P3. Cannabis in addition decreased the amplitude of the parietally recorded P3, while cocaine did not affect this. Neither drugs specifically affected the N2 component, suggesting that pre-motor response inhibitory processes remain unaffected. Neither trait impulsivity nor novelty seeking interacted with drug-induced effects on measures of response inhibition. We conclude that acute drug effects on response inhibition seem to be specific to the later, evaluative stages of response inhibition. The acute effects of cannabis appeared less specific to response inhibition than those of cocaine. Together, the results show that the behavioural effects on response inhibition are reflected in electrophysiological correlates. This study did not support a substantial role of vulnerability personality traits in the acute intoxication stage. © 2015 Society for the Study of Addiction.

An Impulse Based Substructuring approach for impact analysis and load case simulations

NASA Astrophysics Data System (ADS)

Rixen, Daniel J.; van der Valk, Paul L. C.

2013-12-01

In the present paper we outline the basic theory of assembling substructures for which the dynamics are described as Impulse Response Functions. The assembly procedure computes the time response of a system by evaluating per substructure the convolution product between the Impulse Response Functions and the applied forces, including the interface forces that are computed to satisfy the interface compatibility. We call this approach the Impulse Based Substructuring method since it transposes to the time domain the Frequency Based Substructuring approach. In the Impulse Based Substructuring technique the Impulse Response Functions of the substructures can be gathered either from experimental tests using a hammer impact or from time-integration of numerical submodels. In this paper the implementation of the method is outlined for the case when the impulse responses of the substructures are computed numerically. A simple bar example is shown in order to illustrate the concept. The Impulse Based Substructuring allows fast evaluation of impact response of a structure when the impulse response of its components is known. It can thus be used to efficiently optimize designs of consumer products by including impact behavior at the early stage of the design, but also for performing substructured simulations of complex structures such as offshore wind turbines.

Prognostic factors in multiple myeloma: selection using Cox's proportional hazard model.

PubMed

Pasqualetti, P; Collacciani, A; Maccarone, C; Casale, R

1996-01-01

The pretreatment characteristics of 210 patients with multiple myeloma, observed between 1980 and 1994, were evaluated as potential prognostic factors for survival. Multivariate analysis according to Cox's proportional hazard model identified in the 160 dead patients with myeloma, among 26 different single prognostic variables, the following factors in order of importance: beta 2-microglobulin; bone marrow plasma cell percentage, hemoglobinemia, degree of lytic bone lesions, serum creatinine, and serum albumin. By analysis of these variables a prognostic index (PI), that considers the regression coefficients derived by Cox's model of all significant factors, was obtained. Using this it was possible to separate the whole patient group into three stages: stage I (PI < 1.485, 67 patients), stage II (PI: 1.485-2.090, 76 patients), and stage III (PI > 2.090, 67 patients), with a median survivals of 68, 36 and 13 months (P < 0.0001), respectively. Also the responses to therapy (P < 0.0001) and the survival curves (P < 0.00001) presented significant differences among the three subgroups. Knowledge of these factors could be of value in predicting prognosis and in planning therapy in patients with multiple myeloma.

Functional and hypoglycemic properties of nopal cladodes (O. ficus-indica) at different maturity stages using in vitro and in vivo tests.

PubMed

Nuñez-López, María A; Paredes-López, Octavio; Reynoso-Camacho, Rosalía

2013-11-20

Nopal (Opuntia ficus-indica) cladodes are recommended for their therapeutic properties; their maturity stage may affect their biological properties. Cladodes of three maturity stages, from the same crop and location, were dehydrated and evaluated for some of their physicochemical and nutritional characteristics and antidiabetic properties. The flours of small and medium cladodes (SCF and MCF, respectively) had higher contents of dietary fiber, water absorption, swelling, and viscosity compared to those of the large cladode flour (LCF). Streptozotocin-induced diabetic rats, treated with MCF and SCF (doses of 50 mg/kg body weight), showed reduction of postprandial blood glucose on 46.0 and 23.6%, respectively (p < 0.05), in relation to the control; and LCF had no significant effect. In vitro, glucose diffusion tests showed similar ranking by the two former samples, whereas the latter was close to the control. Cladode maturity stages showed different fiber content and produced suspensions with differences in viscosity, which may affect in vitro and in vivo glucose responses.

In vitro and in vivo evaluation of 28DAP010, a novel diamidine for treatment of second-stage African sleeping sickness.

PubMed

Wenzler, Tanja; Yang, Sihyung; Patrick, Donald A; Braissant, Olivier; Ismail, Mohamed A; Tidwell, Richard R; Boykin, David W; Wang, Michael Zhuo; Brun, Reto

2014-08-01

African sleeping sickness is a neglected tropical disease transmitted by tsetse flies. New and better drugs are still needed especially for its second stage, which is fatal if untreated. 28DAP010, a dipyridylbenzene analogue of DB829, is the second simple diamidine found to cure mice with central nervous system infections by a parenteral route of administration. 28DAP010 showed efficacy similar to that of DB829 in dose-response studies in mouse models of first- and second-stage African sleeping sickness. The in vitro time to kill, determined by microcalorimetry, and the parasite clearance time in mice were shorter for 28DAP010 than for DB829. No cross-resistance was observed between 28DAP010 and pentamidine on the tested Trypanosoma brucei gambiense isolates from melarsoprol-refractory patients. 28DAP010 is the second promising preclinical candidate among the diamidines for the treatment of second-stage African sleeping sickness. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Long Live Love. The implementation of a school-based sex-education program in the Netherlands

PubMed Central

Schutte, Lisette; Meertens, Ree M.; Mevissen, Fraukje E. F.; Schaalma, Herman; Meijer, Suzanne; Kok, Gerjo

2014-01-01

Implementation of health education programs is often inadequately considered or not considered at all in planning, developing and evaluating interventions. With the focus being predominantly on the adoption stage, little is known about the factors influencing the implementation and continuation stages of the diffusion process. This study contributes to the understanding of factors that promote or impede each stage of the diffusion process in the school setting using the sex education program Long Live Love (LLL) as an example. A survey integrating different diffusion-related concepts was completed by 130 teachers. Results showed that teacher curriculum-related beliefs were associated with all stages in the diffusion process. Although adoption of LLL was predominantly related to teacher curriculum-related beliefs, implementation completeness and fidelity and continued use of LLL were also enhanced by contextual factors, namely teacher training and interactive context variables (school policy, governing body support and student response), respectively. The results of this study can be used to optimize the adoption, implementation and continuation of school-based (sexual) health promotion programs. PMID:24817522

Typhoid Vaccine in Testing Response to Immune Stress in Patients With Stage I-IIIA Breast Cancer

ClinicalTrials.gov

2017-12-18

Cognitive Side Effects of Cancer Therapy; Depression; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

Apoptosis of non-parasitised red blood cells in Plasmodium yoelii malaria

PubMed Central

Totino, Paulo Renato Rivas; Pinna, Raquel Alves; De-Oliveira, Ana Cecilia Amado Xavier; Banic, Dalma Maria; Daniel-Ribeiro, Cláudio Tadeu; Ferreira-da-Cruz, Maria de Fátima

2013-01-01

Recently, while studying erythrocytic apoptosis during Plasmodium yoelii infection, we observed an increase in the levels of non-parasitised red blood cell (nRBC) apoptosis, which could be related to malarial anaemia. Therefore, in the present study, we attempted to investigate whether nRBC apoptosis is associated with the peripheral RBC count, parasite load or immune response. To this end, BALB/c mice were infected with P. yoelii 17XL and nRBC apoptosis, number of peripheral RBCs, parasitaemia and plasmatic levels of cytokines, nitric oxide and anti-RBC antibodies were evaluated at the early and late stages of anaemia. The apoptosis of nRBCs increased at the late stage and was associated with parasitaemia, but not with the intensity of the immune response. The increased percentage of nRBC apoptosis that was observed when anaemia was accentuated was not related to a reduction in peripheral RBCs. We conclude that nRBC apoptosis in P. yoelii malaria appears to be induced in response to a high parasite load. Further studies on malaria models in which acute anaemia develops during low parasitaemia are needed to identify the potential pathogenic role of nRBC apoptosis. PMID:24037189

Volatiles released from Vaccinium corymbosum were attractive to Aegorhinus superciliosus (Coleoptera: Curculionidae) in an olfactometric bioassay.

PubMed

Parra, Leonardo; Mutis, Ana; Ceballos, Ricardo; Lizama, Marcelo; Pardo, Fernando; Perich, Fernando; Quiroz, Andrés

2009-06-01

The objective of this study was to evaluate the role of host volatiles in the relationship between a blueberry plant Vaccinium corymbosum L. and the raspberry weevil Aegorhinus superciliosus (Guérin) (Coleoptera: Curculionidae), the principal pest of blueberry in the south of Chile. Volatiles from the aerial part of different phenological stages of the host were collected on Porapak Q and analyzed by coupled gas chromatography-mass spectrometry (GC-MS). Several chemical groups were identified including green leaf volatiles, aromatic compounds, and terpenes. The olfactometric responses of A. superciliosus toward different odor sources were studied in a four-arm olfactometer. Blueberry shoots at the phenological stages of fruit set, and blue-pink fruit color elicited the greatest behavioral responses from weevils. Five compounds (2-nonanone, eucalyptol, R- and S-limonene, and 4-ethyl benzaldehyde) elicited an attractant behavioral response from A. superciliosus. The results suggest the host location behavior of A. superciliosus could be mediated by volatiles derived from V. corymbosum. This work has identified a number of compounds with which it is possible to develop a lure for the principal pest of blueberry in southern Chile.

Variation in the suppression or enhancement of responses related to drug habits as a function of stimulus classes and competing response categories.

PubMed

Haertzen, C A; Ross, F E

1980-08-01

Male prisoners who were opiate addicts (N = 47) were given three Process Association Tests of Addiction containing stimuli which evoked responses characteristic of three levels of drug habits: beginning and ending stage of addiction, intermediate stage of addiction, and an advanced level of addiction. Each test required subjects to associate 278 word stimuli with one of five options which were randomly selected from among 20 options covering the stages of addiction, steps in drug taking, and drug effects. The purpose of the study was to determine whether responses to particular options suppressed or enhanced responses to other options. A strong interaction was found between the classes of stimuli and the response options which produced suppression or enhancement. This interaction made it possible to develop a suppression scale to measure the effect of each class of stimulus. Popular responses most frequently suppressed responses of other options. Thus, when the stimuli were clean, responses of "to be clean" and "to live a normal life," which are sensitive indicators of the beginning or ending stages of addiction , suppressed responses of other stages. The response of "to be high," a prime indicator of an intermediate habit, suppressed responses of other options when the stimuli were drug names. Responses of "to be hooked" and "to fix," which are specific indicators of a strong habit, and "to be high," which is a nonspecific indicator of a strong habit, suppressed responses of many other options. In the development of new association tests the analysis of suppression could provide a basis for selectively varying option groupings in order to increase or decrease the frequently of certain responses.

Monitoring and evaluation of disaster response efforts undertaken by local health departments: a rapid realist review.

PubMed

Gossip, Kate; Gouda, Hebe; Lee, Yong Yi; Firth, Sonja; Bermejo, Raoul; Zeck, Willibald; Jimenez Soto, Eliana

2017-06-29

Local health departments are often at the forefront of a disaster response, attending to the immediate trauma inflicted by the disaster and also the long term health consequences. As the frequency and severity of disasters are projected to rise, monitoring and evaluation (M&E) efforts are critical to help local health departments consolidate past experiences and improve future response efforts. Local health departments often conduct M&E work post disaster, however, many of these efforts fail to improve response procedures. We undertook a rapid realist review (RRR) to examine why M&E efforts undertaken by local health departments do not always result in improved disaster response efforts. We aimed to complement existing frameworks by focusing on the most basic and pragmatic steps of a M&E cycle targeted towards continuous system improvements. For these purposes, we developed a theoretical framework that draws on the quality improvement literature to 'frame' the steps in the M&E cycle. This framework encompassed a M&E cycle involving three stages (i.e., document and assess, disseminate and implement) that must be sequentially completed to learn from past experiences and improve future disaster response efforts. We used this framework to guide our examination of the literature and to identify any context-mechanism-outcome (CMO) configurations which describe how M&E may be constrained or enabled at each stage of the M&E cycle. This RRR found a number of explanatory CMO configurations that provide valuable insights into some of the considerations that should be made when using M&E to improve future disaster response efforts. Firstly, to support the accurate documentation and assessment of a disaster response, local health departments should consider how they can: establish a culture of learning within health departments; use embedded training methods; or facilitate external partnerships. Secondly, to enhance the widespread dissemination of lessons learned and facilitate inter-agency learning, evaluation reports should use standardised formats and terminology. Lastly, to increase commitment to improvement processes, local health department leaders should possess positive leadership attributes and encourage shared decision making. This study is among the first to conduct a synthesis of the CMO configurations which facilitate or hinder M&E efforts aimed at improving future disaster responses. It makes a significant contribution to the disaster literature and provides an evidence base that can be used to provide pragmatic guidance for improving M&E efforts of local health departments. PROSPERO 2015: CRD42015023526 .

An Experimental Characterization of Tip Leakage Flows and Corresponding Effects on Multistage Compressor Performance

NASA Astrophysics Data System (ADS)

Berdanier, Reid Adam

The effect of rotor tip clearances in turbomachinery applications has been a primary research interest for nearly 80 years. Over that time, studies have shown increased tip clearance in axial flow compressors typically has a detrimental effect on overall pressure rise capability, isentropic efficiency, and stall margin. With modern engine designs trending toward decreased core sizes to increase propulsive efficiency (by increasing bypass ratio) or additional compression stages to increase thermal efficiency by increasing the overall pressure ratio, blade heights in the rear stages of the high pressure compressor are expected to decrease. These rear stages typically feature smaller blade aspect ratios, for which endwall flows are more important, and the rotor tip clearance height represents a larger fraction of blade span. As a result, data sets collected with large relative rotor tip clearance heights are necessary to facilitate these future small core design goals. This research seeks to characterize rotor tip leakage flows for three tip clearance heights in the Purdue three-stage axial compressor facility (1.5%, 3.0%, and 4.0% as a percentage of overall annulus height). The multistage environment of this compressor provides the unique opportunity to examine tip leakage flow effects due to stage matching, stator-rotor interactions, and rotor-rotor interactions. The important tip leakage flow effects which develop as a result of these interactions are absent for previous studies which have been conducted using single-stage machines or isolated rotors. A series of compressor performance maps comprise points at four corrected speeds for each of the three rotor tip clearance heights. Steady total pressure and total temperature measurements highlight the effects of tip leakage flows on radial profiles and wake shapes throughout the compressor. These data also evaluate tip clearance effects on efficiency, stall margin, and peak pressure rise capability. An emphasis of measurements collected at these part-speed and off-design conditions provides a unique data set for calibrating computational models and predictive algorithms. Further investigations with detailed steady total pressure traverses provide additional insight to tip leakage flow effects on stator performance. A series of data on the 100% corrected speedline further characterize the tip leakage flow using time-resolved measurements from a combination of instrumentation techniques. An array of high-frequency-response piezoresistive pressure transducers installed over the rotors allows quantification of tip leakage flow trajectories. These data, along with measurements from a fast-response total pressure probe downstream of the rotors, evaluate the development of tip leakage flows and assess the corresponding effects of upstream stator wakes. Finally, thermal anemometry measurements collected using the single slanted hot-wire technique evaluate three-dimensional velocity components throughout the compressor. These data facilitate calculations of several flow metrics, including a blockage parameter and phase-locked streamwise vorticity.

Evolving role of FDG-PET/CT in prognostic evaluation of resectable gastric cancer

PubMed Central

De Raffele, Emilio; Mirarchi, Mariateresa; Cuicchi, Dajana; Lecce, Ferdinando; Cola, Bruno

2017-01-01

Gastric cancer (GC) remains a leading cause of cancer death worldwide. Radical gastrectomy is the only potentially curative treatment, and perioperative adjuvant therapies may improve the prognosis after curative resection. Prognosis largely depends on the tumour stage and histology, but the host systemic inflammatory response (SIR) to GC may contribute as well, as has been determined for other malignancies. In GC patients, the potential utility of positron emission tomography/computed tomography (PET/CT) with the imaging radiopharmaceutical 18F-fluorodeoxyglucose (FDG) is still debated, due to its lower sensitivity in diagnosing and staging GC compared to other imaging modalities. There is, however, growing evidence that FDG uptake in the primary tumour and regional lymph nodes may be efficient for predicting prognosis of resected patients and for monitoring tumour response to perioperative treatments, having prognostic value in that it can change therapeutic strategies. Moreover, FDG uptake in bone marrow seems to be significantly associated with SIR to GC and to represent an efficient prognostic factor after curative surgery. In conclusion, PET/CT technology is efficient in GC patients, since it is useful to integrate other imaging modalities in staging tumours and may have prognostic value that can change therapeutic strategies. With ongoing improvements, PET/CT imaging may gain further importance in the management of GC patients. PMID:29097864

Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells

PubMed Central

Das, Rina; Hammamieh, Rasha; Neill, Roger; Ludwig, George V; Eker, Steven; Lincoln, Patrick; Ramamoorthy, Preveen; Dhokalia, Apsara; Mani, Sachin; Mendis, Chanaka; Cummings, Christiano; Kearney, Brian; Royaee, Atabak; Huang, Xiao-Zhe; Paranavitana, Chrysanthi; Smith, Leonard; Peel, Sheila; Kanesa-Thasan, Niranjan; Hoover, David; Lindler, Luther E; Yang, David; Henchal, Erik; Jett, Marti

2008-01-01

Background Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs. Methods To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays. Results We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin. Conclusion Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents. PMID:18667072

Relationship between the Increased Haemostatic Properties of Blood Platelets and Oxidative Stress Level in Multiple Sclerosis Patients with the Secondary Progressive Stage.

PubMed

Morel, Agnieszka; Bijak, Michał; Miller, Elżbieta; Rywaniak, Joanna; Miller, Sergiusz; Saluk, Joanna

2015-01-01

Multiple sclerosis (MS) is the autoimmune disease of the central nervous system with complex pathogenesis, different clinical courses and recurrent neurological relapses and/or progression. Despite various scientific papers that focused on early stage of MS, our study targets selective group of late stage secondary progressive MS patients. The presented work is concerned with the reactivity of blood platelets in primary hemostasis in SP MS patients. 50 SP MS patients and 50 healthy volunteers (never diagnosed with MS or other chronic diseases) were examined to evaluate the biological activity of blood platelets (adhesion, aggregation), especially their response to the most important physiological agonists (thrombin, ADP, and collagen) and the effect of oxidative stress on platelet activity. We found that the blood platelets from SP MS patients were significantly more sensitive to all used agonists in comparison with control group. Moreover, the platelet hemostatic function was advanced in patients suffering from SP MS and positively correlated with increased production of O2 (-∙) in these cells, as well as with Expanded Disability Status Scale. We postulate that the increased oxidative stress in blood platelets in SP MS may be primarily responsible for the altered haemostatic properties of blood platelets.

Relationship between the Increased Haemostatic Properties of Blood Platelets and Oxidative Stress Level in Multiple Sclerosis Patients with the Secondary Progressive Stage

PubMed Central

Bijak, Michał; Miller, Elżbieta; Miller, Sergiusz

2015-01-01

Multiple sclerosis (MS) is the autoimmune disease of the central nervous system with complex pathogenesis, different clinical courses and recurrent neurological relapses and/or progression. Despite various scientific papers that focused on early stage of MS, our study targets selective group of late stage secondary progressive MS patients. The presented work is concerned with the reactivity of blood platelets in primary hemostasis in SP MS patients. 50 SP MS patients and 50 healthy volunteers (never diagnosed with MS or other chronic diseases) were examined to evaluate the biological activity of blood platelets (adhesion, aggregation), especially their response to the most important physiological agonists (thrombin, ADP, and collagen) and the effect of oxidative stress on platelet activity. We found that the blood platelets from SP MS patients were significantly more sensitive to all used agonists in comparison with control group. Moreover, the platelet hemostatic function was advanced in patients suffering from SP MS and positively correlated with increased production of O2 −∙ in these cells, as well as with Expanded Disability Status Scale. We postulate that the increased oxidative stress in blood platelets in SP MS may be primarily responsible for the altered haemostatic properties of blood platelets. PMID:26064417

Hepcidin, Cathelicidin-1 and IL-8 as immunological markers of responsiveness in early developmental stages of rainbow trout.

PubMed

Santana, Paula A; Guzmán, Fanny; Forero, Juan C; Luna, Omar F; Mercado, Luis

2016-09-01

During the early developmental stage of salmonids, high mortality occurs largely as a result of pathogens. These cause low immune competence in fry, producing disease, decreasing production and finally leading to economic losses. Therefore, the aim of this study was to characterise the developmental stages in which rainbow trout acquires immune response capability when challenged with LPS from Pseudomona aeruginosa for 8 h, studying the hepcidin, cathelicidin-1 and IL-8. Total RNA was extracted from fry at 34, 42, 56 and 66 days post hatching (dph). Hepcidin and cathelicidin-1 transcripts were detected only at days 34 and 42, whereas the IL-8 transcript was detected from day 34 to day 66. To analyse the protein expression in the fry, polyclonal anti-peptide antibodies were generated in rabbit. These three immune sera demonstrated the ability to recognise the whole molecule in biological samples. Immunofluorescence showed that skin, gills and intestine mainly responded to the LPS challenge, indicating that these portals of pathogen entry are capturing LPS. This study constitutes a valuable approach, since it has the potential to identify molecules with biological activity that can be used to evaluate the status of fry in culture. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of ionizing radiation on embryos of the tardigrade Milnesium cf. tardigradum at different stages of development.

