Estrogen receptor (α and β) but not androgen receptor expression is correlated with recurrence, progression and survival in post prostatectomy T3N0M0 locally advanced prostate cancer in an urban Greek population

PubMed Central

Megas, Georgios; Chrisofos, Michael; Anastasiou, Ioannis; Tsitlidou, Aida; Choreftaki, Theodosia; Deliveliotis, Charalampos

2015-01-01

The objective of this study was to evaluate the expression of estrogen receptors (ER(α) and ER(β)) and androgen receptors (ARs) as prognostic factors for biochemical recurrence, disease progression and survival in patients with pT3N0M0 prostate cancer (PCa) in an urban Greek population. A total of 100 consecutive patients with pT3N0M0 PCa treated with radical prostatectomy participated in the study. The mean age and follow-up were 64.2 and 6 years, respectively. The HSCORE was used for semi-quantitative analysis of the immunoreactivity of the receptors. The prognostic value of the ER(α) and ER(β) and AR was assessed in terms of recurrence, progression, and survival. AR expression was not associated with any of the above parameters; however, both ERs correlated with the prognosis. A univariate Cox regression analysis showed that ER(α) positive staining was significantly associated with a greater hazard for all outcomes. Increased ER(β) staining was significantly associated with a lower hazard for all outcomes in the univariate analysis. When both ER HSCORES were used for the analysis, it was found that patients with high ER(α) or low ER(β) HSCORES compared with patients with negatively stained ER(α) and >1.7 hSCORE ER(β) had 6.03, 10.93, and 10.53 times greater hazard for biochemical disease recurrence, progression of disease and death, respectively. Multiple Cox proportional hazard analyses showed that the age, preoperative prostate specific antigen, Gleason score and ERs were independent predictors of all outcomes. ER expression is an important prognosticator after radical prostatectomy in patients with pT3N0M0 PCa. By contrast, AR expression has limited prognostic value. PMID:25219910

Estrogen receptor (α and β) but not androgen receptor expression is correlated with recurrence, progression and survival in post prostatectomy T3N0M0 locally advanced prostate cancer in an urban Greek population.

PubMed

Megas, Georgios; Chrisofos, Michael; Anastasiou, Ioannis; Tsitlidou, Aida; Choreftaki, Theodosia; Deliveliotis, Charalampos

2015-01-01

The objective of this study was to evaluate the expression of estrogen receptors (ER(α) and ER(β)) and androgen receptors (ARs) as prognostic factors for biochemical recurrence, disease progression and survival in patients with pT3N0M0 prostate cancer (PCa) in an urban Greek population. A total of 100 consecutive patients with pT3N0M0 PCa treated with radical prostatectomy participated in the study. The mean age and follow-up were 64.2 and 6 years, respectively. The HSCORE was used for semi-quantitative analysis of the immunoreactivity of the receptors. The prognostic value of the ER(α) and ER(β) and AR was assessed in terms of recurrence, progression, and survival. AR expression was not associated with any of the above parameters; however, both ERs correlated with the prognosis. A univariate Cox regression analysis showed that ER(α) positive staining was significantly associated with a greater hazard for all outcomes. Increased ER(β) staining was significantly associated with a lower hazard for all outcomes in the univariate analysis. When both ER HSCORES were used for the analysis, it was found that patients with high ER(α) or low ER(β) HSCORES compared with patients with negatively stained ER(α) and >1.7 hSCORE ER(β) had 6.03, 10.93, and 10.53 times greater hazard for biochemical disease recurrence, progression of disease and death, respectively. Multiple Cox proportional hazard analyses showed that the age, preoperative prostate specific antigen, Gleason score and ERs were independent predictors of all outcomes. ER expression is an important prognosticator after radical prostatectomy in patients with pT3N0M0 PCa. By contrast, AR expression has limited prognostic value.

An audit strategy for progression-free survival

PubMed Central

Dodd, Lori E.; Korn, Edward L.; Freidlin, Boris; Gray, Robert; Bhattacharya, Suman

2010-01-01

Summary In randomized clinical trials, the use of potentially subjective endpoints has led to frequent use of blinded independent central review (BICR) and event adjudication committees to reduce possible bias in treatment effect estimators based on local evaluations (LE). In oncology trials, progression-free survival (PFS) is one such endpoint. PFS requires image interpretation to determine whether a patient’s cancer has progressed, and BICR has been advocated to reduce the potential for endpoints to be biased by knowledge of treatment assignment. There is current debate, however, about the value of such reviews with time-to-event outcomes like PFS. We propose a BICR audit strategy as an alternative to a complete-case BICR to provide assurance of the presence of a treatment effect. We develop an auxiliary-variable estimator of the log-hazard ratio that is more efficient than simply using the audited (i.e., sampled) BICR data for estimation. Our estimator incorporates information from the LE on all the cases and the audited BICR cases, and is an asymptotically unbiased estimator of the log-hazard ratio from BICR. The estimator offers considerable efficiency gains that improve as the correlation between LE and BICR increases. A two-stage auditing strategy is also proposed and evaluated through simulation studies. The method is applied retrospectively to a large oncology trial that had a complete-case BICR, showing the potential for efficiency improvements. PMID:21210772

The NHLBI LAM Registry: Prognostic physiological and radiological biomarkers emerge from a 15-year prospective longitudinal analysis.

PubMed

Gupta, Nishant; Lee, Hye-Seung; Ryu, Jay H; Taveira-DaSilva, Angelo M; Beck, Gerald J; Lee, Jar-Chi; McCarthy, Kevin; Finlay, Geraldine A; Brown, Kevin K; Ruoss, Stephen J; Avila, Nilo A; Moss, Joel; McCormack, Francis X

2018-06-22

The natural history of lymphangioleiomyomatosis is mainly derived from retrospective cohort analyses and remains incompletely understood. A National Institutes of Health LAM Registry was established to define the natural history and identify prognostic biomarkers that can help guide management and decision-making in patients with LAM. A linear mixed effects model was employed to compute the rate of decline of FEV1, and identify variables impacting FEV1 decline among 217 registry patients who enrolled from 1998-2001. Prognostic variables associated with progression to death/lung transplantation were identified using a Cox proportional hazard model. Mean annual decline of FEV1 was 89±53 ml/year, and remained remarkably constant regardless of baseline lung function. FEV1 decline was more rapid in those with greater cyst profusion on CT scan (p=0.02), and in premenopausal subjects (118ml/year) compared to postmenopausal subjects (74ml/year), (p=0.003). There were 26 deaths and 43 lung transplants during the evaluation period. Estimated 5-, 10-, 15-, and 20-year transplant-free survival rates were 95%, 85%, 75%, and 64%, respectively. Postmenopausal status (hazard ratio 0.30, p=0.0002) and higher baseline FEV1 (hazard ratio 0.97, p=0.008) or DLCO (hazard ratio 0.97, p=0.001) were independently associated with a lower risk of progression to death or lung transplantation. The median transplant-free survival in patients with LAM is greater than 20 years. Menopausal status as well as structural and physiological markers of disease severity significantly affect the rate of decline of FEV1 and progression to death or lung transplantation in LAM. Copyright © 2018. Published by Elsevier Inc.

Crack-cocaine use accelerates HIV disease progression in a cohort of HIV-positive drug users.

PubMed

Baum, Marianna K; Rafie, Carlin; Lai, Shenghan; Sales, Sabrina; Page, Bryan; Campa, Adriana

2009-01-01

HIV infection is prevalent among substance abusers. The effects of specific illicit drugs on HIV disease progression have not been established. We evaluated the relationship between substances of abuse and HIV disease progression in a cohort of HIV-1-positive active drug users. A prospective, 30-month, longitudinal study was conducted on 222 HIV-1 seropositive drug users in Miami, FL. History of illicit drug, alcohol, and medication use, CD4+ cell count, and viral load were performed every 6 months. Crack-cocaine users were 2.14 times [95% confidence interval (CI): 1.08 to 4.25, P = 0.029] more likely to present a decline of CD4 to

Next-generation sequencing-based detection of circulating tumour DNA After allogeneic stem cell transplantation for lymphoma.

PubMed

Herrera, Alex F; Kim, Haesook T; Kong, Katherine A; Faham, Malek; Sun, Heather; Sohani, Aliyah R; Alyea, Edwin P; Carlton, Victoria E; Chen, Yi-Bin; Cutler, Corey S; Ho, Vincent T; Koreth, John; Kotwaliwale, Chitra; Nikiforow, Sarah; Ritz, Jerome; Rodig, Scott J; Soiffer, Robert J; Antin, Joseph H; Armand, Philippe

2016-12-01

Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre-specified time points before and after HSCT and were assayed for ctDNA by sequencing of the immunoglobulin or T-cell receptor genes. Tumour clonotypes were identified in 87% of patients with adequate tumour samples. Sixteen of 19 (84%) patients with disease progression after HSCT had detectable ctDNA prior to progression at a median of 3·7 months prior to relapse/progression. Patients with detectable ctDNA 3 months after HSCT had inferior progression-free survival (PFS) (2-year PFS 58% vs. 84% in ctDNA-negative patients, P = 0·033). In multivariate models, detectable ctDNA was associated with increased risk of progression/death (Hazard ratio 3·9, P = 0·003) and increased risk of relapse/progression (Hazard ratio 10·8, P = 0·0006). Detectable ctDNA is associated with an increased risk of relapse/progression, but further validation studies are necessary to confirm these findings and determine the clinical utility of NGS-based minimal residual disease monitoring in lymphoma patients after HSCT. © 2016 John Wiley & Sons Ltd.

Progress in NTHMP Hazard Assessment

USGS Publications Warehouse

Gonzalez, F.I.; Titov, V.V.; Mofjeld, H.O.; Venturato, A.J.; Simmons, R.S.; Hansen, R.; Combellick, Rodney; Eisner, R.K.; Hoirup, D.F.; Yanagi, B.S.; Yong, S.; Darienzo, M.; Priest, G.R.; Crawford, G.L.; Walsh, T.J.

2005-01-01

The Hazard Assessment component of the U.S. National Tsunami Hazard Mitigation Program has completed 22 modeling efforts covering 113 coastal communities with an estimated population of 1.2 million residents that are at risk. Twenty-three evacuation maps have also been completed. Important improvements in organizational structure have been made with the addition of two State geotechnical agency representatives to Steering Group membership, and progress has been made on other improvements suggested by program reviewers. ?? Springer 2005.

Bone Scan Index and Progression-free Survival Data for Progressive Metastatic Castration-resistant Prostate Cancer Patients Who Received ODM-201 in the ARADES Multicentre Study.

PubMed

Reza, Mariana; Jones, Robert; Aspegren, John; Massard, Christophe; Mattila, Leena; Mustonen, Mika; Wollmer, Per; Trägårdh, Elin; Bondesson, Eva; Edenbrandt, Lars; Fizazi, Karim; Bjartell, Anders

2016-12-01

ODM-201, a new-generation androgen receptor inhibitor, has shown clinical efficacy in prostate cancer (PCa). Quantitative methods are needed to accurately assess changes in bone as a measurement of treatment response. The Bone Scan Index (BSI) reflects the percentage of skeletal mass a given tumour affects. To evaluate the predictive value of the BSI in metastatic castration-resistant PCa (mCRPC) patients undergoing treatment with ODM-201. From a total of 134 mCRPC patients who participated in the Activity and Safety of ODM-201 in Patients with Progressive Metastatic Castration-resistant Prostate Cancer clinical trial and received ODM-201, we retrospectively selected all those patients who had bone scan image data of sufficient quality to allow for both baseline and 12-wk follow-up BSI-assessments (n=47). We used the automated EXINI bone BSI software (EXINI Diagnostics AB, Lund, Sweden) to obtain BSI data. We used the Cox proportional hazards model and Kaplan-Meier estimates to investigate the association among BSI, traditional clinical parameters, disease progression, and radiographic progression-free survival (rPFS). In the BSI assessments, at follow-up, patients who had a decrease or at most a 20% increase from BSI baseline had a significantly longer time to progression in bone (median not reached vs 23 wk, hazard ratio [HR]: 0.20; 95% confidence interval [CI], 0.07-0.58; p=0.003) and rPFS (median: 50 wk vs 14 wk; HR: 0.35; 95% CI, 0.17-0.74; p=0.006) than those who had a BSI increase >20% during treatment. The on-treatment change in BSI was significantly associated with rPFS in mCRPC patients, and an increase >20% in BSI predicted reduced rPFS. BSI for quantification of bone metastases may be a valuable complementary method for evaluation of treatment response in mCRPC patients. An increase in Bone Scan Index (BSI) was associated with shorter time to disease progression in patients treated with ODM-201. BSI may be a valuable method of complementing treatment response evaluation in patients with advanced prostate cancer. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Idiopathic Pulmonary Fibrosis: The Association between the Adaptive Multiple Features Method and Fibrosis Outcomes.

PubMed

Salisbury, Margaret L; Lynch, David A; van Beek, Edwin J R; Kazerooni, Ella A; Guo, Junfeng; Xia, Meng; Murray, Susan; Anstrom, Kevin J; Yow, Eric; Martinez, Fernando J; Hoffman, Eric A; Flaherty, Kevin R

2017-04-01

Adaptive multiple features method (AMFM) lung texture analysis software recognizes high-resolution computed tomography (HRCT) patterns. To evaluate AMFM and visual quantification of HRCT patterns and their relationship with disease progression in idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis in a clinical trial of prednisone, azathioprine, and N-acetylcysteine underwent HRCT at study start and finish. Proportion of lung occupied by ground glass, ground glass-reticular (GGR), honeycombing, emphysema, and normal lung densities were measured by AMFM and three radiologists, documenting baseline disease extent and postbaseline change. Disease progression includes composite mortality, hospitalization, and 10% FVC decline. Agreement between visual and AMFM measurements was moderate for GGR (Pearson's correlation r = 0.60, P < 0.0001; mean difference = -0.03 with 95% limits of agreement of -0.19 to 0.14). Baseline extent of GGR was independently associated with disease progression when adjusting for baseline Gender-Age-Physiology stage and smoking status (hazard ratio per 10% visual GGR increase = 1.98, 95% confidence interval [CI] = 1.20-3.28, P = 0.008; and hazard ratio per 10% AMFM GGR increase = 1.36, 95% CI = 1.01-1.84, P = 0.04). Postbaseline visual and AMFM GGR trajectories were correlated with postbaseline FVC trajectory (r = -0.30, 95% CI = -0.46 to -0.11, P = 0.002; and r = -0.25, 95% CI = -0.42 to -0.06, P = 0.01, respectively). More extensive baseline visual and AMFM fibrosis (as measured by GGR densities) is independently associated with elevated hazard for disease progression. Postbaseline change in AMFM-measured and visually measured GGR densities are modestly correlated with change in FVC. AMFM-measured fibrosis is an automated adjunct to existing prognostic markers and may allow for study enrichment with subjects at increased disease progression risk.

Organizing Hazards, Engineering Disasters? Improving the Recognition of Political-Economic Factors in the Creation of Disasters

ERIC Educational Resources Information Center

Freudenburg, William R.; Gramling, Robert; Laska, Shirley; Erikson, Kai T.

2008-01-01

Disaster studies have made important progress in recognizing the unequally distributed consequences of disasters, but there has been less progress in analyzing social factors that help create "natural" disasters. Even well-known patterns of hazard-creation tend to be interpreted generically--as representing "economic development" or…

Annual Research Progress Report (U.S. Army Institute of Dental Research, Washington, DC)

DTIC Science & Technology

1978-10-01

postoperative edema, minimal postoperative scarring, sterilization of infected wounds, minimal pain and a sharply demarcated operative field. This...evaluate pain killing medicaments used in military dental practice. The hazards involved in the use of various drugs will be studied and...Surgical treatment of orofacial wounds frequently requires use of high-speed equipment and ultrasonic sealers. Water from dental units has been

Superiority of delayed risk stratification in differentiated thyroid cancer after total thyroidectomy and radioactive iodine ablation.

PubMed

Hong, Chae Moon; Lee, Won Kee; Jeong, Shin Young; Lee, Sang-Woo; Ahn, Byeong-Cheol; Lee, Jaetae

2014-11-01

The aim of this study was to validate the effectiveness of delayed risk stratification (DRS) in predicting structural progression and compare the predictive value of American Thyroid Association (ATA) risk stratification with that of DRS in patients with differentiated thyroid cancer (DTC). A total of 398 patients with DTC who underwent surgery followed by radioactive iodine ablation were enrolled. Patients were categorized as having excellent response, acceptable response, biochemical incomplete response, or structural incomplete response at 8-15 months' evaluation after radioactive iodine ablation for DRS. Effectiveness of DRS was evaluated according to structural progression-free survival (PFS; median follow-up, 10.7 years). A total of 229 patients (57.5%) were classified as having excellent response, 78 (19.6%) as having acceptable response, 62 (15.6%) as having biochemical incomplete response, and 29 patients (7.3%) as having structural incomplete response. After DRS, 60.2% of intermediate-risk patients and 20.5% of high-risk patients were shifted to the excellent response category. Sixty-nine patients (17.3%) showed structural progression. DRS showed statistical difference in PFS (hazard ratio, 4.268; 95% confidence interval, 3.258-5.477; P<0.001). In multivariate analysis of ATA risk stratification and DRS, DRS was significantly associated with PFS (hazard ratio, 4.383; 95% confidence interval, 3.250-5.912; P<0.001), but ATA risk stratification was not. There was no significant difference in deviances between the use of DRS alone and the use of both DRS and ATA risk stratification (χ=0.103, d.f.=1, P=0.748). DRS is superior to ATA risk stratification in predicting structural disease progression for DTC patients.

Moderate/Severe hyponatremia increases the risk of death among hospitalized Chinese human immunodeficiency virus/acquired immunodeficiency syndrome patients.

PubMed

Xu, Lijun; Ye, Hanhui; Huang, Fan; Yang, Zongxing; Zhu, Biao; Xu, Yan; Qiu, Yunqing; Li, Lanjuan

2014-01-01

To evaluate whether the serum sodium concentration is associated with the progression and long-term prognosis of Chinese HIV/AIDS patients. Three hundred and eighty seven hospitalized patients were recruited into this retrospective cohort study. The strata of serum sodium concentration were moderate/severe hyponatremia, mild hyponatremia and normonatremia. Disease progression was estimated using CD4 counts and the WHO clinical stage. Correlation analysis was used to evaluate the serum sodium concentration with disease progression. The Kaplan-Meier method and the Cox proportional hazards model were used to analyze the effect of different serum sodium levels on survival. In this study 206 patients (53.2%) had hyponatremia, including 10.6% patients with moderate/severe hyponatremia and 42.6% with mild hyponatremia. The serum sodium concentration was significantly correlated with the HIV/AIDS progression (P<0.001). During the follow-up, 100 patients (25.6%) died. The cumulative survival rates of HIV/AIDS patients were 47.8% ± 8.5% in patients with moderate/severe hyponatremia, 59.8% ± 5.0% with mild hyponatremia and 79.9% ± 3.4% with normonatremia (log-rank P<0.001). After adjusting for sex, age, WHO stage, CD4 count, hemoglobin and albumin, the relative hazard was 3.5 (95% CI: 1.9-6.5) for patients with moderate/severe hyponatremia (P<0.001), and 1.5 (95% CI: 0.9-2.4) for those with mild hyponatremia (P = 0.161), compared with normonatremic patients. The serum sodium level is closely correlated with the severity of patients. Only moderate/severe hyponatremia affects the prognosis of Chinese HIV/AIDS patients. Earlier intensive medical managements(including HAART)are necessary to increase the survival rates of Chinese HIV/AIDS patients with moderate/severe hyponatremia.

Cardioversion and subsequent quality of life and natural history of atrial fibrillation.

PubMed

Pokorney, Sean D; Kim, Sunghee; Thomas, Laine; Fonarow, Gregg C; Kowey, Peter R; Gersh, Bernard J; Mahaffey, Kenneth W; Peterson, Eric D; Piccini, Jonathan P

2017-03-01

Cardioversion is a class I procedure for patients with symptomatic atrial fibrillation (AF) pursuing rhythm control. There are few contemporary reports on quality of life and outcomes after cardioversion. Using the nationwide prospective ORBIT-AF registry, cardioversion patients were propensity matched 3:1 to noncardioverted patients and Cox proportional hazards modeling evaluated hospitalization at 1 year in those with and without cardioversion. Cardiovascular outcomes, AF progression, and quality of life were evaluated for the matched cohorts with and without cardioversion. Among 9,642 patients, 817 patients (8%) underwent 906 cardioversions during a median follow-up of 12 (interquartile range 6-18) months. Among matched cardioverted and noncardioverted patients, 1-year cardiovascular hospitalization rates were 43% vs 21% (adjusted hazard ratio 2.2, 95% CI 1.8-2.8, P<.001), and sinus rhythm at both first and second follow-ups was 36% vs 27% (P=.042), respectively. Findings were similar among first-time cardioversion patients. Matched cardioversion patients did not exhibit greater symptom improvement (34% vs 42%) or less symptomatic progression (15% vs 4%) by European Heart Rhythm Association scores. Cardioversion was associated with AF progression with an odds ratio of 1.6 (95% CI 1.2-2.2, P=.001) after cardioversion and 2.7 (P<.001) after first cardioversion vs matched noncardioversion patients. After cardioversion, only 18% of patients not previously on an antiarrhythmic started one, less than 5% underwent ablation, and 22% stopped their antiarrhythmic. Cardioversion was not associated with improved AF-related quality of life or less progression. Many patients who undergo cardioversion do not receive adjunctive rhythm control therapies. These findings may help to better inform therapeutic decision making. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Learn about the Hazardous Waste Electronic Manifest System (e-Manifest)

EPA Pesticide Factsheets

This webpage provides information on EPA's work toward developing a hazardous waste electronic manifest system. Information on the Hazardous Waste Electronic Manifest Establishment Act, progress on the project and frequent questions are available.