PubMed

Beltrán-Pardo, Eliana; Jönsson, K Ingemar; Wojcik, Andrzej; Haghdoost, Siamak; Harms-Ringdahl, Mats; Bermúdez-Cruz, Rosa M; Bernal Villegas, Jaime E

2013-01-01

Tardigrades represent one of the most desiccation and radiation tolerant animals on Earth, and several studies have documented their tolerance in the adult stage. Studies on tolerance during embryological stages are rare, but differential effects of desiccation and freezing on different developmental stages have been reported, as well as dose-dependent effect of gamma irradiation on tardigrade embryos. Here, we report a study evaluating the tolerance of eggs from the eutardigrade Milnesium cf. tardigradum to three doses of gamma radiation (50, 200 and 500 Gy) at the early, middle, and late stage of development. We found that embryos of the middle and late developmental stages were tolerant to all doses, while eggs in the early developmental stage were tolerant only to a dose of 50 Gy, and showed a declining survival with higher dose. We also observed a delay in development of irradiated eggs, suggesting that periods of DNA repair might have taken place after irradiation induced damage. The delay was independent of dose for eggs irradiated in the middle and late stage, possibly indicating a fixed developmental schedule for repair after induced damage. These results show that the tolerance to radiation in tardigrade eggs changes in the course of their development. The mechanisms behind this pattern are unknown, but may relate to changes in mitotic activities over the embryogenesis and/or to activation of response mechanisms to damaged DNA in the course of development.

Effects of Ionizing Radiation on Embryos of the Tardigrade Milnesium cf. tardigradum at Different Stages of Development

PubMed Central

Beltrán-Pardo, Eliana; Jönsson, K. Ingemar; Wojcik, Andrzej; Haghdoost, Siamak; Harms-Ringdahl, Mats; Bermúdez-Cruz, Rosa M.; Bernal Villegas, Jaime E.

2013-01-01

Tardigrades represent one of the most desiccation and radiation tolerant animals on Earth, and several studies have documented their tolerance in the adult stage. Studies on tolerance during embryological stages are rare, but differential effects of desiccation and freezing on different developmental stages have been reported, as well as dose-dependent effect of gamma irradiation on tardigrade embryos. Here, we report a study evaluating the tolerance of eggs from the eutardigrade Milnesium cf. tardigradum to three doses of gamma radiation (50, 200 and 500 Gy) at the early, middle, and late stage of development. We found that embryos of the middle and late developmental stages were tolerant to all doses, while eggs in the early developmental stage were tolerant only to a dose of 50 Gy, and showed a declining survival with higher dose. We also observed a delay in development of irradiated eggs, suggesting that periods of DNA repair might have taken place after irradiation induced damage. The delay was independent of dose for eggs irradiated in the middle and late stage, possibly indicating a fixed developmental schedule for repair after induced damage. These results show that the tolerance to radiation in tardigrade eggs changes in the course of their development. The mechanisms behind this pattern are unknown, but may relate to changes in mitotic activities over the embryogenesis and/or to activation of response mechanisms to damaged DNA in the course of development. PMID:24039737

Evaluation of multifunctional imaging parameters in gastro-oesophageal cancer using F-18-FDG-PET/CT with integrated perfusion CT.

PubMed

Sah, Bert-Ram; Leissing, Christian A; Delso, Gaspar; Ter Voert, Edwin E; Krieg, Stefan; Leibl, Sebastian; Schneider, Paul M; Reiner, Cäcilia S; Hüllner, Martin W; Veit-Haibach, Patrick

2018-05-10

Positron emission tomography (PET) / computed tomography (CT) is among the most frequently used imaging modalities for initial staging of gastro-oesophageal (GE) cancer, whereas CT-perfusion (CTP) provides different multiparametric information. This proof of concept study compares CTP- and PET-parameters in patients with GE cancer to evaluate correlations and a possible prognostic value of a combined PET/CTP imaging procedure. A total of 31 patients with F-18-FDG-PET/CT and CTP studies were prospectively analysed. Patients had adenocarcinoma (n = 22) and oesophageal squamous cell carcinoma (SCC, n = 9). Imaging was performed before start of treatment. CTP parameters [blood flow (BF), blood volume (BV), mean transit time (MTT)] and metabolic parameters [(maximum and mean standardised uptake values and standard deviation (SUVmax, SUVmean, SUVsd), metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG)], as well as flow metabolic product [FMP (BF × SUVmax)] were determined and their relationship was compared. Additionally their association to clinical parameters (differentiation grading, staging, HER2-status, follow-up status) and to histopathological regression (post-neoadjuvant regression grading) was evaluated. Correlation between parameters of both modalities was significant between MTT and MTV (r = 0.375, p = 0.038); no other significant correlation was found. Patients with complete histopathological regression showed significantly lower BF and BV than patients with nearly complete or partial response. TLG and regression grading showed significant correlation with staging. All other quantitative parameters for CTP and PET data did not correlate significantly with histopathological regression grading, differentiation or staging. The combination of PET and CTP parameters (FMP) showed no significant prognostic value. Significant correlations were only found between MTT and MTV, which indicates a possible perfusional/metabolic coupling. Therefore, pre-therapeutic CTP and PET- parameters provide complementary information about the pre-therapeutic tumour status and are not interchangeable. Only CTP parameters might be able to predict complete histopathological regression. On the other hand, only PET parameters are correlated with staging.

Assessment of gene expression profiles in peripheral occlusive arterial disease.

PubMed

Bubenek, Serban; Nastase, Anca; Niculescu, Ana Maria; Baila, Sorin; Herlea, Vlad; Lazar, Vadimir; Paslaru, Liliana; Botezatu, Anca; Tomescu, Dana; Popescu, Irinel; Dima, Simona

2012-01-01

Molecular events responsible for the onset and progression of peripheral occlusive arterial disease (POAD) are incompletely understood. Gene expression profiling may point out relevant features of the disease. Tissue samples were collected as operatory waste from a total of 36 patients with (n = 18) and without (n = 18) POAD. The tissues were histologically evaluated, and the patients with POAD were classified according to Leriche-Fontaine (LF) classification: 11% with stage IIB, 22% with stage III, and 67% with stage IV. Total RNA was isolated from all samples and hybridized onto Agilent 4×44K Oligo microarray slides. The bioinformatic analysis identified genes differentially expressed between control and pathologic tissues. Ten genes with a fold change ≥ 2 (1 with a fold change ≥ 1.8) were selected for quantitative polymerase chain reaction validation (GPC3, CFD, GDF10, ITLN1, TSPAN8, MMP28, NNMT, SERPINA5, LUM, and FDXR). C-reactive protein (CRP) was assessed with a specific assay, while nicotinamide N-methyltransferase (NNMT) was evaluated in the patient serum by enzyme-linked immunosorbent assay. A multiple regression analysis showed that the level of CRP in the serum is correlated with the POAD LF stages (r(2) = 0.22, P = 0.046) and that serum NNMT is higher in IV LF POAD patients (P = 0.005). The mRNA gene expression of LUM is correlated with the LF stage (r(2) = 0.45, P = 0.009), and the mRNA level of ITLN1 is correlated with the ankle-brachial index (r(2) = 0.42, P = 0.008). Our analysis shows that NNMT, ITLN1, LUM, CFD, and TSPAN8 in combination with other known markers, such as CRP, could be evaluated as a panel of biomarkers of POAD. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Surgical treatment analysis of idiopathic esophageal achalasia.

PubMed

Aquino, José Luis Braga de; Said, Marcelo Manzano; Pereira, Douglas Rizzanti; Amaral, Paula Casals do; Lima, Juliana Carolina Alves; Leandro-Merhi, Vânia Aparecida

2015-01-01

Idiopathic esophageal achalasia is an inflammatory disease of unknown origin, characterized by aperistalsis of the esophageal body and failure of the lower esophageal sphincter in response to swallowing, with consequent dysphagia. To demonstrate the results of surgical therapy in these patients, evaluating the occurred local and systemic complications. Were studied retrospectively 32 patients, 22 of whom presented non-advanced stage of the disease (Stage I/II) and 10 with advanced disease (Stage III/IV). All of them had the clinical conditions to be submitted to surgery. The diagnoses were done by clinical, endoscopic, cardiological, radiological and esophageal manometry analysis. Pre-surgical evaluation was done with a questionnaire based on the most predisposing factors in the development of the disease and the surgical indication was based on the stage of the disease. The patients with non-advanced stages were submitted to cardiomyotomy with fundoplication, wherein in the post-surgical early assessment, only one (4,4%) presented pulmonary infection, but had a good outcome. In patients with advanced disease, seven were submitted to esophageal mucosectomy preserving the muscular layer, wherein one patient (14,2%) presented dehiscence of gastric cervical esophagus anastomosis as well as pulmonary infection; all of these complications were resolved with proper specific treatment; the other three patients with advanced stage were submitted to transmediastinal esophagectomy; two of them presented hydropneumothorax with good evolution, and one of them also presented fistula of the cervical esophagogastric anastomosis, but with spontaneous healing after conservative treatment and nutritional support. The two patients with fistula of the cervical anastomosis progressed to stenosis, with good results after endoscopic dilations. In the medium and long term assessment done in 23 patients, all of them reported improvement in life quality, with return to swallowing. The strategy proposed for the surgical treatment of idiopathic esophageal achalasia according to the stages of the disease was of great value, due to post-surgical low morbidity complications and proper recovery of swallowing.

Balancing risk and benefit in early-stage classical Hodgkin lymphoma.

PubMed

Bröckelmann, Paul J; Sasse, Stephanie; Engert, Andreas

2018-04-12

With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (2×ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT). In patients with early-stage unfavorable disease (ie, limited stage with RFs), 4 cycles of chemotherapy are usually consolidated with 30-Gy IF/ISRT. Compared with 4×ABVD, 2 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (2×BEACOPP escalated ) followed by 2×ABVD improved 5-year progression-free survival (PFS), with similar 5-year overall survival. Recently, treatment strategies based on [ 18 F]fluorodeoxyglucose positron emission tomography (PET) response were evaluated. In early-stage unfavorable HL, a majority of patients achieved a negative interim PET after 2×ABVD and an excellent outcome after 4×ABVD, whereas in those with a positive interim PET, 2×BEACOPP escalated improved 5-year PFS. Furthermore, a PET-guided RT approach was evaluated to decrease long-term toxicity. Although both the RAPID and H10 trials reported poorer disease control without RT, PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity (eg, because of sex, age, or disease localization). Implementation of drugs such as the anti-CD30 antibody-drug conjugate brentuximab vedotin or the anti-programmed death 1 antibodies nivolumab or pembrolizumab might allow further reduction of overall mortality and improve quality of life in affected patients. © 2018 by The American Society of Hematology.

The impact of early psychosocial intervention on self-efficacy of care recipient/carer dyads living with early stage dementia - A mixed methods study.

PubMed

Stockwell-Smith, G; Moyle, W; Kellett, U

2018-05-13

To evaluate the effect of a targeted community-based psychosocial intervention on self-efficacy outcomes for care recipient/carer dyads living with early-stage dementia. There is increasing interest in the role of self-efficacy and self-management structures in determining positive outcomes for people with dementia. The assumption is that care recipient/carer dyads who receive early support to identify and adjust to dementia related changes will cope better in the long-term. An explanatory sequential mixed-method design was employed. Primarily quantitative with qualitative data providing a supportive secondary role to expand on and illuminate the quantitative findings. 88 dyads were recruited and allocated on a regional basis to an intervention or control group. Intervention group dyads received the Early Diagnosis Dyadic Intervention. Control group dyads received two information manuals. Quantitative data were collected at three time-points. Qualitative data were collected via evaluation questionnaires and semi-structured interviews. Intervention structure, content and delivery were acceptable to the dyads but few quantitative self-efficacy findings reached statistical significance. Improvements in self-efficacy were evident in the post-intervention evaluation qualitative responses where dyads expressed greater confidence in identifying and accessing community support. There is an urgent need for effective psychosocial interventions to help reduce the impact of dementia symptoms on patients, carers and society. This study makes an important contribution to our understanding of the capacity of psychosocial interventions to improve self-efficacy outcomes for care recipient/carer dyads with early-stage dementia while also illustrating the challenges associated with measuring self-efficacy in the early stages of the condition. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Evaluation of an Internet, Stage-Based Physical Activity Intervention.

ERIC Educational Resources Information Center

Hager, Ronald L.; Hardy, Aaron; Aldana, Steven G.; George, James D.

2002-01-01

Evaluated the impact of online, stage-based materials on exercise behavior and stage of readiness to change. College faculty participated in stage-based, action-message, or control groups. Occupational and leisure activity, 7-day physical activity, exercise self-efficacy, and stage of readiness to change were assessed at baseline and 6 weeks.…

Evaluation of an intelligent wheelchair system for older adults with cognitive impairments

PubMed Central

2013-01-01

Background Older adults are the most prevalent wheelchair users in Canada. Yet, cognitive impairments may prevent an older adult from being allowed to use a powered wheelchair due to safety and usability concerns. To address this issue, an add-on Intelligent Wheelchair System (IWS) was developed to help older adults with cognitive impairments drive a powered wheelchair safely and effectively. When attached to a powered wheelchair, the IWS adds a vision-based anti-collision feature that prevents the wheelchair from hitting obstacles and a navigation assistance feature that plays audio prompts to help users manoeuvre around obstacles. Methods A two stage evaluation was conducted to test the efficacy of the IWS. Stage One: Environment of Use – the IWS’s anti-collision and navigation features were evaluated against objects found in a long-term care facility. Six different collision scenarios (wall, walker, cane, no object, moving and stationary person) and three different navigation scenarios (object on left, object on right, and no object) were performed. Signal detection theory was used to categorize the response of the system in each scenario. Stage Two: User Trials – single-subject research design was used to evaluate the impact of the IWS on older adults with cognitive impairment. Participants were asked to drive a powered wheelchair through a structured obstacle course in two phases: 1) with the IWS and 2) without the IWS. Measurements of safety and usability were taken and compared between the two phases. Visual analysis and phase averages were used to analyze the single-subject data. Results Stage One: The IWS performed correctly for all environmental anti-collision and navigation scenarios. Stage Two: Two participants completed the trials. The IWS was able to limit the number of collisions that occurred with a powered wheelchair and lower the perceived workload for driving a powered wheelchair. However, the objective performance (time to complete course) of users navigating their environment did not improve with the IWS. Conclusions This study shows the efficacy of the IWS in performing with a potential environment of use, and benefiting members of its desired user population to increase safety and lower perceived demands of powered wheelchair driving. PMID:23924489

Bringing interdisciplinary and multicultural team building to health care education: the downstate team-building initiative.

PubMed

Hope, Joanie Mayer; Lugassy, Daniel; Meyer, Rina; Jeanty, Freida; Myers, Stephanie; Jones, Sadie; Bradley, Joann; Mitchell, Rena; Cramer, Eva

2005-01-01

To evaluate the impact of the Downstate Team-Building Initiative (DTBI), a model multicultural and interdisciplinary health care team-building program for health professions students. A total of 65 students representing seven health disciplines participated in DTBI's first three years (one cohort per year since implementation). During the 18-session curriculum, students self-evaluated their group's progress through Tuckman's four team-development stages (FORMING, STORMING, NORMING, PERFORMING) on an 11-point scale. Students completed matched pre- and postintervention program evaluations assessing five variables: interdisciplinary understanding, interdisciplinary attitudes, teamwork skills, multicultural skills, and team atmosphere. After participation, students completed narrative follow-up questionnaires investigating impact one and two years after program completion. Each year's team development curve followed a similar logarithmic trajectory. Cohort 1 remained in team development stage 3 (NORMING) while Cohorts 2 and 3 advanced into the final stage-PERFORMING. A total of 34 matched pre- and postintervention evaluations showed significant change in all major variables: Team atmosphere and group teamwork skills improved most (48% and 44%, respectively). Interdisciplinary understanding improved 42%. Individual multicultural skills (defined by ability to address racism, homophobia, and sexism) started at the highest baseline and improved the least (13%). Group multicultural skills improved 36%. Of 23 responses to the follow-up surveys, 22 (96%) stated DTBI was a meaningful educational experience applicable to their current clinical surroundings. DTBI successfully united students across health discipline, ethnicity, socioeconomic class, gender, and sexual orientation into functioning teams. The model represents an effective approach to teaching health care team building and demonstrates benefits in both preclinical and clinical years of training.

Persuasion stage in adoption theory: a cognitive response-cognitive structure assessment of source credibility and tax-incentive effects on consumer decision making for residential solar systems. [Suburbs of Baltimore

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

Batory, S.S.

1981-01-01

The research objective was to learn more about the consumer's acceptance or rejection process toward a major residential energy innovation, a solar-generated water heating system. An experiment was conducted that evaluated one aspect of solar's commercialization, the persuasion stage in new-product-adoption decision making. A test of source credibility and monetary incentive effects on the consumer's decision-making processes was carried out. The experiment contained two message sources: the Department of Energy (a high credibility source) and a homebuilder (a moderate credibility source), and three levels of incentives, a tax credit equal to 40% of the solar unit purchase price, a 20%more » tax credit, and no tax credit. Subjects were randomly assigned to either a control group or one of six experimental treatments in a 2 x 3 fixed-effects factorial design. Subjects were 226 adult homeowners drawn from the suburbs of Baltimore, Maryland. The research postulated and tested a process of acceptance or rejection of innovations which was based on a cognitive-response/cognitive-structure paradigm of decision making. This process is called the persuasion stage by adoption theorists. Cognitive responses, beliefs, attitudes, and behavioral measures were the dependent variables. Consumers were shown to confront or debate incoming information by comparing it to their existing cognitive structure. This comparison process generated cognitive responses which led to changes in beliefs, attitudes, and behavior toward the innovation. The findings confirm that the federal government's intervention in the marketplace is having a favorable effect on the adoption decision process toward solar-generated water heating.« less

A Phase I Study of Unimolecular Pentavalent (Globo-H-GM2-sTn-TF-Tn) Immunization of Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer in First Remission.

PubMed

O'Cearbhaill, Roisin E; Ragupathi, Govind; Zhu, Jianglong; Wan, Qian; Mironov, Svetlana; Yang, Guangbin; Spassova, Maria K; Iasonos, Alexia; Kravetz, Sara; Ouerfelli, Ouathek; Spriggs, David R; Danishefsky, Samuel J; Sabbatini, Paul J

2016-04-22

We conducted a phase I study in ovarian cancer patients to evaluate the safety and immunogenicity of a synthetic unimolecular pentavalent carbohydrate vaccine (Globo-H, GM2, sTn, TF, and Tn) supported on a peptide backbone, conjugated to keyhole limpet haemocyanin (KLH), and mixed with immunological adjuvant QS-21. Twenty-four advanced-stage, poor-risk, first-remission ovarian cancer patients were enrolled from January 2011-Septermber 2013. Three dose levels were planned (25, 50, 100 mcg) with three cohorts of six patients each, with an additional 6-patient expansion cohort at the MTD. ELISA serologic IgM and IgG responses for each antigen was defined as positive response if antibody titers were ≥1:80 over the respective patient's pre-vaccination serum. The study would be considered positive if at least four of 12 patients treated at the MTD showed immune responses for at least three of the five antigens. Twenty-four patients (median age, 54 years [range, 36-68]) were included in the safety analysis. Histology was high-grade serous in 22 patients (92%); 18 had stage III and six stage IV disease. The vaccine was well-tolerated at all doses, with no DLTs. At the highest treated dose, IgG and/or IgM responses were recorded against ≥3 antigens in 9/12 patients (75%), ≥4 in 7/12 (58%), and 5 in 3/12 (25%). With a median follow-up of 19 months (range, 2-39), 20 patients (83%) recurred and six (25%) died. The unimolecular pentavalent vaccine construct was shown to be safe and immunogenic. Such a construct greatly simplifies regulatory requirements and manufacturing, facilitates scalability, and provides adaptability.

Efficacy of Doxycycline in the Treatment of Syphilis.

PubMed

Dai, Ting; Qu, Rui; Liu, Jinfen; Zhou, Pingyu; Wang, Qianqiu

2017-01-01

Doxycycline is an alternative antibiotic drug for the treatment of syphilis, but data on its efficacy, especially data on its efficacy against late latent syphilis, are limited. A retrospective study was conducted to evaluate the effectiveness of doxycycline for the treatment of patients with different stages of syphilis. Patients who received doxycycline treatment between June 2011 and June 2014 were involved. The serological response to doxycycline was defined as either a negative toluidine red unheated serum test (TRUST) result or a ≥4-fold decrease in titer at 12 months following the treatment. Univariate and multivariate logistic regression analyses were performed to identify factors associated with the serological response. During the study period, a total of 163 syphilis patients were treated with doxycycline, and 118 patients completed doxycycline treatment and the 12-month follow-up. Among the 118 patients, the serological response rate at 12 months was 100.0% (7/7) in patients with primary syphilis, 96.9% (62/64) in patients with secondary syphilis, 91.3% (21/23) in patients with early latent syphilis, and 79.2% (19/24) in patients with late latent syphilis. The total serological response rates were 92.4% (109/118) for preprotocol (PP) patients and 66.9% (109/163) for all intention-to-treat (ITT) patients. In multivariate analysis, patients who serologically responded at 12 months following treatment were positively associated with a higher baseline TRUST titer and an earlier syphilis stage than nonresponders. Our study showed excellent treatment outcomes in patients with different stages of syphilis. Our data, along with those from other reports, support the usage of doxycycline as a good alternative therapeutic option in the treatment of syphilis. Copyright © 2016 American Society for Microbiology.

A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube

PubMed Central

Herzog, Thomas J.; Monk, Bradley J.; Rose, Peter G.; Braly, Patricia; Hines, Jeffrey F.; Bell, Maria C.; Wenham, Robert M.; Secord, Angeles Alvarez; Roman, Lynda D.; Einstein, Mark H.; Drake, Richard D.; Childs, Barrett H.

2017-01-01

Objective To determine the safety and efficacy of the novel combination of docetaxel, oxaliplatin, and bevacizumab as first-line treatment of advanced cancer of the ovary, peritoneum or fallopian tube after initial debulking surgery. Methods Eligible patients (stage IB-IV) were treated with 6 cycles of oxaliplatin (85 mg/m2), docetaxel (75 mg/m2), and bevacizumab (15 mg/kg) every 3 weeks, followed by single-agent bevacizumab 15 mg/kg every 3 weeks to complete one year of therapy. The primary endpoint was 12-month progression-free survival (PFS). Results A total of 132 patients (80 with measurable disease at baseline; 52 with non-measurable, evaluable disease at baseline) enrolled and received study treatment. At diagnosis, 76.5% of patients had stage III disease and 20% had stage IV. 62.9% were optimally cytoreduced. The most common grade 3/4 adverse events were neutropenia (42.4%), leukopenia (13.6%), hypertension (8.3%), fatigue (6.1%), and nausea (6.1%). One patient (0.8%) had a fatal gastrointestinal perforation. The best overall confirmed response rate (complete response + partial response [measurable disease subgroup]) was 58.6% (95% CI 49%, 67%). CA-125 response rates for the measurable and non-measurable disease subgroups were 83.0% and 81.5%, respectively. The 12-month PFS rate for the measurable disease subgroup was 65.7% (95% CI 53.4%, 76.7%); median PFS was 16.3 (95% CI 12.6, 19.6) months. Median overall survival was 47.3 (95% CI 34.1, upper limit not applicable) months. Conclusions This novel treatment regimen may provide a promising therapeutic approach for women with ovarian, primary peritoneal, or fallopian tube carcinoma. No unanticipated safety concerns were identified. PMID:24476788

Object permanence development in infants with motor handicaps.

PubMed

Fetters, L

1981-03-01

This study was an investigation of the effects of a motor handicap on the development of object permanence in the young child. Motor abilities were evaluated for 12 infants aged 13 to 29 months. Based on this evaluation, the children were described as manipulators or nonmanipulators in reference to their upper extremity skills. Their stage of object permanence was assessed using traditional and nontraditional assessments. Heart rate and visual tracking were recorded during the nontraditional assessment. Heart rate did not significantly relate to visual fixation or search response. There was, however, a significant difference (p less than .02) between stage achievement with traditional testing and age-appropriate levels. There was no significant difference between the nontraditional assessment and the age-appropriate levels. In addition, there was no significant difference in the development of object permanence between infants described as manipulators and those described as nonmanipulators. The last two findings suggest that infants with motor handicaps may develop object permanence at the expected ages, according to a nontraditional assessment.

Materials Approach to Dissecting Surface Responses in the Attachment Stages of Biofouling Organisms

DTIC Science & Technology

2016-04-25

their settlement behavior in regards to the coating surfaces. 5) Multivariate statistical analysis was used to examine the effect (if any) of the...applied to glass rods and were deployed in the field to evaluate settlement preferences. Canonical Analysis of Principal Coordinates were applied to...the influence of coating surface properties on the patterns in settlement observed in the field in the extension of this work over the coming year

Transcriptome profiling and cataloging differential gene expression in floral buds of fertile and sterile lines of cotton (Gossypium hirsutum L.).

PubMed

Hamid, Rasmieh; Tomar, Rukam S; Marashi, Hassan; Shafaroudi, Saeid Malekzadeh; Golakiya, Balaji A; Mohsenpour, Motahhareh

2018-06-20

Cytoplasmic Male Sterility is maternally inherited trait in plants, characterized by failure to produce functional pollen during anther development. Anther development is modulated through the interaction of nuclear and mitochondrial genes. In the present study, differential gene expression of floral buds at the sporogenous stage (SS) and microsporocyte stage (MS) between CGMS and its fertile maintainer line of cotton plants was studied. A total of 320 significantly differentially expressed genes, including 20 down-regulated and 37 up-regulated in CGMS comparing with its maintainer line at the SS stage, as well as and 89 down-regulated and 4 up-regulated in CGMS compared to the fertile line at MS stage. Comparing the two stages in the same line, there were 6 down-regulated differentially expressed genes only induced in CGMS and 9 up-regulated differentially expressed gene only induced in its maintainer. GO analysis revealed essential genes responsible for pollen development, and cytoskeleton category show differential expression between the fertile and CGMS lines. Validation studies by qRT-PCR shows concordance with RNA-seq result. A set of novel SSRs identified in this study can be used in evaluating genetic relationships among cultivars, QTL mapping, and marker-assisted breeding. We reported aberrant expression of genes related to pollen exine formation, and synthesis of pectin lyase, myosine heavy chain, tubulin, actin-beta, heat shock protein and myeloblastosis (MYB) protein as targets for CMS in cotton. The results of this study contribute to basic information for future screening of genes and identification of molecular portraits responsible for CMS as well as to elucidate molecular mechanisms that lead to CMS in cotton. Copyright © 2018 Elsevier B.V. All rights reserved.

Efficacy and safety of nab-paclitaxel in patients with previously treated metastatic colorectal cancer: a phase II COLO-001 trial.

PubMed

Ducreux, Michel; Bennouna, Jaafar; Adenis, Antoine; Conroy, Thierry; Lièvre, Astrid; Portales, Fabienne; Jeanes, Julie; Li, Li; Romano, Alfredo

2017-01-01

This single-arm, phase II trial evaluated nab-paclitaxel monotherapy in pretreated patients with metastatic colorectal cancer (mCRC). Patients with mCRC (RAS wild-type and RAS mutant cohorts) received nab-paclitaxel 125 mg/m 2 days 1, 8, and 15 (28-day cycle). The primary endpoint was investigator-assessed progression-free survival (PFS) rate at week 8; secondary endpoints included overall survival, overall response rate, and safety. Stage 1 planned enrollment was 15 patients per cohort per Simon 2-stage design. Stage 2 enrollment was to continue unless ≤8 of the first 15 patients per cohort achieved PFS at 8 weeks. Stage 1 enrolled 41 patients (RAS wild type: n = 18; RAS mutant: n = 23). In both RAS cohorts, 3 of 15 patients initially enrolled were progression-free at week 8 (20%; 95% CI 4.0-48.0). Median PFS was 8.1 weeks (95% CI 7.7-8.6) and 7.9 weeks (95% CI 7.6-8.0) for RAS wild-type and RAS mutant cohorts, respectively. There were no complete or partial responses. The overall disease control rate was 16% (95% CI 6.0-32.0), and rates were similar in the RAS wild-type and RAS mutant cohorts (18 and 15%, respectively). No new safety signals were reported; the most common grade ≥3 adverse events included neutropenia, asthenia, and peripheral neuropathy. This study did not progress to stage 2 per the preplanned statistical stopping rule. In patients with heavily pretreated mCRC, nab-paclitaxel did not demonstrate promising antitumor activity; further assessment of nab-paclitaxel monotherapy in this population of patients is not supported. NCT02103062.

Role of ground ice dynamics and ecological feedbacks in recent ice wedge degradation and stabilization

USGS Publications Warehouse

Mark Torre Jorgenson,; Mikhail Kanevskiy,; Yuri Shur,; Natalia Moskalenko,; Dana Brown,; Wickland, Kimberly P.; Striegl, Robert G.; Koch, Joshua C.

2015-01-01

Ground ice is abundant in the upper permafrost throughout the Arctic and fundamentally affects terrain responses to climate warming. Ice wedges, which form near the surface and are the dominant type of massive ice in the Arctic, are particularly vulnerable to warming. Yet processes controlling ice wedge degradation and stabilization are poorly understood. Here we quantified ice wedge volume and degradation rates, compared ground ice characteristics and thermal regimes across a sequence of five degradation and stabilization stages and evaluated biophysical feedbacks controlling permafrost stability near Prudhoe Bay, Alaska. Mean ice wedge volume in the top 3 m of permafrost was 21%. Imagery from 1949 to 2012 showed thermokarst extent (area of water-filled troughs) was relatively small from 1949 (0.9%) to 1988 (1.5%), abruptly increased by 2004 (6.3%) and increased slightly by 2012 (7.5%). Mean annual surface temperatures varied by 4.9°C among degradation and stabilization stages and by 9.9°C from polygon center to deep lake bottom. Mean thicknesses of the active layer, ice-poor transient layer, ice-rich intermediate layer, thermokarst cave ice, and wedge ice varied substantially among stages. In early stages, thaw settlement caused water to impound in thermokarst troughs, creating positive feedbacks that increased net radiation, soil heat flux, and soil temperatures. Plant growth and organic matter accumulation in the degraded troughs provided negative feedbacks that allowed ground ice to aggrade and heave the surface, thus reducing surface water depth and soil temperatures in later stages. The ground ice dynamics and ecological feedbacks greatly complicate efforts to assess permafrost responses to climate change.

Improved tolerance to post-anthesis drought stress by pre-drought priming at vegetative stages in drought-tolerant and -sensitive wheat cultivars.

PubMed

Abid, Muhammad; Tian, Zhongwei; Ata-Ul-Karim, Syed Tahir; Liu, Yang; Cui, Yakun; Zahoor, Rizwan; Jiang, Dong; Dai, Tingbo

2016-09-01

Wheat crop endures a considerable penalty of yield reduction to escape the drought events during post-anthesis period. Drought priming under a pre-drought stress can enhance the crop potential to tolerate the subsequent drought stress by triggering a faster and stronger defense mechanism. Towards these understandings, a set of controlled moderate drought stress at 55-60% field capacity (FC) was developed to prime the plants of two wheat cultivars namely Luhan-7 (drought tolerant) and Yangmai-16 (drought sensitive) during tillering (Feekes 2 stage) and jointing (Feekes 6 stage), respectively. The comparative response of primed and non-primed plants, cultivars and priming stages was evaluated by applying a subsequent severe drought stress at 7 days after anthesis. The results showed that primed plants of both cultivars showed higher potential to tolerate the post-anthesis drought stress through improved leaf water potential, more chlorophyll, and ribulose-1, 5-bisphosphate carboxylase/oxygenase contents, enhanced photosynthesis, better photoprotection and efficient enzymatic antioxidant system leading to less yield reductions. The primed plants of Luhan-7 showed higher capability to adapt the drought stress events than Yangmai-16. The positive effects of drought priming to sustain higher grain yield were pronounced in plants primed at tillering than those primed at jointing. In consequence, upregulated functioning of photosynthetic apparatus and efficient enzymatic antioxidant activities in primed plants indicated their superior potential to alleviate a subsequently occurring drought stress, which contributed to lower yield reductions than non-primed plants. However, genotypic and priming stages differences in response to drought stress also contributed to affect the capability of primed plants to tolerate the post-anthesis drought stress conditions in wheat. Copyright © 2016. Published by Elsevier Masson SAS.

Complications and troubleshooting of sacral neuromodulation therapy.

PubMed

Hijaz, Adonis; Vasavada, Sandip

2005-02-01

As evident from the authors' series, the complications of sacral neuromodulation have changed with the introduction of the tined lead and the placement of the generator over the back. In the earlier series, most complications were related to pain at the generator site, which was rare in the authors' series. The posterior location of the generator seems to be better tolerated than the anterior location, which could explain the rare need for revisions for pain at the generator site. Lead migration was observed in 8.4% of the original sacral neuromodulation study group series. This was seen rarely in the authors' series in either stage-one or stage-two revisions. As part of the routine work-up of patients who present with decreased function after a successful period response in stage two, the authors obtain a lateral radiograph of the sacrum; the authors have made the diagnosis of lead migration rarely (1/130; 0.6%). Spinelli and colleagues reported on the use of the tined lead in 15 patients, and observed no lead migration during either the screening period (average 38.8 days) or during follow-up of IPG implantation cases (average 11 months). The total infection rate in the whole series was 18/180 (10%), which was slightly higher than that reported by the sacral neuromodulation study group (6.1%). Revision rates for stage one and stage two were 12.2% and 20%, respectively. The revision rate in the original study group was 33.3%. Thus, with advancing technology, new problems may arise, but the implanting physician should be aware of the ways to evaluate and manage these complications and appropriately troubleshoot patients with suboptimal responses.

Role of ground ice dynamics and ecological feedbacks in recent ice wedge degradation and stabilization

NASA Astrophysics Data System (ADS)

Jorgenson, M. T.; Kanevskiy, M.; Shur, Y.; Moskalenko, N.; Brown, D. R. N.; Wickland, K.; Striegl, R.; Koch, J.

2015-11-01

Ground ice is abundant in the upper permafrost throughout the Arctic and fundamentally affects terrain responses to climate warming. Ice wedges, which form near the surface and are the dominant type of massive ice in the Arctic, are particularly vulnerable to warming. Yet processes controlling ice wedge degradation and stabilization are poorly understood. Here we quantified ice wedge volume and degradation rates, compared ground ice characteristics and thermal regimes across a sequence of five degradation and stabilization stages and evaluated biophysical feedbacks controlling permafrost stability near Prudhoe Bay, Alaska. Mean ice wedge volume in the top 3 m of permafrost was 21%. Imagery from 1949 to 2012 showed thermokarst extent (area of water-filled troughs) was relatively small from 1949 (0.9%) to 1988 (1.5%), abruptly increased by 2004 (6.3%) and increased slightly by 2012 (7.5%). Mean annual surface temperatures varied by 4.9°C among degradation and stabilization stages and by 9.9°C from polygon center to deep lake bottom. Mean thicknesses of the active layer, ice-poor transient layer, ice-rich intermediate layer, thermokarst cave ice, and wedge ice varied substantially among stages. In early stages, thaw settlement caused water to impound in thermokarst troughs, creating positive feedbacks that increased net radiation, soil heat flux, and soil temperatures. Plant growth and organic matter accumulation in the degraded troughs provided negative feedbacks that allowed ground ice to aggrade and heave the surface, thus reducing surface water depth and soil temperatures in later stages. The ground ice dynamics and ecological feedbacks greatly complicate efforts to assess permafrost responses to climate change.

Children's Responses to Fantasy in Relation to Their Stages of Intellectual Development.

ERIC Educational Resources Information Center

Harms, Jeanne McLain

Girls' responses to fantasy in children's literature as related to a conceptual framework (extrapolated from books of modern fantasy) of intellectual development (based on Piaget's theoretical formulations) were investigated. The three stages of thinking corresponded to the ages of the subjects: five year olds represented the preoperational stage,…

Effect of a central redistribution of fluid volume on response to lower-body negative pressure

NASA Technical Reports Server (NTRS)

Tomaselli, Clare M.; Frey, Mary A. B.; Kenney, Richard A.; Hoffler, G. Wyckliffe

1990-01-01

Cardiovascular responses to lower-body negative pressure (LBNP) were studied following 1 hour of 6-deg head-down tilt to determine whether a redistribution of blood volume toward the central circulation modifies the subsequent response to orthostatic stress. Responses of 12 men, ages 30-39 years, were evaluated by electrocardiography, impedance cardiography, sphygmomanometry, and measurement of calf circumference. During the LBNP that followed head-down tilt, as compared with control LBNP (no preceding head-down tilt) subjects, had smaller stroke volume and cardiac output, greater total peripheral resistance, and less calf enlargement. These differences reflect differences in the variables immediately preceding LBNP. Magnitudes of the responses from pre-LBNP to each pressure stage of the LBNP procedure did not differ between protocols. Mean and diastolic arterial pressures were slightly elevated after LBNP-control, but they fell slightly during LBNP post-tilt.

Lymph node fibrosis: a structural barrier to unleashing effective vaccine immunity.

PubMed

Julg, Boris; Alter, Galit

2018-05-21

There is marked variability in vaccine efficacy among global populations. In particular, individuals in low- to middle-income countries have been shown to be less responsive to vaccines than those from developed nations. Several factors, including endemic infections, nutrition, genetics, and gut microbiome composition, have been proposed to underlie discrepancies in vaccine response. In this issue of the JCI, Kityo et al. evaluated response to yellow fever virus vaccine, inflammation, and lymphatic tissue architecture and fibrosis in three cohorts: two from the U.S. and one from Uganda. Compared with the U.S. subjects, the Ugandan cohort exhibited enhanced cytokine responses, increased lymph node fibrosis, reduced CD4+ T cell levels, and reduced vaccine response. Together, these results provide a link among chronic inflammation, damaged lymphoid architecture, and poor vaccine outcome, and set the stage for future studies to identify strategies to overcome these barriers.

MRI and PET Imaging in Predicting Treatment Response in Patients With Stage IB-IVA Cervical Cancer

ClinicalTrials.gov

2018-06-18

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Cervical Undifferentiated Carcinoma; Recurrent Cervical Carcinoma; Stage IB2 Cervical Cancer; Stage II Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

FLT PET in Measuring Treatment Response in Patients With Newly Diagnosed Estrogen Receptor-Positive, HER2-Negative Stage I-III Breast Cancer

ClinicalTrials.gov

2018-04-13

Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Modeling cost-effectiveness and health gains of a "universal" versus "prioritized" hepatitis C virus treatment policy in a real-life cohort.

PubMed

Kondili, Loreta A; Romano, Federica; Rolli, Francesca Romana; Ruggeri, Matteo; Rosato, Stefano; Brunetto, Maurizia Rossana; Zignego, Anna Linda; Ciancio, Alessia; Di Leo, Alfredo; Raimondo, Giovanni; Ferrari, Carlo; Taliani, Gloria; Borgia, Guglielmo; Santantonio, Teresa Antonia; Blanc, Pierluigi; Gaeta, Giovanni Battista; Gasbarrini, Antonio; Chessa, Luchino; Erne, Elke Maria; Villa, Erica; Ieluzzi, Donatella; Russo, Francesco Paolo; Andreone, Pietro; Vinci, Maria; Coppola, Carmine; Chemello, Liliana; Madonia, Salvatore; Verucchi, Gabriella; Persico, Marcello; Zuin, Massimo; Puoti, Massimo; Alberti, Alfredo; Nardone, Gerardo; Massari, Marco; Montalto, Giuseppe; Foti, Giuseppe; Rumi, Maria Grazia; Quaranta, Maria Giovanna; Cicchetti, Americo; Craxì, Antonio; Vella, Stefano

2017-12-01

We evaluated the cost-effectiveness of two alternative direct-acting antiviral (DAA) treatment policies in a real-life cohort of hepatitis C virus-infected patients: policy 1, "universal," treat all patients, regardless of fibrosis stage; policy 2, treat only "prioritized" patients, delay treatment of the remaining patients until reaching stage F3. A liver disease progression Markov model, which used a lifetime horizon and health care system perspective, was applied to the PITER cohort (representative of Italian hepatitis C virus-infected patients in care). Specifically, 8,125 patients naive to DAA treatment, without clinical, sociodemographic, or insurance restrictions, were used to evaluate the policies' cost-effectiveness. The patients' age and fibrosis stage, assumed DAA treatment cost of €15,000/patient, and the Italian liver disease costs were used to evaluate quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European scenario analysis was performed, resampling the study population, using the mean European country-specific health states costs and mean treatment cost of €30,000. For the Italian base-case analysis, the cost-effective ICER obtained using policy 1 was €8,775/QALY. ICERs remained cost-effective in 94%-97% of the 10,000 probabilistic simulations. For the European treatment scenario the ICER obtained using policy 1 was €19,541.75/QALY. ICER was sensitive to variations in DAA costs, in the utility value of patients in fibrosis stages F0-F3 post-sustained virological response, and in the transition probabilities from F0 to F3. The ICERs decrease with decreasing DAA prices, becoming cost-saving for the base price (€15,000) discounts of at least 75% applied in patients with F0-F2 fibrosis. Extending hepatitis C virus treatment to patients in any fibrosis stage improves health outcomes and is cost-effective; cost-effectiveness significantly increases when lowering treatment prices in early fibrosis stages. (Hepatology 2017;66:1814-1825). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

Gender role across development in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

PubMed

Long, Dominique N; Wisniewski, Amy B; Migeon, Claude J

2004-10-01

This study evaluated the degree of femininity and masculinity at different developmental stages in a group of adult women, some of whom were exposed to elevated prenatal adrenal androgens as a result of congenital adrenal hyperplasia (CAH) due to 21 hydroxylase (21-OH) deficiency. Women who had presented to the Johns Hopkins Hospital Pediatric Endocrine Clinic for treatment of CAH due to 21-OH deficiency were included. The control group consisted of sisters of CAH participants and women referred for evaluation of polycystic ovary syndrome. Study participants were given a questionnaire asking them to indicate their degree of masculinity and femininity during childhood, adolescence, and adulthood. In addition, participants were asked questions related to their play behavior during childhood, including playmate preferences, toy preferences, and admiration of male or female characters during fantasy play. Across participant groups, self-reported femininity decreased in a dose response manner, according to prenatal androgen exposure. For all groups, femininity increased through developmental stages. Women with salt-losing CAH remained less feminine than controls into adulthood. Conversely, self-reported masculinity increased in a dose-response manner, according to prenatal androgen exposure, across participant groups. Women with CAH showed a decrease in masculinity across developmental stages, such that by adulthood, there were no significant differences in masculinity between controls and the women with CAH. Women with salt-losing CAH were more likely to recall preferences for boy playmates, male-typical toys, and admiration for male characters during childhood than other study participants. Our data support the effect of both prenatal androgen exposure and socialization on gender role behavior in adult women with CAH due to 21-OH deficiency.

Lethal and sublethal toxicity of the industrial chemical epichlorohydrin on Rhinella arenarum (Anura, Bufonidae) embryos and larvae.

PubMed

Hutler Wolkowicz, Ianina R; Aronzon, Carolina M; Pérez Coll, Cristina S

2013-12-15

Lethal and sublethal toxicity of the major chemical used in epoxide compounds, epichlorohydrin (ECH) was evaluated on the early life cycle of the common South American toad, Rhinella arenarum (Anura, Bufonidae). The stages evaluated were (according to Del Conte and Sirlin): early blastula (S.3-S.4), gastrula (S.10-S.12), rotation (S.15), tail bud (S.17), muscular response (S.18), gill circulation (S.20), open mouth (S.21), opercular folds (S.23) and complete operculum (S.25). The LC50 and EC50 values for lethal and sublethal effects were calculated. The early blastula was the most sensitive stage to ECH both for continuously and pulse-exposures (LC50-24h=50.9 mg L(-1)), while S.20 was the most resistant (LC50-24h=104.9 mg L(-1)). Among sublethal effects, early blastula was also the most sensitive stage (LOEC-48 h=20 mg L(-1)) and it has a Teratogenic Index of 2.5, which indicates the teratogenic potential of the substance. The main abnormalities were persistent yolk plugs, cell dissociation, tumors, hydropsy, oral malformations, axial/tail flexures, delayed development and reduced body size. ECH also caused neurotoxicity including scarce response to stimuli, reduction in the food intake, general weakness, spasms and shortening, erratic or circular swimming. Industrial contamination is considered an important factor on the decline of amphibian populations. Considering the available information about ECH's toxicity and its potential hazard to the environment, this work shows the first results of its developmental toxicity on a native amphibian species, Rhinella arenarum. Copyright © 2013 Elsevier B.V. All rights reserved.