The Association of Statin Use with Age-Related Macular Degeneration Progression: The Age-Related Eye Disease Study 2 Report Number 9.

PubMed

Al-Holou, Shaza N; Tucker, William R; Agrón, Elvira; Clemons, Traci E; Cukras, Catherine; Ferris, Frederick L; Chew, Emily Y

2015-12-01

To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50 to 85 years. Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke-all known to be associated with statin use-were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses adjusting for the competing risk of death were also performed. Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.83-1.41; P = 0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29). Furthermore, subgroup analyses of persons with or without late AMD at baseline and the various components of late AMD (neovascular AMD, central GA, or any GA) also showed no statistically significant association of statin use with progression to AMD. Statin use was not statistically significantly associated with progression to late AMD in the AREDS2 participants, and these findings are consistent with findings in the majority of previous studies. Statins have been demonstrated to reduce the risk of cardiovascular disease, but our data do not provide evidence of a beneficial effect on slowing AMD progression. Published by Elsevier Inc.

Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy

PubMed Central

Devillier, Raynier; Coso, Diane; Castagna, Luca; Brenot Rossi, Isabelle; Anastasia, Antonella; Chiti, Arturo; Ivanov, Vadim; Schiano, Jean Marc; Santoro, Armando; Chabannon, Christian; Balzarotti, Monica; Blaise, Didier; Bouabdallah, Reda

2012-01-01

Background High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin’s lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin’s lymphoma. Design and Methods We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin’s lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation. Results Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to 43% (P=0.034). Multivariate analysis showed that positron emission tomography status (hazard ratio: 5.26 [2.57–10.73]) and tandem transplantation (hazard ratio: 0.39 [0.19–0.78]) but not risk factors at relapse (hazard ratio: 1.77 [0.80–3.92]) significantly influenced progression-free survival, while only tomography status significantly influenced overall survival (hazard ratio: 4.03 [1.38–11.75]). Conclusions In patients with relapsed/refractory Hodgkin’s lymphoma responding to prior salvage therapy, positron emission tomography response at time of autologous stem cell transplantation favorably influences outcome and enables identification of patients requiring single or tandem transplantation. PMID:22271893

A systematic assessment of the state of hazardous waste clean-up technologies. Quarterly technical progress report, April 1--June 30, 1993

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

Berg, M.T.; Reed, B.E.; Gabr, M.

1993-07-01

West Virginia University (WVU) and the US DOE Morgantown Energy Technology Center (METC) entered into a Cooperative Agreement on August 29, 1992 entitled ``Decontamination Systems Information and Research Programs.`` Stipulated within the Agreement is the requirement that WVU submit to METC a series of Technical Progress Report for Year 1 of the Agreement. This report reflects the progress and/or efforts performed on the following nine technical projects encompassed by the Year 1 Agreement for the period of April 1 through June 30, 1993: Systematic assessment of the state of hazardous waste clean-up technologies; site remediation technologies -- drain-enhanced soil flushingmore » (DESF) for organic contaminants removal; site remediation technologies -- in situ bioremediation of organic contaminants; excavation systems for hazardous waste sites; chemical destruction of polychlorinated biphenyls; development of organic sensors -- monolayer and multilayer self-assembled films for chemical sensors; Winfield lock and dam remediation; Assessments of Technologies for hazardous waste site remediation -- non-treatment technologies and pilot scale test facility implementation; and remediation of hazardous sites with stream reforming.« less

Retinopathy predicts progression of fasting plasma glucose: An Early Diabetes Intervention Program (EDIP) Analysis

PubMed Central

Patel, Yash R.; Kirkman, M. Sue; Considine, Robert V; Hannon, Tamara S; Mather, Kieren J

2017-01-01

Background Retinopathy is increasingly recognized in prediabetic populations, and may herald increased risk of metabolic worsening. The Early Diabetes Intervention Program (EDIP) evaluated worsening of glycemia in screen-detected Type 2 diabetes, following participants for up to 5 years. Here we have evaluated whether the presence of retinopathy at the time of detection of diabetes was associated with accelerated progression of glycemia. Methods We prospectively studied 194 participants from EDIP with available baseline retinal photographs. Retinopathy was determined at baseline using 7-field fundus photography and defined as an Early Treatment of Diabetic Retinopathy Study Scale grading score of ≥20. Results At baseline, 12% of participants had classical retinal lesions indicating retinopathy. In univariate Cox proportional hazard analysis, the presence of retinopathy at baseline was associated with a doubled risk of progression of fasting plasma glucose (HR 2.02; 95% CI 1.05–3.89). The retinopathy effect was robust to individual adjustment for age and glucose, the most potent determinants of progression in EDIP. Conclusion Retinopathy was associated with increased risk of progression of fasting plasma glucose among adults with screen-detected, early diabetes. Early detection of retinopathy may help individualize more aggressive therapy to prevent progressive metabolic worsening in early diabetes. PMID:28003103

Reducing Vulnerability of Coastal Communities to Coastal Hazards through Building Community Resilience

NASA Astrophysics Data System (ADS)

Bhj, Premathilake

2010-05-01

Reducing Vulnerability of Coastal Communities to Coastal Hazards through Building Community Resilience B H J Premathilake Coast Conservation Department Sri Lanka Email: bhjprem@yahoo.com This paper contains two parts; Part one describes the comprehensive approach adopted by our project to build social, economical, institutional and environmental resilience of the tsunami affected communities in Sri Lanka to cope with future natural disasters. Community development, Coastal resource management and Disaster management are the three pillars of this model and these were built simultaneously to bring the community into a higher level of resilience to coastal hazards. Second part describes the application of Coastal Community Resilience (CCR) Assessment framework to evaluate the progress achieved by the project in building overall resilience of the communities during its period. It further describes how to estimate the contribution of this specific project for the improved resilience status of the selected communities in a multi stakeholder environment.

Remedying CERCLA`s natural resource damages provision: Incorporation of the public trust doctrine into natural resource damage actions

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

Chase, A.R.

When Congress enacted the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), it ushered in a sweeping approach to controlling the environmental effects of improper hazardous waste disposal. CERCLA`s cleanup provisions, which focus on removal and remediation of hazardous substances from inactive hazardous waste sites, have progressed through more than a decade of litigation and a great deal of public debate. However, CERCLA`s natural resource damage provisions have not shared this same degree of progress.

Common Genetic Variation in CYP17A1 and Response to Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer

PubMed Central

Binder, Moritz; Zhang, Ben Y.; Hillman, David W.; Kohli, Rhea; Kohli, Tanvi; Lee, Adam; Kohli, Manish

2016-01-01

Treatment with abiraterone acetate and prednisone (AA/P) prolongs survival in metastatic castration-resistant prostate cancer (mCRPC) patients. We evaluated the genetic variation in CYP17A1 as predictive of response to AA/P. A prospective collection of germline DNA prior to AA/P initiation and follow-up of a mCRPC cohort was performed. Five common single-nucleotide polymorphisms (SNPs) in CYP17A1 identified using a haplotype-based tagging algorithm were genotyped. Clinical outcomes included biochemical response and time to biochemical progression on AA/P. Logistic regression was used to assess the association between tag SNPs and biochemical response. Proportional hazards regression was used to assess the association between tag SNPs and time to biochemical progression. Odds or hazard ratio per minor allele were estimated and p-values below 0.05 were considered statistically significant. Germline DNA was successfully genotyped for four tag SNPs in 87 patients. The median age was 73 years (54–90); the median prostate-specific antigen was 66 ng/dL (0.1–99.9). A single SNP, rs2486758, was associated with lower odds of experiencing a biochemical response (Odds ratio 0.22, 95% confidence interval 0.07–0.63, p = 0.005) and a shorter time to biochemical progression (Hazard ratio 2.23, 95% confidence interval 1.39–3.56, p < 0.001). This tag SNP located in the promoter region of CYP17A1 will need further validation as a predictive biomarker for AA/P therapy. PMID:27409606

PROSPECT: Profiling of Resistance Patterns & Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax and Therapeutic Target Identification

DTIC Science & Technology

2012-06-01

neoadjuvant therapies on disease-free, progression-free, and overall survival will vary across prognostically distinct groups. 3. Specific molecular... prognostically distinct subpopulations of patients with resectable NSCLC, and to assess the extent to which these molecular profiles correlate with tumor...overall survival, and will use Cox proportional hazards models and recursive partitioning methods to identify important biomarkers and prognostically

Cellular proliferation and regeneration following tissue damage. Progress report. [Eyes

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

Harding, C.V.

1976-10-01

Results are reported from a study of wound healing in tissues of the eye, particularly lens, cornea, and surrounding tissues. The reactions of these tissues to mechanical injuries, as well as injuries induced by chemotoxic agents were studied. It is postulated that a better understanding of the basic reactions of the eye to injurious agents may be of importance in the evaluation of potential environmental hazards.

St. Louis Area Earthquake Hazards Mapping Project - A Progress Report-November 2008

USGS Publications Warehouse

Karadeniz, D.; Rogers, J.D.; Williams, R.A.; Cramer, C.H.; Bauer, R.A.; Hoffman, D.; Chung, J.; Hempen, G.L.; Steckel, P.H.; Boyd, O.L.; Watkins, C.M.; McCallister, N.S.; Schweig, E.

2009-01-01

St. Louis has experienced minor earthquake damage at least 12 times in the past 200 years. Because of this history and its proximity to known active earthquake zones, the St. Louis Area Earthquake Hazards Mapping Project (SLAEHMP) is producing digital maps that show variability of earthquake hazards, including liquefaction and ground shaking, in the St. Louis area. The maps will be available free via the internet. Although not site specific enough to indicate the hazard at a house-by-house resolution, they can be customized by the user to show specific areas of interest, such as neighborhoods or transportation routes. Earthquakes currently cannot be predicted, but scientists can estimate how strongly the ground is likely to shake as the result of an earthquake. Earthquake hazard maps provide one way of conveying such estimates. The U.S. Geological Survey (USGS), which produces earthquake hazard maps for the Nation, is working with local partners to develop detailed maps for urban areas vulnerable to strong ground shaking. These partners, which along with the USGS comprise the SLAEHMP, include the Missouri University of Science and Technology-Rolla (Missouri S&T), Missouri Department of Natural Resources (MDNR), Illinois State Geological Survey (ISGS), Saint Louis University, Missouri State Emergency Management Agency, and URS Corporation. Preliminary hazard maps covering a test portion of the 29-quadrangle St. Louis study area have been produced and are currently being evaluated by the SLAEHMP. A USGS Fact Sheet summarizing this project was produced and almost 1000 copies have been distributed at several public outreach meetings and field trips that have featured the SLAEHMP (Williams and others, 2007). In addition, a USGS website focusing on the SLAEHMP, which provides links to project results and relevant earthquake hazard information, can be found at: http://earthquake.usgs.gov/regional/ceus/urban_map/st_louis/index.php. This progress report summarizes the methodology and data used to generate these preliminary maps. For more details about many of the topics in this summary the reader is referred to the Karadeniz (2007) and Chung (2007) Ph.D. theses.

77 FR 65574 - Notice of Proposed Information Collection: Healthy Homes and Lead Hazard Control Programs Data...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-29

... Information Collection: Healthy Homes and Lead Hazard Control Programs Data Collection--Progress Reporting AGENCY: Office of Healthy Homes and Lead Hazard Control, HUD. ACTION: Notice. SUMMARY: The revised... of Healthy Homes and Lead Hazard Control, Department of Housing and Urban Development, 451 7th Street...

Spatially explicit risk approach for multi-hazard assessment and management in marine environment: The case study of the Adriatic Sea.

PubMed

Furlan, Elisa; Torresan, Silvia; Critto, Andrea; Marcomini, Antonio

2018-03-15

In the last few decades the health of marine ecosystems has been progressively endangered by the anthropogenic presence. Natural and human-made pressures, as well as climate change effects, are posing increasing threats on marine areas, triggering alteration of biological, chemical and physical processes. Planning of marine areas has become a challenge for decision makers involved in the design of sustainable management options. In order to address threats posed by climate drivers in combination with local to regional anthropogenic pressures affecting marine ecosystems and activities, a multi-hazard assessment methodology was developed and applied to the Adriatic Sea for the reference scenario 2000-2015. Through a four-stages process based on the consecutive analysis of hazard, exposure, vulnerability and risk the methodology allows a semi-quantitative evaluation of the relative risk from anthropogenic and natural sources to multiple endpoints, thus supporting the identification and ranking of areas and targets more likely to be at risk. Resulting output showed that the higher relative hazard scores are linked to exogenic pressures (e.g. sea surface temperature variation) while the lower ones resulted from endogenic and more localized stressors (e.g. abrasion, nutrient input). Relatively very high scores were observed for vulnerability over the whole case study for almost all the considered pressures, showing seagrasses meadows, maërl and coral beds as the most susceptible targets. The approach outlined in this study provides planners and decision makers a quick-screening tool to evaluate progress towards attaining a good environmental status and to identify marine areas where management actions and adaptation strategies would be best targeted. Moreover, by focusing on risks induced by land-based drivers, resulting output can support the design of infrastructures for reducing pressures on the sea, contributing to improve the land-sea interface management. Copyright © 2017 Elsevier B.V. All rights reserved.

Sunlight exposure and sun sensitivity associated with disability progression in multiple sclerosis.

PubMed

D'hooghe, M B; Haentjens, P; Nagels, G; Garmyn, M; De Keyser, J

2012-04-01

Sunlight and vitamin D have been inversely associated with the risk of multiple sclerosis (MS). We investigated sunlight exposure and sun sensitivity in relation to disability progression in MS. We conducted a survey among persons with MS, registered by the Flemish MS society, Belgium, and stratified data according to relapsing-onset and progressive-onset MS. We used Kaplan-Meier survival and Cox proportional hazard regression analyses with time to Expanded Disability Status Scale (EDSS) 6 as outcome measure. Hazard ratios for the time from onset and from birth were calculated for the potentially predictive variables, adjusting for age at onset, gender and immunomodulatory treatment. 704 (51.3%) of the 1372 respondents had reached EDSS 6. In relapsing-onset MS, respondents reporting equal or higher levels of sun exposure than persons of the same age in the last 10 years had a decreased risk of reaching EDSS 6. In progressive-onset MS, increased sun sensitivity was associated with an increased hazard of reaching EDSS 6. The association of higher sun exposure with a better outcome in relapsing-onset MS may be explained by either a protective effect or reverse causality. Mechanisms underlying sun sensitivity might influence progression in progressive-onset MS.

Hepatic Fibrosis Progression in HIV-Hepatitis C Virus Co-Infection--The Effect of Sex on Risk of Significant Fibrosis Measured by Aspartate-to-Platelet Ratio Index.

PubMed

Rollet-Kurhajec, Kathleen C; Moodie, Erica E M; Walmsley, Sharon; Cooper, Curtis; Pick, Neora; Klein, Marina B

2015-01-01

In Hepatitis C virus (HCV) mono-infection, male sex is associated with faster liver fibrosis progression but the effects of sex have not been well studied in HIV-HCV co-infected patients. We examined the influence of sex on progression to significant liver fibrosis in HIV-HCV co-infected adults receiving antiretroviral therapy (ART) using the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate biomarker of liver fibrosis. We evaluated 308 HIV infected, HCV RNA positive participants of a Canadian multicentre prospective cohort receiving antiretrovirals and without significant liver fibrosis or end-stage liver disease at baseline. We used multivariate discrete-time proportional hazards models to assess the effect of sex on time to significant fibrosis (APRI≥1.5) adjusting for baseline age, alcohol use, cigarette smoking, HCV duration, and APRI and time-updated CD4 count and HIV RNA. Overall, 55 (18%) participants developed an APRI ≥ 1.5 over 544 person-years of at-risk follow-up time; 18 (21%) women (incidence rate (IR)=14.0/100 PY; 7.5-20.4) and 37 (17%) men (IR=8.9/100 PY; 6.0-11.8). Women had more favourable profiles with respect to traditional risk factors for liver disease progression (younger, shorter duration of HCV infection and less alcohol use). Despite this, female sex was associated with a greater than two-fold increased risk of fibrosis progression (adjusted hazard rate (HR) =2.23; 1.22-4.08). HIV-HCV co-infected women receiving antiretroviral therapy were at significantly greater risk of progressing to liver fibrosis as measured by APRI compared with men. Enhanced efforts to engage and treat co-infected women for HCV are needed.

Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia.

PubMed

Seymour, John F; Kipps, Thomas J; Eichhorst, Barbara; Hillmen, Peter; D'Rozario, James; Assouline, Sarit; Owen, Carolyn; Gerecitano, John; Robak, Tadeusz; De la Serna, Javier; Jaeger, Ulrich; Cartron, Guillaume; Montillo, Marco; Humerickhouse, Rod; Punnoose, Elizabeth A; Li, Yan; Boyer, Michelle; Humphrey, Kathryn; Mobasher, Mehrdad; Kater, Arnon P

2018-03-22

Venetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We evaluated the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. In this randomized, open-label, phase 3 trial, we randomly assigned 389 patients to receive venetoclax for up to 2 years (from day 1 of cycle 1) plus rituximab for the first 6 months (venetoclax-rituximab group) or bendamustine plus rituximab for 6 months (bendamustine-rituximab group). The trial design did not include crossover to venetoclax plus rituximab for patients in the bendamustine-rituximab group in whom progression occurred. The primary end point was investigator-assessed progression-free survival. After a median follow-up period of 23.8 months, the rate of investigator-assessed progression-free survival was significantly higher in the venetoclax-rituximab group (32 events of progression or death in 194 patients) than in the bendamustine-rituximab group (114 events in 195 patients); the 2-year rates of progression-free survival were 84.9% and 36.3%, respectively (hazard ratio for progression or death, 0.17; 95% confidence interval [CI], 0.11 to 0.25; P<0.001 by the stratified log-rank test). The benefit was maintained across all clinical and biologic subgroups, including the subgroup of patients with chromosome 17p deletion; the 2-year rate of progression-free survival among patients with chromosome 17p deletion was 81.5% in the venetoclax-rituximab group versus 27.8% in the bendamustine-rituximab group (hazard ratio, 0.13; 95% CI, 0.05 to 0.29), and the 2-year rate among those without chromosome 17p deletion was 85.9% versus 41.0% (hazard ratio, 0.19; 95% CI, 0.12 to 0.32). The benefit of venetoclax plus rituximab over bendamustine plus rituximab was confirmed by an independent review committee assessment of progression-free survival and other secondary efficacy end points. The rate of grade 3 or 4 neutropenia was higher in the venetoclax-rituximab group than in the bendamustine-rituximab group, but the rates of grade 3 or 4 febrile neutropenia and infections or infestations were lower with venetoclax than with bendamustine. The rate of grade 3 or 4 tumor lysis syndrome in the venetoclax-rituximab group was 3.1% (6 of 194 patients). Among patients with relapsed or refractory chronic lymphocytic leukemia, venetoclax plus rituximab resulted in significantly higher rates of progression-free survival than bendamustine plus rituximab. (Funded by Genentech and AbbVie; ClinicalTrials.gov number, NCT02005471 .).

Serum Urate at Trial Entry and ALS Progression in EMPOWER

PubMed Central

O'Reilly, Éilis J.; Liu, Dawei; Johns, Donald R.; Cudkowicz, Merit E.; Paganoni, Sabrina; Schwarzschild, Michael A.; Leitner, Melanie; Ascherio, Alberto

2017-01-01

Objective Determine whether serum urate predicts ALS progression. Methods The study population comprised adult participants of EMPOWER (n=942), a phase III clinical trial to evaluate the efficacy of dexpramipexole to treat ALS. Urate was measured in blood samples collected during enrollment as part of the routine block chemistry. Outcomes Combined assessment of function and survival rank (CAFs), and time to death, by 12 months. Results In women there was not a significant relation between urate and outcomes. In men, outcomes improved with increasing urate (comparing highest to lowest urate quartile: CAFS was 53 points better with p for trend=0.04; and hazard ratio for death was 0.60 with p for trend=0.07), but with adjustment for body mass index (BMI) at baseline, a predictor of both urate levels and prognosis, associations were attenuated and no longer statistically significant. Overall, participants with urate levels equal to or above the median (5.1 mg/dL) appeared to have a survival advantage compared to those below (hazard ratio adjusted for BMI: 0.67; 95% confidence interval: 0.47 to 0.95). Conclusion These findings suggest that while the association between urate at baseline and ALS progression is partially explained by BMI, there may be an independent beneficial effect of urate. PMID:27677562

Subjective cognitive concerns and neuropsychiatric predictors of progression to the early clinical stages of Alzheimer disease.

PubMed

Donovan, Nancy J; Amariglio, Rebecca E; Zoller, Amy S; Rudel, Rebecca K; Gomez-Isla, Teresa; Blacker, Deborah; Hyman, Bradley T; Locascio, Joseph J; Johnson, Keith A; Sperling, Reisa A; Marshall, Gad A; Rentz, Dorene M

2014-12-01

To examine neuropsychiatric and neuropsychological predictors of progression from normal to early clinical stages of Alzheimer disease (AD). From a total sample of 559 older adults from the Massachusetts Alzheimer's Disease Research Center longitudinal cohort, 454 were included in the primary analysis: 283 with clinically normal cognition (CN), 115 with mild cognitive impairment (MCI), and 56 with subjective cognitive concerns (SCC) but no objective impairment, a proposed transitional group between CN and MCI. Two latent cognitive factors (memory-semantic, attention-executive) and two neuropsychiatric factors (affective, psychotic) were derived from the Alzheimer's Disease Centers' Uniform Data Set neuropsychological battery and Neuropsychiatric Inventory brief questionnaire. Factors were analyzed as predictors of time to progression to a worse diagnosis using a Cox proportional hazards regression model with backward elimination. Covariates included baseline diagnosis, gender, age, education, prior depression, antidepressant medication, symptom duration, and interaction terms. Higher/better memory-semantic factor score predicted lower hazard of progression (hazard ratio [HR] = 0.4 for 1 standard deviation [SD] increase, p <0.0001), and higher/worse affective factor score predicted higher hazard (HR = 1.3 for one SD increase, p = 0.01). No other predictors were significant in adjusted analyses. Using diagnosis as a sole predictor of transition to MCI, the SCC diagnosis carried a fourfold risk of progression compared with CN (HR = 4.1, p <0.0001). These results identify affective and memory-semantic factors as significant predictors of more rapid progression from normal to early stages of cognitive decline and highlight the subgroup of cognitively normal elderly with SCC as those with elevated risk of progression to MCI. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Evaluating progress in reducing workplace violence: trends in Washington State workers' compensation claims rates, 1997-2007.