CT in the clinical and prognostic evaluation of acute graft-vs-host disease of the gastrointestinal tract

PubMed Central

Shimoni, A; Rimon, U; Hertz, M; Yerushalmi, R; Amitai, M; Portnoy, O; Guranda, L; Nagler, A; Apter, S

2012-01-01

Objective To determine the role of abdominal CT in assessment of severity and prognosis of patients with acute gastrointestinal (GI) graft-vs-host disease (GVHD). Methods During 2000–2004, 41 patients with a clinical diagnosis of acute GI-GVHD were evaluated. CTs were examined for intestinal and extra-intestinal abnormalities, and correlated with clinical staging and outcome. Results 20 patients had GVHD clinical Stage I–II and 21 had Stage III–IV. 39 (95%) had abnormal CT appearances. The most consistent finding was bowel wall thickening: small (n=14, 34%) or large (n=5, 12%) bowel, or both (n=20, 49%). Other manifestations included bowel dilatation (n=7, 17%), mucosal enhancement (n=6, 15%) and gastric wall thickening (n=9, 38%). Extra-intestinal findings included mesenteric stranding (n=25, 61%), ascites (n=17, 41%), biliary abnormalities (n=12, 29%) and urinary excretion of orally administered gastrografin (n=12, 44%). Diffuse small-bowel thickening and any involvement of the large bowel were associated with severe clinical presentation. Diffuse small-bowel disease correlated with poor prognosis. 8 of 21 patients responded to therapy, compared with 15 of 20 patients with other patterns (p=0.02), and the cumulative incidence of GVHD-related death was 62% and 24%, respectively (p=0.01). Overall survival was not significantly different between patients with diffuse small-bowel disease and patients with other patterns (p=0.31). Colonic disease correlated with severity of GVHD (p=0.04), but not with response to therapy or prognosis (p=0.45). Conclusion GVHD often presented with abdominal CT abnormalities. Diffuse small-bowel disease was associated with poor therapeutic response. CT may play a role in supporting clinical diagnosis of GI GVHD and determining prognosis. PMID:22128129

Catathrenia: Parasomnia or Uncommon Feature of Sleep Disordered Breathing?

PubMed Central

Guilleminault, Christian; Hagen, Chad C.; Khaja, Aliuddin M

2008-01-01

Objective: We report a series of seven consecutive cases of catathrenia (sleep related groaning) that differ from limited previous reports in the literature with regard to sleep stage and response to treatment. Background: Catathrenia was recently defined as a parasomnia in the International Classification of Sleep Disorders Diagnostic and Coding Manual (ICSD-2), but there is debate about its classification, and its response to CPAP is unknown. Methods: We present 7 consecutive patients presenting with catathrenia over a 5-year period. They were all young women, ranging in age from 20 to 34 years with a body mass index (BMI) <25. They underwent standard clinical evaluation, questionnaires, physical exam, craniofacial evaluations, and nocturnal polysomnography. All seven were titrated on continuous passive airway pressure (CPAP) treatment for sleep disordered breathing then offered surgical treatment if unable to tolerate or adhere to CPAP recommendations. Results: Groaning was present throughout all stages of sleep. The mean (SD) AHI and RDI were 3.2 (0.56) and 13.1 (2.4) respectively. CPAP resolved groaning in all cases. 5 patients (71%) elected subsequent surgical intervention. Three of the 4 that followed up after surgery required adjuvant oral appliance treatment, but all four ultimately had resolution of groaning. Conclusions: Catathrenia may have subtypes related to sleep stage specificity or presence of sleep disordered breathing. In our heterogeneous group of non-obese women with a normal AHI and elevated RDI, CPAP and select soft tissue surgeries of the upper airway (often augmented with an oral appliance) successfully treated nocturnal groaning. Citation: Guilleminault C; Hagen CC; Khaja AM. Catathrenia: parasomnia or uncommon feature of sleep disordered breathing?. SLEEP 2008;31(1):132-139. PMID:18220087

Sensory modulation disorder symptoms in anorexia nervosa and bulimia nervosa: A pilot study.

PubMed

Brand-Gothelf, Ayelet; Parush, Shula; Eitan, Yehudith; Admoni, Shai; Gur, Eitan; Stein, Daniel

2016-01-01

Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) may exhibit reduced ability to modulate sensory, physiological, and affective responses. The aim of the present study is to assess sensory modulation disorder (SMD) symptoms in patients with AN and BN. We assessed female adolescent and young adult inpatients with restrictive type anorexia nervosa (AN-R; n = 20) and BN (n = 20) evaluated in the acute stage of their illness, and 27 female controls. Another group of 20 inpatients with AN-R was assessed on admission and discharge, upon achieving their required weight. Participants completed standardized questionnaires assessing the severity of their eating disorder (ED) and the sensory responsiveness questionnaire (SRQ). Inpatients with AN-R demonstrated elevated overall sensory over-responsiveness as well as elevated scores on the taste/gustatory, vestibular/kinesthetic and somatosensory/tactile SRQ modalities compared with patients with BN and controls. Significant correlations between the severity of sensory over-responsiveness and ED-related symptomatology were found in acutely-ill patients with AN-R and to a lesser extent, following weight restoration. Elevated sensory over-responsiveness was retained in weight-restored inpatients with AN-R. Inpatients with BN demonstrated greater sensory under-responsiveness in the intensity subscale of the SRQ, but not in the frequency and combined SRQ dimensions. Female inpatients with AN-R exhibited sensory over-responsiveness both in the acute stage of their illness and following weight restoration, suggesting that sensory over-responsiveness may represent a trait related to the illness itself above and beyond the influence of malnutrition. The finding for sensory under-responsiveness in BN is less consistent. © 2015 Wiley Periodicals, Inc.

Miscellaneous indications in bone scintigraphy: metabolic bone diseases and malignant bone tumors.

PubMed

Cook, Gary J R; Gnanasegaran, Gopinath; Chua, Sue

2010-01-01

The diphosphonate bone scan is ideally suited to assess many global, focal or multifocal metabolic bone disorders and there remains a role for conventional bone scintigraphy in metabolic bone disorders at diagnosis, investigation of complications, and treatment response assessment. In contrast, the role of bone scintigraphy in the evaluation of primary malignant bone tumors has reduced with the improvement of morphologic imaging, such as computed tomography and magnetic resonance imaging. However, an increasing role for (18)F-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography is emerging as a functional assessment at diagnosis, staging, and neoadjuvant treatment response assessment.

Fulvestrant and Palbociclib in Treating Older Patients With Hormone Responsive Breast Cancer That Cannot Be Removed by Surgery

ClinicalTrials.gov

2016-09-21

Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Fused Mycobacterium tuberculosis multi-stage immunogens with an Fc-delivery system as a promising approach for the development of a tuberculosis vaccine.

PubMed

Mosavat, Arman; Soleimanpour, Saman; Farsiani, Hadi; Sadeghian, Hamid; Ghazvini, Kiarash; Sankian, Mojtaba; Jamehdar, Saeid Amel; Rezaee, Seyed Abdolrahim

2016-04-01

Tuberculosis (TB) remains a major health problem worldwide. Currently, the Bacilli Calmette-Guérin (BCG) is the only available licensed TB vaccine, which has low efficacy in protection against adult pulmonary TB. Therefore, the development of a safe and effective vaccine against TB needs global attention. In the present study, a novel multi-stage subunit vaccine candidate from culture filtrate protein-10 (CFP-10) and heat shock protein X (HspX) of Mycobacterium tuberculosis fused to the Fc domain of mouse IgG2a as a selective delivery system for antigen-presenting cells (APCs) was produced and its immunogenicity assessed. The optimized gene constructs were introduced into pPICZαA expression vectors, and the resultant plasmids (pPICZαA-CFP-10:Hspx:Fcγ2a and pPICZαA-CFP-10:Hspx:His) were transferred into Pichia pastoris by electroporation. The identification of both purified recombinant fusion proteins was evaluated by SDS-PAGE and immunoblotting. Then the immunogenicity of the recombinant proteins with and without BCG was evaluated in BALB/c mice by assessing the level of IFN-γ, IL-12, IL-4, IL-17 and TGF-β cytokines. Both multi-stage vaccines (CFP-10:HspX:Fcγ2a and CFP-10:HspX:His) induced Th1-type cellular responses by producing high level of IFN-γ (272 pg/mL, p<0.001) and IL-12 (191 pg/mL, p<0.001). However, the Fc-tagged recombinant protein induced more effective Th1-type cellular responses with a low level of IL-4 (10 pg/mL) compared to the CFP-10:HspX:His group. The production of IFN-γ to CFP-10:HspX:Fcγ2a was markedly consistent and showed an increasing trend for IL-12 compared with the BCG or CFP-10:HspX:His primed and boosted groups. Findings revealed that CFP-10:Hspx:Fcγ2a fusion protein can elicit strong Th1 antigen-specific immune responses in favor of protective immunity in mice and could provide new insight for introducing an effective multi-stage subunit vaccine against TB. Copyright © 2016 Elsevier B.V. All rights reserved.

[Response of soil hydrolase and oxidoreductase activities to free-air carbon dioxide enrichment (FACE) under rice-wheat rotation].

PubMed

Zhang, Yulan; Zhang, Lili; Chen, Lijun; Wu, Zhijie

2004-06-01

This paper studied the response of soil urease, phosphatase, arylsulphatase and dehydrogenase to 200 micromol x mol(-1) CO2 elevation under rice-wheat rotation. The results showed that under CO2 elevation, the urease activity in 0-10 cm soil layer was decreased at the early growth stages of wheat but increased at its booting stage; the activity increased at the early growth stages of rice but decreased at its ripening stage. Phosphatase activity was increased during the whole growth period of wheat; the activity increased at the tillering stage of rice but decreased at its later growth stages. Arylsulphatase activity was decreased at the over-wintering and booting stages of wheat but increased at its tillering and ripening stages. Dehydrogenase activity was decreased at the early growth stages of wheat and rice, but increased at their late growth stages.

Estimating neural response functions from fMRI

PubMed Central

Kumar, Sukhbinder; Penny, William

2014-01-01

This paper proposes a methodology for estimating Neural Response Functions (NRFs) from fMRI data. These NRFs describe non-linear relationships between experimental stimuli and neuronal population responses. The method is based on a two-stage model comprising an NRF and a Hemodynamic Response Function (HRF) that are simultaneously fitted to fMRI data using a Bayesian optimization algorithm. This algorithm also produces a model evidence score, providing a formal model comparison method for evaluating alternative NRFs. The HRF is characterized using previously established “Balloon” and BOLD signal models. We illustrate the method with two example applications based on fMRI studies of the auditory system. In the first, we estimate the time constants of repetition suppression and facilitation, and in the second we estimate the parameters of population receptive fields in a tonotopic mapping study. PMID:24847246

Pitfalls and Limitations of Diffusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Urinary Bladder Cancer

PubMed Central

Lin, Wei-Ching; Chen, Jeon-Hor

2015-01-01

Adequately selecting a therapeutic approach for bladder cancer depends on accurate grading and staging. Substantial inaccuracy of clinical staging with bimanual examination, cystoscopy, and transurethral resection of bladder tumor has facilitated the increasing utility of magnetic resonance imaging to evaluate bladder cancer. Diffusion-weighted imaging (DWI) is a noninvasive functional magnetic resonance imaging technique. The high tissue contrast between cancers and surrounding tissues on DWI is derived from the difference of water molecules motion. DWI is potentially a useful tool for the detection, characterization, and staging of bladder cancers; it can also monitor posttreatment response and provide information on predicting tumor biophysical behaviors. Despite advancements in DWI techniques and the use of quantitative analysis to evaluate the apparent diffusion coefficient values, there are some inherent limitations in DWI interpretation related to relatively poor spatial resolution, lack of cancer specificity, and lack of standardized image acquisition protocols and data analysis procedures that restrict the application of DWI and reproducibility of apparent diffusion coefficient values. In addition, inadequate bladder distension, artifacts, thinness of bladder wall, cancerous mimickers of normal bladder wall and benign lesions, and variations in the manifestation of bladder cancer may interfere with diagnosis and monitoring of treatment. Recognition of these pitfalls and limitations can minimize their impact on image interpretation, and carefully applying the analyzed results and combining with pathologic grading and staging to clinical practice can contribute to the selection of an adequate treatment method to improve patient care. PMID:26055180

Toward a Measure of Accountability in Nursing: A Three-Stage Validation Study.

PubMed

Drach-Zahavy, Anat; Leonenko, Marina; Srulovici, Einav

2018-06-04

To develop and psychometrically evaluate a three-dimensional questionnaire suitable for evaluating personal and organizational accountability in nurses. Accountability is defined as a three-dimensional value, directing professionals to take responsibility for their decisions and actions, to be willing to explain them (transparency) and to be judged according to society's accepted values (answerability). Despite the relatively clear definition, measurement of accountability lags well behind. Existing self-report questionnaires do not fully capture the complexity of the concept; nor do they capture the different sources of accountability (e.g., personal accountability, organizational accountability). A three-stage measure development. Data were collected during 2015-2016. In Phase 1, an initial database of items (N = 74) was developed, based on literature review and qualitative study, establishing face and content validity. In Phase 2, the face, content, construct and criterion-related validity of the initial questionnaires (19 items for personal and organizational accountability questionnaire) was established with a sample of 229 nurses. In Phase 3, the final questionnaires (19 items each) were validated with a new sample of 329 nurses and established construct validity. The final version of the instruments comprised 19 items, suitable for assessing personal and organizational accountability. The questionnaire referred to the dimensions of responsibility, transparency and answerability. The findings established the instrument's content, construct and criterion-related validity, as well as good internal reliability. The questionnaire portrays accountability in nursing, by capturing nurses' subjective perceptions of accountability dimensions (responsibility, transparency, answerability), as demonstrated by personal and organizational values. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Minimal olfactory perception during sleep: why odor alarms will not work for humans.

PubMed

Carskadon, Mary A; Herz, Rachel S

2004-05-01

To examine olfactory arousal threshold during sleep in comparison to an auditory tone. On night 1, participants rated odor intensity when awake and experienced olfactory stimuli during stage 1 sleep. Night 2 involved stage 2, stage 4, and rapid-eye-movement (REM) sleep trials using the "staircase" threshold-detection method. Electroencephalogram, electrooculogram, electromyogram, electrocardiogram, and respiration were recorded along with behavioral response. An 800-Hz tone was given on trials when odors failed to arouse. Participants slept in individual rooms. Stimulus-delivery systems were operated from a separate room, where an experimenter observed physiologic recordings and behavioral responses. Three healthy men and 3 women aged 20 to 25 years (mean, 22 years). Two odorants, peppermint and pyridine, at 4 concentrations were presented through nasal cannulas using an air-dilution olfactometer. Tones were played over a speaker. Behavioral (button press and oral) responses, electroencephalographic activation, and changes in breathing and heart rate were assessed. Participants responded to odors on 92% of stage 1 sleep trials. Peppermint was ineffective in stages 2, 4, and REM sleep. Pyridine produced behavioral threshold on 45% of stage 2 trials, none in stage 4, and one third of REM sleep trials. Tones were effective on at least 75% of trials. Heart rate increased significantly only following behavioral responses to odors or tones across sleep stages. The data indicate that human olfaction is not reliably capable of alerting a sleeper.

Upper stage technology evaluation studies

NASA Technical Reports Server (NTRS)

1972-01-01

Studies to evaluate advanced technology relative to chemical upper stages and orbit-to-orbit stages are reported. The work described includes: development of LH2/LOX stage data, development of data to indicate stage sensitivity to engine tolerance, modified thermal routines to accommodate storable propellants, added stage geometries to computer program for monopropellant configurations, determination of the relative gain obtainable through improvement of stage mass fraction, future propulsion concepts, effect of ultrahigh chamber-pressure increases, and relative gains obtainable through improved mass fraction.

Controlling the invasive diatom Didymosphenia geminata: an ecotoxicity assessment of four potential biocides.

PubMed

Jellyman, P G; Clearwater, S J; Clayton, J S; Kilroy, C; Blair, N; Hickey, C W; Biggs, B J F

2011-07-01

In 2004, an invasive mat-forming freshwater diatom, Didymosphenia geminata (didymo), was found in New Zealand causing concern with regard to potential consequences for local freshwater ecosystems. A four-stage research program was initiated to identify methods to control D. geminata. This article reports the results of Stage 2, in which four potential control compounds [Gemex™ (a chelated copper formulation), EDTA, Hydrothol®191, and Organic Interceptor™ (a pine oil formulation)] selected in Stage 1 were evaluated for their biocidal efficacy on D. geminata and effects on non-target organisms using both artificial stream and laboratory trials. Artificial stream trials evaluated the mortality rates of D. geminata and fishes to three concentrations of the four biocides, whereas laboratory toxicity trials tested the response of green alga and cladocera to a range of biocide concentrations and exposure times. In artificial stream trials, Gemex and Organic Interceptor were the most effective biocides against D. geminata for a number of measured indices; however, exposure of fishes to Organic Interceptor resulted in high mortality rates. Laboratory toxicity testing indicated that Gemex might negatively affect sensitive stream invertebrates, based on the cladoceran sensitivity at the proposed river control dose. A decision support matrix evaluated the four biocides based on nine criteria stipulated by river stakeholders (effectiveness, non-target species impacts, stalk removal, degradation profile, risks to health and safety, ease of application, neutralization potential, cost, and local regulatory requirements) and Gemex was identified as the product warranting further refinement prior to an in-river trial.

A Framework for Assessing Health Risk of Environmental ...

EPA Pesticide Factsheets

EPA released the final report entitled, A Framework for Assessing Health Risk of Environmental Exposures to Children, which examines the impact of potential exposures during developmental lifestages and subsequent lifestages, while emphasizing the iterative nature of the analysis phase with a multidisciplinary team. Major findings and conclusions: This report outlines the framework in which mode of action(s) (MOA) can be considered across life stages. The framework is based upon existing approaches adopted in the Framework on Cumulative Risk Assessment and identifies existing guidance, guidelines and policy papers that relate to children's health risk assessment. It emphasizes the importance of an iterative approach between hazard, dose response, and exposure analyses. In addition, it includes discussion of principles for weight of evidence consideration across life stages for the hazard characterization database.Key science/assessment issues:This framework addresses the questions of why and how an improved children's health risk assessment will strengthen the overall risk assessment process across the Agency. This approach improves the scientific explanation of children's risk and will add value by: 1) providing for a more complete evaluation of the potential for vulnerability at different life stages, including a focus on the underlying biological events and critical developmental periods for incorporating MOA considerations; 2) evaluating of the potential fo

Generation of an antibody that recognizes Plasmodium chabaudi cysteine protease (chabaupain-1) in both sexual and asexual parasite life cycle and evaluation of chabaupain-1 vaccine potential.

PubMed

Armada, Ana; Gazarini, Marcos L; Gonçalves, Lídia M; Antunes, Sandra; Custódio, Ana; Rodrigues, Armanda; Almeida, António J; Silveira, Henrique; Rosário, Virgílio do; Santos-Gomes, Gabriela; Domingos, Ana

2013-09-01

Malaria cysteine proteases have been shown to be immunogenic and are being exploited as serodiagnostic markers, drug and vaccine targets. Several Plasmodium spp. cysteine proteases have been described and the best characterized of these are the falcipains, a family of papain-family enzymes. Falcipain-2 and falcipain-3 act in concert with other proteases to hydrolyze host erythrocyte hemoglobin in the parasite food vacuole. Falcipain-1 has less similarity to the other falcipains and its physiological role in parasite asexual blood stage still remains uncertain. Immunolocalization studies using an antibody developed against the Plasmodium chabaudi recombinant chabaupain-1, the falcipain-1 ortholog, were performed confirming its cellular localization in both erythrocyte and mosquito ookinete stage. Immunostaining of chabaupain-1 preferentially in apical portion of parasite ookinete suggests that this protease may be related with parasite egression from mosquito midgut. Immune responses to chabaupain-1 were evaluated using two different adjuvants, chitosan nanoparticles and hydroxide aluminum. Mice immunized with the recombinant protein alone or in association with nanoparticles were challenged with P. chabaudi showing that immunization with the recombinant protein confers partial protection to blood stage infection in BALB/c animal model. Copyright © 2013 Elsevier Inc. All rights reserved.

Clinical evaluation of endometriosis and differential response to surgical therapy with and without application of Oxiplex/AP* adhesion barrier gel.

PubMed

diZerega, Gere S; Coad, James; Donnez, Jacques

2007-03-01

To correlate parameters of endometriosis obtained during routine clinical evaluation with the subsequent formation of adhesions following surgical treatment by laparoscopy. Randomized, controlled, double-blind, clinical trial. Tertiary referral centers for the treatment of endometriosis. Thirty-seven patients (65 with adnexa) with stage I-III endometriosis; endometrioma-only patients were excluded. Laparoscopic surgical treatment of endometriosis, followed by randomization to Oxiplex/AP (FzioMed, Inc., San Luis Obispo, California) gel treatment (treated group) of adnexa, or surgery alone (control group); follow-up laparoscopy 6-10 weeks later. Adnexal Americn Fertility Society score, correlated with color and location of endometriosis, as well as stage of disease determined by masked review of videotapes. Control patients with at least 50% red lesions had a greater increase in ipsilateral adnexal adhesion scores than patients with mostly black or white and/or clear lesions. Treated patients with red lesions had a greater decrease in adnexal adhesion scores than control patients. There was a correlation between baseline endometriosis stage and postoperative adhesion formation in control patients, but not treated patients. Patients with red endometriotic lesions had greater increases in their adhesion scores than patients with only black, white, and/or clear lesions. Oxiplex/AP gel was effective in reducing adhesions, compared to surgery alone, in all groups.

Role of temporal processing stages by inferior temporal neurons in facial recognition.

PubMed

Sugase-Miyamoto, Yasuko; Matsumoto, Narihisa; Kawano, Kenji

2011-01-01

In this review, we focus on the role of temporal stages of encoded facial information in the visual system, which might enable the efficient determination of species, identity, and expression. Facial recognition is an important function of our brain and is known to be processed in the ventral visual pathway, where visual signals are processed through areas V1, V2, V4, and the inferior temporal (IT) cortex. In the IT cortex, neurons show selective responses to complex visual images such as faces, and at each stage along the pathway the stimulus selectivity of the neural responses becomes sharper, particularly in the later portion of the responses. In the IT cortex of the monkey, facial information is represented by different temporal stages of neural responses, as shown in our previous study: the initial transient response of face-responsive neurons represents information about global categories, i.e., human vs. monkey vs. simple shapes, whilst the later portion of these responses represents information about detailed facial categories, i.e., expression and/or identity. This suggests that the temporal stages of the neuronal firing pattern play an important role in the coding of visual stimuli, including faces. This type of coding may be a plausible mechanism underlying the temporal dynamics of recognition, including the process of detection/categorization followed by the identification of objects. Recent single-unit studies in monkeys have also provided evidence consistent with the important role of the temporal stages of encoded facial information. For example, view-invariant facial identity information is represented in the response at a later period within a region of face-selective neurons. Consistent with these findings, temporally modulated neural activity has also been observed in human studies. These results suggest a close correlation between the temporal processing stages of facial information by IT neurons and the temporal dynamics of face recognition.

Role of Temporal Processing Stages by Inferior Temporal Neurons in Facial Recognition

PubMed Central

Sugase-Miyamoto, Yasuko; Matsumoto, Narihisa; Kawano, Kenji

2011-01-01

In this review, we focus on the role of temporal stages of encoded facial information in the visual system, which might enable the efficient determination of species, identity, and expression. Facial recognition is an important function of our brain and is known to be processed in the ventral visual pathway, where visual signals are processed through areas V1, V2, V4, and the inferior temporal (IT) cortex. In the IT cortex, neurons show selective responses to complex visual images such as faces, and at each stage along the pathway the stimulus selectivity of the neural responses becomes sharper, particularly in the later portion of the responses. In the IT cortex of the monkey, facial information is represented by different temporal stages of neural responses, as shown in our previous study: the initial transient response of face-responsive neurons represents information about global categories, i.e., human vs. monkey vs. simple shapes, whilst the later portion of these responses represents information about detailed facial categories, i.e., expression and/or identity. This suggests that the temporal stages of the neuronal firing pattern play an important role in the coding of visual stimuli, including faces. This type of coding may be a plausible mechanism underlying the temporal dynamics of recognition, including the process of detection/categorization followed by the identification of objects. Recent single-unit studies in monkeys have also provided evidence consistent with the important role of the temporal stages of encoded facial information. For example, view-invariant facial identity information is represented in the response at a later period within a region of face-selective neurons. Consistent with these findings, temporally modulated neural activity has also been observed in human studies. These results suggest a close correlation between the temporal processing stages of facial information by IT neurons and the temporal dynamics of face recognition. PMID:21734904

Extending Vulnerability Assessment to Include Life Stages Considerations

PubMed Central

Hodgson, Emma E.; Essington, Timothy E.; Kaplan, Isaac C.

2016-01-01

Species are experiencing a suite of novel stressors from anthropogenic activities that have impacts at multiple scales. Vulnerability assessment is one tool to evaluate the likely impacts that these stressors pose to species so that high-vulnerability cases can be identified and prioritized for monitoring, protection, or mitigation. Commonly used semi-quantitative methods lack a framework to explicitly account for differences in exposure to stressors and organism responses across life stages. Here we propose a modification to commonly used spatial vulnerability assessment methods that includes such an approach, using ocean acidification in the California Current as an illustrative case study. Life stage considerations were included by assessing vulnerability of each life stage to ocean acidification and were used to estimate population vulnerability in two ways. We set population vulnerability equal to: (1) the maximum stage vulnerability and (2) a weighted mean across all stages, with weights calculated using Lefkovitch matrix models. Vulnerability was found to vary across life stages for the six species explored in this case study: two krill–Euphausia pacifica and Thysanoessa spinifera, pteropod–Limacina helicina, pink shrimp–Pandalus jordani, Dungeness crab–Metacarcinus magister and Pacific hake–Merluccius productus. The maximum vulnerability estimates ranged from larval to subadult and adult stages with no consistent stage having maximum vulnerability across species. Similarly, integrated vulnerability metrics varied greatly across species. A comparison showed that some species had vulnerabilities that were similar between the two metrics, while other species’ vulnerabilities varied substantially between the two metrics. These differences primarily resulted from cases where the most vulnerable stage had a low relative weight. We compare these methods and explore circumstances where each method may be appropriate. PMID:27416031

Extending Vulnerability Assessment to Include Life Stages Considerations.

PubMed

Hodgson, Emma E; Essington, Timothy E; Kaplan, Isaac C

2016-01-01

Species are experiencing a suite of novel stressors from anthropogenic activities that have impacts at multiple scales. Vulnerability assessment is one tool to evaluate the likely impacts that these stressors pose to species so that high-vulnerability cases can be identified and prioritized for monitoring, protection, or mitigation. Commonly used semi-quantitative methods lack a framework to explicitly account for differences in exposure to stressors and organism responses across life stages. Here we propose a modification to commonly used spatial vulnerability assessment methods that includes such an approach, using ocean acidification in the California Current as an illustrative case study. Life stage considerations were included by assessing vulnerability of each life stage to ocean acidification and were used to estimate population vulnerability in two ways. We set population vulnerability equal to: (1) the maximum stage vulnerability and (2) a weighted mean across all stages, with weights calculated using Lefkovitch matrix models. Vulnerability was found to vary across life stages for the six species explored in this case study: two krill-Euphausia pacifica and Thysanoessa spinifera, pteropod-Limacina helicina, pink shrimp-Pandalus jordani, Dungeness crab-Metacarcinus magister and Pacific hake-Merluccius productus. The maximum vulnerability estimates ranged from larval to subadult and adult stages with no consistent stage having maximum vulnerability across species. Similarly, integrated vulnerability metrics varied greatly across species. A comparison showed that some species had vulnerabilities that were similar between the two metrics, while other species' vulnerabilities varied substantially between the two metrics. These differences primarily resulted from cases where the most vulnerable stage had a low relative weight. We compare these methods and explore circumstances where each method may be appropriate.

Genetic architecture of cold tolerance in rice (Oryza sativa) determined through high resolution genome-wide analysis

PubMed Central

Shakiba, Ehsan; Edwards, Jeremy D.; Jodari, Farman; Duke, Sara E.; Baldo, Angela M.; Korniliev, Pavel; McCouch, Susan R.; Eizenga, Georgia C.

2017-01-01

Cold temperature is an important abiotic stress which negatively affects morphological development and seed production in rice (Oryza sativa L.). At the seedling stage, cold stress causes poor germination, seedling injury and poor stand establishment; and at the reproductive stage cold decreases seed yield. The Rice Diversity Panel 1 (RDP1) is a global collection of over 400 O. sativa accessions representing the five major subpopulations from the INDICA and JAPONICA varietal groups, with a genotypic dataset consisting of 700,000 SNP markers. The objectives of this study were to evaluate the RDP1 accessions for the complex, quantitatively inherited cold tolerance traits at the germination and reproductive stages, and to conduct genome-wide association (GWA) mapping to identify SNPs and candidate genes associated with cold stress at these stages. GWA mapping of the germination index (calculated as percent germination in cold divided by warm treatment) revealed 42 quantitative trait loci (QTLs) associated with cold tolerance at the seedling stage, including 18 in the panel as a whole, seven in temperate japonica, six in tropical japonica, 14 in JAPONICA, and nine in INDICA, with five shared across all subpopulations. Twenty-two of these QTLs co-localized with 32 previously reported cold tolerance QTLs. GWA mapping of cold tolerance at the reproductive stage detected 29 QTLs, including seven associated with percent sterility, ten with seed weight per panicle, 14 with seed weight per plant and one region overlapping for two traits. Fifteen co-localized with previously reported QTLs for cold tolerance or yield components. Candidate gene ontology searches revealed these QTLs were associated with significant enrichment for genes related to with lipid metabolism, response to stimuli, response to biotic stimuli (suggesting cross-talk between biotic and abiotic stresses), and oxygen binding. Overall the JAPONICA accessions were more tolerant to cold stress than INDICA accessions. PMID:28282385

Flight and Integrated Vehicle Testing: Laying the Groundwork for the Next Generation of Space Exploration Launch Vehicles

NASA Technical Reports Server (NTRS)

Taylor, J. L.; Cockrell, C. E.

2009-01-01

Integrated vehicle testing will be critical to ensuring proper vehicle integration of the Ares I crew launch vehicle and Ares V cargo launch vehicle. The Ares Projects, based at Marshall Space Flight Center in Alabama, created the Flight and Integrated Test Office (FITO) as a separate team to ensure that testing is an integral part of the vehicle development process. As its name indicates, FITO is responsible for managing flight testing for the Ares vehicles. FITO personnel are well on the way toward assembling and flying the first flight test vehicle of Ares I, the Ares I-X. This suborbital development flight will evaluate the performance of Ares I from liftoff to first stage separation, testing flight control algorithms, vehicle roll control, separation and recovery systems, and ground operations. Ares I-X is now scheduled to fly in summer 2009. The follow-on flight, Ares I-Y, will test a full five-segment first stage booster and will include cryogenic propellants in the upper stage, an upper stage engine simulator, and an active launch abort system. The following flight, Orion 1, will be the first flight of an active upper stage and upper stage engine, as well as the first uncrewed flight of an Orion spacecraft into orbit. The Ares Projects are using an incremental buildup of flight capabilities prior to the first operational crewed flight of Ares I and the Orion crew exploration vehicle in 2015. In addition to flight testing, the FITO team will be responsible for conducting hardware, software, and ground vibration tests of the integrated launch vehicle. These efforts will include verifying hardware, software, and ground handling interfaces. Through flight and integrated testing, the Ares Projects will identify and mitigate risks early as the United States prepares to take its next giant leaps to the Moon and beyond.

Life stage influences the resistance and resilience of black mangrove forests to winter climate extremes

USGS Publications Warehouse

Osland, Michael J.; Day, Richard H.; From, Andrew S.; McCoy, Megan L.; McLeod, Jennie L.; Kelleway, Jeffrey

2015-01-01

In subtropical coastal wetlands on multiple continents, climate change-induced reductions in the frequency and intensity of freezing temperatures are expected to lead to the expansion of woody plants (i.e., mangrove forests) at the expense of tidal grasslands (i.e., salt marshes). Since some ecosystem goods and services would be affected by mangrove range expansion, there is a need to better understand mangrove sensitivity to freezing temperatures as well as the implications of changing winter climate extremes for mangrove-salt marsh interactions. In this study, we investigated the following questions: (1) how does plant life stage (i.e., ontogeny) influence the resistance and resilience of black mangrove (Avicennia germinans) forests to freezing temperatures; and (2) how might differential life stage responses to freeze events affect the rate of mangrove expansion and salt marsh displacement due to climate change? To address these questions, we quantified freeze damage and recovery for different life stages (seedling, short tree, and tall tree) following extreme winter air temperature events that occurred near the northern range limit of A. germinans in North America. We found that life stage affects black mangrove forest resistance and resilience to winter climate extremes in a nonlinear fashion. Resistance to winter climate extremes was high for tall A. germinans trees and seedlings, but lowest for short trees. Resilience was highest for tall A. germinans trees. These results suggest the presence of positive feedbacks and indicate that climate-change induced decreases in the frequency and intensity of extreme minimum air temperatures could lead to a nonlinear increase in mangrove forest resistance and resilience. This feedback could accelerate future mangrove expansion and salt marsh loss at rates beyond what would be predicted from climate change alone. In general terms, our study highlights the importance of accounting for differential life stage responses and positive feedbacks when evaluating the ecological effects of changes in the frequency and magnitude of climate extremes.

Practice Patterns of Radiation Field Design for Sentinel Lymph Node-Positive Early-Stage Breast Cancer.

PubMed

Azghadi, Soheila; Daly, Megan; Mayadev, Jyoti

2016-10-01

Recent randomized trials have led to decreased use of completion axillary lymph node dissection (ALND) in early-stage breast cancer patients with a positive sentinel lymph node (SLN), causing controversy surrounding radiotherapy coverage of the axilla. We investigated the practice variation among radiation oncologists for regional nodal coverage for clinicopathologic scenarios and evaluated axillary field design decision-making processes. A customized, web-based questionnaire was e-mailed to 983 community (n = 617) and academic (n = 366) radiation oncologists with a breast cancer subspecialty practicing in the United States. The survey consisted of 18 multiple-choice questions evaluating general clinical preferences surrounding radiation therapy (RT) field design for patients with early-stage breast cancer and a positive SLN. Seven case scenarios were developed to investigate the field design in the setting of specific clinical and pathologic risk factors. Nodal coverage was classified as standard tangents (STs), high tangents (HTs), STs and a supraclavicular field (SCF), or STs and full axillary coverage (AX). A total of 145 evaluable responses were collected, with a response rate of 15.0%. Of the respondents, 12 (8.3%) reported using completion ALND for patients with 1 to 3 positive SLNs without extracapsular extension (ECE) and 66 (45.5%) performed ALND with 1 to 3 positive SLNs with ECE. For micrometastatic SLNs, with no lymphovascular system invasion, 115 (87.1%) used STs or HTs. The use of neoadjuvant chemotherapy (NAC) influenced RT field design for patients with a positive SLN without ECE, with 64 (48.5%) using STs and SCF or STs and AX treatment without NAC and 94 (70.7%) using SCF and AX after NAC. With macrometastatic SLN involvement, most respondents preferred SCF (45.27%) and AX (45.66%). In contrast, for micrometastatic involvement, HTs (43.61%) were frequently chosen. Forty (27.8%) reported using online predictive nomograms to predict further axillary involvement, with no difference between the academic and community radiation oncologists (P = .11). In SLN biopsy-positive early-stage breast cancer with omission of completion ALND, axillary RT is increasing used to cover the undissected axilla. Most respondents use SCF or AX for patients with low to intermediate pathologic features. Online prediction nomograms are used by a few practitioners to assist in clinical decision-making in this setting. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of FDG-PET scans in staging, response assessment, and follow-up care for non-small cell lung cancer

PubMed Central

Cuaron, John; Dunphy, Mark; Rimner, Andreas

2013-01-01

The integral role of positron-emission tomography (PET) using the glucose analog tracer fluorine-18 fluorodeoxyglucose (FDG) in the staging of non-small cell lung cancer (NSCLC) is well established. Evidence is emerging for the role of PET in response assessment to neoadjuvant therapy, combined-modality therapy, and early detection of recurrence. Here, we review the current literature on these aspects of PET in the management of NSCLC. FDG-PET, particularly integrated 18F-FDG-PET/CT, scans have become a standard test in the staging of local tumor extent, mediastinal lymph node involvement, and distant metastatic disease in NSCLC. 18F-FDG-PET sensitivity is generally superior to computed tomography (CT) scans alone. Local tumor extent and T stage can be more accurately determined with FDG-PET in certain cases, especially in areas of post-obstructive atelectasis or low CT density variation. FDG-PET sensitivity is decreased in tumors <1 cm, at least in part due to respiratory motion. False-negative results can occur in areas of low tumor burden, e.g., small lymph nodes or ground-glass opacities. 18F-FDG-PET-CT nodal staging is more accurate than CT alone, as hilar and mediastinal involvement is often detected first on 18F-FDG-PET scan when CT criteria for malignant involvement are not met. 18F-FDG-PET scans have widely replaced bone scintography for assessing distant metastases, except for the brain, which still warrants dedicated brain imaging. 18F-FDG uptake has also been shown to vary between histologies, with adenocarcinomas generally being less FDG avid than squamous cell carcinomas. 18F-FDG-PET scans are useful to detect recurrences, but are currently not recommended for routine follow-up. Typically, patients are followed with chest CT scans every 3–6 months, using 18F-FDG-PET to evaluate equivocal CT findings. As high 18F-FDG uptake can occur in infectious, inflammatory, and other non-neoplastic conditions, 18F-FDG-PET-positive findings require pathological confirmation in most cases. There is increased interest in the prognostic and predictive role of FDG-PET scans. Studies show that absence of metabolic response to neoadjuvant therapy correlates with poor pathologic response, and a favorable 18F-FDG-PET response appears to be associated with improved survival. Further work is underway to identify subsets of patients that might benefit individualized management based on FDG-PET. PMID:23316478

Role of FDG-PET scans in staging, response assessment, and follow-up care for non-small cell lung cancer.

PubMed

Cuaron, John; Dunphy, Mark; Rimner, Andreas

2012-01-01

The integral role of positron-emission tomography (PET) using the glucose analog tracer fluorine-18 fluorodeoxyglucose (FDG) in the staging of non-small cell lung cancer (NSCLC) is well established. Evidence is emerging for the role of PET in response assessment to neoadjuvant therapy, combined-modality therapy, and early detection of recurrence. Here, we review the current literature on these aspects of PET in the management of NSCLC. FDG-PET, particularly integrated (18)F-FDG-PET/CT, scans have become a standard test in the staging of local tumor extent, mediastinal lymph node involvement, and distant metastatic disease in NSCLC. (18)F-FDG-PET sensitivity is generally superior to computed tomography (CT) scans alone. Local tumor extent and T stage can be more accurately determined with FDG-PET in certain cases, especially in areas of post-obstructive atelectasis or low CT density variation. FDG-PET sensitivity is decreased in tumors <1 cm, at least in part due to respiratory motion. False-negative results can occur in areas of low tumor burden, e.g., small lymph nodes or ground-glass opacities. (18)F-FDG-PET-CT nodal staging is more accurate than CT alone, as hilar and mediastinal involvement is often detected first on (18)F-FDG-PET scan when CT criteria for malignant involvement are not met. (18)F-FDG-PET scans have widely replaced bone scintography for assessing distant metastases, except for the brain, which still warrants dedicated brain imaging. (18)F-FDG uptake has also been shown to vary between histologies, with adenocarcinomas generally being less FDG avid than squamous cell carcinomas. (18)F-FDG-PET scans are useful to detect recurrences, but are currently not recommended for routine follow-up. Typically, patients are followed with chest CT scans every 3-6 months, using (18)F-FDG-PET to evaluate equivocal CT findings. As high (18)F-FDG uptake can occur in infectious, inflammatory, and other non-neoplastic conditions, (18)F-FDG-PET-positive findings require pathological confirmation in most cases. There is increased interest in the prognostic and predictive role of FDG-PET scans. Studies show that absence of metabolic response to neoadjuvant therapy correlates with poor pathologic response, and a favorable (18)F-FDG-PET response appears to be associated with improved survival. Further work is underway to identify subsets of patients that might benefit individualized management based on FDG-PET.

High-Throughput Screening of Chemical Effects on Steroidogenesis Using H295R Human Adrenocortical Carcinoma Cells.

PubMed

Karmaus, Agnes L; Toole, Colleen M; Filer, Dayne L; Lewis, Kenneth C; Martin, Matthew T

2016-04-01

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ≥ 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into 5 distinct profiles generally representing putative mechanisms of action, including CYP17A1 and HSD3B inhibition. A distinct pattern was observed between imidazole and triazole fungicides suggesting potentially distinct mechanisms of action. From a chemical testing and prioritization perspective, this assay platform provides a robust model for high-throughput screening of chemicals for effects on steroidogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

High-Throughput Screening of Chemical Effects on Steroidogenesis Using H295R Human Adrenocortical Carcinoma Cells

PubMed Central

Toole, Colleen M.; Filer, Dayne L.; Lewis, Kenneth C.; Martin, Matthew T.

2016-01-01

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ≥ 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into 5 distinct profiles generally representing putative mechanisms of action, including CYP17A1 and HSD3B inhibition. A distinct pattern was observed between imidazole and triazole fungicides suggesting potentially distinct mechanisms of action. From a chemical testing and prioritization perspective, this assay platform provides a robust model for high-throughput screening of chemicals for effects on steroidogenesis. PMID:26781511

Behavioral alterations of zebrafish larvae after early embryonic exposure to ketamine.

PubMed

Félix, Luís M; Antunes, Luís M; Coimbra, Ana M; Valentim, Ana M

2017-02-01

Ketamine has been associated with pediatric risks that include neurocognitive impairment and long-term behavioral disorders. However, the neurobehavioral effects of ketamine exposure in early development remain uncertain. This study aimed to test stage- and dose-dependent effects of ketamine exposure on certain brain functions by evaluating alterations in locomotion, anxiety-like and avoidance behaviors, as well as socialization. Embryos were exposed to different concentrations of ketamine (0, 0.2, 0.4, and 0.8 mg mL -1 ) for 20 min during the 256-cell (2.5 h post fertilization-hpf), 50% epiboly (5.5 hpf), and 1-4 somites (10.5 hpf) stages. General exploratory activities, natural escape-like responses, and social interactions were analyzed under continuous light or under a moving light stimulus. A dose-dependent decrease in the overall mean speed was perceived in the embryos exposed during the 256-cell stage. These results were related to previously observed head and eye malformations, following ketamine exposure at this stage and may indicate possible neurobehavioral disorders when ketamine exposure is performed at this stage. Results also showed that ketamine exposure during the 50% epiboly and 1-4 somites stages induced a significant increment of the anxiety-like behavior and a decrease in avoidance behavior in all exposed groups. Overall, the results validate the neurodevelopmental risks of early-life exposure to ketamine.

Application of Boston matrix combined with SWOT analysis on operational development and evaluations of hospital development.