PubMed

Foley, Michael; Rauser, Edmund

2012-01-01

This study reports trends in the pattern of injuries related to workplace violence over the period 1997-2007. It tracks occupations and industries at elevated risk of workplace violence with a special focus on the persistently high claims rates among healthcare and social assistance workers. Industry and occupational incidence rates were calculated using workers' compensation and employment security data from Washington State. Violence-related claims rates among certain Healthcare and Social Assistance industries remained particularly high. Incidents where workers were injured by clients or patients predominated. By contrast, claims rates in retail trade have fallen substantially. Progress to reduce violence has been made in most of the highest hazard industries within the Healthcare and Social Assistance sector with the notable exception of psychiatric hospitals and facilities caring for the developmentally disabled. State legislation requiring healthcare workplaces to address hazards for workplace violence has had mixed results. Insufficient staffing, inadequate violence prevention training and sporadic management attention are seen as the key barriers to violence prevention in healthcare/social assistance workplaces.

Role of hepatic resection for patients with carcinoid heart disease.

PubMed

Bernheim, Alain M; Connolly, Heidi M; Rubin, Joseph; Møller, Jacob E; Scott, Christopher G; Nagorney, David M; Pellikka, Patricia A

2008-02-01

To evaluate the effects of resection of hepatic carcinoid metastases on progression and prognosis of carcinoid heart disease. From our database of 265 consecutive patients diagnosed as having carcinoid heart disease from January 1, 1980, through December 31, 2005, we calculated survival from first diagnosis of cardiac involvement. Hepatic resection during follow-up was entered as a time-dependent covariable in a multivariable analysis. In patients with serial echocardiograms more than 1 year apart without intervening cardiac surgery, a previously validated cardiac severity score was calculated. A score increase that exceeded 25% was considered relevant progression. Hepatic resection was performed in 31 patients (12%) during follow-up. Five-year survival was significantly higher in these patients (86.5%; 95% confidence interval [CI], 73.5%-100.0%) than in patients without hepatic resection (29.0%; 95% CI, 23.3%-36.1%; univariable hazard ratio for hepatic resection, 0.25; 95% CI 0.12-0.53; P<.001). Hepatic resection remained strongly associated with improved prognosis in multivariable analysis (hazard ratio, 0.31; 95% CI, 0.14-0.66; P=.003). Among 77 patients (29%) with serial echocardiograms, 10 (13%) underwent hepatic resection during follow-up; resection was independently associated with decreased risk of cardiac progression (odds ratio, 0.29; 95% CI, 0.06-0.75; P=.03). Despite the limitations of this retrospective nonrandomized study, our data suggest that patients with carcinoid heart disease who undergo hepatic resection have decreased cardiac progression and improved prognosis. Eligible patients should be considered for hepatic surgery.

The Prognostic Value of Histopathologic Lesions in Native Kidney Biopsy Specimens: Results from the Boston Kidney Biopsy Cohort Study.

PubMed

Srivastava, Anand; Palsson, Ragnar; Kaze, Arnaud D; Chen, Margaret E; Palacios, Polly; Sabbisetti, Venkata; Betensky, Rebecca A; Steinman, Theodore I; Thadhani, Ravi I; McMahon, Gearoid M; Stillman, Isaac E; Rennke, Helmut G; Waikar, Sushrut S

2018-06-04

Background Few studies have evaluated whether histopathologic lesions on kidney biopsy provide prognostic information beyond clinical and laboratory data. Methods We enrolled 676 individuals undergoing native kidney biopsy at three tertiary care hospitals into a prospective, observational cohort study. Biopsy specimens were adjudicated for semiquantitative scores in 13 categories of histopathology by two experienced renal pathologists. Proportional hazards models tested the association between histopathologic lesions and risk of kidney disease progression (≥40% eGFR decline or RRT). Results Mean baseline eGFR was 57.5±36.0 ml/min per 1.73 m 2 During follow-up (median, 34.3 months), 199 individuals suffered kidney disease progression. After adjustment for demographics, clinicopathologic diagnosis, and laboratory values, the following lesions (hazard ratio; 95% confidence interval) were independently associated with progression: inflammation in nonfibrosed interstitium (0.52; 0.32 to 0.83), moderate and severe versus minimal interstitial fibrosis/tubular atrophy (2.14; 1.24 to 3.69 and 3.42; 1.99 to 5.87, respectively), moderate and severe versus minimal global glomerulosclerosis (2.17; 1.36 to 3.45 and 3.31; 2.04 to 5.38, respectively), moderate and severe versus minimal arterial sclerosis (1.78; 1.15 to 2.74 and 1.64; 1.04 to 2.60, respectively), and moderate and severe versus minimal arteriolar sclerosis (1.63; 1.08 to 2.46 and 2.33; 1.42 to 3.83, respectively). An 11-point chronicity score derived from semiquantitative assessments of chronic lesions independently associated with higher risk of kidney disease progression (hazard ratio per one-point increase, 1.19; 95% confidence interval, 1.12 to 1.27). Conclusions Across a diverse group of kidney diseases, histopathologic lesions on kidney biopsy provide prognostic information, even after adjustment for proteinuria and eGFR. Copyright © 2018 by the American Society of Nephrology.

Progression-free survival results in postmenopausal Asian women: subgroup analysis from a phase III randomized trial of fulvestrant 500 mg vs anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON).

PubMed

Noguchi, Shinzaburo; Ellis, Matthew J; Robertson, John F R; Thirlwell, Jackie; Fazal, Mehdi; Shao, Zhimin

2018-05-01

The international, phase III FALCON study (NCT01602380) in postmenopausal patients with hormone receptor-positive, locally advanced/metastatic breast cancer (LA/MBC) who had not received prior endocrine therapy, demonstrated statistically significant improvement in progression-free survival (PFS) for patients who received fulvestrant 500 mg vs anastrozole 1 mg. This subgroup analysis evaluated PFS in Asian (randomized in China, Japan, or Taiwan) and non-Asian patients from the FALCON study. Eligible patients (estrogen receptor- and/or progesterone receptor-positive LA/MBC; World Health Organization performance status 0-2; ≥ 1 measurable/non-measurable lesion[s]) were randomized. PFS was assessed via Response Evaluation Criteria in Solid Tumours version 1.1, surgery/radiotherapy for disease worsening, or death (any cause). Secondary endpoints included: objective response rate, clinical benefit rate, duration of response, and duration of clinical benefit. Consistency of effect across subgroups was assessed via hazard ratios and 95% confidence intervals (CIs) using a log-rank test. Adverse events (AEs) were evaluated. Of the 462 randomized patients, the Asian and non-Asian subgroups comprised 67 and 395 patients, respectively. In the Asian subgroup, median PFS was 16.6 and 15.9 months with fulvestrant and anastrozole, respectively (hazard ratio 0.81; 95% CI 0.44-1.50). In the non-Asian subgroup, median PFS was 16.5 and 13.8 months, respectively (hazard ratio 0.79; 95% CI 0.62-1.01). Secondary outcomes were numerically improved with fulvestrant vs anastrozole in both subgroups. AE profiles were generally consistent between Asian and non-Asian subgroups. Results of this subgroup analysis suggest that treatment effects in the Asian patient subgroup are broadly consistent with the non-Asian population.

The Association of Statin Use with Age-Related Macular Degeneration Progression The Age-Related Eye Disease Study 2 Report Number 9

PubMed Central

Al-Holou, Shaza N.; Tucker, William R.; Agrón, Elvira; Clemons, Traci E.; Cukras, Catherine; Ferris, Frederick L.; Chew, Emily Y.

2015-01-01

Objective/purpose To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Design Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Subjects Age-Related Eye Disease Study 2 participants, aged 50 to 85 years. Methods Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke, all known to be associated with statin use, were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses were also performed adjusting for the competing risk of death. Main Outcome Measures Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Results Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratios [HR] of 1.08, 95% confidence intervals [CI] of 0.83–1.41, P=0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant with HR: 0.81, 95% CI: 0.55–1.20, P=0.29. Further subgroup analyses of persons with or without late AMD at baseline to the various components of late AMD (neovascular, central geographic atrophy, or any geographic atrophy) also showed no statistically significant association of statin use with progression to AMD. Conclusions Statin use was not statistically significantly associated with the progression to late AMD in the AREDS2 participants, and these findings are consistent with the findings in the majority of previous studies. Statins have been demonstrated to reduce the risks of cardiovascular disease, but our data do not provide evidence of a beneficial effect on slowing AMD progression. PMID:26435335

Risk of Visual Field Progression in Glaucoma Patients with Progressive Retinal Nerve Fiber Layer Thinning: A 5-Year Prospective Study.

PubMed

Yu, Marco; Lin, Chen; Weinreb, Robert N; Lai, Gilda; Chiu, Vivian; Leung, Christopher Kai-Shun

2016-06-01

To investigate whether progressive retinal nerve fiber layer (RNFL) thinning is predictive of progressive visual field (VF) loss in glaucoma. Prospective study. A total of 139 primary open-angle glaucoma patients (240 eyes) followed up for ≥5 years. Retinal nerve fiber layer imaging and VF testing were performed at ∼4-month intervals. Progressive RNFL thinning was determined by event analysis (Guided Progression Analysis [GPA]) and trend analysis (Trend-based Progression Analysis [TPA]) of serial registered RNFL thickness maps. VF progression was detected according to the Early Manifest Glaucoma Trial (EMGT) ("likely progression") and pointwise linear regression (PLR) criteria (≥3 contiguous locations with sensitivity change <0 decibels [dB]/year at P < 0.01). Hazard ratios (HRs) for predicting VF progression were calculated by Cox proportional hazard modeling with progressive RNFL thinning as a time-dependent covariate. The specificity of GPA/TPA for detection of RNFL changes was determined by the proportion of eyes with significant RNFL thinning/thickening in 25 normal subjects followed weekly for 8 consecutive weeks and the proportion with significant RNFL thickening in the glaucoma group. The HRs of VF progression. A total of 65 (27.1%) and 117 eyes (48.8%) had progressive RNFL thinning based on GPA and TPA, respectively, and 30 (12.5%) and 39 eyes (16.3%) had VF progression per the EMGT and PLR criteria, respectively, during follow-up. Eyes with progressive RNFL thinning had lower VF survival estimates and a faster decline of visual field index than eyes without. Progressive RNFL thinning predicted the development of VF progression with HRs of 8.44 (95% confidence interval, 3.30-21.61) (EMGT criteria) and 5.11 (2.51-10.42) (PLR criteria) for TPA and 3.95 (1.74-8.93) (EMGT criteria) and 3.81 (1.83-7.92) (PLR criteria) for GPA after controlling for baseline covariates. The specificities of GPA and TPA were 100% (83.4%-100.0%) in the normal group and 81.7% (76.2%-86.4%) and 84.2% (78.9%-88.6%), respectively, in the glaucoma group. Progressive RNFL thinning determined by GPA and TPA is predictive of detectable functional decline in glaucoma. This finding underscores the significance of detecting progressive RNFL thinning and its relevance to initiate or augment treatment for glaucoma patients. Regulatory authorities may consider progressive RNFL thinning as an outcome measure in clinical trials for evaluation of glaucoma treatment. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Methodologies For A Physically Based Rockfall Hazard Assessment

NASA Astrophysics Data System (ADS)

Agliardi, F.; Crosta, G. B.; Guzzetti, F.; Marian, M.

Rockfall hazard assessment is an important land planning tool in alpine areas, where settlements progressively expand across rockfall prone areas, rising the vulnerability of the elements at risk, the worth of potential losses and the restoration costs. Nev- ertheless, hazard definition is not simple to achieve in practice and sound, physically based assessment methodologies are still missing. In addition, the high mobility of rockfalls implies a more difficult hazard definition with respect to other slope insta- bilities for which runout is minimal. When coping with rockfalls, hazard assessment involves complex definitions for "occurrence probability" and "intensity". The local occurrence probability must derive from the combination of the triggering probability (related to the geomechanical susceptibility of rock masses to fail) and the transit or impact probability at a given location (related to the motion of falling blocks). The intensity (or magnitude) of a rockfall is a complex function of mass, velocity and fly height of involved blocks that can be defined in many different ways depending on the adopted physical description and "destructiveness" criterion. This work is an attempt to evaluate rockfall hazard using the results of numerical modelling performed by an original 3D rockfall simulation program. This is based on a kinematic algorithm and allows the spatially distributed simulation of rockfall motions on a three-dimensional topography described by a DTM. The code provides raster maps portraying the max- imum frequency of transit, velocity and height of blocks at each model cell, easily combined in a GIS in order to produce physically based rockfall hazard maps. The results of some three dimensional rockfall models, performed at both regional and lo- cal scale in areas where rockfall related problems are well known, have been used to assess rockfall hazard, by adopting an objective approach based on three-dimensional matrixes providing a positional "hazard index". Different hazard maps have been ob- tained combining and classifying variables in different ways. The performance of the different hazard maps has been evaluated on the basis of past rockfall events and com- pared to the results of existing methodologies. The sensitivity of the hazard index with respect to the included variables and their combinations is discussed in order to constrain as objective as possible assessment criteria.

Pazopanib Maintenance Therapy in East Asian Women With Advanced Epithelial Ovarian Cancer: Results From AGO-OVAR16 and an East Asian Study.

PubMed

Kim, Jae-Weon; Mahner, Sven; Wu, Ling-Ying; Shoji, Tadahiro; Kim, Byoung-Gie; Zhu, Jian-Qing; Takano, Tadao; Park, Sang-Yoon; Kong, Bei-Hua; Wu, Qiang; Wang, Kung-Liahng; Ngan, Hextan Ys; Liu, Ji-Hong; Wei, Li-Hui; Mitrica, Ionel; Zhang, Pingkuan; Crescenzo, Rocco; Wang, Qiong; Cox, Charles J; Harter, Philipp; du Bois, Andreas

2018-01-01

The recent phase 3 trial AGO-OVAR16 demonstrated that pazopanib maintenance improved median progression-free survival in patients with ovarian cancer whose disease did not progress during first-line treatment. However, this improvement was not seen in the subset of East Asian patients. The current analysis evaluated the efficacy and safety of pazopanib maintenance in East Asian patients from AGO-OVAR16 and a separate East Asian study. East Asian patients from AGO-OVAR16 (n = 209) and the East Asian study (N = 145) were randomized 1:1 to receive pazopanib 800 mg/d or placebo for up to 24 months. The primary end point for each study was progression-free survival by RECIST (Response Evaluation Criteria in Solid Tumors) based on investigator assessment. Clinical and genetics data were analyzed separately by study or pooled according to separate predetermined statistical plans. Pazopanib maintenance had a detrimental effect on median progression-free survival versus placebo in East Asian patients from the combined studies (n = 354; 17.9 vs 21.5 months; hazard ratio, 1.114; 95% confidence interval, 0.818-1.518; P = 0.4928). Pazopanib maintenance showed a disadvantage in overall survival in East Asian patients from AGO-OVAR16 versus placebo (hazard ratio, 1.706; 95% confidence interval, 1.010-2.883; P = 0.0465); overall survival analysis was not performed in the East Asian study because of insufficient event numbers. Pazopanib-treated patients had a significantly higher incidence of grade 3 or higher hypertension (27%) and neutropenia (13%) versus placebo. The treatment effect of maintenance pazopanib in East Asian patients seemed to differ from that in non-Asian patients. In study-specific and pooled analyses, none of the potential factors analyzed could satisfactorily explain the different efficacy results of pazopanib in East Asian patients.

Moderate/Severe Hyponatremia Increases the Risk of Death among Hospitalized Chinese Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Patients

PubMed Central

Xu, Lijun; Ye, Hanhui; Huang, Fan; Yang, Zongxing; Zhu, Biao; Xu, Yan; Qiu, Yunqing; Li, Lanjuan

2014-01-01

Objectives To evaluate whether the serum sodium concentration is associated with the progression and long-term prognosis of Chinese HIV/AIDS patients. Methods Three hundred and eighty seven hospitalized patients were recruited into this retrospective cohort study. The strata of serum sodium concentration were moderate/severe hyponatremia, mild hyponatremia and normonatremia. Disease progression was estimated using CD4 counts and the WHO clinical stage. Correlation analysis was used to evaluate the serum sodium concentration with disease progression. The Kaplan-Meier method and the Cox proportional hazards model were used to analyze the effect of different serum sodium levels on survival. Results In this study 206 patients (53.2%) had hyponatremia, including 10.6% patients with moderate/severe hyponatremia and 42.6% with mild hyponatremia. The serum sodium concentration was significantly correlated with the HIV/AIDS progression (P<0.001). During the follow-up, 100 patients (25.6%) died. The cumulative survival rates of HIV/AIDS patients were 47.8%±8.5% in patients with moderate/severe hyponatremia, 59.8%±5.0% with mild hyponatremia and 79.9%±3.4% with normonatremia (log-rank P<0.001). After adjusting for sex, age, WHO stage, CD4 count, hemoglobin and albumin, the relative hazard was 3.5 (95% CI: 1.9–6.5) for patients with moderate/severe hyponatremia (P<0.001), and 1.5 (95% CI: 0.9–2.4) for those with mild hyponatremia (P = 0.161), compared with normonatremic patients. Conclusions The serum sodium level is closely correlated with the severity of patients. Only moderate/severe hyponatremia affects the prognosis of Chinese HIV/AIDS patients. Earlier intensive medical managements(including HAART)are necessary to increase the survival rates of Chinese HIV/AIDS patients with moderate/severe hyponatremia. PMID:25360785

Automation for System Safety Analysis

NASA Technical Reports Server (NTRS)

Malin, Jane T.; Fleming, Land; Throop, David; Thronesbery, Carroll; Flores, Joshua; Bennett, Ted; Wennberg, Paul

2009-01-01

This presentation describes work to integrate a set of tools to support early model-based analysis of failures and hazards due to system-software interactions. The tools perform and assist analysts in the following tasks: 1) extract model parts from text for architecture and safety/hazard models; 2) combine the parts with library information to develop the models for visualization and analysis; 3) perform graph analysis and simulation to identify and evaluate possible paths from hazard sources to vulnerable entities and functions, in nominal and anomalous system-software configurations and scenarios; and 4) identify resulting candidate scenarios for software integration testing. There has been significant technical progress in model extraction from Orion program text sources, architecture model derivation (components and connections) and documentation of extraction sources. Models have been derived from Internal Interface Requirements Documents (IIRDs) and FMEA documents. Linguistic text processing is used to extract model parts and relationships, and the Aerospace Ontology also aids automated model development from the extracted information. Visualizations of these models assist analysts in requirements overview and in checking consistency and completeness.

Evaluation of US Veterans Nutrition Education for Diabetes Prevention.

PubMed

Erickson, Megan; Braun, Katie; List, Riesa; Utech, Anne; Moore, Carolyn; White, Donna L; Garcia, Jose M

2016-09-01

Evaluate the effectiveness of nutrition education interventions for diabetes prevention. Retrospective cohort design. Tertiary-care US Veterans' Hospital, July 2007 to July 2012, using pre-existing database. Prediabetic, adult veterans (n = 372), mostly men (94.4%, n = 351). Visits with existing nutrition education classes were collected. diabetes status; predictors: visits/encounters, age, body mass index, weight change, and hemoglobin A1c. Cox proportional hazards method, χ(2) test, and logistic regression. In this sample, prediabetic veterans who received nutrition education were less likely to develop diabetes when compared with prediabetic veterans who did not receive nutrition education (hazard ratio, 0.71; 95% confidence interval, 0.55-0.92; P < .01). This difference remained significant after adjusting for body mass index and weight change. Nutrition education was significantly associated with preventing the progression from prediabetes to diabetes in US Veterans participating in a nutrition education intervention at the Michael E. DeBakey Veterans Affairs Medical Center. Copyright © 2016 Society for Nutrition Education and Behavior. All rights reserved.

Hazard-evaluation and technical assistance report TA 78-12, Oregon State University, Corvallis, Oregon

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

Not Available

A hazard evaluation and technical assistance survey of the biology-botany science building at the University of Oregon, Corvallis Campus to determine a possible etiologic agent responsible for nervous-system complaints among employees was conducted. Upon occupation of the new building formerly healthy plants transplanted to the new laboratories died. Since that time, a plant pathologist died of a neurological disease and three other professors contracted a similar progressive neurological disease. The ventilation system of the building was studied. Fume-hood rates were measured and air-inlet filters were analyzed. In addition, medical interviews of employees were conducted, medical histories obtained, and consultations withmore » their physicians held. If there is a single process endemic among the present staff, it could not be identified, although there are definitely similarities in complaints. No pathophysiological link between the fatal neurological diseases and current complaints among the staff was found. No clear-cut etiologic relationship between the work environment and symptoms was apparent.« less

Cytogenetic clonal evolution in myelodysplastic syndromes is associated with inferior prognosis.

PubMed

Neukirchen, Judith; Lauseker, Michael; Hildebrandt, Barbara; Nolting, Ann-Christin; Kaivers, Jennifer; Kobbe, Guido; Gattermann, Norbert; Haas, Rainer; Germing, Ulrich

2017-12-01

The karyotype of bone marrow cells at the time of diagnosis is a strong prognostic parameter for overall survival as well as acute myeloid leukemia (AML) progression in patients with myelodysplastic syndromes (MDS). However, to the authors' knowledge, few data exist regarding the prognostic impact of cytogenetic clonal evolution during the course of MDS. The authors evaluated follow-up karyotype analyses in 549 patients from the Dusseldorf MDS Registry. Clonal evolution was detectable in 24% of the entire cohort and in 18% of 294 patients receiving best supportive care. The authors noted a clear adverse effect of clonal evolution on the risk of leukemic transformation (hazard ratio, 2.233; P = .036) and overall survival (hazard ratio, 3.677; P<.001). The authors also analyzed the prognostic influence of subclones detectable at the time of diagnosis. Again, such a finding was associated with a significantly shorter overall survival and a higher 5-year-probability of acute myeloid leukemia progression (30% vs 22%). The results of the current study support the belief that follow-up karyotype analyses should be performed, especially in patients with lower-risk and intermediate-risk MDS, to identify those patients who are at higher risk of disease progression and therefore might benefit from earlier or more intensive treatment. Cancer 2017;123:4608-4616. © 2017 American Cancer Society. © 2017 American Cancer Society.

Serum urate at trial entry and ALS progression in EMPOWER.

PubMed

O'Reilly, ÉIlis J; Liu, Dawei; Johns, Donald R; Cudkowicz, Merit E; Paganoni, Sabrina; Schwarzschild, Michael A; Leitner, Melanie; Ascherio, Alberto

2017-02-01

Our objective was to determine whether serum urate predicts ALS progression. A study population comprised adult participants of EMPOWER (n = 942), a phase III clinical trial to evaluate the efficacy of dexpramipexole to treat ALS. Urate was measured in blood samples collected during enrollment as part of the routine block chemistry. We measured outcomes by combined assessment of function and survival rank (CAFs), and time to death, by 12 months. Results showed that in females there was not a significant relation between urate and outcomes. In males, outcomes improved with increasing urate (comparing highest to lowest urate quartile: CAFS was 53 points better with p for trend = 0.04; and hazard ratio for death was 0.60 with p for trend = 0.07), but with adjustment for body mass index (BMI) at baseline, a predictor of both urate levels and prognosis, associations were attenuated and no longer statistically significant. Overall, participants with urate levels equal to or above the median (5.1 mg/dl) appeared to have a survival advantage compared to those below (hazard ratio adjusted for BMI: 0.67; 95% confidence interval 0.47-0.95). In conclusion, these findings suggest that while the association between urate at baseline and ALS progression is partially explained by BMI, there may be an independent beneficial effect of urate.

Expression of decoy receptor 3 in kidneys is associated with allograft survival after kidney transplant rejection.

PubMed

Weng, Shuo-Chun; Shu, Kuo-Hsiung; Wu, Ming-Ju; Wen, Mei-Chin; Hsieh, Shie-Liang; Chen, Nien-Jung; Tarng, Der-Cherng

2015-09-03

Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression. The primary end point was doubling of serum creatinine and/or graft failure. A multivariate Cox proportional hazards model was used to assess the risk of DcR3 expression in rejected kidney grafts toward the renal end point. In total, RTRs with kidney allograft rejection were evaluated and the median follow-up was 30.9 months. The greater expression of DcR3 immunoreactivity in RTECs was correlated with a higher rate of the histopathological concordance of acute T cell-mediated rejection. Compared with 65 non-progressors, 31 progressors had higher DcR3 expression (HDE) regardless of the traditional risk factors. Cox regression analysis showed HDE was significantly associated with the risk of renal end point with a hazard ratio of 3.19 (95% confidence interval, 1.40 to 7.27; P = 0.006) after adjusting for other variables. In repetitive biopsies, HDE in tissue showed rapid kidney disease progression due to persistent inflammation.

The safety of hormonal contraceptives for women living with HIV and their sexual partners.

PubMed

Phillips, Sharon J; Polis, Chelsea B; Curtis, Kathryn M

2016-01-01

Hormonal contraceptives are important for the health and well-being of some women living with HIV, so evaluation of evidence regarding their safety vis-à-vis HIV-related risks is important. We updated two prior systematic reviews on the impact of hormonal contraception (HC) on HIV disease progression and female-to-male HIV transmission. One new study finds no increased risk for HIV disease progression or death associated with oral contraceptive use [adjusted (adj) hazard ratio (HR) 0.83, confidence interval [CI] 0.48-1.44] or injectables (adj HR 0.72, CI 0.53-0.98). Three new studies did not find significantly increased risks for measures of female-to-male HIV transmission with HC use. Hormonal contraceptive methods do not appear to accelerate HIV disease progression. More research is needed to clarify whether HC impacts HIV transmissibility. Copyright © 2016. Published by Elsevier Inc.

C-reactive protein as a marker of melanoma progression.

PubMed

Fang, Shenying; Wang, Yuling; Sui, Dawen; Liu, Huey; Ross, Merrick I; Gershenwald, Jeffrey E; Cormier, Janice N; Royal, Richard E; Lucci, Anthony; Schacherer, Christopher W; Gardner, Julie M; Reveille, John D; Bassett, Roland L; Wang, Li-E; Wei, Qingyi; Amos, Christopher I; Lee, Jeffrey E

2015-04-20

To investigate the association between blood levels of C-reactive protein (CRP) in patients with melanoma and overall survival (OS), melanoma-specific survival (MSS), and disease-free survival. Two independent sets of plasma samples from a total of 1,144 patients with melanoma (587 initial and 557 confirmatory) were available for CRP determination. Kaplan-Meier method and Cox regression were used to evaluate the relationship between CRP and clinical outcome. Among 115 patients who underwent sequential blood draws, we evaluated the relationship between change in disease status and change in CRP using nonparametric tests. Elevated CRP level was associated with poorer OS and MSS in the initial, confirmatory, and combined data sets (combined data set: OS hazard ratio, 1.44 per unit increase of logarithmic CRP; 95% CI, 1.30 to 1.59; P < .001; MSS hazard ratio, 1.51 per unit increase of logarithmic CRP; 95% CI, 1.36 to 1.68; P < .001). These findings persisted after multivariable adjustment. As compared with CRP < 10 mg/L, CRP ≥ 10 mg/L conferred poorer OS in patients with any-stage, stage I/II, or stage III/IV disease and poorer disease-free survival in those with stage I/II disease. In patients who underwent sequential evaluation of CRP, an association was identified between an increase in CRP and melanoma disease progression. CRP is an independent prognostic marker in patients with melanoma. CRP measurement should be considered for incorporation into prospective studies of outcome in patients with melanoma and clinical trials of systemic therapies for those with melanoma. © 2015 by American Society of Clinical Oncology.

C-Reactive Protein As a Marker of Melanoma Progression

PubMed Central

Fang, Shenying; Wang, Yuling; Sui, Dawen; Liu, Huey; Ross, Merrick I.; Gershenwald, Jeffrey E.; Cormier, Janice N.; Royal, Richard E.; Lucci, Anthony; Schacherer, Christopher W.; Gardner, Julie M.; Reveille, John D.; Bassett, Roland L.; Wang, Li-E; Wei, Qingyi; Amos, Christopher I.; Lee, Jeffrey E.

2015-01-01

Purpose To investigate the association between blood levels of C-reactive protein (CRP) in patients with melanoma and overall survival (OS), melanoma-specific survival (MSS), and disease-free survival. Patients and Methods Two independent sets of plasma samples from a total of 1,144 patients with melanoma (587 initial and 557 confirmatory) were available for CRP determination. Kaplan-Meier method and Cox regression were used to evaluate the relationship between CRP and clinical outcome. Among 115 patients who underwent sequential blood draws, we evaluated the relationship between change in disease status and change in CRP using nonparametric tests. Results Elevated CRP level was associated with poorer OS and MSS in the initial, confirmatory, and combined data sets (combined data set: OS hazard ratio, 1.44 per unit increase of logarithmic CRP; 95% CI, 1.30 to 1.59; P < .001; MSS hazard ratio, 1.51 per unit increase of logarithmic CRP; 95% CI, 1.36 to 1.68; P < .001). These findings persisted after multivariable adjustment. As compared with CRP < 10 mg/L, CRP ≥ 10 mg/L conferred poorer OS in patients with any-stage, stage I/II, or stage III/IV disease and poorer disease-free survival in those with stage I/II disease. In patients who underwent sequential evaluation of CRP, an association was identified between an increase in CRP and melanoma disease progression. Conclusion CRP is an independent prognostic marker in patients with melanoma. CRP measurement should be considered for incorporation into prospective studies of outcome in patients with melanoma and clinical trials of systemic therapies for those with melanoma. PMID:25779565

Genome-wide Association Study Implicates PARD3B-based AIDS Restriction

PubMed Central

Nelson, George W.; Lautenberger, James A.; Chinn, Leslie; McIntosh, Carl; Johnson, Randall C.; Sezgin, Efe; Kessing, Bailey; Malasky, Michael; Hendrickson, Sher L.; Pontius, Joan; Tang, Minzhong; An, Ping; Winkler, Cheryl A.; Limou, Sophie; Le Clerc, Sigrid; Delaneau, Olivier; Zagury, Jean-François; Schuitemaker, Hanneke; van Manen, Daniëlle; Bream, Jay H.; Gomperts, Edward D.; Buchbinder, Susan; Goedert, James J.; Kirk, Gregory D.; O'Brien, Stephen J.

2011-01-01

Background. Host genetic variation influences human immunodeficiency virus (HIV) infection and progression to AIDS. Here we used clinically well-characterized subjects from 5 pretreatment HIV/AIDS cohorts for a genome-wide association study to identify gene associations with rate of AIDS progression. Methods.  European American HIV seroconverters (n = 755) were interrogated for single-nucleotide polymorphisms (SNPs) (n = 700,022) associated with progression to AIDS 1987 (Cox proportional hazards regression analysis, co-dominant model). Results.  Association with slower progression was observed for SNPs in the gene PARD3B. One of these, rs11884476, reached genome-wide significance (relative hazard = 0.3; P =3. 370 × 10−9) after statistical correction for 700,022 SNPs and contributes 4.52% of the overall variance in AIDS progression in this study. Nine of the top-ranked SNPs define a PARD3B haplotype that also displays significant association with progression to AIDS (hazard ratio, 0.3; P = 3.220 × 10−8). One of these SNPs, rs10185378, is a predicted exonic splicing enhancer; significant alteration in the expression profile of PARD3B splicing transcripts was observed in B cell lines with alternate rs10185378 genotypes. This SNP was typed in European cohorts of rapid progressors and was found to be protective for AIDS 1993 definition (odds ratio, 0.43, P = .025). Conclusions. These observations suggest a potential unsuspected pathway of host genetic influence on the dynamics of AIDS progression. PMID:21502085

Ischemic diabetic retinopathy as a possible prognostic factor for chronic kidney disease progression

PubMed Central

Lee, W J; Sobrin, L; Kang, M H; Seong, M; Kim, Y J; Yi, J-H; Miller, J W; Cho, H Y

2014-01-01

Purpose To assess the value of diabetic retinopathy (DR) severity as a possible predictive prognostic factor for the progression of chronic kidney disease (CKD). Patients and methods Retrospective cohort study. Patients (51) who were initially diagnosed with DR and CKD were enrolled and their medical records were evaluated. The following ophthalmic factors were assessed by fluorescein angiography at the initial visit: area of capillary nonperfusion, presence of neovascularization and vitreous hemorrhage, and DR grade. The effect of these factors on CKD progression over the 2-year period of the study, defined as doubling of serum creatinine or the development of end-stage renal disease requiring dialysis or renal transplant, was evaluated. Results The study included 51 patients with DR and CKD; of these, 11 patients (21.6%) were found to have proliferative DR (PDR) and seven patients (13.7%) had high-risk PDR at baseline. Patients with ischemic DR, who showed extensive capillary nonperfusion (≥10 optic disc areas) in the retina, had a greater risk for CKD progression (hazard ratio=6.64; P=0.002). Conclusion We found that extensive capillary nonperfusion in the retina greatly increased the risk of progression of CKD in patients with DR. This suggests that the retina and the kidney may have shared risk factors for microvascular disease secondary to diabetes mellitus, and emphasizes the need for a team approach to diabetes care. PMID:24993319

Preventing the progression to type 2 diabetes mellitus in adults at high risk: a systematic review and network meta-analysis of lifestyle, pharmacological and surgical interventions.

PubMed

Stevens, John W; Khunti, Kamlesh; Harvey, Rebecca; Johnson, Maxine; Preston, Louise; Woods, Helen Buckley; Davies, Melanie; Goyder, Elizabeth

2015-03-01

Individuals with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) have an increased risk of progression to Type 2 diabetes mellitus. The objective of this review was to quantify the effectiveness of lifestyle, pharmacological and surgical interventions in reducing the progression to Type 2 diabetes mellitus in people with IFG or IGT. A systematic review was carried out. A network meta-analysis (NMA) of log-hazard ratios was performed. Results are presented as hazard ratios and the probabilities of treatment rankings. 30 studies were included in the NMA. There was a reduced hazard of progression to Type 2 diabetes mellitus associated with all interventions versus standard lifestyle advice; glipizide, diet plus pioglitazone, diet plus exercise plus metformin plus rosiglitazone, diet plus exercise plus orlistat, diet plus exercise plus pedometer, rosiglitazone, orlistat and diet plus exercise plus voglibose produced the greatest effects. Lifestyle and some pharmacological interventions are beneficial in reducing the risk of progression to Type 2 diabetes mellitus. Lifestyle interventions require significant behaviour changes that may be achieved through incentives such as the use of pedometers. Adverse events and cost of pharmacological interventions should be taken into account when considering potential risks and benefits. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Enzalutamide in metastatic prostate cancer before chemotherapy.

PubMed

Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana E; Loriot, Yohann; Sternberg, Cora N; Higano, Celestia S; Iversen, Peter; Bhattacharya, Suman; Carles, Joan; Chowdhury, Simon; Davis, Ian D; de Bono, Johann S; Evans, Christopher P; Fizazi, Karim; Joshua, Anthony M; Kim, Choung-Soo; Kimura, Go; Mainwaring, Paul; Mansbach, Harry; Miller, Kurt; Noonberg, Sarah B; Perabo, Frank; Phung, De; Saad, Fred; Scher, Howard I; Taplin, Mary-Ellen; Venner, Peter M; Tombal, Bertrand

2014-07-31

Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy. In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression-free survival and overall survival. The study was stopped after a planned interim analysis, conducted when 540 deaths had been reported, showed a benefit of the active treatment. The rate of radiographic progression-free survival at 12 months was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence interval [CI], 0.15 to 0.23; P<0.001). A total of 626 patients (72%) in the enzalutamide group, as compared with 532 patients (63%) in the placebo group, were alive at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; P<0.001). The benefit of enzalutamide was shown with respect to all secondary end points, including the time until the initiation of cytotoxic chemotherapy (hazard ratio, 0.35), the time until the first skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P<0.001 for all comparisons). Fatigue and hypertension were the most common clinically relevant adverse events associated with enzalutamide treatment. Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas Pharma; PREVAIL ClinicalTrials.gov number, NCT01212991.).

Prognostic value of sex-hormone receptor expression in non-muscle-invasive bladder cancer.

PubMed

Nam, Jong Kil; Park, Sung Woo; Lee, Sang Don; Chung, Moon Kee

2014-09-01

We investigated sex-hormone receptor expression as predicting factor of recurrence and progression in patients with non-muscle invasive bladder cancer. We retrospectively evaluated tumor specimens from patients treated for transitional cell carcinoma of the bladder at our institution between January 2006 and January 2011. Performing immunohistochemistry using a monoclonal androgen receptor antibody and monoclonal estrogen receptor-beta antibody on paraffin-embedded tissue sections, we assessed the relationship of immunohistochemistry results and prognostic factors such as recurrence and progression. A total of 169 patients with bladder cancer were evaluated in this study. Sixty-threepatients had expressed androgen receptors and 52 patients had estrogen receptor beta. On univariable analysis, androgen receptor expression was significant lower in recurrence rates (p=0.001), and estrogen receptor beta expression was significant higher in progression rates (p=0.004). On multivariable analysis, significant association was found between androgen receptor expression and lower recurrence rates (hazard ratio=0.500; 95% confidence interval, 0.294 to 0.852; p=0.011), but estrogen receptor beta expression was not significantly associated with progression rates. We concluded that the possibility of recurrence was low when the androgen receptor was expressed in the bladder cancer specimen and it could be the predicting factor of the stage, number of tumors, carcinoma in situ lesion and recurrence.

Hepatic Fibrosis Progression in HIV-Hepatitis C Virus Co-Infection – The Effect of Sex on Risk of Significant Fibrosis Measured by Aspartate-to-Platelet Ratio Index

PubMed Central

Rollet-Kurhajec, Kathleen C.; Moodie, Erica E. M.; Walmsley, Sharon; Cooper, Curtis; Pick, Neora; Klein, Marina B.

2015-01-01

Background In Hepatitis C virus (HCV) mono-infection, male sex is associated with faster liver fibrosis progression but the effects of sex have not been well studied in HIV-HCV co-infected patients. We examined the influence of sex on progression to significant liver fibrosis in HIV-HCV co-infected adults receiving antiretroviral therapy (ART) using the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate biomarker of liver fibrosis. Methods We evaluated 308 HIV infected, HCV RNA positive participants of a Canadian multicentre prospective cohort receiving antiretrovirals and without significant liver fibrosis or end-stage liver disease at baseline. We used multivariate discrete-time proportional hazards models to assess the effect of sex on time to significant fibrosis (APRI≥1.5) adjusting for baseline age, alcohol use, cigarette smoking, HCV duration, and APRI and time-updated CD4 count and HIV RNA. Results Overall, 55 (18%) participants developed an APRI ≥ 1.5 over 544 person-years of at-risk follow-up time; 18 (21%) women (incidence rate (IR)=14.0/100 PY; 7.5-20.4) and 37 (17%) men (IR=8.9/100 PY; 6.0-11.8). Women had more favourable profiles with respect to traditional risk factors for liver disease progression (younger, shorter duration of HCV infection and less alcohol use). Despite this, female sex was associated with a greater than two-fold increased risk of fibrosis progression (adjusted hazard rate (HR) =2.23; 1.22-4.08). Conclusions HIV-HCV co-infected women receiving antiretroviral therapy were at significantly greater risk of progressing to liver fibrosis as measured by APRI compared with men. Enhanced efforts to engage and treat co-infected women for HCV are needed. PMID:26090666

Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.

PubMed

Choueiri, Toni K; Escudier, Bernard; Powles, Thomas; Mainwaring, Paul N; Rini, Brian I; Donskov, Frede; Hammers, Hans; Hutson, Thomas E; Lee, Jae-Lyun; Peltola, Katriina; Roth, Bruce J; Bjarnason, Georg A; Géczi, Lajos; Keam, Bhumsuk; Maroto, Pablo; Heng, Daniel Y C; Schmidinger, Manuela; Kantoff, Philip W; Borgman-Hagey, Anne; Hessel, Colin; Scheffold, Christian; Schwab, Gisela M; Tannir, Nizar M; Motzer, Robert J

2015-11-05

Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily. The primary end point was progression-free survival. Secondary efficacy end points were overall survival and objective response rate. Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The rate of progression or death was 42% lower with cabozantinib than with everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P<0.001). The objective response rate was 21% with cabozantinib and 5% with everolimus (P<0.001). A planned interim analysis showed that overall survival was longer with cabozantinib than with everolimus (hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P=0.005) but did not cross the significance boundary for the interim analysis. Adverse events were managed with dose reductions; doses were reduced in 60% of the patients who received cabozantinib and in 25% of those who received everolimus. Discontinuation of study treatment owing to adverse events occurred in 9% of the patients who received cabozantinib and in 10% of those who received everolimus. Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. (Funded by Exelixis; METEOR ClinicalTrials.gov number, NCT01865747.).

Pre-cART Elevation of CRP and CD4+ T-Cell Immune Activation Associated With HIV Clinical Progression in a Multinational Case-Cohort Study.

PubMed

Balagopal, Ashwin; Asmuth, David M; Yang, Wei-Teng; Campbell, Thomas B; Gupte, Nikhil; Smeaton, Laura; Kanyama, Cecilia; Grinsztejn, Beatriz; Santos, Breno; Supparatpinyo, Khuanchai; Badal-Faesen, Sharlaa; Lama, Javier R; Lalloo, Umesh G; Zulu, Fatima; Pawar, Jyoti S; Riviere, Cynthia; Kumarasamy, Nagalingeswaran; Hakim, James; Li, Xiao-Dong; Pollard, Richard B; Semba, Richard D; Thomas, David L; Bollinger, Robert C; Gupta, Amita

2015-10-01

Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore, some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators. A case-cohort study (n = 470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings clinical trial (1571 HIV treatment-naive adults who initiated cART; CD4 T-cell count <300 cells/mm; 9 countries) was conducted. A subcohort of 30 participants per country was randomly selected; additional cases were added from the main cohort. Cases [n = 236 (random subcohort 36; main cohort 200)] had clinical progression (incident WHO stage 3/4 event or death) within 96 weeks after cART initiation. Immune activation biomarkers were quantified pre-cART. Associations between biomarkers and clinical progression were examined using weighted multivariable Cox-proportional hazards models. Median age was 35 years, 45% were women, 49% black, 31% Asian, and 9% white. Median CD4 T-cell count was 167 cells per cubic millimeter. In multivariate analysis, highest quartile C-reactive protein concentration [adjusted hazard ratio (aHR), 2.53; 95% confidence interval (CI): 1.02 to 6.28] and CD4 T-cell activation (aHR, 5.18; 95% CI: 1.09 to 24.47) were associated with primary outcomes, compared with lowest quartiles. sCD14 had a trend toward association with clinical failure (aHR, 2.24; 95% CI: 0.96 to 5.21). Measuring C-reactive protein and CD4 T-cell activation may identify patients with CD4 T-cell counts <300 cells per cubic millimeter at risk for early clinical progression when initiating cART. Additional vigilance and symptom-based screening may be required in this subset of patients even after beginning cART.