PubMed

Tao, Z-Q; Shi, A-M

2016-05-01

The aim of this study is to explore the application of Boston matrix combined with SWOT analysis on operational development and evaluations of hospital departments. We selected 73 clinical and medical technology departments of our hospital from 2011 to 2013, and evaluated our hospital by Boston matrix combined with SWOT analysis according to the volume of services, medical quality, work efficiency, patients' evaluations, development capacity, operational capability, economic benefits, comprehensive evaluation of hospital achievement, innovation ability of hospital, influence of hospital, human resources of hospital, health insurance costs, etc. It was found that among clinical departments, there were 11 in Stars (22.4%), 17 in cash cow (34.7%), 15 in question marks (31.2%), 6 Dogs (12.2%), 16 in the youth stage of life cycle assessment (27.6%), 14 in the prime stage (24.1%), 12 in the stationary stage (20.7%), 9 in the aristocracy stage (15.5%) and 7 in the recession stage (12.1%). Among medical technology departments, there were 5 in Stars (20.8%), 1 in Cash cow (4.2%), 10 in question marks (41.6%), 8 Dogs (29.1%), 9 in the youth stage of life cycle assessment (37.5%), 4 in the prime stage (16.7%), 4 in the stable stage (16.7%), 1 in the aristocracy stage (4.2%) and 6 in the recession stage (25%). In conclusion, Boston matrix combined with SWOT analysis is suitable for operational development and comprehensive evaluations of hospital development, and it plays an important role in providing hospitals with development strategies.

Selection of response criteria for clinical trials of sarcoma treatment.

PubMed

Schuetze, Scott M; Baker, Laurence H; Benjamin, Robert S; Canetta, Renzo

2008-01-01

Soft tissue sarcomas are a heterogeneous group of malignancies arising from mesenchymal tissues. A large number of new therapies are being evaluated in patients with sarcomas, and consensus criteria defining treatment responses are essential for comparison of results from studies completed by different research groups. The 1979 World Health Organization (WHO) handbook set forth operationally defined criteria for response evaluation in solid tumors that were updated in 2000 with the publication of the Response Evaluation Criteria in Solid Tumors (RECIST). There have been significant advances in tumor imaging, however, that are not reflected in the RECIST. For example, computed tomography (CT) slice thickness has been reduced from 10 mm to < or =2.5 mm, allowing for more reproducible and accurate measurement of smaller lesions. Combination of imaging techniques, such as positron emission tomography with fluorine-18-fluorodeoxyglucose (18FDG-PET) and CT can provide investigators and clinicians with both anatomical and functional information regarding tumors, and there is now a large body of evidence demonstrating the effectiveness of PET/CT and other newer imaging methods for the detection and staging of tumors as well as early determination of responses to therapy. The application of newer imaging methods has the potential to decrease both the sample sizes required for, and duration of, clinical trials by providing an early indication of therapeutic response that is well correlated with clinical outcomes, such as time to tumor progression or overall survival. The results summarized in this review support the conclusion that the RECIST and the WHO criteria for evaluation of response in solid tumors need to be modernized. In addition, there is a current need for prospective trials to compare new response criteria with established endpoints and to validate imaging-based response rates as surrogate endpoints for clinical trials of new agents for sarcoma and other solid tumors.

Damage progression in Composite Structures

NASA Technical Reports Server (NTRS)

Minnetyan, Levon

1996-01-01

A computational simulation tool is used to evaluate the various stages of damage progression in composite materials during Iosipescu sheat testing. Unidirectional composite specimens with either the major or minor material axis in the load direction are considered. Damage progression characteristics are described for each specimen using two types of boundary conditions. A procedure is outlined regarding the use of computational simulation in composites testing. Iosipescu shear testing using the V-notched beam specimen is a convenient method to measure both shear strength and shear stiffness simultaneously. The evaluation of composite test response can be made more productive and informative via computational simulation of progressive damage and fracture. Computational simulation performs a complete evaluation of laminated composite fracture via assessment of ply and subply level damage/fracture processes.

A whole-killed, blood-stage lysate vaccine protects against the malaria liver stage.

PubMed

Lu, X; Liu, T; Zhu, F; Chen, L; Xu, W

2017-01-01

Although the attenuated sporozoite is the most efficient vaccine to prevent infection with the malaria parasite, the limitation of a source of sterile sporozoites greatly hampers its application. In this study, we found that the whole-killed, blood-stage lysate vaccine could confer protection against the blood stage as well as the liver stage. Although the protective immunity induced by the whole-organism vaccine against the blood stage is dependent on parasite-specific CD4 + T-cell responses and antibodies, in mice immunized with the whole-killed, blood-stage lysate vaccine, CD8 + , but not CD4 + effector T-cell responses greatly contributed to protection against the liver stage. Thus, our data suggested that the whole-killed, blood-stage lysate vaccine could be an alternative promising strategy to prevent malaria infection and to reduce the morbidity and mortality of patients with malaria. © 2016 John Wiley & Sons Ltd.

Teamwork in perioperative nursing. Understanding team development, effectiveness, evaluation.

PubMed

Farley, M J

1991-03-01

Teams are an essential part of perioperative nursing practice. Nurses who have a knowledge of teamwork and experience in working on teams have a greater understanding of the processes and problems involved as teams develop from new, immature teams to those that are mature and effective. This understanding will assist nurses in helping their teams achieve a higher level of productivity, and members will be more satisfied with team efforts. Team development progresses through several stages. Each stage has certain characteristics and desired outcomes. At each stage, team members and leaders have certain responsibilities. Team growth does not take place automatically and inevitably, but as a consequence of conscious and unconscious efforts of its leader and members to solve problems and satisfy needs. Building and maintaining a team is certainly work, but work that brings a great deal of satisfaction and feelings of pride in accomplishment. According to I Tenzer, RN, MS, teamwork "is not a panacea; it is a viable approach to developing a hospital's most valuable resource--people."

4(1H)-Pyridone and 4(1H)-Quinolone Derivatives as Antimalarials with Erythrocytic, Exoerythrocytic, and Transmission Blocking Activities

PubMed Central

Monastyrskyi, Andrii; Kyle, Dennis E.; Manetsch, Roman

2015-01-01

Infectious diseases are the second leading cause of deaths in the world with malaria being responsible for approximately the same amount of deaths as cancer in 2012. Despite the success in malaria prevention and control measures decreasing the disease mortality rate by 45% since 2000, the development of single-dose therapeutics with radical cure potential is required to completely eradicate this deadly condition. Targeting multiple stages of the malaria parasite is becoming a primary requirement for new candidates in antimalarial drug discovery and development. Recently, 4(1H)-pyridone, 4(1H)-quinolone, 1,2,3,4-tetrahydroacridone, and phenoxyethoxy-4(1H)-quinolone chemotypes have been shown to be antimalarials with blood stage activity, liver stage activity, and transmission blocking activity. Advancements in structure-activity relationship and structure-property relationship studies, biological evaluation in vitro and in vivo, as well as pharmacokinetics of the 4(1H)-pyridone and 4(1H)-quinolone chemotypes will be discussed. PMID:25116582

Reliability of an incremental exercise test to evaluate acute blood lactate, heart rate and body temperature responses in Labrador retrievers.

PubMed

Ferasin, Luca; Marcora, Samuele

2009-10-01

Thirteen healthy Labrador retrievers underwent a 5-stage incremental treadmill exercise test to assess its reliability. Blood lactate (BL), heart rate (HR), and body temperature (BT) were measured at rest, after each stage of exercise, and after a 20-min recovery. Reproducibility was assessed by repeating the test after 7 days. Two-way MANOVAs revealed significant differences between consecutive stages, and between values at rest and after recovery. There was also a significant reduction in physiological strain between the first and second trial (learning effect). Test reliability expressed as typical error (BL = 0.22 mmol/l, HR = 9.81 bpm, BT = 0.22 degrees C), coefficient of variation (BL = 19.3%, HR = 7.9% and BT = 0.6%) and test-retest correlation (BL = 0.89, HR = 0.96, BT = 0.95) was good. Results support test reproducibility although the learning effect needs to be controlled when investigating the exercise-related problems commonly observed in this breed.

[Evaluation of psychophysiological status and performance ability in patients with hypertensive disease employed under strained working conditions].

PubMed

Zamotaev, Iu N; Enikeev, A Kh

2009-01-01

The aim of this work was to study psychophysiological functions in HD subjects during strenuous conveyor-belt work. It involved 225 participants of whom 195 presented with different stages of HD. Group 1 (n = 65) included patients with prehypertension, group 2 (n = 69) with stage 1 HD, group 3 (n = 61) with stage II HD. Control group comprised 30 healthy subjects. The groups were matched for clinical and demographic characteristics. It was shown that performance efficiency of the conveyor-belt workers decreased with increasing HD severity. Mental functioning was the first to be affected suggesting impairment of sensorimotor coordination and attention. Moreover, the performance correlated with the patients" age and length of work. The worst results of simple and complex visual-motor reaction time tests were obtained in patients above 40 years with more than 10 years" conveyor-work experience. Close relation of performance efficiency to psychosomatic condition reflects interplay of regulatory mechanisms responsible for optimal adaptation of the organism to strenuous work.

DECISION-MAKING ALIGNED WITH RAPID-CYCLE EVALUATION IN HEALTH CARE.

PubMed

Schneeweiss, Sebastian; Shrank, William H; Ruhl, Michael; Maclure, Malcolm

2015-01-01

Availability of real-time electronic healthcare data provides new opportunities for rapid-cycle evaluation (RCE) of health technologies, including healthcare delivery and payment programs. We aim to align decision-making processes with stages of RCE to optimize the usefulness and impact of rapid results. Rational decisions about program adoption depend on program effect size in relation to externalities, including implementation cost, sustainability, and likelihood of broad adoption. Drawing on case studies and experience from drug safety monitoring, we examine how decision makers have used scientific evidence on complex interventions in the past. We clarify how RCE alters the nature of policy decisions; develop the RAPID framework for synchronizing decision-maker activities with stages of RCE; and provide guidelines on evidence thresholds for incremental decision-making. In contrast to traditional evaluations, RCE provides early evidence on effectiveness and facilitates a stepped approach to decision making in expectation of future regularly updated evidence. RCE allows for identification of trends in adjusted effect size. It supports adapting a program in midstream in response to interim findings, or adapting the evaluation strategy to identify true improvements earlier. The 5-step RAPID approach that utilizes the cumulating evidence of program effectiveness over time could increase policy-makers' confidence in expediting decisions. RCE enables a step-wise approach to HTA decision-making, based on gradually emerging evidence, reducing delays in decision-making processes after traditional one-time evaluations.

Regional brain activity during early-stage intense romantic love predicted relationship outcomes after 40 months: an fMRI assessment.

PubMed

Xu, Xiaomeng; Brown, Lucy; Aron, Arthur; Cao, Guikang; Feng, Tingyong; Acevedo, Bianca; Weng, Xuchu

2012-09-20

Early-stage romantic love is associated with activation in reward and motivation systems of the brain. Can these localized activations, or others, predict long-term relationship stability? We contacted participants from a previous fMRI study of early-stage love by Xu et al. [34] after 40 months from initial assessments. We compared brain activation during the initial assessment at early-stage love for those who were still together at 40 months and those who were apart, and surveyed those still together about their relationship happiness and commitment at 40 months. Six participants who were still with their partners at 40 months (compared to six who had broken up) showed less activation during early-stage love in the medial orbitofrontal cortex, right subcallosal cingulate and right accumbens, regions implicated in long-term love and relationship satisfaction [1,2]. These regions of deactivation at the early stage of love were also negatively correlated with relationship happiness scores collected at 40 months. Other areas involved were the caudate tail, and temporal and parietal lobes. These data are preliminary evidence that neural responses in the early stages of romantic love can predict relationship stability and quality up to 40 months later in the relationship. The brain regions involved suggest that forebrain reward functions may be predictive for relationship stability, as well as regions involved in social evaluation, emotional regulation, and mood. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The surface charge of trypanosomatids.

PubMed

Souto-Padrón, Thaïs

2002-12-01

The surface charge of trypanosomatids was evaluated by means of the binding of cationic particles, as visualized by electron microscopy and by direct measurements of the electrophoretic mobility of cells. The results obtained indicate that most of the trypanosomatids exhibit a negatively charged surface whose value is species specific and varies according to the developmental stages. Sialic acids associated with glycoproteins, glycolipids and phosphate groups are the major components responsible for the net negative surface charge of the trypanosomatids.

Genetic Mutations in Blood and Tissue Samples in Predicting Response to Treatment in Patients With Locally Advanced Rectal Cancer Undergoing Chemoradiation

ClinicalTrials.gov

2017-09-08

Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

Music performance anxiety in skilled pianists: effects of social-evaluative performance situation on subjective, autonomic, and electromyographic reactions.

PubMed

Yoshie, Michiko; Kudo, Kazutoshi; Murakoshi, Takayuki; Ohtsuki, Tatsuyuki

2009-11-01

Music performance anxiety (MPA), or stage fright in music performance, is a serious problem for many musicians, because performance impairment accompanied by MPA can threaten their career. The present study sought to clarify on how a social-evaluative performance situation affects subjective, autonomic, and motor stress responses in pianists. Measurements of subjective state anxiety, heart rate (HR), sweat rate (SR), and electromyographic (EMG) activity of upper extremity muscles were obtained while 18 skilled pianists performed a solo piano piece(s) of their choice under stressful (competition) and non-stressful (rehearsal) conditions. Participants reported greater anxiety in the competition condition, which confirmed the effectiveness of stress manipulation. The HR and SR considerably increased from the rehearsal to competition condition reflecting the activation of sympathetic division of the autonomic nervous system. Furthermore, participants showed higher levels of the EMG magnitude of proximal muscles (biceps brachii and upper trapezius) and the co-contraction of antagonistic muscles in the forearm (extensor digitorum communis and flexor digitorum superficialis) in the competition condition. Although these responses can be interpreted as integral components of an adaptive biological system that creates a state of motor readiness in an unstable or unpredictable environment, they can adversely influence pianists by disrupting their fine motor control on stage and by increasing the risk of playing-related musculoskeletal disorders.

Management of advanced pancreatic cancer in daily clinical practice.

PubMed

Giuliani, Jacopo; Piacentini, Paolo; Bonetti, Andrea

2016-01-01

The aim of this outcome study was to evaluate the management of advanced pancreatic cancer in a real-world clinical practice; few such experiences have been reported in the literature. A retrospective analysis was performed of all consecutive patients with advanced pancreatic ductal adenocarcinoma followed at our medical oncology unit between January 2003 and December 2013. We evaluated 78 patients, mostly with metastatic disease (64.1%). Median follow-up was 10.77 months, by which time 74 patients (94.9%) had died. Median overall survival was 8.29 months. Median age was 67 years. In univariate analysis, pain at onset (p = 0.020), ECOG performance status (p<0.001), stage (p = 0.047), first-line chemotherapy (p<0.001), second-line chemotherapy (p<0.001) and weight loss at diagnosis (p = 0.029) were factors that had an impact on overall survival. In multivariate analysis, the presence of pain at onset (p = 0.043), stage (p = 0.003) and second-line chemotherapy (p = 0.004) were confirmed as independent prognostic factors. Our data, derived from daily clinical practice, confirmed advanced pancreatic cancer as an aggressive malignant disease with a very short expected survival. Second-line treatment seems to provide an advantage in terms of overall survival in patients who showed a partial response as their best response to first-line treatment.

Role of (18)F-FDG PET-CT in head and neck squamous cell carcinoma.

PubMed

Castaldi, P; Leccisotti, L; Bussu, F; Miccichè, F; Rufini, V

2013-02-01

The role of PET-CT imaging in head and neck squamous cell carcinoma during pre-treatment staging, radiotherapy planning, treatment response assessment and post-therapy follow-up is reviewed with focus on current evidence, controversial issues and future clinical applications. In staging, the role of (18)F-FDG PET-CT is well recognized for detecting cervical nodal involvement as well as for exclusion of distant metastases and synchronous primary tumours. In the evaluation of treatment response, the high negative predictive value of (18)F-FDG PET-CT performed at least 8 weeks from the end of radio-chemotherapy allows prevention of unnecessary diagnostic invasive procedures and neck dissection in many patients, with a significant impact on clinical outcome. On the other hand, in this setting, the low positive predictive value due to possible post-radiation inflammation findings requires special care before making a clinical decision. Controversial data are currently available on the role of PET imaging during the course of radio-chemotherapy. The prognostic role of (18)F-FDG PET-CT imaging in head and neck squamous cell carcinoma is recently emerging, in addition to the utility of this technique in evaluation of the tumour volume for planning radiation therapy. Additionally, new PET radiopharmaceuticals could provide considerable information on specific tumour characteristics, thus overcoming the limitations of (18)F-FDG.

Low doses of killed parasite in CpG elicit vigorous CD4+ T cell responses against blood-stage malaria in mice

PubMed Central

Pinzon-Charry, Alberto; McPhun, Virginia; Kienzle, Vivian; Hirunpetcharat, Chakrit; Engwerda, Christian; McCarthy, James; Good, Michael F.

2010-01-01

Development of a vaccine that targets blood-stage malaria parasites is imperative if we are to sustainably reduce the morbidity and mortality caused by this infection. Such a vaccine should elicit long-lasting immune responses against conserved determinants in the parasite population. Most blood-stage vaccines, however, induce protective antibodies against surface antigens, which tend to be polymorphic. Cell-mediated responses, on the other hand, offer the theoretical advantage of targeting internal antigens that are more likely to be conserved. Nonetheless, few of the current blood-stage vaccine candidates are able to harness vigorous T cell immunity. Here, we present what we believe to be a novel blood-stage whole-organism vaccine that, by combining low doses of killed parasite with CpG-oligodeoxynucleotide (CpG-ODN) adjuvant, was able to elicit strong and cross-reactive T cell responses in mice. Our data demonstrate that immunization of mice with 1,000 killed parasites in CpG-ODN engendered durable and cross-strain protection by inducing a vigorous response that was dependent on CD4+ T cells, IFN-γ, and nitric oxide. If applicable to humans, this approach should facilitate the generation of robust, cross-reactive T cell responses against malaria as well as antigen availability for vaccine manufacture. PMID:20628205

Profiling of Disease-Related Metabolites in Grapevine Internode Tissues Infected with Agrobacterium vitis

PubMed Central

Jung, Sung-Min; Hur, Youn-Young; Preece, John E.; Fiehn, Oliver; Kim, Young-Ho

2016-01-01

Green shoot cuttings of 10 different grapevine species were inoculated with Agrobacterium vitis to find disease-related metabolites in the grapevine. Crown galls formed 60 days after inoculation varied in gall severity (GS) evaluated by gall incidence (GI) and gall diameter (GD), which were classified into three response types as RR (low GI and small GD), SR (high GI and small GD), and SS (high GI and large GD), corresponding to resistant, moderately resistant, and susceptible responses, respectively. In this, 4, 4, and 2 Vitis species were classified into RR, SR, and SS, respectively. Gas chromatography mass spectrometry (GC-MS) analysis of the grapevine stem metabolites with A. vitis infection showed 134 metabolites in various compound classes critically occurred, which were differentially clustered with the response types by the principal component analysis. Multivariate analysis of the metabolite profile revealed that 11 metabolites increased significantly in relation to the response types, mostly at post-inoculation stages, more prevalently (8 metabolites) at two days after inoculation than other stages, and more related to SS (7 metabolites) than RR (3 metabolites) or SR (one metabolite). This suggests most of the disease-related metabolites may be rarely pre-existing but mostly induced by pathogen infection largely for facilitating gall development except stilbene compound resveratrol, a phytoalexin that may be involved in the resistance response. All of these aspects may be used for the selection of resistant grapevine cultivars and their rootstocks for the control of the crown gall disease of the grapevine. PMID:27904455

The shadow of a doubt? Evidence for perceptuo-motor linkage during auditory and audiovisual close-shadowing

PubMed Central

Scarbel, Lucie; Beautemps, Denis; Schwartz, Jean-Luc; Sato, Marc

2014-01-01

One classical argument in favor of a functional role of the motor system in speech perception comes from the close-shadowing task in which a subject has to identify and to repeat as quickly as possible an auditory speech stimulus. The fact that close-shadowing can occur very rapidly and much faster than manual identification of the speech target is taken to suggest that perceptually induced speech representations are already shaped in a motor-compatible format. Another argument is provided by audiovisual interactions often interpreted as referring to a multisensory-motor framework. In this study, we attempted to combine these two paradigms by testing whether the visual modality could speed motor response in a close-shadowing task. To this aim, both oral and manual responses were evaluated during the perception of auditory and audiovisual speech stimuli, clear or embedded in white noise. Overall, oral responses were faster than manual ones, but it also appeared that they were less accurate in noise, which suggests that motor representations evoked by the speech input could be rough at a first processing stage. In the presence of acoustic noise, the audiovisual modality led to both faster and more accurate responses than the auditory modality. No interaction was however, observed between modality and response. Altogether, these results are interpreted within a two-stage sensory-motor framework, in which the auditory and visual streams are integrated together and with internally generated motor representations before a final decision may be available. PMID:25009512

Shape-Shifted Red Blood Cells: A Novel Red Blood Cell Stage?

PubMed Central

Chico, Verónica; Puente-Marin, Sara; Ciordia, Sergio; Mena, María Carmen; Carracedo, Begoña; Mercado, Luis; Coll, Julio

2018-01-01

Primitive nucleated erythroid cells in the bloodstream have long been suggested to be more similar to nucleated red cells of fish, amphibians, and birds than the red cells of fetal and adult mammals. Rainbow trout Ficoll-purified red blood cells (RBCs) cultured in vitro undergo morphological changes, especially when exposed to stress, and enter a new cell stage that we have coined shape-shifted RBCs (shRBCs). We have characterized these shRBCs using transmission electron microscopy (TEM) micrographs, Wright–Giemsa staining, cell marker immunostaining, and transcriptomic and proteomic evaluation. shRBCs showed reduced density of the cytoplasm, hemoglobin loss, decondensed chromatin in the nucleus, and striking expression of the B lymphocyte molecular marker IgM. In addition, shRBCs shared some features of mammalian primitive pyrenocytes (extruded nucleus surrounded by a thin rim of cytoplasm and phosphatidylserine (PS) exposure on cell surface). These shRBCs were transiently observed in heat-stressed rainbow trout bloodstream for three days. Functional network analysis of combined transcriptomic and proteomic studies resulted in the identification of proteins involved in pathways related to the regulation of cell morphogenesis involved in differentiation, cellular response to stress, and immune system process. In addition, shRBCs increased interleukin 8 (IL8), interleukin 1 β (IL1β), interferon ɣ (IFNɣ), and natural killer enhancing factor (NKEF) protein production in response to viral hemorrhagic septicemia virus (VHSV). In conclusion, shRBCs may represent a novel cell stage that participates in roles related to immune response mediation, homeostasis, and the differentiation and development of blood cells. PMID:29671811

Biweekly irinotecan plus bolus 5-fluorouracil and folinic acid in patients with advanced stage colorectal cancer.

PubMed

Yalcin, Suayib; Oksuzoglu, Berna; Tekuzman, Gülten; Engin, Hüseyin; Celik, Ismail; Turker, Alev; Barista, Ibrahim; Gullu, Ibrahim; Guler, Nilufer; Altundag, Kadri; Ozisik, Yavuz; Kars, Ayse

2003-11-01

In this study, we evaluated the efficacy and tolerability of biweekly irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and folinic acid (FA) regimen (IFL) in patients with advanced stage colorectal cancer. A total of 28 patients were examined. The median age was 51 years (range, 30-74 years). One treatment cycle consisted of CPT-11 180 mg/m(2) on days 1 and 15; 5-FU 425 mg/m(2) on days 1, 2, 15 and 16; and FA 20 mg/m(2) on days 1, 2, 15 and 16, every 4 weeks. A total of 119 cycles (median, 4.0 cycles) were administered. Of the 28 patients, 18 received the chemotherapy as first line treatment, seven received it as second line and three received it as third line. An overall objective response rate of 21.5% was achieved in the patient group. However, the overall response rate for the 18 patients receiving first line treatment was 27.7%. The median response duration was 10.5 months (range, 3-19 months). An additional 28.6% of the patients had stable disease for a median duration of 6.5 months (range, 3-8 months). Median time to disease progression was 4.5 months (range, 1-22+ months) and median overall survival time was 11+ months (95% confidence interval, 9-15 months). Toxicities were mild and manageable. We conclude that biweekly IFL is a practical and tolerable treatment option with a disease control rate of 50.1% in patients with advanced stage colorectal cancer.

Shape-Shifted Red Blood Cells: A Novel Red Blood Cell Stage?

PubMed

Chico, Verónica; Puente-Marin, Sara; Nombela, Iván; Ciordia, Sergio; Mena, María Carmen; Carracedo, Begoña; Villena, Alberto; Mercado, Luis; Coll, Julio; Ortega-Villaizan, María Del Mar

2018-04-19

Primitive nucleated erythroid cells in the bloodstream have long been suggested to be more similar to nucleated red cells of fish, amphibians, and birds than the red cells of fetal and adult mammals. Rainbow trout Ficoll-purified red blood cells (RBCs) cultured in vitro undergo morphological changes, especially when exposed to stress, and enter a new cell stage that we have coined shape-shifted RBCs (shRBCs). We have characterized these shRBCs using transmission electron microscopy (TEM) micrographs, Wright⁻Giemsa staining, cell marker immunostaining, and transcriptomic and proteomic evaluation. shRBCs showed reduced density of the cytoplasm, hemoglobin loss, decondensed chromatin in the nucleus, and striking expression of the B lymphocyte molecular marker IgM. In addition, shRBCs shared some features of mammalian primitive pyrenocytes (extruded nucleus surrounded by a thin rim of cytoplasm and phosphatidylserine (PS) exposure on cell surface). These shRBCs were transiently observed in heat-stressed rainbow trout bloodstream for three days. Functional network analysis of combined transcriptomic and proteomic studies resulted in the identification of proteins involved in pathways related to the regulation of cell morphogenesis involved in differentiation, cellular response to stress, and immune system process. In addition, shRBCs increased interleukin 8 (IL8), interleukin 1 β (IL1β), interferon ɣ (IFNɣ), and natural killer enhancing factor (NKEF) protein production in response to viral hemorrhagic septicemia virus (VHSV). In conclusion, shRBCs may represent a novel cell stage that participates in roles related to immune response mediation, homeostasis, and the differentiation and development of blood cells.

Evidence for the involvement of hydraulic root or shoot adjustments as mechanisms underlying water deficit tolerance in two Sorghum bicolor genotypes.

PubMed

Sutka, Moira R; Manzur, Milena E; Vitali, Victoria A; Micheletto, Sandra; Amodeo, Gabriela

2016-03-15

Sorghum bicolor (L.) Moench is an ancient drought-tolerant crop with potential to sustain high yields even in those environments where water is limiting. Understanding the performance of this species in early phenological stages could be a useful tool for future yield improvement programs. The aim of this work was to study the response of Sorghum seedlings under water deficit conditions in two genotypes (RedLandB2 and IS9530) that are currently employed in Argentina. Morphological and physiological traits were studied to present an integrated analysis of the shoot and root responses. Although both genotypes initially developed a conserved and indistinguishable response in terms of drought tolerance parameters (growth rate, biomass reallocation, etc.), water regulation displayed different underlying strategies. To avoid water loss, both genotypes adjusted their plant hydraulic resistance at different levels: RedLandB2 regulated shoot resistance through stomata (isohydric strategy), while IS9530 controlled root resistance (anisohydric strategy). Moreover, only in IS9530 was root hydraulic conductance restricted in the presence of HgCl2, in agreement with water movement through cell-to-cell pathways and aquaporins activity. The different responses between genotypes suggest a distinct strategy at the seedling stage and add new information that should be considered when evaluating Sorghum phenotypic plasticity in changing environments. Copyright © 2016 Elsevier GmbH. All rights reserved.

A phase 2, open-label, multi-center study of amuvatinib in combination with platinum etoposide chemotherapy in platinum-refractory small cell lung cancer patients

PubMed Central

Byers, Lauren Averett; Horn, Leora; Ghandi, Jitendra; Kloecker, Goetz; Owonikoko, Taofeek; Waqar, Saiama Naheed; Krzakowski, Maciej; Cardnell, Robert J.; Fujimoto, Junya; Taverna, Pietro; Azab, Mohammad; Camidge, David Ross

2017-01-01

Background Amuvatinib (MP-470) is a multi-targeted kinase inhibitor with potent activity against c-Kit, synergistic with DNA-damaging agents. We evaluated amuvatinib in combination with platinum-etoposide (EP) chemotherapy by objective response rate, survival, and tolerability in platinum-refractory small cell lung cancer (SCLC) patients. Methods This study used a Simon 2-stage design requiring ≥3 centrally confirmed responses in the first 21 subjects. Subjects received EP with 300 mg amuvatinib orally three times daily in cycles of 21 days. A three-day amuvatinib run-in period before EP occurred in Cycle 1. Subjects received the same EP chemotherapy regimen given prior to progression/relapse. Results Among 23 subjects treated, we observed four PRs (17.4%) per RECIST 1.1, only two of which were centrally confirmed (8.7%, response duration 119, 151 days). Three subjects (13%) had confirmed stable disease. c-Kit H-score was ≥100 in two subjects whose respective durations of disease control were 151 and 256 days. Conclusions The addition of amuvatinib to EP chemotherapy in unselected, platinum-refractory SCLC did not meet the primary endpoint of ≥3 confirmed responses in stage 1. However, high c-Kit expression in two subjects with durable disease control suggests the potential for further study of amuvatinib in SCLC patients with high c-Kit expression. PMID:29113403

A phase 2, open-label, multi-center study of amuvatinib in combination with platinum etoposide chemotherapy in platinum-refractory small cell lung cancer patients.

PubMed

Byers, Lauren Averett; Horn, Leora; Ghandi, Jitendra; Kloecker, Goetz; Owonikoko, Taofeek; Waqar, Saiama Naheed; Krzakowski, Maciej; Cardnell, Robert J; Fujimoto, Junya; Taverna, Pietro; Azab, Mohammad; Camidge, David Ross

2017-10-06

Amuvatinib (MP-470) is a multi-targeted kinase inhibitor with potent activity against c-Kit, synergistic with DNA-damaging agents. We evaluated amuvatinib in combination with platinum-etoposide (EP) chemotherapy by objective response rate, survival, and tolerability in platinum-refractory small cell lung cancer (SCLC) patients. This study used a Simon 2-stage design requiring ≥3 centrally confirmed responses in the first 21 subjects. Subjects received EP with 300 mg amuvatinib orally three times daily in cycles of 21 days. A three-day amuvatinib run-in period before EP occurred in Cycle 1. Subjects received the same EP chemotherapy regimen given prior to progression/relapse. Among 23 subjects treated, we observed four PRs (17.4%) per RECIST 1.1, only two of which were centrally confirmed (8.7%, response duration 119, 151 days). Three subjects (13%) had confirmed stable disease. c-Kit H-score was ≥100 in two subjects whose respective durations of disease control were 151 and 256 days. The addition of amuvatinib to EP chemotherapy in unselected, platinum-refractory SCLC did not meet the primary endpoint of ≥3 confirmed responses in stage 1. However, high c-Kit expression in two subjects with durable disease control suggests the potential for further study of amuvatinib in SCLC patients with high c-Kit expression.

Influence of lactation stage and some flock management practices on sensory characteristics of goat milk from Brazilian Saanen breed.

PubMed

de Cássia Ramos do Egypto Queiroga, Rita; Costa, Roberto Germano; Madruga, Marta Suely; de Medeiros, Ariosvaldo Nunes; Dos Santos Garruti, Deborah; Magnani, Marciane; de Souza, Evandro Leite

2016-04-01

This study evaluated the influence of lactation stage (early, middle, late) and management practices (milking hygiene and buck presence) on the sensory attributes of Saanen goat milk. Goats were randomly divided in four groups in respect of different milking sanitary procedures and the presence/absence of the buck in the barn. Milk samples were analyzed for sensory attributes including quantitative descriptive analysis (QDA) and acceptance. The milking hygiene practice caused no significant influence on microbiological parameters. Results of QDA revealed that the buck presence increased the characteristic odor of milk at the middle and late lactation stages. The off-odor and off-flavor descriptors showed a distinct response since a higher intensity of these sensory characteristics was noted in the samples obtained from goats maintained without the buck. Odor and flavor contributed most in characterizing the different samples regardless of the management practice and lactation stage. The acceptance of odor showed to be influenced only by the lactation stage, while the acceptance of flavor was only through the presence of the buck. Odor acceptance correlated negatively to off-odor and off-flavor, suggesting that these two sensory attributes impaired the preference for the aroma of the milk samples. © 2015 Japanese Society of Animal Science.

C5b-9 Staining Correlates With Clinical and Tumor Stage in Gastric Adenocarcinoma.

PubMed

Chen, Jian; Yang, Wei-Jun; Sun, Hai-Jian; Yang, Xia; Wu, Yu-Zhang

2016-08-01

The complement system is a critical part of the immune response, acting in defense against viral infections, clearance of immune complexes, and maintenance of tissue homeostasis. Upregulated expression of the terminal complement complex, C5b-9, has been observed on various tumor cells, such as stomach carcinoma cells, and on cells in the necrotic regions of these tumors as well; however, whether and how C5b-9 is related to gastric cancer progression and severity remains unknown. In this study, human gastric adenocarcinoma (HGAC) tissues (n=47 cases) and patient-matched adjacent nontumoral parenchyma (n=20 cases) were evaluated by tissue microarray and immunohistochemistry. The HGAC tissues showed upregulated C5b-9 expression. Multinomial logistic regression and likelihood ratio testing showed that overexpression of C5b-9 in HGAC tissue was significantly correlated with clinical stage (P=0.007) and tumor stage (P=0.005), but not with tumor distant organ metastasis, lymphoid nodal status, sex, or age. Patients with late-stage gastric adenocarcinoma had a higher amount of tumor cells showing positive staining for C5b-9 than patients with early-stage disease. These results may help in diagnosis and assessment of disease severity of human gastric carcinoma.

Skin blood flow in patients with stage 5 chronic kidney disease on hemodialysis.

PubMed

Ngo, Binh; Rongey, Christine; Hiscox, Bryan; Rendell, Marc; Woodley, David; Smogorzewski, Miroslaw

2010-09-01

We have shown previously that skin perfusion is reduced in patients with diabetes mellitus (DM). Patients with diabetes and with chronic kidney disease (CKD) stage 5 were having advanced microangiopathy. In this cross-sectional study, we measured skin blood flow in DM and non-DM patients on dialysis to assess whether any differences exist in skin perfusion in those 2 groups of patients. A total of 25 patients with DM (aged 59.9 +/- 2.2 years) and 24 patients with non-DM CKD stage 5 (44.6 +/- 2.9 years) on hemodialysis (HD) were studied. Ten healthy subjects (37 +/- 4.3 years) were used as a control group. Skin blood flow (SBF) was measured using Vasamedic Model 403B laser Doppler device (Vasamedics Inc., St. Paul, MN) in a standardized way at the plantar and dorsal surface of the finger and toe and at the pretibial surface of the leg at 2 different local skin temperatures of 35 degrees C and 44 degrees C. Laboratory biochemical data were collected at the time of SBF study. The SBF measured at 35 degrees C was lower in the patients with DM on dialysis as compared with healthy subjects and non-DM dialysis patients. The SBF response to the increase in temperature of the probe to 44 degrees C was 70% to 80% lower in DM patients as compared with healthy subjects and non-DM patients. However, non-DM subjects who displayed SBF similar to control subjects at 35 degrees C, had impaired response in SBF at 44 degrees C as well. Patients with lower serum albumin exhibited lower SBF even after adjustment for age. SBF is impaired in patients with stage 5 CKD on HD, particularly in those with DM as a cause of CKD. SBF negatively correlated with age and albumin (nutritional status) in DM and non-DM patients with stage 5 CKD on HD. Measurement of SBF can be useful in the evaluation of vasculopathy in CKD population and can potentially be used for assessment of vascular response during specific clinical intervention. Copyright 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Targeting Angiotensin II Type-1 Receptor (AT1R) Inhibits the Harmful Phenotype of Plasmodium-Specific CD8+ T Cells during Blood-Stage Malaria.

PubMed

Silva-Filho, João L; Caruso-Neves, Celso; Pinheiro, Ana A S

2017-01-01

CD8 + T-cell response is critical in the pathogenesis of cerebral malaria during blood-stage. Our group and other have been shown that angiotensin II (Ang II) and its receptor AT 1 (AT 1 R), a key effector axis of renin-angiotensin system (RAS), have immune regulatory effects on T cells. Previously, we showed that inhibition of AT 1 R signaling protects mice against the lethal disease induced by Plasmodium berghei ANKA infection However, most of the Ang II/AT 1 R actions were characterized by using only pharmacological approaches, the effects of which may not always be due to a specific receptor blockade. In addition, the mechanisms of action of the AT 1 R in inducing the pathogenic activity of Plasmodium -specific CD8 + T cells during blood-stage were not determined. Here, we examined how angiotensin II/AT 1 R axis promotes the harmful response of Plasmodium -specific CD8 + T-cell during blood-stage by using genetic and pharmacological approaches. We evaluated the response of wild-type (WT) and AT 1 R -/- Plasmodium -specific CD8 + T cells in mice infected with a transgenic PbA lineage expressing ovalbumin; and in parallel infected mice receiving WT Plasmodium -specific CD8 + T cells were treated with losartan (AT 1 R antagonist) or captopril (ACE inhibitor). Both, AT 1 R -/- OT-I cells and WT OT-I cells from losartan- or captopril-treated mice showed lower expansion, reduced IL-2 production and IL-2Rα expression, lower activation (lower expression of CD69, CD44 and CD160) and lower exhaustion profiles. AT 1 R -/- OT-I cells also exhibit lower expression of the integrin LFA-1 and the chemokine receptors CCR5 and CXCR3, known to play a key role in the development of cerebral malaria. Moreover, AT 1 R -/- OT-I cells produce lower amounts of IFN-γ and TNF-α and show lower degranulation upon restimulation. In conclusion, our results show the pivotal mechanisms of AT 1 R-induced harmful phenotype of Plasmodium -specific CD8 + T cells during blood-stage malaria.

Postural habits of young adults and possibilities of modification.

PubMed

Nowotny-Czupryna, Olga; Czupryna, Krzysztof; Bąk, Krzysztof; Wróblewska, Ewa; Rottermund, Jerzy

2013-01-01

The aim of the study was to assess postural habits in young, healthy people, identify correlations between postural errors and pain and attempt to modify bad habits. 144 people, aged 18-23 were enrolled. The intervention consisted of 4 stages: Stage 1 - identification of postural habits, description of responses to stress, back pain frequency and intensity (Jackson & Moskowitz); Stage 2 - correction of habitual position with the help of a physiotherapist, briefing about ergonomic everyday behaviours and consequences of continued non-ergonomic behaviours, Stage 3 - follow-up examination: self-assessment of changes, evaluation of the effects of modifications, determination of causes for discontinuing the behaviour modification programme, where applicable; and Stage 4 - final examination, assessment of results. Correlations were sought between inappropriate postural behaviour in various positions and between non-ergonomic postural behaviour and pain location and response to stress. Statistical analysis was carried out with Excel and Statistica v. 7.1. A non-parametric χ(2) test was used at p<0.005. All participants presented poor postural patterns in the standing, sitting and recumbent position. Back pain was reported by half of the participants. Statistically significant relationships between pain and habitual positions were noted with regard to the cervical and lumbar spine and also for abdominal pain as a response to stress in people with excessive thoracic kyphosis. Behaviour modifications caused or intensified lumbar pain or thigh muscle pain. Positive outcomes included better urination and/or defecation and greater comfort in assuming the different positions and performing activities of daily living in these positions. Some examinees discontinued behaviour modification during the first month after the initial instruction and the majority did so over the next three months. 1. Non-ergonomic postural behaviours are common among young people. 2. Changing the body position does not eliminate the impact of the inappropriate habit. 3. An attempt to modify non-ergonomic postural behaviours usually results in pain, which may act as a demotivating factor. 4. Discomfort associated with the modification of habitual postural behaviours is reduced after 3-4 months of regular training.

The predictive adaptive response: modeling the life-history evolution of the butterfly Bicyclus anynana in seasonal environments.

PubMed

van den Heuvel, Joost; Saastamoinen, Marjo; Brakefield, Paul M; Kirkwood, Thomas B L; Zwaan, Bas J; Shanley, Daryl P

2013-02-01

A predictive adaptive response (PAR) is a type of developmental plasticity where the response to an environmental cue is not immediately advantageous but instead is later in life. The PAR is a way for organisms to maximize fitness in varying environments. Insects living in seasonal environments are valuable model systems for testing the existence and form of PAR. Previous manipulations of the larval and the adult environments of the butterfly Bicyclus anynana have shown that individuals that were food restricted during the larval stage coped better with forced flight during the adult stage compared to those with optimal conditions in the larval stage. Here, we describe a state-dependent energy allocation model, which we use to test whether such a response to food restriction could be adaptive in nature where this butterfly exhibits seasonal cycles. The results from the model confirm the responses obtained in our previous experimental work and show how such an outcome was facilitated by resource allocation patterns to the thorax during the pupal stage. We conclude that for B. anynana, early-stage cues can direct development toward a better adapted phenotype later in life and, therefore, that a PAR has evolved in this species.

Presence of early stage cancer does not impair the early protein metabolic response to major surgery

PubMed Central

Klimberg, V. Suzanne; Allasia, Arianna; Deutz, Nicolaas EP

2017-01-01

Abstract Background Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. Methods In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post‐absorptive state and net protein anabolic response to a meal. Results Major surgery resulted in an up‐regulation of post‐absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2 = 0.85, P < 0.001) was independent of the presence of non‐cachectic early stage breast cancer or surgery. Conclusions The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after major surgery in patients with non‐cachectic breast cancer. This indicates that the acute anabolic potential to conventional feeding is maintained in non‐cachectic early stage breast cancer after major surgery. PMID:28093897

Mechanisms of animal diapause: recent developments from nematodes, crustaceans, insects, and fish

PubMed Central

Denlinger, David L.; Podrabsky, Jason E.; Roy, Richard

2016-01-01

Life cycle delays are beneficial for opportunistic species encountering suboptimal environments. Many animals display a programmed arrest of development (diapause) at some stage(s) of their development, and the diapause state may or may not be associated with some degree of metabolic depression. In this review, we will evaluate current advancements in our understanding of the mechanisms responsible for the remarkable phenotype, as well as environmental cues that signal entry and termination of the state. The developmental stage at which diapause occurs dictates and constrains the mechanisms governing diapause. Considerable progress has been made in clarifying proximal mechanisms of metabolic arrest and the signaling pathways like insulin/Foxo that control gene expression patterns. Overlapping themes are also seen in mechanisms that control cell cycle arrest. Evidence is emerging for epigenetic contributions to diapause regulation via small RNAs in nematodes, crustaceans, insects, and fish. Knockdown of circadian clock genes in selected insect species supports the importance of clock genes in the photoperiodic response that cues diapause. A large suite of chaperone-like proteins, expressed during diapause, protects biological structures during long periods of energy-limited stasis. More information is needed to paint a complete picture of how environmental cues are coupled to the signal transduction that initiates the complex diapause phenotype, as well as molecular explanations for how the state is terminated. Excellent examples of molecular memory in post-dauer animals have been documented in Caenorhabditis elegans. It is clear that a single suite of mechanisms does not regulate diapause across all species and developmental stages. PMID:27053646

Mechanisms of animal diapause: recent developments from nematodes, crustaceans, insects, and fish.

PubMed

Hand, Steven C; Denlinger, David L; Podrabsky, Jason E; Roy, Richard

2016-06-01

Life cycle delays are beneficial for opportunistic species encountering suboptimal environments. Many animals display a programmed arrest of development (diapause) at some stage(s) of their development, and the diapause state may or may not be associated with some degree of metabolic depression. In this review, we will evaluate current advancements in our understanding of the mechanisms responsible for the remarkable phenotype, as well as environmental cues that signal entry and termination of the state. The developmental stage at which diapause occurs dictates and constrains the mechanisms governing diapause. Considerable progress has been made in clarifying proximal mechanisms of metabolic arrest and the signaling pathways like insulin/Foxo that control gene expression patterns. Overlapping themes are also seen in mechanisms that control cell cycle arrest. Evidence is emerging for epigenetic contributions to diapause regulation via small RNAs in nematodes, crustaceans, insects, and fish. Knockdown of circadian clock genes in selected insect species supports the importance of clock genes in the photoperiodic response that cues diapause. A large suite of chaperone-like proteins, expressed during diapause, protects biological structures during long periods of energy-limited stasis. More information is needed to paint a complete picture of how environmental cues are coupled to the signal transduction that initiates the complex diapause phenotype, as well as molecular explanations for how the state is terminated. Excellent examples of molecular memory in post-dauer animals have been documented in Caenorhabditis elegans It is clear that a single suite of mechanisms does not regulate diapause across all species and developmental stages. Copyright © 2016 the American Physiological Society.