Pre-cART Elevation of CRP and CD4+ T-cell Immune Activation Associated with HIV Clinical Progression in a Multinational Case-Cohort Study

PubMed Central

Balagopal, Ashwin; Asmuth, David M.; Yang, Wei-Teng; Campbell, Thomas B.; Gupte, Nikhil; Smeaton, Laura; Kanyama, Cecilia; Grinsztejn, Beatriz; Santos, Breno; Supparatpinyo, Khuanchai; Badal-Faesen, Sharlaa; Lama, Javier R.; Lalloo, Umesh G.; Zulu, Fatima; Pawar, Jyoti S; Riviere, Cynthia; Kumarasamy, Nagalingeswaran; Hakim, James; Li, Xiao-Dong; Pollard, Richard B.; Semba, Richard D.; Thomas, David L.; Bollinger, Robert C.; Gupta, Amita

2015-01-01

Background Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators. Methods A case-cohort study (n=470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) clinical trial (1571 HIV treatment-naïve adults who initiated cART; CD4+ T cell count <300 cells/mm3; nine countries) was conducted. A subcohort of 30 participants/country was randomly selected; additional cases were added from the main cohort. Cases (n=236 [random subcohort–36; main cohort–200]) had clinical progression (incident WHO Stage 3/4 event or death) within 96 weeks following cART initiation. Immune activation biomarkers were quantified pre-cART. Associations between biomarkers and clinical progression were examined using weighted multivariable Cox-proportional hazards models. Results Median age was 35 years, 45% were women, 49% black, 31% Asian, and 9% white. Median CD4+ T-cell count was 167 cells/mm3. In multivariate analysis, highest quartile CRP concentration (adjusted hazards ratio [aHR] 2.53, 95%CI 1.02-6.28) and CD4+ T-cell activation (aHR 5.18, 95CI 1.09-24.47) were associated with primary outcomes, compared to lowest quartiles. sCD14 had a trend towards association with clinical failure (aHR 2.24, 95%CI 0.96–5.21). Conclusions Measuring CRP and CD4+ T-cell activation may identify patients with CD4+ T cell counts < 300 cells/mm3 at risk for early clinical progression when initiating cART. Additional vigilance and symptom-based screening may be required in this subset of patients even after beginning cART. PMID:26017661

Occupational and environmental risk factors for chronic rhinosinusitis: a systematic review.

PubMed

Sundaresan, Agnes S; Hirsch, Annemarie G; Storm, Margaret; Tan, Bruce K; Kennedy, Thomas L; Greene, J Scott; Kern, Robert C; Schwartz, Brian S

2015-11-01

Chronic rhinosinusitis (CRS) is a prevalent and disabling paranasal sinus disease, with a likely multifactorial etiology potentially including hazardous occupational and environmental exposures. We completed a systematic review of the occupational and environmental literature to evaluate the quality of evidence of the role that hazardous exposures might play in CRS. We searched PubMed for studies of CRS and following exposure categories: occupation, employment, work, industry, air pollution, agriculture, farming, environment, chemicals, roadways, disaster, and traffic. We abstracted information from the final set of articles across 6 primary domains: study design; population; exposures evaluated; exposure assessment; CRS definition; and results. We identified 41 articles from 1080 manuscripts: 37 occupational risk papers, 1 environmental risk paper, and 3 papers studying both categories of exposures. None of the 41 studies used a CRS definition consistent with current diagnostic guidelines. Exposure assessment was generally dependent on self-report or binary measurements of exposure based on industry of employment. Only grain, dairy, and swine operations among farmers were evaluated by more than 1 study using a common approach to defining CRS, but employment in these settings was not consistently associated with CRS. The multiple other exposures did not meet quality standards for reporting associations or were not evaluated by more than 1 study. The current state of the literature allows us to make very few conclusions about the role of hazardous occupational or environmental exposures in CRS, leaving a critical knowledge gap regarding potentially modifiable risk factors for disease onset and progression. © 2015 ARS-AAOA, LLC.

Monitoring the Hazards of Silicic Volcanoes with Remote Sensing

NASA Technical Reports Server (NTRS)

Fink, Jonathan; Wessels, Rick; Eisinger, Chris; Ramsey, Michael; Hellman, Melanie; Kuhn, Sally

2004-01-01

This report details the final progress on the Solid Earth and Natural Hazards project: Monitoring of Hazards of Silicic Volcanoes with Remote Sensing (SENH99-0000-0159). The original award went to Arizona State University (ASU) with Dr. Jonathan Fink as the P.I. and Dr. Michael Ramsey as the Co-I. In May 2000, Dr. Ramsey left ASU to take a tenure-track faculty position at the University of Pittsburgh. The principle investigators and NASA Headquarters agreed to split the grant award at the HQ level and therefore avoid the double overhead charges that would arise from a university subcontract. The objectives of the science were divided, and coordinated yearly progress reports have been submitted from each University. This report details the final progress on work carried out at Arizona State. A report by Dr. Ramsey at the University of Pittsburgh has already been submitted. The work from both institutions is closely related and this report will reflect that connection.

Exercise capacity and progression from prehypertension to hypertension.

PubMed

Faselis, Charles; Doumas, Michael; Kokkinos, John Peter; Panagiotakos, Demosthenes; Kheirbek, Raya; Sheriff, Helen M; Hare, Katherine; Papademetriou, Vasilios; Fletcher, Ross; Kokkinos, Peter

2012-08-01

Prehypertension is likely to progress to hypertension. The rate of progression is determined mostly by age and resting blood pressure but may also be attenuated by increased fitness. A graded exercise test was performed in 2303 men with prehypertension at the Veterans Affairs Medical Centers in Washington, DC. Four fitness categories were defined, based on peak metabolic equivalents (METs) achieved. We assessed the association between exercise capacity and rate of progression to hypertension (HTN). The median follow-up period was 7.8 years (mean (± SD) 9.2±6.1 years). The incidence rate of progression from prehypertension to hypertension was 34.4 per 1000 person-years. Exercise capacity was a strong and independent predictor of the rate of progression. Compared to the High-Fit individuals (>10.0 METs), the adjusted risk for developing HTN was 66% higher (hazard ratio, 1.66; 95% CI, 1.2 to 2.2; P=0.001) for the Low-Fit and, similarly, 72% higher (hazard ratio, 1.72; 95% CI, 1.2 to 2.3; P=0.001) for the Least-Fit individuals, whereas it was only 36% for the Moderate-Fit (hazard ratio, 1.36; 95% CI, 0.99 to 1.80; P=0.056). Significant predictors for the progression to HTN were also age (19% per 10 years), resting systolic blood pressure (16% per 10 mm Hg), body mass index (15.3% per 5 U), and type 2 diabetes mellitus (2-fold). In conclusion, an inverse, S-shaped association was shown between exercise capacity and the rate of progression from prehypertension to hypertension in middle-aged and older male veterans. The protective effects of fitness were evident when exercise capacity exceeded 8.5 METs. These findings emphasize the importance of fitness in the prevention of hypertension.

Pregnancy and HIV Disease Progression in an Early Infection Cohort from Five African Countries.

PubMed

Wall, Kristin M; Rida, Wasima; Haddad, Lisa B; Kamali, Anatoli; Karita, Etienne; Lakhi, Shabir; Kilembe, William; Allen, Susan; Inambao, Mubiana; Yang, Annie H; Latka, Mary H; Anzala, Omu; Sanders, Eduard J; Bekker, Linda-Gail; Edward, Vinodh A; Price, Matt A

2017-03-01

Understanding associations between pregnancy and HIV disease progression is critical to provide appropriate counseling and care to HIV-positive women. From 2006 to 2011, women less than age 40 with incident HIV infection were enrolled in an early HIV infection cohort in Kenya, Rwanda, South Africa, Uganda, and Zambia. Time-dependent Cox models evaluated associations between pregnancy and HIV disease progression. Clinical progression was defined as a single CD4 measurement <200 cells/μl, percent CD4 <14%, or category C event, with censoring at antiretroviral (ART) initiation for reasons other than prevention of mother-to-child transmission (PMTCT). Immunologic progression was defined as two consecutive CD4s ≤350 cells/μl or a single CD4 ≤350 cells/μl followed by non-PMTCT ART initiation. Generalized estimating equations assessed changes in CD4 before and after pregnancy. Among 222 women, 63 experienced clinical progression during 783.5 person-years at risk (8.0/100). Among 205 women, 87 experienced immunologic progression during 680.1 person-years at risk (12.8/100). The association between pregnancy and clinical progression was adjusted hazard ratio [aHR] = 0.7; 95% confidence interval (CI): 0.2, 1.8. The association between pregnancy and immunologic progression was aHR = 1.7; 95% CI: 0.9, 3.3. Models controlled for age; human leukocyte antigen alleles A*03:01, B*45, B*57; CD4 set point; and HIV-1 subtype. CD4 measurements before versus after pregnancies were not different. In this cohort, pregnancy was not associated with increased clinical or immunologic HIV progression. Similarly, we did not observe meaningful deleterious associations of pregnancy with CD4s. Our findings suggest that HIV-positive women may become pregnant without harmful health effects occurring during the pregnancy. Evaluation of longer-term impact of pregnancy on progression is warranted.

Pregnancy and HIV Disease Progression in an Early Infection Cohort from Five African Countries

PubMed Central

Rida, Wasima; Haddad, Lisa B.; Kamali, Anatoli; Karita, Etienne; Lakhi, Shabir; Kilembe, William; Allen, Susan; Inambao, Mubiana; Yang, Annie H.; Latka, Mary H.; Anzala, Omu; Sanders, Eduard J.; Bekker, Linda-Gail; Edward, Vinodh A.; Price, Matt A.

2017-01-01

Background: Understanding associations between pregnancy and HIV disease progression is critical to provide appropriate counseling and care to HIV-positive women. Methods: From 2006 to 2011, women less than age 40 with incident HIV infection were enrolled in an early HIV infection cohort in Kenya, Rwanda, South Africa, Uganda, and Zambia. Time-dependent Cox models evaluated associations between pregnancy and HIV disease progression. Clinical progression was defined as a single CD4 measurement <200 cells/μl, percent CD4 <14%, or category C event, with censoring at antiretroviral (ART) initiation for reasons other than prevention of mother-to-child transmission (PMTCT). Immunologic progression was defined as two consecutive CD4s ≤350 cells/μl or a single CD4 ≤350 cells/μl followed by non-PMTCT ART initiation. Generalized estimating equations assessed changes in CD4 before and after pregnancy. Results: Among 222 women, 63 experienced clinical progression during 783.5 person-years at risk (8.0/100). Among 205 women, 87 experienced immunologic progression during 680.1 person-years at risk (12.8/100). The association between pregnancy and clinical progression was adjusted hazard ratio [aHR] = 0.7; 95% confidence interval (CI): 0.2, 1.8. The association between pregnancy and immunologic progression was aHR = 1.7; 95% CI: 0.9, 3.3. Models controlled for age; human leukocyte antigen alleles A*03:01, B*45, B*57; CD4 set point; and HIV-1 subtype. CD4 measurements before versus after pregnancies were not different. Conclusions: In this cohort, pregnancy was not associated with increased clinical or immunologic HIV progression. Similarly, we did not observe meaningful deleterious associations of pregnancy with CD4s. Our findings suggest that HIV-positive women may become pregnant without harmful health effects occurring during the pregnancy. Evaluation of longer-term impact of pregnancy on progression is warranted. PMID:27893488

Lung disease and coal mining: what pulmonologists need to know.

PubMed

Go, Leonard H T; Krefft, Silpa D; Cohen, Robert A; Rose, Cecile S

2016-03-01

Coal mine workers are at risk for a range of chronic respiratory diseases including coal workers' pneumoconiosis, diffuse dust-related fibrosis, and chronic obstructive pulmonary disease. The purpose of this review is to describe coal mining processes and associated exposures to inform the diagnostic evaluation of miners with respiratory symptoms. Although rates of coal workers' pneumoconiosis declined after regulations were enacted in the 1970s, more recent data shows a reversal in this downward trend. Rapidly progressive pneumoconiosis with progressive massive fibrosis (complicated coal workers' pneumoconiosis) is being observed with increased frequency in United States coal miners, with histologic findings of silicosis and mixed-dust pneumoconiosis. There is increasing evidence of decline in lung function in individuals with pneumoconiosis. Multiple recent cohort studies suggest increased risk of lung cancer in coal miners. A detailed understanding of coal mining methods and processes allows clinicians to better evaluate and confirm chronic lung diseases caused by inhalational hazards in the mine atmosphere.

Technology Development, Evaluation, and Application (TDEA) FY 1998 Progress Report Environment, Safety, and Health (ESH) Division

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

Larry G. Hoffman; Kenneth Alvar; Thomas Buhl

1999-06-01

This progress report presents the results of 10 projects funded ($504K) in FY98 by the Technology Development, Evaluation, and Application (TDEA) Committee of the Environment, Safety, and Health Division. Nine projects are new for this year; two projects were completed in their third and final TDEA-funded year. As a result of their TDEA-funded projects, investigators have published 19 papers in professional journals, proceedings, or Los Alamos reports and presented their work at professional meetings. Supplemental funds and in-kind contributions, such as staff time, instrument use, and work space were also provided to the TDEA-funded projects by organizations external to ESHmore » Division. Products generated from the projects funded in FY98 included a new extremity dosimeter that replaced the previously used finger-ring dosimeters, a light and easy-to-use detector to measure energy deposited by neutron interactions, and a device that will allow workers to determine the severity of a hazard.« less

Information Extraction for System-Software Safety Analysis: Calendar Year 2008 Year-End Report

NASA Technical Reports Server (NTRS)

Malin, Jane T.

2009-01-01

This annual report describes work to integrate a set of tools to support early model-based analysis of failures and hazards due to system-software interactions. The tools perform and assist analysts in the following tasks: 1) extract model parts from text for architecture and safety/hazard models; 2) combine the parts with library information to develop the models for visualization and analysis; 3) perform graph analysis and simulation to identify and evaluate possible paths from hazard sources to vulnerable entities and functions, in nominal and anomalous system-software configurations and scenarios; and 4) identify resulting candidate scenarios for software integration testing. There has been significant technical progress in model extraction from Orion program text sources, architecture model derivation (components and connections) and documentation of extraction sources. Models have been derived from Internal Interface Requirements Documents (IIRDs) and FMEA documents. Linguistic text processing is used to extract model parts and relationships, and the Aerospace Ontology also aids automated model development from the extracted information. Visualizations of these models assist analysts in requirements overview and in checking consistency and completeness.

Using SAR and GPS for Hazard Management and Response: Progress and Examples from the Advanced Rapid Imaging and Analysis (ARIA) Project

NASA Astrophysics Data System (ADS)

Owen, S. E.; Simons, M.; Hua, H.; Yun, S. H.; Agram, P. S.; Milillo, P.; Sacco, G. F.; Webb, F.; Rosen, P. A.; Lundgren, P.; Milillo, G.; Manipon, G. J. M.; Moore, A. W.; Liu, Z.; Polet, J.; Cruz, J.

2014-12-01

ARIA is a joint JPL/Caltech project to automate synthetic aperture radar (SAR) and GPS imaging capabilities for scientific understanding, hazard response, and societal benefit. We have built a prototype SAR and GPS data system that forms the foundation for hazard monitoring and response capability, as well as providing imaging capabilities important for science studies. Together, InSAR and GPS have the ability to capture surface deformation in high spatial and temporal resolution. For earthquakes, this deformation provides information that is complementary to seismic data on location, geometry and magnitude of earthquakes. Accurate location information is critical for understanding the regions affected by damaging shaking. Regular surface deformation measurements from SAR and GPS are useful for monitoring changes related to many processes that are important for hazard and resource management such as volcanic deformation, groundwater withdrawal, and landsliding. Observations of SAR coherence change have a demonstrated use for damage assessment for hazards such as earthquakes, tsunamis, hurricanes, and volcanic eruptions. These damage assessment maps can be made from imagery taken day or night and are not affected by clouds, making them valuable complements to optical imagery. The coherence change caused by the damage from hazards (building collapse, flooding, ash fall) is also detectable with intelligent algorithms, allowing for rapid generation of damage assessment maps over large areas at fine resolution, down to the spatial scale of single family homes. We will present the progress and results we have made on automating the analysis of SAR data for hazard monitoring and response using data from the Italian Space Agency's (ASI) COSMO-SkyMed constellation of X-band SAR satellites. Since the beginning of our project with ASI, our team has imaged deformation and coherence change caused by many natural hazard events around the world. We will present progress on our data system technology that enables rapid and reliable production of imagery. Lastly, we participated in the March 2014 FEMA exercise based on a repeat of the 1964 M9.2 Alaska earthquake, providing simulated data products for use in this hazards response exercise. We will present lessons learned from this and other simulation exercises.

Derivation of genetic biomarkers for cancer risk stratification in Barrett's oesophagus: a prospective cohort study

PubMed Central

Timmer, Margriet R.; Martinez, Pierre; Lau, Chiu T.; Westra, Wytske M.; Calpe, Silvia; Rygiel, Agnieszka M.; Rosmolen, Wilda D.; Meijer, Sybren L.; ten Kate, Fiebo J.W.; Dijkgraaf, Marcel G.W.; Mallant-Hent, Rosalie C.; Naber, Anton H.J.; van Oijen, Arnoud H.A.M.; Baak, Lubbertus C.; Scholten, Pieter; Böhmer, Clarisse J.M.; Fockens, Paul; Maley, Carlo C.; Graham, Trevor A.; Bergman, Jacques J.G.H.M.; Krishnadath, Kausilia K.

2016-01-01

Objective The risk of developing adenocarcinoma in non-dysplastic Barrett's oesophagus is low and difficult to predict. Accurate tools for risk stratification are needed to increase the efficiency of surveillance. We aimed to develop a prediction model for progression using clinical variables and genetic markers. Methods In a prospective cohort of patients with non-dysplastic Barrett's oesophagus, we evaluated six molecular markers: p16, p53, Her-2/neu, 20q, MYC, and aneusomy by DNA fluorescence in situ hybridisation on brush cytology specimens. Primary study outcomes were the development of high-grade dysplasia or oesophageal adenocarcinoma. The most predictive clinical variables and markers were determined using Cox proportional-hazards models, receiver-operating-characteristic curves and a leave-one-out analysis. Results A total of 428 patients participated (345 men; median age 60 years) with a cumulative follow-up of 2019 patient-years (median 45 months per patient). Of these patients, 22 progressed; nine developed high-grade dysplasia and 13 oesophageal adenocarcinoma. The clinical variables, age and circumferential Barrett's length, and the markers, p16 loss, MYC gain, and aneusomy, were significantly associated with progression on univariate analysis. We defined an ‘Abnormal Marker Count’ that counted abnormalities in p16, MYC and aneusomy, which significantly improved risk prediction beyond using just age and Barrett's length. In multivariate analysis, these three factors identified a high-risk group with an 8.7-fold (95% CI, 2.6 to 29.8) increased hazard ratio compared with the low-risk group, with an area under the curve of 0.76 (95% CI, 0.66 to 0.86). Conclusion A prediction model based on age, Barrett's length, and the markers p16, MYC, and aneusomy determines progression risk in non-dysplastic Barrett's oesophagus. PMID:26104750

Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

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

Chen, James X.; Rose, Steven; White, Sarah B.

PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Coxmore » proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p < 0.05). Tumor burden >50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.« less

Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

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

Freedland, Stephen J., E-mail: steve.freedland@duke.edu; Department of Surgery; Department of Pathology, Duke University School of Medicine, Durham, North Carolina

Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-upmore » for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.« less

St. Louis Area Earthquake Hazards Mapping Project - December 2008-June 2009 Progress Report

USGS Publications Warehouse

Williams, R.A.; Bauer, R.A.; Boyd, O.S.; Chung, J.; Cramer, C.H.; Gaunt, D.A.; Hempen, G.L.; Hoffman, D.; McCallister, N.S.; Prewett, J.L.; Rogers, J.D.; Steckel, P.J.; Watkins, C.M.

2009-01-01

This report summarizes the mission, the project background, the participants, and the progress of the St. Louis Area Earthquake Hazards Mapping Project (SLAEHMP) for the period from December 2008 through June 2009. During this period, the SLAEHMP held five conference calls and two face-to-face meetings in St. Louis, participated in several earthquake awareness public meetings, held one outreach field trip for the business and government community, collected and compiled new borehole and digital elevation data from partners, and published a project summary.

Developmental Neurotoxicity Testing: A Path Forward

EPA Science Inventory

Great progress has been made over the past 40 years in understanding the hazards of exposure to a small number of developmental neurotoxicants. Lead, PCBs, and methylmercury are all good examples of science-based approaches to characterizing the hazard to the developing nervous s...

Propensity Score–Matched Analysis of Comprehensive Local Therapy for Oligometastatic Non-Small Cell Lung Cancer That Did Not Progress After Front-Line Chemotherapy

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

Sheu, Tommy; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Heymach, John V.