Effects of icotinib on early-stage non-small-cell lung cancer as neoadjuvant treatment with different epidermal growth factor receptor phenotypes.

PubMed

Wang, Tao; Liu, Yang; Zhou, Bin; Wang, Zhi; Liang, Naichao; Zhang, Yundong; Dong, Zhouhuan; Li, Jie

2016-01-01

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated efficacy in treating advanced non-small-cell lung cancer (NSCLC). Preliminary findings suggested that EGFR-TKIs might also be beneficial in neoadjuvant therapy in treating NSCLC. Therefore, this study aimed to evaluate the efficacy and safety of neoadjuvant therapy with icotinib in patients with early-stage NSCLC. We retrospectively reviewed the medical history of patients who were initially diagnosed with stage IA-IIIA NSCLC and were under icotinib administration before surgery between December 2011 and December 2014. Tumor assessment was conducted between the second and fourth week from initial icotinib treatment. The association between personal characteristics, smoking status, disease stage, EGFR mutation status, and clinical outcomes were investigated using multivariate logistic regression analysis. A total of 67 patients with NSCLC were reviewed, and approximately half (38/67) of them were identified as having EGFR-mutant tumors. The overall response rate of all patients was 26.7% at 2-4 weeks' assessment. Multivariate analysis showed that female sex (38.5% versus 10.7% in males, P=0.028) and EGFR mutation status (42.1% versus 6.9% in EGFR wild type, P=0.011) were independent predictive factors. The analysis also showed that the most common adverse effects were rash (43.3%) and dry skin (34.4%), which were tolerable. Icotinib induced clinical response with minimal toxicity as neoadjuvant treatment in early NSCLC, especially in patients with common EGFR mutations. Further studies are warranted to confirm our findings.

Verification and Validation of Digitally Upgraded Control Rooms

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

Boring, Ronald; Lau, Nathan

2015-09-01

As nuclear power plants undertake main control room modernization, a challenge is the lack of a clearly defined human factors process to follow. Verification and validation (V&V) as applied in the nuclear power community has tended to involve efforts such as integrated system validation, which comes at the tail end of the design stage. To fill in guidance gaps and create a step-by-step process for control room modernization, we have developed the Guideline for Operational Nuclear Usability and Knowledge Elicitation (GONUKE). This approach builds on best practices in the software industry, which prescribe an iterative user-centered approach featuring multiple cyclesmore » of design and evaluation. Nuclear regulatory guidance for control room design emphasizes summative evaluation—which occurs after the design is complete. In the GONUKE approach, evaluation is also performed at the formative stage of design—early in the design cycle using mockups and prototypes for evaluation. The evaluation may involve expert review (e.g., software heuristic evaluation at the formative stage and design verification against human factors standards like NUREG-0700 at the summative stage). The evaluation may also involve user testing (e.g., usability testing at the formative stage and integrated system validation at the summative stage). An additional, often overlooked component of evaluation is knowledge elicitation, which captures operator insights into the system. In this report we outline these evaluation types across design phases that support the overall modernization process. The objective is to provide industry-suitable guidance for steps to be taken in support of the design and evaluation of a new human-machine interface (HMI) in the control room. We suggest the value of early-stage V&V and highlight how this early-stage V&V can help improve the design process for control room modernization. We argue that there is a need to overcome two shortcomings of V&V in current practice—the propensity for late-stage V&V and the use of increasingly complex psychological assessment measures for V&V.« less

Value of Surveillance Studies for Patients With Stage I to II Diffuse Large B-Cell Lymphoma in the Rituximab Era

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

Hiniker, Susan M.; Pollom, Erqi L.; Khodadoust, Michael S.

2015-05-01

Background: The role of surveillance studies in limited-stage diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been well defined. We sought to evaluate the use of imaging (computed tomography [CT] and positron emission tomography [PET]-CT) scans and lactate dehydrogenase (LDH) in surveillance of patients with stage I to II DLBCL. Methods: A retrospective analysis was performed of patients who received definitive treatment between 2000 and 2013. Results: One hundred sixty-two consecutive patients with stage I to II DLBCL were treated with chemotherapy +/− rituximab, radiation, or combined modality therapy. The 5-year rates of overall survival (OS) and freedommore » from progression (FFP) were 81.2% and 80.8%, respectively. Of the 162 patients, 124 (77%) were followed up with at least 1 surveillance PET scan beyond end-of-treatment scans; of those, 94 of 124 (76%) achieved a complete metabolic response on PET scan after completion of chemotherapy, and this was associated with superior FFP (P=.01, HR=0.3) and OS (P=.01, HR 0.3). Eighteen patients experienced relapse after initial response to therapy. Nine relapses were initially suspected by surveillance imaging studies (8 PET, 1 CT), and 9 were suspected clinically (5 by patient-reported symptoms and 4 by symptoms and physical examination). No relapses were detected by surveillance LDH. The median duration from initiation of treatment to relapse was 14.3 months among patients with relapses suspected by imaging, and 59.8 months among patients with relapses suspected clinically (P=.077). There was no significant difference in OS from date of first therapy or OS after relapse between patients whose relapse was suspected by imaging versus clinically. Thirteen of 18 patients underwent successful salvage therapy after relapse. Conclusions: A complete response on PET scan immediately after initial chemotherapy is associated with superior FFP and OS in stage I to II DLBCL. The use of PET scans as posttreatment surveillance is not associated with a survival advantage. LDH is not a sensitive marker for relapse. Our results argue for limiting the use of posttreatment surveillance in patients with limited-stage DLBCL.« less

High Resolution Flash Flood Forecasting Using a Wireless Sensor Network in the Dallas-Fort Worth Metroplex

NASA Astrophysics Data System (ADS)

Bartos, M. D.; Kerkez, B.; Noh, S.; Seo, D. J.

2017-12-01

In this study, we develop and evaluate a high resolution urban flash flood monitoring system using a wireless sensor network (WSN), a real-time rainfall-runoff model, and spatially-explicit radar rainfall predictions. Flooding is the leading cause of natural disaster fatalities in the US, with flash flooding in particular responsible for a majority of flooding deaths. While many riverine flood models have been operationalized into early warning systems, there is currently no model that is capable of reliably predicting flash floods in urban areas. Urban flash floods are particularly difficult to model due to a lack of rainfall and runoff data at appropriate scales. To address this problem, we develop a wide-area flood-monitoring wireless sensor network for the Dallas-Fort Worth metroplex, and use this network to characterize rainfall-runoff response over multiple heterogeneous catchments. First, we deploy a network of 22 wireless sensor nodes to collect real-time stream stage measurements over catchments ranging from 2-80 km2 in size. Next, we characterize the rainfall-runoff response of each catchment by combining stream stage data with gage and radar-based precipitation measurements. Finally, we demonstrate the potential for real-time flash flood prediction by joining the derived rainfall-runoff models with real-time radar rainfall predictions. We find that runoff response is highly heterogeneous among catchments, with large variabilities in runoff response detected even among nearby gages. However, when spatially-explicit rainfall fields are included, spatial variability in runoff response is largely captured. This result highlights the importance of increased spatial coverage for flash flood prediction.

Simultaneous transcriptome analysis of Colletotrichum gloeosporioides and tomato fruit pathosystem reveals novel fungal pathogenicity and fruit defense strategies.

PubMed

Alkan, Noam; Friedlander, Gilgi; Ment, Dana; Prusky, Dov; Fluhr, Robert

2015-01-01

The fungus Colletotrichum gloeosporioides breaches the fruit cuticle but remains quiescent until fruit ripening signals a switch to necrotrophy, culminating in devastating anthracnose disease. There is a need to understand the distinct fungal arms strategy and the simultaneous fruit response. Transcriptome analysis of fungal-fruit interactions was carried out concurrently in the appressoria, quiescent and necrotrophic stages. Conidia germinating on unripe fruit cuticle showed stage-specific transcription that was accompanied by massive fruit defense responses. The subsequent quiescent stage showed the development of dendritic-like structures and swollen hyphae within the fruit epidermis. The quiescent fungal transcriptome was characterized by activation of chromatin remodeling genes and unsuspected environmental alkalization. Fruit response was portrayed by continued highly integrated massive up-regulation of defense genes. During cuticle infection of green or ripe fruit, fungi recapitulate the same developmental stages but with differing quiescent time spans. The necrotrophic stage showed a dramatic shift in fungal metabolism and up-regulation of pathogenicity factors. Fruit response to necrotrophy showed activation of the salicylic acid pathway, climaxing in cell death. Transcriptome analysis of C. gloeosporioides infection of fruit reveals its distinct stage-specific lifestyle and the concurrent changing fruit response, deepening our perception of the unfolding fungal-fruit arms and defenses race. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Gamma-delta T cell responses in subclinical and clinical stages of Bovine Mycobacterium Avium Paratuberculosis infection

USDA-ARS?s Scientific Manuscript database

The early immune response to Mycobacterium avium subsp. paratuberculosis (MAP) in cattle is characterized by a Th1-like immune response effective in controlling bacterial proliferation during the subclinical stage of infection. In young calves nearly 60% of circulating lymphocytes are gamma delta T ...

Evaluation of Liver Biomarkers as Prognostic Factors for Outcomes to Yttrium-90 Radioembolization of Primary and Secondary Liver Malignancies.

PubMed

Henrie, Adam M; Wittstrom, Kristina; Delu, Adam; Deming, Paulina

2015-09-01

The objective of this study was to examine indicators of liver function and inflammation for prognostic value in predicting outcomes to yttrium-90 radioembolization (RE). In a retrospective analysis, markers of liver function and inflammation, biomarkers required to stage liver function and inflammation, and data regarding survival, tumor response, and progression after RE were recorded. Univariate regression models were used to investigate the prognostic value of liver biomarkers in predicting outcome to RE as measured by survival, tumor progression, and radiographic and biochemical tumor response. Markers from all malignancy types were analyzed together. A subgroup analysis was performed on markers from patients with metastatic colorectal cancer. A total of 31 patients received RE from 2004 to 2014. Median survival after RE for all malignancies combined was 13.6 months (95% CI: 6.7-17.6 months). Results from an exploratory analysis of patient data suggest that liver biomarkers, including albumin concentrations, international normalized ratio, bilirubin concentrations, and the model for end-stage liver disease score, possess prognostic value in predicting outcomes to RE.

A Comparison of FLT to FDG PET/CT in the Early Assessment of Chemotherapy Response in Stage IB-IIIA Resectable NSCLC

ClinicalTrials.gov

2017-01-27

Recurrent Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

Community-based infant hearing screening in a developing country: parental uptake of follow-up services.

PubMed

Olusanya, Bolajoko O; Akinyemi, Oladele O

2009-02-23

Universal newborn hearing screening is now considered an essential public health care for the early detection of disabling life-long childhood hearing impairment globally. However, like any health interventions in early childhood, parental support and participation is essential for achieving satisfactory uptake of services. This study set out to determine maternal/infant socio-demographic factors associated with follow-up compliance in community-based infant hearing screening programmes in a developing country. After health educational/counselling sessions, infants attending routine childhood immunisation clinics at four primary care centres were enrolled into a two-stage infant hearing screening programme consisting of a first-stage screening with transient-evoked otoacoustic emissions and second-stage screening with automated auditory brainstem response. Infants referred after the second-stage screening were scheduled for diagnostic evaluation within three months. Maternal and infant factors associated with completion of the hearing screening protocol were determined with multivariable logistic regression analysis. No mother declined participation during the study period. A total of 285 out of 2,003 eligible infants were referred after the first-stage screening out of which 148 (51.9%) did not return for the second-stage, while 32 (39.0%) of the 82 infants scheduled for diagnostic evaluation defaulted. Mothers who delivered outside hospitals were significantly more likely to return for follow-up screening than those who delivered in hospitals (Odds ratio: 1.62; 95% confidence intervals: 0.98 - 2.70; p = 0.062). No other factors correlated with follow-up compliance for screening and diagnostic services. Place of delivery was the only factor that correlated albeit marginally with infant hearing screening compliance in this population. The likely influence of issues such as the number of return visits for follow-up services, ineffective tracking system and the prevailing unfavourable cultural perception towards childhood deafness on non-compliance independently or through these factors warrant further investigation.

Parameter Stability of the Functional–Structural Plant Model GREENLAB as Affected by Variation within Populations, among Seasons and among Growth Stages

PubMed Central

Ma, Yuntao; Li, Baoguo; Zhan, Zhigang; Guo, Yan; Luquet, Delphine; de Reffye, Philippe; Dingkuhn, Michael

2007-01-01

Background and Aims It is increasingly accepted that crop models, if they are to simulate genotype-specific behaviour accurately, should simulate the morphogenetic process generating plant architecture. A functional–structural plant model, GREENLAB, was previously presented and validated for maize. The model is based on a recursive mathematical process, with parameters whose values cannot be measured directly and need to be optimized statistically. This study aims at evaluating the stability of GREENLAB parameters in response to three types of phenotype variability: (1) among individuals from a common population; (2) among populations subjected to different environments (seasons); and (3) among different development stages of the same plants. Methods Five field experiments were conducted in the course of 4 years on irrigated fields near Beijing, China. Detailed observations were conducted throughout the seasons on the dimensions and fresh biomass of all above-ground plant organs for each metamer. Growth stage-specific target files were assembled from the data for GREENLAB parameter optimization. Optimization was conducted for specific developmental stages or the entire growth cycle, for individual plants (replicates), and for different seasons. Parameter stability was evaluated by comparing their CV with that of phenotype observation for the different sources of variability. A reduced data set was developed for easier model parameterization using one season, and validated for the four other seasons. Key Results and Conclusions The analysis of parameter stability among plants sharing the same environment and among populations grown in different environments indicated that the model explains some of the inter-seasonal variability of phenotype (parameters varied less than the phenotype itself), but not inter-plant variability (parameter and phenotype variability were similar). Parameter variability among developmental stages was small, indicating that parameter values were largely development-stage independent. The authors suggest that the high level of parameter stability observed in GREENLAB can be used to conduct comparisons among genotypes and, ultimately, genetic analyses. PMID:17158141

Community-based infant hearing screening in a developing country: parental uptake of follow-up services

PubMed Central

Olusanya, Bolajoko O; Akinyemi, Oladele O

2009-01-01

Background Universal newborn hearing screening is now considered an essential public health care for the early detection of disabling life-long childhood hearing impairment globally. However, like any health interventions in early childhood, parental support and participation is essential for achieving satisfactory uptake of services. This study set out to determine maternal/infant socio-demographic factors associated with follow-up compliance in community-based infant hearing screening programmes in a developing country. Methods After health educational/counselling sessions, infants attending routine childhood immunisation clinics at four primary care centres were enrolled into a two-stage infant hearing screening programme consisting of a first-stage screening with transient-evoked otoacoustic emissions and second-stage screening with automated auditory brainstem response. Infants referred after the second-stage screening were scheduled for diagnostic evaluation within three months. Maternal and infant factors associated with completion of the hearing screening protocol were determined with multivariable logistic regression analysis. Results No mother declined participation during the study period. A total of 285 out of 2,003 eligible infants were referred after the first-stage screening out of which 148 (51.9%) did not return for the second-stage, while 32 (39.0%) of the 82 infants scheduled for diagnostic evaluation defaulted. Mothers who delivered outside hospitals were significantly more likely to return for follow-up screening than those who delivered in hospitals (Odds ratio: 1.62; 95% confidence intervals: 0.98 – 2.70; p = 0.062). No other factors correlated with follow-up compliance for screening and diagnostic services. Conclusion Place of delivery was the only factor that correlated albeit marginally with infant hearing screening compliance in this population. The likely influence of issues such as the number of return visits for follow-up services, ineffective tracking system and the prevailing unfavourable cultural perception towards childhood deafness on non-compliance independently or through these factors warrant further investigation. PMID:19236718

Probabilistic risk assessment of the effect of acidified seawater on development stages of sea urchin (Strongylocentrotus droebachiensis).

PubMed

Chen, Wei-Yu; Lin, Hsing-Chieh

2018-05-01

Growing evidence indicates that ocean acidification has a significant impact on calcifying marine organisms. However, there is a lack of exposure risk assessments for aquatic organisms under future environmentally relevant ocean acidification scenarios. The objective of this study was to investigate the probabilistic effects of acidified seawater on the life-stage response dynamics of fertilization, larvae growth, and larvae mortality of the green sea urchin (Strongylocentrotus droebachiensis). We incorporated the regulation of primary body cavity (PBC) pH in response to seawater pH into the assessment by constructing an explicit model to assess effective life-stage response dynamics to seawater or PBC pH levels. The likelihood of exposure to ocean acidification was also evaluated by addressing the uncertainties of the risk characterization. For unsuccessful fertilization, the estimated 50% effect level of seawater acidification (EC50 SW ) was 0.55 ± 0.014 (mean ± SE) pH units. This life stage was more sensitive than growth inhibition and mortality, for which the EC50 values were 1.13 and 1.03 pH units, respectively. The estimated 50% effect levels of PBC pH (EC50 PBC ) were 0.99 ± 0.05 and 0.88 ± 0.006 pH units for growth inhibition and mortality, respectively. We also predicted the probability distributions for seawater and PBC pH levels in 2100. The level of unsuccessful fertilization had 50 and 90% probability risks of 5.07-24.51 (95% CI) and 0-6.95%, respectively. We conclude that this probabilistic risk analysis model is parsimonious enough to quantify the multiple vulnerabilities of the green sea urchin while addressing the systemic effects of ocean acidification. This study found a high potential risk of acidification affecting the fertilization of the green sea urchin, whereas there was no evidence for adverse effects on growth and mortality resulting from exposure to the predicted acidified environment.

Event-Based Analysis of Rainfall-Runoff Response to Assess Wetland-Stream Interaction in the Prairie Pothole Region

NASA Astrophysics Data System (ADS)

Haque, M. A.; Ross, C.; Schmall, A.; Bansah, S.; Ali, G.

2016-12-01

Process-based understanding of wetland response to precipitation is needed to quantify the extent to which non-floodplain wetlands - such as Prairie potholes - generate flow and transmit that flow to nearby streams. While measuring wetland-stream (W-S) interaction is difficult, it is possible to infer it by examining hysteresis characteristics between wetland and stream stage during individual precipitation events. Hence, to evaluate W-S interaction, 10 intact and 10 altered/lost potholes were selected for study; they are located in Broughton's Creek Watershed (Manitoba, Canada) on both sides of a 5 km creek reach. Stilling wells (i.e., above ground wells) were deployed in the intact and altered wetlands to monitor surface water level fluctuations while water table wells were drilled below drainage ditches to a depth of 1 m to monitor shallow groundwater fluctuations. All stilling wells and water table wells were equipped with capacitance water level loggers to monitor fluctuations in surface water and shallow groundwater every 15 minutes. In 2013 (normal year) and 2014 (wet year), 15+ precipitation events were identified and scatter plots of wetland (x-axis) versus stream (y-axis) stage were built to identify W-S hysteretic dynamics. Initial data analysis reveals that in dry antecedent conditions, intact and altered wetlands show clockwise W-S relations, while drained wetlands show anticlockwise W-S hysteresis. However, in wetter antecedent conditions, all wetland types show anticlockwise hysteresis. Future analysis will target the identification of thresholds in antecedent moisture conditions that determine significant changes in event wetland response characteristics (e.g., the delay between the start of rainfall and stream stage, the maximum water level rise in each wetland during each event, the delay between the start of rainfall and peak wetland stage) as well as hysteresis properties (e.g., gradient and area of the hysteresis loop).

Identifying prognostic intratumor heterogeneity using pre- and post-radiotherapy 18F-FDG PET images for pancreatic cancer patients.

PubMed

Yue, Yong; Osipov, Arsen; Fraass, Benedick; Sandler, Howard; Zhang, Xiao; Nissen, Nicholas; Hendifar, Andrew; Tuli, Richard

2017-02-01

To stratify risks of pancreatic adenocarcinoma (PA) patients using pre- and post-radiotherapy (RT) PET/CT images, and to assess the prognostic value of texture variations in predicting therapy response of patients. Twenty-six PA patients treated with RT from 2011-2013 with pre- and post-treatment 18F-FDG-PET/CT scans were identified. Tumor locoregional texture was calculated using 3D kernel-based approach, and texture variations were identified by fitting discrepancies of texture maps of pre- and post-treatment images. A total of 48 texture and clinical variables were identified and evaluated for association with overall survival (OS). The prognostic heterogeneity features were selected using lasso/elastic net regression, and further were evaluated by multivariate Cox analysis. Median age was 69 y (range, 46-86 y). The texture map and temporal variations between pre- and post-treatment were well characterized by histograms and statistical fitting. The lasso analysis identified seven predictors (age, node stage, post-RT SUVmax, variations of homogeneity, variance, sum mean, and cluster tendency). The multivariate Cox analysis identified five significant variables: age, node stage, variations of homogeneity, variance, and cluster tendency (with P=0.020, 0.040, 0.065, 0.078, and 0.081, respectively). The patients were stratified into two groups based on the risk score of multivariate analysis with log-rank P=0.001: a low risk group (n=11) with a longer mean OS (29.3 months) and higher texture variation (>30%), and a high risk group (n=15) with a shorter mean OS (17.7 months) and lower texture variation (<15%). Locoregional metabolic texture response provides a feasible approach for evaluating and predicting clinical outcomes following treatment of PA with RT. The proposed method can be used to stratify patient risk and help select appropriate treatment strategies for individual patients toward implementing response-driven adaptive RT.