2014-11-15

Purpose: To retrospectively analyze factors influencing survival in patients with non-small cell lung cancer presenting with ≤3 synchronous metastatic lesions. Methods and Materials: We identified 90 patients presenting between 1998 and 2012 with non-small cell lung cancer and ≤3 metastatic lesions who had received at least 2 cycles of chemotherapy followed by surgery or radiation therapy before disease progression. The median number of chemotherapy cycles before comprehensive local therapy (CLT) (including concurrent chemoradiation as first-line therapy) was 6. Factors potentially affecting overall (OS) or progression-free survival (PFS) were evaluated with Cox proportional hazards regression. Propensity score matching was used to assessmore » the efficacy of CLT. Results: Median follow-up time was 46.6 months. Benefits in OS (27.1 vs 13.1 months) and PFS (11.3 months vs 8.0 months) were found with CLT, and the differences were statistically significant when propensity score matching was used (P ≤ .01). On adjusted analysis, CLT had a statistically significant benefit in terms of OS (hazard ratio, 0.37; 95% confidence interval, 0.20-0.70; P ≤ .01) but not PFS (P=.10). In an adjusted subgroup analysis of patients receiving CLT, favorable performance status (hazard ratio, 0.43; 95% confidence interval, 0.22-0.84; P=.01) was found to predict improved OS. Conclusions: Comprehensive local therapy was associated with improved OS in an adjusted analysis and seemed to favorably influence OS and PFS when factors such as N status, number of metastatic lesions, and disease sites were controlled for with propensity score–matched analysis. Patients with favorable performance status had improved outcomes with CLT. Ultimately, prospective, randomized trials are needed to provide definitive evidence as to the optimal treatment approach for this patient population.« less

Propensity score-matched analysis of comprehensive local therapy for oligometastatic non-small cell lung cancer that did not progress after front-line chemotherapy.

PubMed

Sheu, Tommy; Heymach, John V; Swisher, Stephen G; Rao, Ganesh; Weinberg, Jeffrey S; Mehran, Reza; McAleer, Mary Frances; Liao, Zhongxing; Aloia, Thomas A; Gomez, Daniel R

2014-11-15

To retrospectively analyze factors influencing survival in patients with non-small cell lung cancer presenting with ≤3 synchronous metastatic lesions. We identified 90 patients presenting between 1998 and 2012 with non-small cell lung cancer and ≤3 metastatic lesions who had received at least 2 cycles of chemotherapy followed by surgery or radiation therapy before disease progression. The median number of chemotherapy cycles before comprehensive local therapy (CLT) (including concurrent chemoradiation as first-line therapy) was 6. Factors potentially affecting overall (OS) or progression-free survival (PFS) were evaluated with Cox proportional hazards regression. Propensity score matching was used to assess the efficacy of CLT. Median follow-up time was 46.6 months. Benefits in OS (27.1 vs 13.1 months) and PFS (11.3 months vs 8.0 months) were found with CLT, and the differences were statistically significant when propensity score matching was used (P ≤ .01). On adjusted analysis, CLT had a statistically significant benefit in terms of OS (hazard ratio, 0.37; 95% confidence interval, 0.20-0.70; P ≤ .01) but not PFS (P=.10). In an adjusted subgroup analysis of patients receiving CLT, favorable performance status (hazard ratio, 0.43; 95% confidence interval, 0.22-0.84; P=.01) was found to predict improved OS. Comprehensive local therapy was associated with improved OS in an adjusted analysis and seemed to favorably influence OS and PFS when factors such as N status, number of metastatic lesions, and disease sites were controlled for with propensity score-matched analysis. Patients with favorable performance status had improved outcomes with CLT. Ultimately, prospective, randomized trials are needed to provide definitive evidence as to the optimal treatment approach for this patient population. Copyright © 2014 Elsevier Inc. All rights reserved.

US Efforts in Support of Examinations at Fukushima Daiichi – 2016 Evaluations

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

Amway, P.; Andrews, N.; Bixby, Willis

Although it is clear that the accident signatures from each unit at the Fukushima Daiichi Nuclear Power Station (NPS) [Daiichi] differ, much is not known about the end-state of core materials within these units. Some of this uncertainty can be attributed to a lack of information related to cooling system operation and cooling water injection. There is also uncertainty in our understanding of phenomena affecting: a) in-vessel core damage progression during severe accidents in boiling water reactors (BWRs), and b) accident progression after vessel failure (ex-vessel progression) for BWRs and Pressurized Water Reactors (PWRs). These uncertainties arise due to limitedmore » full scale prototypic data. Similar to what occurred after the accident at Three Mile Island Unit 2, these Daiichi units offer the international community a means to reduce such uncertainties by obtaining prototypic data from multiple full-scale BWR severe accidents. Information obtained from Daiichi is required to inform Decontamination and Decommissioning activities, improving the ability of the Tokyo Electric Power Company Holdings (TEPCO) to characterize potential hazards and to ensure the safety of workers involved with cleanup activities. This document reports recent results from the US Forensics Effort to use information obtained by TEPCO to enhance the safety of existing and future nuclear power plant designs. This Forensics Effort, which is sponsored by the Reactor Safety Technologies Pathway of the Department of Energy Office of Nuclear Energy Light Water Reactor (LWR) Sustainability Program, consists of a group of US experts in LWR safety and plant operations that have identified examination needs and are evaluating TEPCO information from Daiichi that address these needs. Examples presented in this report demonstrate that significant safety insights are being obtained in the areas of component performance, fission product release and transport, debris end-state location, and combustible gas generation and transport. In addition to reducing uncertainties related to severe accident modeling progression, these insights are being used to update guidance for severe accident prevention, mitigation, and emergency planning. Furthermore, reduced uncertainties in modeling the events at Daiichi will improve the realism of reactor safety evaluations and inform future D&D activities by improving the capability for characterizing potential hazards to workers involved with cleanup activities.« less

Risk factors for hazardous events in olfactory-impaired patients.

PubMed

Pence, Taylor S; Reiter, Evan R; DiNardo, Laurence J; Costanzo, Richard M

2014-10-01

Normal olfaction provides essential cues to allow early detection and avoidance of potentially hazardous situations. Thus, patients with impaired olfaction may be at increased risk of experiencing certain hazardous events such as cooking or house fires, delayed detection of gas leaks, and exposure to or ingestion of toxic substances. To identify risk factors and potential trends over time in olfactory-related hazardous events in patients with impaired olfactory function. Retrospective cohort study of 1047 patients presenting to a university smell and taste clinic between 1983 and 2013. A total of 704 patients had both clinical olfactory testing and a hazard interview and were studied. On the basis of olfactory function testing results, patients were categorized as normosmic (n = 161), mildly hyposmic (n = 99), moderately hyposmic (n = 93), severely hyposmic (n = 142), and anosmic (n = 209). Patient evaluation including interview, examination, and olfactory testing. Incidence of specific olfaction-related hazardous events (ie, burning pots and/or pans, starting a fire while cooking, inability to detect gas leaks, inability to detect smoke, and ingestion of toxic substances or spoiled foods) by degree of olfactory impairment. The incidence of having experienced any hazardous event progressively increased with degree of impairment: normosmic (18.0%), mildly hyposmic (22.2%), moderately hyposmic (31.2%), severely hyposmic (32.4%), and anosmic (39.2%). Over 3 decades there was no significant change in the overall incidence of hazardous events. Analysis of demographic data (age, sex, race, smoking status, and etiology) revealed significant differences in the incidence of hazardous events based on age (among 397 patients <65 years, 148 [37.3%] with hazardous event, vs 31 of 146 patients ≥65 years [21.3%]; P < .001), sex (among 278 women, 106 [38.1%] with hazardous event, vs 73 of 265 men [27.6%]; P = .009), and race (among 98 African Americans, 41 [41.8%] with hazardous event, vs 134 of 434 whites [30.9%]; P = .04). Increased level of olfactory impairment portends an increased risk of experiencing a hazardous event. Risk is further impacted by individuals' age, sex, and race. These results may assist health care practitioners in counseling patients on the risks associated with olfactory impairment.

Evaluation of the male reproductive toxicity of gallium arsenide.

PubMed

Bomhard, Ernst M; Cohen, Samuel M; Gelbke, Heinz-Peter; Williams, Gary M

2012-10-01

Gallium arsenide is an important semiconductor material marketed in the shape of wafers and thus is not hazardous to the end user. Exposure to GaAs particles may, however, occur during manufacture and processing. Potential hazards require evaluation. In 14-week inhalation studies with small GaAs particles, testicular effects have been reported in rats and mice. These effects occurred only in animals whose lungs showed marked inflammation and also had hematologic changes indicating anemia and hemolysis. The time- and concentration-dependent progressive nature of the lung and blood effects together with bioavailability data on gallium and arsenic lead us to conclude that the testicular/sperm effects are secondary to hypoxemia resulting from lung damage rather than due to a direct chemical effect of gallium or arsenide. Conditions leading to such primary effects are not expected to occur in humans at production and processing sites. This has to be taken into consideration for any classification decision for reproductive toxicity; especially a category 1 according to the EU CLP system is not warranted. Copyright © 2012 Elsevier Inc. All rights reserved.

Occupational hazard evaluation model underground coal mine based on unascertained measurement theory

NASA Astrophysics Data System (ADS)

Deng, Quanlong; Jiang, Zhongan; Sun, Yaru; Peng, Ya

2017-05-01

In order to study how to comprehensively evaluate the influence of several occupational hazard on miners’ physical and mental health, based on unascertained measurement theory, occupational hazard evaluation indicator system was established to make quantitative and qualitative analysis. Determining every indicator weight by information entropy and estimating the occupational hazard level by credible degree recognition criteria, the evaluation model was programmed by Visual Basic, applying the evaluation model to occupational hazard comprehensive evaluation of six posts under a coal mine, and the occupational hazard degree was graded, the evaluation results are consistent with actual situation. The results show that dust and noise is most obvious among the coal mine occupational hazard factors. Excavation face support workers are most affected, secondly, heading machine drivers, coal cutter drivers, coalface move support workers, the occupational hazard degree of these four types workers is II mild level. The occupational hazard degree of ventilation workers and safety inspection workers is I level. The evaluation model could evaluate underground coal mine objectively and accurately, and can be employed to the actual engineering.

Tobacco Smoking and Increased Risk of Death and Progression for Patients With p16-Positive and p16-Negative Oropharyngeal Cancer

PubMed Central

Gillison, Maura L.; Zhang, Qiang; Jordan, Richard; Xiao, Weihong; Westra, William H.; Trotti, Andy; Spencer, Sharon; Harris, Jonathan; Chung, Christine H.; Ang, K. Kian

2012-01-01

Purpose Tobacco smoking is associated with oropharynx cancer survival, but to what extent cancer progression or death increases with increasing tobacco exposure is unknown. Patients and Methods Patients with oropharynx cancer enrolled onto a phase III trial of radiotherapy from 1991 to 1997 (Radiation Therapy Oncology Group [RTOG] 9003) or of chemoradiotherapy from 2002 to 2005 (RTOG 0129) were evaluated for tumor human papillomavirus status by a surrogate, p16 immunohistochemistry, and for tobacco exposure by a standardized questionnaire. Associations between tobacco exposure and overall survival (OS) and progression-free survival (PFS) were estimated by Cox proportional hazards models. Results Prevalence of p16-positive cancer was 39.5% among patients in RTOG 9003 and 68.0% in RTOG 0129. Median pack-years of tobacco smoking were lower among p16-positive than p16-negative patients in both trials (RTOG 9003: 29 v 45.9 pack-years; P = .02; RTOG 0129: 10 v 40 pack-years; P < .001). After adjustment for p16 and other factors, risk of progression (PFS) or death (OS) increased by 1% per pack-year (for both, hazard ratio [HR], 1.01; 95% CI, 1.00 to 1.01; P = .002) or 2% per year of smoking (for both, HR, 1.02; 95% CI, 1.01 to 1.03; P < .001) in both trials. In RTOG 9003, risk of death doubled (HR, 2.19; 95% CI, 1.46 to 3.28) among those who smoked during radiotherapy after accounting for pack-years and other factors, and risk of second primary tumors increased by 1.5% per pack-year (HR, 1.015; 95% CI, 1.005 to 1.026). Conclusion Risk of oropharyngeal cancer progression and death increases directly as a function of tobacco exposure at diagnosis and during therapy and is independent of tumor p16 status and treatment. PMID:22565003

Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia.

PubMed

Byrd, John C; Brown, Jennifer R; O'Brien, Susan; Barrientos, Jacqueline C; Kay, Neil E; Reddy, Nishitha M; Coutre, Steven; Tam, Constantine S; Mulligan, Stephen P; Jaeger, Ulrich; Devereux, Steve; Barr, Paul M; Furman, Richard R; Kipps, Thomas J; Cymbalista, Florence; Pocock, Christopher; Thornton, Patrick; Caligaris-Cappio, Federico; Robak, Tadeusz; Delgado, Julio; Schuster, Stephen J; Montillo, Marco; Schuh, Anna; de Vos, Sven; Gill, Devinder; Bloor, Adrian; Dearden, Claire; Moreno, Carol; Jones, Jeffrey J; Chu, Alvina D; Fardis, Maria; McGreivy, Jesse; Clow, Fong; James, Danelle F; Hillmen, Peter

2014-07-17

In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase, in patients at risk for a poor outcome. In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. At a median follow-up of 9.4 months, ibrutinib significantly improved progression-free survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P=0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL. (Funded by Pharmacyclics and Janssen; RESONATE ClinicalTrials.gov number, NCT01578707.).

Ibrutinib versus Ofatumumab in Previously Treated Chronic Lymphoid Leukemia

PubMed Central

Byrd, J.C.; Brown, J.R.; O’Brien, S.; Barrientos, J.C.; Kay, N.E.; Reddy, N.M.; Coutre, S.; Tam, C.S.; Mulligan, S.P.; Jaeger, U.; Devereux, S.; Barr, P.M.; Furman, R.R.; Kipps, T.J.; Cymbalista, F.; Pocock, C.; Thornton, P.; Caligaris-Cappio, F.; Robak, T.; Delgado, J.; Schuster, S.J.; Montillo, M.; Schuh, A.; de Vos, S.; Gill, D.; Bloor, A.; Dearden, C.; Moreno, C.; Jones, J.J.; Chu, A.D.; Fardis, M.; McGreivy, J.; Clow, F.; James, D.F.; Hillmen, P.

2014-01-01

Background In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton’s tyrosine kinase, in patients at risk for a poor outcome. Methods In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. Results At a median follow-up of 9.4 months, ibrutinib significantly improved progression-free survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P = 0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. Conclusions Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL. (Funded by Pharmacyclics and Janssen; RESONATE ClinicalTrials.gov number, NCT01578707.) PMID:24881631

Hazards in volcanic arcs

NASA Astrophysics Data System (ADS)

Sparks, S. R.

2008-12-01

Volcanic eruptions in arcs are complex natural phenomena, involving the movement of magma to the Earth's surface and interactions with the surrounding crust during ascent and with the surface environment during eruption, resulting in secondary hazards. Magma changes its properties profoundly during ascent and eruption and many of the underlying processes of heat and mass transfer and physical property changes that govern volcanic flows and magmatic interactions with the environment are highly non-linear. Major direct hazards include tephra fall, pyroclastic flows from explosions and dome collapse, volcanic blasts, lahars, debris avalanches and tsunamis. There are also health hazards related to emissions of gases and very fine volcanic ash. These hazards and progress in their assessment are illustrated mainly from the ongoing eruption of the Soufriere Hills volcano. Montserrat. There are both epistemic and aleatory uncertainties in the assessment of volcanic hazards, which can be large, making precise prediction a formidable objective. Indeed in certain respects volcanic systems and hazardous phenomena may be intrinsically unpredictable. As with other natural phenomena, predictions and hazards inevitably have to be expressed in probabilistic terms that take account of these uncertainties. Despite these limitations significant progress is being made in the ability to anticipate volcanic activity in volcanic arcs and, in favourable circumstances, make robust hazards assessments and predictions. Improvements in monitoring ground deformation, gas emissions and seismicity are being combined with more advanced models of volcanic flows and their interactions with the environment. In addition more structured and systematic methods for assessing hazards and risk are emerging that allow impartial advice to be given to authorities during volcanic crises. There remain significant issues of how scientific advice and associated uncertainties are communicated to provide effective mitigation during volcanic crises.

A Multi-state Model for Designing Clinical Trials for Testing Overall Survival Allowing for Crossover after Progression

PubMed Central

Xia, Fang; George, Stephen L.; Wang, Xiaofei

2015-01-01

In designing a clinical trial for comparing two or more treatments with respect to overall survival (OS), a proportional hazards assumption is commonly made. However, in many cancer clinical trials, patients pass through various disease states prior to death and because of this may receive treatments other than originally assigned. For example, patients may crossover from the control treatment to the experimental treatment at progression. Even without crossover, the survival pattern after progression may be very different than the pattern prior to progression. The proportional hazards assumption will not hold in these situations and the design power calculated on this assumption will not be correct. In this paper we describe a simple and intuitive multi-state model allowing for progression, death before progression, post-progression survival and crossover after progression and apply this model to the design of clinical trials for comparing the OS of two treatments. For given values of the parameters of the multi-state model, we simulate the required number of deaths to achieve a specified power and the distribution of time required to achieve the requisite number of deaths. The results may be quite different from those derived using the usual PH assumption. PMID:27239255

Progress in Development of an Airborne Turbulence Detection System

NASA Technical Reports Server (NTRS)

Hamilton, David W.; Proctor, Fred H.

2006-01-01

Aircraft encounters with turbulence are the leading cause of in-flight injuries (Tyrvanas 2003) and have occasionally resulted in passenger and crew fatalities. Most of these injuries are caused by sudden and unexpected encounters with severe turbulence in and around convective activity (Kaplan et al 2005). To alleviate this problem, the Turbulence Prediction and Warning Systems (TPAWS) element of NASA s Aviation Safety program has investigated technologies to detect and warn of hazardous in-flight turbulence. This effort has required the numerical modeling of atmospheric convection: 1) for characterizing convectively induced turbulence (CIT) environments, 2) for defining turbulence hazard metrics, and 3) as a means of providing realistic three-dimensional data sets that can be used to test and evaluate turbulence detection sensors. The data sets are being made available to industry and the FAA for certification of future airborne turbulence-detection systems (ATDS) with warning capability. Early in the TPAWS project, a radar-based ATDS was installed and flight tested on NASA s research aircraft, a B-757. This ATDS utilized new algorithms and hazard metrics that were developed for use with existing airborne predictive windshear radars, thus avoiding the installation of new hardware. This system was designed to detect and warn of hazardous CIT even in regions with weak radar reflectivity (i.e. 5-15 dBz). Results from an initial flight test of the ATDS were discussed in Hamilton and Proctor (2002a; 2002b). In companion papers (Proctor et al 2002a; 2002b), a numerical simulation of the most significant encounter from that flight test was presented. Since the presentation of these papers a second flight test has been conducted providing additional cases for examination. In this paper, we will present results from NASA s flight test and a numerical model simulation of a turbulence environment encountered on 30 April 2002. Progress leading towards FAA certification of industry built ATDS will also be discussed.

76 FR 57024 - Notice of Teleconference of the Chronic Hazard Advisory Panel on Phthalates and Phthalate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-15

... Product Safety Improvement Act of 2008 (CPSIA) (Pub. L. 110- 314). The CHAP will discuss its progress... CONSUMER PRODUCT SAFETY COMMISSION Notice of Teleconference of the Chronic Hazard Advisory Panel on Phthalates and Phthalate Substitutes AGENCY: Consumer Product Safety Commission. ACTION: Notice of...

3-Dimensional magnetic resonance spectroscopic imaging at 3 Tesla for early response assessment of glioblastoma patients during external beam radiation therapy.

PubMed

Muruganandham, Manickam; Clerkin, Patrick P; Smith, Brian J; Anderson, Carryn M; Morris, Ann; Capizzano, Aristides A; Magnotta, Vincent; McGuire, Sarah M; Smith, Mark C; Bayouth, John E; Buatti, John M

2014-09-01

To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested. Published by Elsevier Inc.

3D-MR Spectroscopic Imaging at 3Tesla for Early Response Assessment of Glioblastoma Patients during External Beam Radiation Therapy

PubMed Central

Muruganandham, Manickam; Clerkin, Patrick P; Smith, Brian J; Anderson, Carryn M; Morris, Ann; Capizzano, Aristides A; Magnotta, Vincent; McGuire, Sarah M; Smith, Mark C; Bayouth, John E; Buatti, John M

2014-01-01

Purpose To evaluate the utility of 3D-MR proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium enhanced MR images at simulation and at boost treatment planning after 17-20 fractions of radiotherapy. All patients received standard radiotherapy with temozolomide and follow-up with every two month MR scans. Progression free survival was defined using MacDonald criteria. MRSI images obtained at initial simulation were analyzed for choline / N-acetylaspartate ratios (Cho/NAA) on a voxel by voxel basis with abnormal activity defined as Cho/NAA ≥ 2. These images were compared on anatomically matched MRSI data collected after 3 weeks of radiotherapy. Changes in Cho/NAA between pre-therapy and 3rd week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results After 8.6 months (median follow-up), 50% of patients had progressed based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (p< 0.01). Patients with an increase in mean or median Cho/NAA values at the 3rd week RT scan had a significantly greater chance of early progression (p <0.01). An increased Cho/NAA at the 3rd week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval 1.10-6.71, p= 0.03). Most patients received the prescription dose of RT to the Cho/NAA ≥ 2 volume, which was where recurrence most often occurred. Conclusion Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested. PMID:24986746

3-Dimensional Magnetic Resonance Spectroscopic Imaging at 3 Tesla for Early Response Assessment of Glioblastoma Patients During External Beam Radiation Therapy

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

Muruganandham, Manickam; Clerkin, Patrick P.; Smith, Brian J.

Purpose: To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials: Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al.more » MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results: After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. Conclusion: Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested.« less

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer.

PubMed

Fizazi, Karim; Tran, NamPhuong; Fein, Luis; Matsubara, Nobuaki; Rodriguez-Antolin, Alfredo; Alekseev, Boris Y; Özgüroğlu, Mustafa; Ye, Dingwei; Feyerabend, Susan; Protheroe, Andrew; De Porre, Peter; Kheoh, Thian; Park, Youn C; Todd, Mary B; Chi, Kim N

2017-07-27

Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer. In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 1199 patients to receive either androgen-deprivation therapy plus abiraterone acetate (1000 mg daily, given once daily as four 250-mg tablets) plus prednisone (5 mg daily) (the abiraterone group) or androgen-deprivation therapy plus dual placebos (the placebo group). The two primary end points were overall survival and radiographic progression-free survival. After a median follow-up of 30.4 months at a planned interim analysis (after 406 patients had died), the median overall survival was significantly longer in the abiraterone group than in the placebo group (not reached vs. 34.7 months) (hazard ratio for death, 0.62; 95% confidence interval [CI], 0.51 to 0.76; P<0.001). The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group (hazard ratio for disease progression or death, 0.47; 95% CI, 0.39 to 0.55; P<0.001). Significantly better outcomes in all secondary end points were observed in the abiraterone group, including the time until pain progression, next subsequent therapy for prostate cancer, initiation of chemotherapy, and prostate-specific antigen progression (P<0.001 for all comparisons), along with next symptomatic skeletal events (P=0.009). These findings led to the unanimous recommendation by the independent data and safety monitoring committee that the trial be unblinded and crossover be allowed for patients in the placebo group to receive abiraterone. Rates of grade 3 hypertension and hypokalemia were higher in the abiraterone group. The addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly increased overall survival and radiographic progression-free survival in men with newly diagnosed, metastatic, castration-sensitive prostate cancer. (Funded by Janssen Research and Development; LATITUDE ClinicalTrials.gov number, NCT01715285 .).

Stereotactic Radiosurgery for the Treatment of Primary and Metastatic Spinal Sarcomas

PubMed Central

Balagamwala, Ehsan H.; Angelov, Lilyana; Suh, John H.; Djemil, Toufik; Magnelli, Anthony; Qi, Peng; Zhuang, Tingliang; Godley, Andrew

2016-01-01

Purpose: Despite advancements in local and systemic therapy, metastasis remains common in the natural history of sarcomas. Unfortunately, such metastases are the most significant source of morbidity and mortality in this heterogeneous disease. As a classically radioresistant histology, stereotactic radiosurgery has emerged to control spinal sarcomas and provide palliation. However, there is a lack of data regarding pain relief and relapse following stereotactic radiosurgery. Methods: We queried a retrospective institutional database of patients who underwent spine stereotactic radiosurgery for primary and metastatic sarcomas. The primary outcome was pain relief following stereotactic radiosurgery. Secondary outcomes included progression of pain, radiographic failure, and development of toxicities following treatment. Results: Forty treatment sites were eligible for inclusion; the median prescription dose was 16 Gy in a single fraction. Median time to radiographic failure was 14 months. At 6 and 12 months, radiographic control was 63% and 51%, respectively. Among patients presenting with pain, median time to pain relief was 1 month. Actuarial pain relief at 6 months was 82%. Median time to pain progression was 10 months; at 12 months, actuarial pain progression was 51%. Following multivariate analysis, presence of neurologic deficit at consult (hazard ratio: 2.48, P < .01) and presence of extraspinal bone metastases (hazard ratio: 2.83, P < .01) were associated with pain relief. Greater pain at consult (hazard ratio: 1.92, P < .01), prior radiotherapy (hazard ratio: 4.65, P = .02), and greater number of irradiated vertebral levels were associated with pain progression. Conclusions: Local treatment of spinal sarcomas has remained a challenge for decades, with poor rates of local control and limited pain relief following conventional radiotherapy. In this series, pain relief was achieved in 82% of treatments at 6 months, with half of patients experiencing pain progression by 12 months. Given minimal toxicity and suboptimal pain control at 12 months, dose escalation beyond 16 Gy is warranted. PMID:27074915

Everolimus for Advanced Pancreatic Neuroendocrine Tumours: A Subgroup Analysis Evaluating Japanese Patients in the RADIANT-3 Trial

PubMed Central

Ito, Tetsuhide; Okusaka, Takuji; Ikeda, Masafumi; Igarashi, Hisato; Morizane, Chigusa; Nakachi, Kohei; Tajima, Takeshi; Kasuga, Akio; Fujita, Yoshie; Furuse, Junji

2012-01-01

Objective Everolimus, an inhibitor of the mammalian target of rapamycin, has recently demonstrated efficacy and safety in a Phase III, double-blind, randomized trial (RADIANT-3) in 410 patients with low- or intermediate-grade advanced pancreatic neuroendocrine tumours. Everolimus 10 mg/day provided a 2.4-fold improvement compared with placebo in progression-free survival, representing a 65% risk reduction for progression. The purpose of this analysis was to investigate the efficacy and safety of everolimus in the Japanese subgroup enrolled in the RADIANT-3 study. Methods Subgroup analysis of the Japanese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally (n = 23) and matching placebo (n = 17). The primary endpoint was progression-free survival. Safety was evaluated on the basis of the incidence of adverse drug reactions. Results Progression-free survival was significantly prolonged with everolimus compared with placebo. The median progression-free survival was 19.45 months (95% confidence interval, 8.31–not available) with everolimus vs 2.83 months (95% confidence interval, 2.46–8.34) with placebo, resulting in an 81% risk reduction in progression (hazard ratio, 0.19; 95% confidence interval, 0.08–0.48; P< 0.001). Adverse drug reactions occurred in all 23 (100%) Japanese patients receiving everolimus and in 13 (77%) patients receiving placebo; most were grade 1/2 in severity. The most common adverse drug reactions in the everolimus group were rash (n = 20; 87%), stomatitis (n = 17; 74%), infections (n = 15; 65%), nail disorders (n = 12; 52%), epistaxis (n = 10; 44%) and pneumonitis (n = 10; 44%). Conclusions These results support the use of everolimus as a valuable treatment option for Japanese patients with advanced pancreatic neuroendocrine tumours. PMID:22859827

Should we use standard survival models or the illness-death model for interval-censored data to investigate risk factors of chronic kidney disease progression?

PubMed

Boucquemont, Julie; Metzger, Marie; Combe, Christian; Stengel, Bénédicte; Leffondre, Karen

2014-01-01

In studies investigating risk factors of chronic kidney disease (CKD) progression, one may be interested in estimating factors effects on both a fall of glomerular filtration rate (GFR) below a specific level (i.e., a CKD stage) and death. Such studies have to account for the fact that GFR is measured at intermittent visit only, which implies that progression to the stage of interest is unknown for patients who die before being observed at that stage. Our objective was to compare the results of an illness-death model that handles this uncertainty, with frequently used survival models. This study included 1,519 patients from the NephroTest cohort with CKD stages 1-4 at baseline (69% males, 59±15 years, median protein/creatinine ratio [PCR] 27.4 mg/mmol) and subsequent annual measures of GFR (follow-up time 4.3±2.7 years). Each model was used to estimate the effects of sex, age, PCR, and GFR at baseline on the hazards of progression to CKD stage 5 (GFR<15 mL/min/1.73 m2, n = 282 observed) and death (n = 168). For progression to stage 5, there were only minor differences between results from the different models. The differences between results were higher for the hazard of death before or after progression. Our results also suggest that previous findings on the effect of age on end-stage renal disease are more likely due to a strong impact of age on death than to an effect on progression. The probabilities of progression were systematically under-estimated with the survival model as compared with the illness-death model. This study illustrates the advantages of the illness-death model for accurately estimating the effects of risk factors on the hazard of progression and death, and probabilities of progression. It avoids the need to choose arbitrary time-to-event and time-to-censoring, while accounting for both interval censoring and competition by death, using a single analytical model.

Evaluating hazardous air pollutants in Australia.

PubMed

Hinwood, A L; Di Marco, P N

2002-12-27

Hazardous air pollutants (HAPS) have been evaluated for their health and environmental significance on a targeted and campaign basis in Australia until recently. Individual States and Territories have been undertaking targeted monitoring studies and have numerous control strategies aimed at controlling HAPS emissions with the focus largely on volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs) and selected heavy metals, with some limited work on exposure assessment. There has been little evaluation of the potential health or environmental effects of the monitored concentrations of these substances and few toxicological or epidemiological studies have been conducted-none in the community setting in Australia. Moreover, there has not been an agreed method for assessing risks from HAPS in ambient air, with different jurisdictions utilising different international benchmarks. Recently, the National Environmental Health (EnHealth) Council commenced developing a risk assessment methodology, which is being used in the development of ambient air quality guidelines for selected HAPS in Western Australia. In 1999, the Commonwealth Government established the Living Cities-Toxics Program, designed to assess the state of knowledge on HAPS in Australia with the aims of identifying and prioritising HAPS, identifying information gaps and informing the development of national air quality standards and national management strategies. The Commonwealth Government commenced a number of projects in 2000 to progress these aims.

High-Throughput Toxicity Testing: New Strategies for ...

EPA Pesticide Factsheets

In recent years, the food industry has made progress in improving safety testing methods focused on microbial contaminants in order to promote food safety. However, food industry toxicologists must also assess the safety of food-relevant chemicals including pesticides, direct additives, and food contact substances. With the rapidly growing use of new food additives, as well as innovation in food contact substance development, an interest in exploring the use of high-throughput chemical safety testing approaches has emerged. Currently, the field of toxicology is undergoing a paradigm shift in how chemical hazards can be evaluated. Since there are tens of thousands of chemicals in use, many of which have little to no hazard information and there are limited resources (namely time and money) for testing these chemicals, it is necessary to prioritize which chemicals require further safety testing to better protect human health. Advances in biochemistry and computational toxicology have paved the way for animal-free (in vitro) high-throughput screening which can characterize chemical interactions with highly specific biological processes. Screening approaches are not novel; in fact, quantitative high-throughput screening (qHTS) methods that incorporate dose-response evaluation have been widely used in the pharmaceutical industry. For toxicological evaluation and prioritization, it is the throughput as well as the cost- and time-efficient nature of qHTS that makes it

The effect of preexisting respiratory co-morbidities on burn outcomes☆

PubMed Central

Knowlin, Laquanda T.; Stanford, Lindsay B.; Cairns, Bruce A.; Charles, Anthony G.

2018-01-01

Introduction Burns cause physiologic changes in multiple organ systems in the body. Burn mortality is usually attributable to pulmonary complications, which can occur in up to 41% of patients admitted to the hospital after burn. Patients with preexisting comorbidities such as chronic lung diseases may be more susceptible. We therefore sought to examine the impact of preexisting respiratory disease on burn outcomes. Methods A retrospective analysis of patients admitted to a regional burn center from 2002–2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, smoker status, length of hospital stay, and days of mechanical ventilation. Bivariate analysis was performed and Cox regression modeling using significant variables was utilized to estimate hazard of progression to mechanical ventilation and mortality. Results There were a total of 7640 patients over the study period. Overall survival rate was 96%. 8% (n=672) had a preexisting respiratory disease. Chronic lung disease patients had a higher mortality rate (7%) compared to those without lung disease (4%, p<0.01). The adjusted Cox regression model to estimate the hazard of progression to mechanical ventilation in patients with respiratory disease was 21% higher compared to those without respiratory disease (HR=1.21, 95% CI=1.01–1.44). The hazard of progression to mortality is 56% higher (HR=1.56, 95% CI=1.10–2.19) for patients with pre-existing respiratory disease compared to those without respiratory disease after controlling for patient demographics and injury characteristics. Conclusion Preexisting chronic respiratory disease significantly increases the hazard of progression to mechanical ventilation and mortality in patients following burn. Given the increasing number of Americans with chronic respiratory diseases, there will likely be a greater number of individuals at risk for worse outcomes following burn. PMID:28341260

The effect of preexisting respiratory co-morbidities on burn outcomes.

PubMed

Knowlin, Laquanda T; Stanford, Lindsay B; Cairns, Bruce A; Charles, Anthony G

2017-03-01

Burns cause physiologic changes in multiple organ systems in the body. Burn mortality is usually attributable to pulmonary complications, which can occur in up to 41% of patients admitted to the hospital after burn. Patients with preexisting comorbidities such as chronic lung diseases may be more susceptible. We therefore sought to examine the impact of preexisting respiratory disease on burn outcomes. A retrospective analysis of patients admitted to a regional burn center from 2002-2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, smoker status, length of hospital stay, and days of mechanical ventilation. Bivariate analysis was performed and Cox regression modeling using significant variables was utilized to estimate hazard of progression to mechanical ventilation and mortality. There were a total of 7640 patients over the study period. Overall survival rate was 96%. 8% (n=672) had a preexisting respiratory disease. Chronic lung disease patients had a higher mortality rate (7%) compared to those without lung disease (4%, p<0.01). The adjusted Cox regression model to estimate the hazard of progression to mechanical ventilation in patients with respiratory disease was 21% higher compared to those without respiratory disease (HR=1.21, 95% CI=1.01-1.44). The hazard of progression to mortality is 56% higher (HR=1.56, 95% CI=1.10-2.19) for patients with pre-existing respiratory disease compared to those without respiratory disease after controlling for patient demographics and injury characteristics. Preexisting chronic respiratory disease significantly increases the hazard of progression to mechanical ventilation and mortality in patients following burn. Given the increasing number of Americans with chronic respiratory diseases, there will likely be a greater number of individuals at risk for worse outcomes following burn. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

78 FR 60755 - Hazardous Materials: Enhanced Enforcement Procedures-Resumption of Transportation

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

.... Summary of MAP-21 and Final Rule V. Summary Review of Amendments VI. Regulatory Analyses and Notices A.... Executive Summary On July 6, 2012, the President signed the Moving Ahead for Progress in the 21st Century Act, or the MAP-21, which included the Hazardous Materials Transportation Safety Improvement Act of...

78 FR 30258 - Hazardous Materials: Enhanced Enforcement Procedures-Resumption of Transportation

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-22

... 21st Century Act, or the MAP-21, which included the Hazardous Materials Transportation Safety... 6, 2012, the President signed the Moving Ahead for Progress in the 21st Century Act, or the MAP-21... This NPRM In MAP-21 Congress directed the Secretary to address certain transportation matters related...

Innovative hazard detection and avoidance strategy for autonomous safe planetary landing

NASA Astrophysics Data System (ADS)

Jiang, Xiuqiang; Li, Shuang; Tao, Ting

2016-09-01

Autonomous hazard detection and avoidance (AHDA) is one of the key technologies for future safe planetary landing missions. In this paper, we address the latest progress on planetary autonomous hazard detection and avoidance technologies. First, the innovative autonomous relay hazard detection and avoidance strategy adopted in Chang'e-3 lunar soft landing mission and its flight results are reported in detail. Second, two new conceptual candidate schemes of hazard detection and avoidance are presented based on the Chang'e-3 AHDA system and the latest developing technologies for the future planetary missions, and some preliminary testing results are also given. Finally, the related supporting technologies for the two candidate schemes above are analyzed.

Lymphocyte-to-monocyte ratio is associated with survival in pembrolizumab-treated metastatic melanoma patients.

PubMed

Failing, Jarrett J; Yan, Yiyi; Porrata, Luis F; Markovic, Svetomir N

2017-12-01

The peripheral blood lymphocyte-to-monocyte ratio (LMR) has been associated with prognosis in many malignancies including metastatic melanoma. However, it has not been studied in patients treated with immune checkpoint inhibitors. In this study, we analyzed the baseline LMR with progression-free survival (PFS) and overall survival (OS) in metastatic melanoma patients treated with pembrolizumab. A total of 133 patients with metastatic melanoma treated with pembrolizumab were included in this retrospective study. LMR was calculated from pretherapy peripheral blood counts and the optimal cutoff value was determined by a receiver operator characteristic curve. PFS and OS were evaluated using the Kaplan-Meier method and multivariate Cox proportional hazard modeling. Patients with an LMR of at least 1.7 showed improved PFS (hazard ratio=0.55; 95% confidence interval: 0.34-0.92; P=0.024) and OS (hazard ratio=0.29; 95% confidence interval: 0.15-0.59; P=0.0007). The baseline LMR is associated with PFS and OS in metastatic melanoma patients treated with pembrolizumab, and could represent a convenient and cost-effective prognostic biomarker. Validation of these findings in an independent cohort is needed.

Environmental Hazards Assessment Program. Quarterly report, July--September 1995

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

NONE

This report describes activities and reports on progress for the first quarter (July--September) of the fourth year of the grant to support the Environmental Hazards Assessment Program (EHAP) at the Medical University of South Carolina. It reports progress against the grant objectives and the Program Implementation Plan published at the end of the first year of the grant. The objectives of EHAP stated in the proposal to DOE are to: (1) develop a holistic, national basis for risk assessment, risk management, and risk communication that recognizes the direct impact of environmental hazards on the health and well-being of all; (2)more » develop a pool of talented scientists and experts in cleanup activities, especially in human health aspects; and (3) identify needs and develop programs addressing the critical shortage of well-educated, highly-skilled technical and scientific personnel to address the health-oriented aspects of environmental restoration and waste management.« less

Pyrotechnic hazards classification and evaluation program. Phase 3, segments 1-4: Investigation of sensitivity test methods and procedures for pyrotechnic hazards evaluation and classification, part A

NASA Technical Reports Server (NTRS)

1971-01-01

The findings, conclusions, and recommendations relative to the investigations conducted to evaluate tests for classifying pyrotechnic materials and end items as to their hazard potential are presented. Information required to establish an applicable means of determining the potential hazards of pyrotechnics is described. Hazard evaluations are based on the peak overpressure or impulse resulting from the explosion as a function of distance from the source. Other hazard classification tests include dust ignition sensitivity, impact ignition sensitivity, spark ignition sensitivity, and differential thermal analysis.

A difference in systolic blood pressure between arms is a novel predictor of the development and progression of diabetic nephropathy in patients with type 2 diabetes.

PubMed

Okada, Hiroshi; Fukui, Michiaki; Tanaka, Muhei; Matsumoto, Shinobu; Iwase, Hiroya; Kobayashi, Kanae; Asano, Mai; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto

2013-10-01

Recent studies have suggested that a difference in systolic blood pressure (SBP) between arms is associated with both vascular disease and mortality. The aim of this study was to investigate the relationship between a difference in SBP between arms and change in urinary albumin excretion or development of albuminuria in patients with type 2 diabetes. We measured SBP in 408 consecutive patients with type 2 diabetes, and calculated a difference in SBP between arms. We performed follow-up study to assess change in urinary albumin excretion or development of albuminuria, mean interval of which was 4.6 ± 1.7 years. We then evaluated the relationship of a difference in SBP between arms to diabetic nephropathy using multiple regression analysis and multiple Cox regression model. Multiple regression analyses demonstrated that a difference in SBP between arms was independently associated with change in urinary albumin excretion (β = 0.1869, P = 0.0010). Adjusted Cox regression analyses demonstrated that a difference in SBP between arms was associated with an increased hazard of development of albuminuria; hazard ratio was 1.215 (95% confidence interval 1.077-1.376). Moreover, the risk of development of albuminuria was increased in patients with a difference in SBP of equal to or more than 10 mmHg between arms; hazard ratio was 4.168 (95% confidence interval 1.478-11.70). A difference in SBP between arms could be a novel predictor of the development and progression of diabetic nephropathy in patients with type 2 diabetes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Risk factors for progression to invasive carcinoma in patients with borderline ovarian tumors.

PubMed

Song, Taejong; Lee, Yoo-Young; Choi, Chel Hun; Kim, Tae-Joong; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

2014-09-01

The aim of this study was to identify risk factors for progression to invasive carcinoma in patients with borderline ovarian tumors (BOTs). We performed a retrospective review of all patients treated and followed for BOTs between 1996 and 2011. Multivariate Cox proportional hazards model analysis was performed to identify independent risk factors for progression to invasive carcinoma. A total of 364 patients were identified. During the median follow-up of 53.8 months, 31 patients (8.5%) developed recurrent disease: 12 (3.3%) had recurrent disease with progression to invasive carcinoma, and 19 (5.2%) had recurrent disease with borderline histology. Disease-related deaths (7/364; 1.7%) were observed only in patients with progression to invasive carcinoma. The multivariate analysis showed that independent risk factors for progression to invasive carcinoma were advanced disease stage (hazard ratio [HR], 5.59; P = 0.005), age 65 years or older (HR, 5.13; P = 0.037), and the presence of microinvasion (HR, 3.71; P = 0.047). These 3 factors were also independently related to overall survival. Although patients with BOTs have an excellent prognosis, the risk of progression to invasive carcinoma and thereby death remains. Therefore, physicians should pay closer attention to BOT patients with these risk factors (ie, advanced disease stage, old age, and microinvasion), and more careful surveillance for progression to invasive carcinoma is needed.

Predictors of Recurrence, Progression, and Retreatment in Basilar Tip Aneurysms: A Location-Controlled Analysis.

PubMed

Abecassis, Isaac Josh; Sen, Rajeev D; Barber, Jason; Shetty, Rakshith; Kelly, Cory M; Ghodke, Basavaraj V; Hallam, Danial K; Levitt, Michael R; Kim, Louis J; Sekhar, Laligam N

2018-06-14

Endovascular treatment of intracranial aneurysms is associated with higher rates of recurrence and retreatment, though contemporary rates and risk factors for basilar tip aneurysms (BTAs) are less well-described. To characterize progression, retreatement, and retreated progression of BTAs treated with microsurgical or endovascular interventions. We retrospectively reviewed records for 141 consecutive BTA patients. We included 158 anterior communicating artery (ACoA) and 118 middle cerebral artery (MCA) aneurysms as controls. Univariate and multivariate analyses were used to calculate rates of progression (recurrence of previously obliterated aneurysms and progression of known residual aneurysm dome or neck), retreatment, and retreated progression. Kaplan-Meier analysis was used to characterize 24-mo event rates for primary outcome prediction. Of 141 BTA patients, 62.4% were ruptured and 37.6% were unruptured. Average radiographical follow-up was 33 mo. Among ruptured aneurysms treated with clipping, there were 2 rehemorrhages due to recurrence (6.1%), and none in any other cohorts. Overall rates of progression (28.9%), retreatment (28.9%), and retreated progression (24.7%) were not significantly different between surgical and endovascular subgroups, though ruptured aneurysms had higher event rates. Multivariate modeling confirmed rupture status (P = .003, hazard ratio = 0.14) and aneurysm dome width (P = .005, hazard ratio = 1.23) as independent predictors of progression requiring retreatment. In a separate multivariate analysis with ACoA and MCA aneurysms, basilar tip location was an independent predictor of progression, retreatment, and retreated progression. BTAs have higher rates of progression and retreated progression than other aneurysm locations, independent of treatment modality. Rupture status and dome width are risk factors for progression requiring retreatment.

The utility of the apolipoprotein A1 remnant ratio in predicting incidence coronary heart disease in a primary prevention cohort: The Jackson Heart Study.

PubMed

May, Heidi T; Nelson, John R; Lirette, Seth T; Kulkarni, Krishnaji R; Anderson, Jeffrey L; Griswold, Michael E; Horne, Benjamin D; Correa, Adolfo; Muhlestein, Joseph B

2016-05-01

Dyslipidemia plays a significant role in the progression of cardiovascular disease. The apolipoprotein (apo) A1 remnant ratio (apo A1/VLDL3-C + IDL-C) has recently been shown to be a strong predictor of death/myocardial infarction risk among women >50 years undergoing angiography. However, whether this ratio is associated with coronary heart disease risk among other populations is unknown. We evaluated the apo A1 remnant ratio and its components for coronary heart disease incidence. Observational. Participants (N = 4722) of the Jackson Heart Study were evaluated. Baseline clinical characteristics and lipoprotein subfractions (Vertical Auto Profile method) were collected. Cox hazard regression analysis, adjusted by standard cardiovascular risk factors, was utilized to determine associations of lipoproteins with coronary heart disease. Those with new-onset coronary heart disease were older, diabetic, smokers, had less education, used more lipid-lowering medication, and had a more atherogenic lipoprotein profile. After adjustment, the apo A1 remnant ratio (hazard ratio = 0.67 per 1-SD, p = 0.002) was strongly associated with coronary heart disease incidence. This association appears to be driven by the IDL-C denominator (hazard ratio = 1.23 per 1-SD, p = 0.007). Remnants (hazard ratio = 1.21 per 1-SD, p = 0.017), but not apo A1 (hazard ratio = 0.85 per 1-SD, p = 0.121) or VLDL3-C (hazard ratio = 1.13 per 1-SD, p = 0.120) were associated with coronary heart disease. Standard lipids were not associated with coronary heart disease incidence. We found the apo A1 remnant ratio to be strongly associated with coronary heart disease. This ratio appears to better stratify risk than standard lipids, apo A1, and remnants among a primary prevention cohort of African Americans. Its utility requires further study as a lipoprotein management target for risk reduction. © The European Society of Cardiology 2015.

A framework for profiling the characteristics of risk governance in natural hazard contexts

NASA Astrophysics Data System (ADS)

Walker, G.; Tweed, F.; Whittle, R.

2014-01-01

Over recent decades there have been moves away from traditional forms of government towards broader practices of "governance". These moves are as relevant to the handling of natural hazards as they are to other societal concerns. Key characteristics of such changes include the emergence of multi-level governance processes, shifts away from the exercise of centralised authority towards the involvement and collaboration of a multiplicity of actors, the creation of new forms of authority and control, and changing distributions of responsibilities between the state and other actors. However, the extent to which these shifts have taken place across the varied national contexts in Europe and can be observed specifically in relation to the governance of natural hazards is not at all clear. Such developments may also be evaluated in different ways; where some might see progressive reforms, others might see damaging undermining of established arrangements. In this paper, we propose a risk governance profiling framework that can be used to draw out the key characteristics of the ways in which natural hazards are governed in a particular governance setting. The framework can be flexibly applied in relation to a specific hazard and national, regional or local context, and enables qualitative profiling across a spectrum of eight key governance characteristics. Past trends and likely future changes can also be represented. We discuss the formulation of this framework as well as giving examples of profiles for different hazards in different parts of Europe. We suggest ways in which comparisons can be made between governance profiles, providing a stimulus and focus for debate and discussion around the trends of change in governance practice that have been, and are continuing, to take place.

Tulane/Xavier University Hazardous Materials in Aquatic Environments of the Mississippi River Basin. Quarterly progress report, January 1, 1995--March 31, 1995

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

NONE

1995-05-01

This progress report covers activities for the period January 1 - March 31, 1995 on project concerning `Hazardous Materials in Aquatic Environments of the Mississippi River Basin.` The following activities are each summarized by bullets denoting significant experiments/findings: biotic and abiotic studies on the biological fate, transport and ecotoxicity of toxic and hazardous waste in the Mississippi River Basin; assessment of mechanisms of metal-induced reproductive toxicity in quatic species as a biomarker of exposure; hazardous wastes in aquatic environments: biological uptake and metabolism studies; ecological sentinels of aquatic contamination in the lower Mississippi River system; bioremediation of selected contaminants inmore » aquatic environments of the Mississippi River Basin; a sensitive rapid on-sit immunoassay for heavy metal contamination; pore-level flow, transport, agglomeration and reaction kinetics of microorganism; biomarkers of exposure and ecotoxicity in the Mississippi River Basin; natural and active chemical remediation of toxic metals, organics and radionuclides in the aquatic environment; expert geographical information systems for assessing hazardous wastes in aquatic environments; enhancement of environmental education; and a number of just initiated projects including fate and transport of contaminants in aquatic environments; photocatalytic remediation; radionuclide fate and modeling from Chernobyl.« less

Implication of human telomerase reverse transcriptase in cervical carcinogenesis and cancer recurrence.

PubMed

Wang, P-H; Ko, J-L

2006-01-01

The objective of this study was to evaluate the implication of human telomerase reverse transcriptase (hTERT) in cervical carcinogenesis and cancer recurrence. One hundred three cases of uterine cervix, including 20 normal, 13 low-grade squamous intraepithelial lesion (LSIL), 30 high-grade squamous intraepithelial lesion (HSIL), and 40 squamous cell carcinoma (SCC) tissues, were evaluated for hTERT immunoreactivity. The expressions of hTERT in normal, LSIL, HSIL, and SCC tissues were compared by Fisher exact or Chi-square test. The relationships between hTERT and clinicopathologic variables of SCC were also assessed. Furthermore, SCC patients were subdivided into negative and positive hTERT expression subgroups, and Kaplan-Meier curves were used to plot the cumulative recurrence hazard for 5 years. There was a significant difference for hTERT expression between LSIL and HSIL subgroups (P < 0.001) but no significant difference between normal and LSIL as well as HSIL and SCC subgroups. For SCC patients, hTERT expression was positive in lymph nodes, vagina, and parametrium metastastic cases. However, it did not reach a significant difference. The cumulative recurrence hazard for 5 years was about 29% in positive hTERT expression subgroup compared to 0% in negative hTERT subgroup (P = 0.2866). In conclusion, a point stage of HSIL exists in the progression of cervical carcinogenesis when the hTERT expression increases significantly. Moreover, SCC patients with positive hTERT expression may have higher cumulative recurrence hazard.

Evaluation of biotechnology-derived novel proteins for the risk of food-allergic potential: advances in the development of animal models and future challenges.

PubMed

Ahuja, Varun; Quatchadze, Maria; Ahuja, Vaishali; Stelter, Daniela; Albrecht, Achim; Stahlmann, Ralf

2010-12-01

Increasing concern from the public about the safety of genetically modified food has made critical to have suitable methods for recognizing associated potential hazards. Hierarchical approaches to allergenicity determination were proposed, and these include evaluation of the structural and sequence homology and serological identity of novel proteins with existing allergens, measuring the resistance to proteolytic digestion and assessment of sensitizing potential using animal models. Allergic individuals have a predisposed (i.e. atopic) genetic background, and a close resemblance to this setup is therefore desirable in animal models, which is possible by using a strain of an animal species that is prone for allergic disorders. So far, none of the animal model has been validated for the purpose of hazard identification in the context of safety assessment. However, the available knowledge suggests that the judicious use of an appropriate animal model could provide important information about the allergic potential of novel proteins. This paper provides an up-to-date review of the progress made in the field of development of in vivo models in this direction and the further goals that have to be achieved.

Study of the application of ERTS-A imagery to fracture-related mine safety hazards in the coal mining industry

NASA Technical Reports Server (NTRS)

Wier, C. E.; Wobber, F. J. (Principal Investigator); Russell, O. R.; Amato, R. V.

1972-01-01

The author has identified the following significant results. Various data compilation and analysis activities in support of ERTS-1 imagery interpretation are in progress or are completed. These include the compilation of mine accident data, areas of mine roof instability and the analysis of high altitude color infrared photography and low altitude color and color infrared photography which was acquired by NASA in support of the project. The photography reveals that many fracture lineaments are detectable through a varied thickness of glacial till. These data will be compiled on a series of 1:250,000 scale base maps and evaluated for a correlation between fracture zones and mine accidents and rooffalls. Due to high occurrence of cloud cover in the project area and to the delay in imagery shipments, little progress has been made in the analysis of ERTS-1 imagery.

Association of the HLA-B*52 allele with non-progression to AIDS in Brazilian HIV-1-infected individuals.

PubMed

Teixeira, S L M; de Sá, N B R; Campos, D P; Coelho, A B; Guimarães, M L; Leite, T C N F; Veloso, V G; Morgado, M G

2014-04-01

Several human leukocyte antigen (HLA) class I alleles are associated with the susceptibility to human immunodeficiency virus-1 (HIV-1) infection and/or AIDS progression. Of these, the HLA-B alleles are considered the strongest genetic determinant of disease outcome. We evaluated the influence of the HLA-B alleles on AIDS progression among HIV-1-positive individuals from Rio de Janeiro, Brazil, who were categorized as rapid progressors (RPs), typical progressors (TPs) or long-term non-progressors (LTNPs). In this study, significant differences in HLA-B allele frequencies were observed among the three progression groups for the B*48, B*49 and B*52 alleles. After controlling for other factors associated with AIDS progression, the presence of the B*52 allele was shown to be a significant protective factor (hazard ratio (HR) 0.49 (95% confidence interval (CI) 0.27-0.90) P<0.03). Although no direct association was observed between the presence of the B*27 or B*57 allele and the LTNP profile compared with the TP or RP groups, the adjusted model confirmed that these alleles are protective factors against AIDS progression (HR 0.62 (95% CI 0.38-0.99) P<0.05), as previously described. These data corroborate the existence of significant differences in HLA-B allele frequencies among the distinct AIDS progression profiles and further elucidate the role of HLA alleles in the outcome of HIV infections in diverse populations.

Fibrosis progression in African Americans and Caucasian Americans with chronic hepatitis C.

PubMed

Terrault, Norah A; Im, Kelly; Boylan, Ross; Bacchetti, Peter; Kleiner, David E; Fontana, Robert J; Hoofnagle, Jay H; Belle, Steven H

2008-12-01

Prior studies suggest the rate of liver fibrosis progression is slower in African Americans (AAs) than Caucasian Americans (CAs) with chronic HCV infection. With a multi-state Markov model, fibrosis progression was evaluated in a well-characterized cohort of 143 AA and 157 CA adults with untreated chronic HCV genotype 1 infection. In subjects with a history of injection drug use, duration of infection was imputed from a fitted risk model rather than assumed to be the reported first year of use. The distribution of Ishak fibrosis stages was 0 (8.7%), 1/2 (55.7%), 3/4 (29.3%), and 5/6 (6.3%) and was similar in AAs and CAs (P = .22). After adjusting for biopsy adequacy, AAs had a 10% lower rate of fibrosis progression than did CAs, but the difference was not statistically significant (hazard ratio, 0.90; 95% confidence interval, 0.72-1.12). The overall 20-year estimates of probabilities of progression from stage 0 to stages 1/2, 3/4, and 5/6 were 59.3%, 28.8%, and 4.7%, respectively. The estimated median time from no fibrosis to cirrhosis was 79 years for the entire cohort and 74 and 83 years for CAs and AAs, respectively. In 3-variable models including race and biopsy adequacy, the factors significantly associated with fibrosis progression were age when infected, steatosis, ALT level, and necroinflammatory score. The rates of fibrosis progression were slow and did not appear to differ substantially between AAs and CAs.

78 FR 16189 - Transportation of Agricultural Commodities

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-14

... 32934, respectively, of the Moving Ahead for Progress in the 21st Century Act (MAP-21). Although prior statutory exemptions involving agriculture are unchanged, some of these exemptions overlap with MAP-21... HM Hazardous Materials HOS Hours of Service MAP-21 Moving Ahead for Progress in the 21st Century Act...

Notification: EPA Progress on Meeting Resource Conservation and Recovery Act Statutory Mandate for Minimum Frequency of Inspections at Hazardous Waste Disposal Facilities

EPA Pesticide Factsheets

Project #OPE-FY15-0018, January 20, 2015. The EPA OIG plans to begin preliminary research on EPA’s progress in meeting minimum inspection requirements under the RCRA at treatment, storage and disposal facilities (TSDFs).

Rates and Durability of Response to Salvage Radiation Therapy Among Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma

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

Tseng, Yolanda D., E-mail: ydt2@uw.edu; Chen, Yu-Hui; Catalano, Paul J.

Purpose: To evaluate the response rate (RR) and time to local recurrence (TTLR) among patients who received salvage radiation therapy for relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) and investigate whether RR and TTLR differed according to disease characteristics. Methods and Materials: A retrospective review was performed for all patients who completed a course of salvage radiation therapy between January 2001 and May 2011 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Separate analyses were conducted for patients treated with palliative and curative intent. Predictors of RR for each subgroup were assessed using a generalized estimating equation model. For patients treatedmore » with curative intent, local control (LC) and progression-free survival were estimated with the Kaplan-Meier method; predictors for TTLR were evaluated using a Cox proportional hazards regression model. Results: Salvage radiation therapy was used to treat 110 patients to 121 sites (76 curative, 45 palliative). Salvage radiation therapy was given as part of consolidation in 18% of patients treated with curative intent. Median dose was 37.8 Gy, with 58% and 36% of curative and palliative patients, respectively, receiving 39.6 Gy or higher. The RR was high (86% curative, 84% palliative). With a median follow-up of 4.8 years among living patients, 5-year LC and progression-free survival for curative patients were 66% and 34%, respectively. Refractory disease (hazard ratio 3.3; P=.024) and lack of response to initial chemotherapy (hazard ratio 4.3; P=.007) but not dose (P=.93) were associated with shorter TTLR. Despite doses of 39.6 Gy or higher, 2-year LC was only 61% for definitive patients with refractory disease or disease that did not respond to initial chemotherapy. Conclusions: Relapsed or refractory aggressive NHL is responsive to salvage radiation therapy, and durable LC can be achieved in some cases. However, refractory disease is associated with a shorter TTLR, suggesting that radiation dose escalation, addition of radiosensitizers, or a combination of both may be indicated in these patients.« less

Prolonged Effect of Intensive Therapy on the Risk of Retinopathy Complications in Patients With Type 1 Diabetes Mellitus

PubMed Central

2009-01-01

Objective To examine the persistence of the original treatment effects 10 years after the Diabetes Control and Complications Trial (DCCT) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. In the DCCT, intensive therapy aimed at near-normal glycemia reduced the risk of microvascular complications of type 1 diabetes mellitus compared with conventional therapy. Methods Retinopathy was evaluated by fundus photography in 1211 subjects at EDIC year 10. Further 3-step progression on the Early Treatment Diabetic Retinopathy Study scale from DCCT closeout was the primary outcome. Results After 10 years of EDIC follow-up, there was no significant difference in mean glycated hemoglobin levels (8.07% vs 7.98%) between the original treatment groups. Nevertheless, compared with the former conventional treatment group, the former intensive group had significantly lower incidences from DCCT close of further retinopathy progression and proliferative retinopathy or worse (hazard reductions, 53%-56%; P<.001). The risk (hazard) reductions at 10 years of EDIC were attenuated compared with the 70% to 71% over the first 4 years of EDIC (P<.001). The persistent beneficial effects of former intensive therapy were largely explained by the difference in glycated hemoglobin levels during DCCT. Conclusion The persistent difference in diabetic retinopathy between former intensive and conventional therapy (“metabolic memory”) continues for at least 10 years but may be waning. PMID:19064853

Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer.

PubMed

Mirza, Mansoor R; Monk, Bradley J; Herrstedt, Jørn; Oza, Amit M; Mahner, Sven; Redondo, Andrés; Fabbro, Michel; Ledermann, Jonathan A; Lorusso, Domenica; Vergote, Ignace; Ben-Baruch, Noa E; Marth, Christian; Mądry, Radosław; Christensen, René D; Berek, Jonathan S; Dørum, Anne; Tinker, Anna V; du Bois, Andreas; González-Martín, Antonio; Follana, Philippe; Benigno, Benedict; Rosenberg, Per; Gilbert, Lucy; Rimel, Bobbie J; Buscema, Joseph; Balser, John P; Agarwal, Shefali; Matulonis, Ursula A

2016-12-01

Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival. Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P<0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications. Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274 .).

TU-CD-BRB-08: Radiomic Analysis of FDG-PET Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated with SBRT

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

Cui, Y; Shirato, H; Song, J

2015-06-15

Purpose: This study aims to identify novel prognostic imaging biomarkers in locally advanced pancreatic cancer (LAPC) using quantitative, high-throughput image analysis. Methods: 86 patients with LAPC receiving chemotherapy followed by SBRT were retrospectively studied. All patients had a baseline FDG-PET scan prior to SBRT. For each patient, we extracted 435 PET imaging features of five types: statistical, morphological, textural, histogram, and wavelet. These features went through redundancy checks, robustness analysis, as well as a prescreening process based on their concordance indices with respect to the relevant outcomes. We then performed principle component analysis on the remaining features (number ranged frommore » 10 to 16), and fitted a Cox proportional hazard regression model using the first 3 principle components. Kaplan-Meier analysis was used to assess the ability to distinguish high versus low-risk patients separated by median predicted survival. To avoid overfitting, all evaluations were based on leave-one-out cross validation (LOOCV), in which each holdout patient was assigned to a risk group according to the model obtained from a separate training set. Results: For predicting overall survival (OS), the most dominant imaging features were wavelet coefficients. There was a statistically significant difference in OS between patients with predicted high and low-risk based on LOOCV (hazard ratio: 2.26, p<0.001). Similar imaging features were also strongly associated with local progression-free survival (LPFS) (hazard ratio: 1.53, p=0.026) on LOOCV. In comparison, neither SUVmax nor TLG was associated with LPFS (p=0.103, p=0.433) (Table 1). Results for progression-free survival and distant progression-free survival showed similar trends. Conclusion: Radiomic analysis identified novel imaging features that showed improved prognostic value over conventional methods. These features characterize the degree of intra-tumor heterogeneity reflected on FDG-PET images, and their biological underpinnings warrant further investigation. If validated in large, prospective cohorts, this method could be used to stratify patients based on individualized risk.« less

Effective tree hazard control on forested recreation sites...losses and protection costs evaluated

Treesearch

Lee A. Paine

1967-01-01

Effectiveness of hazard control was evaluated by analyzing data on tree failures, accidents, and control costs on California recreation sites. Results indicate that reduction of limb hazard in oaks and bole hazard in conifers is the most effective form of control. Least effective is limb hazard reduction in conifers. After hazard control goals or control budgets have...

Subsystem Hazard Analysis Methodology for the Ares I Upper Stage Source Controlled Items

NASA Technical Reports Server (NTRS)

Mitchell, Michael S.; Winner, David R.

2010-01-01

This article describes processes involved in developing subsystem hazard analyses for Source Controlled Items (SCI), specific components, sub-assemblies, and/or piece parts, of the NASA ARES I Upper Stage (US) project. SCIs will be designed, developed and /or procured by Boeing as an end item or an off-the-shelf item. Objectives include explaining the methodology, tools, stakeholders and products involved in development of these hazard analyses. Progress made and further challenges in identifying potential subsystem hazards are also provided in an effort to assist the System Safety community in understanding one part of the ARES I Upper Stage project.

Prospective randomized study to assess the efficacy of site and rate of atrial pacing on long-term progression of atrial fibrillation in sick sinus syndrome: Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) Study.

PubMed

Lau, Chu-Pak; Tachapong, Ngarmukos; Wang, Chun-Chieh; Wang, Jing-Feng; Abe, Haruhiko; Kong, Chi-Woon; Liew, Reginald; Shin, Dong-Gu; Padeletti, Luigi; Kim, You-Ho; Omar, Razali; Jirarojanakorn, Kreingkrai; Kim, Yoon-Nyun; Chen, Mien-Cheng; Sriratanasathavorn, Charn; Munawar, Muhammad; Kam, Ruth; Chen, Jan-Yow; Cho, Yong-Keun; Li, Yi-Gang; Wu, Shu-Lin; Bailleul, Christophe; Tse, Hung-Fat

2013-08-13

Atrial-based pacing is associated with lower risk of atrial fibrillation (AF) in sick sinus syndrome compared with ventricular pacing; nevertheless, the impact of site and rate of atrial pacing on progression of AF remains unclear. We evaluated whether long-term atrial pacing at the right atrial (RA) appendage versus the low RA septum with (ON) or without (OFF) a continuous atrial overdrive pacing algorithm can prevent the development of persistent AF. We randomized 385 patients with paroxysmal AF and sick sinus syndrome in whom a pacemaker was indicated to pacing at RA appendage ON (n=98), RA appendage OFF (n=99), RA septum ON (n=92), or RA septum OFF (n=96). The primary outcome was the occurrence of persistent AF (AF documented at least 7 days apart or need for cardioversion). Demographic data were homogeneous across both pacing site (RA appendage/RA septum) and atrial overdrive pacing (ON/OFF). After a mean follow-up of 3.1 years, persistent AF occurred in 99 patients (25.8%; annual rate of persistent AF, 8.3%). Alternative site pacing at the RA septum versus conventional RA appendage (hazard ratio=1.18; 95% confidence interval, 0.79-1.75; P=0.65) or continuous atrial overdrive pacing ON versus OFF (hazard ratio=1.17; 95% confidence interval, 0.79-1.74; P=0.69) did not prevent the development of persistent AF. In patients with paroxysmal AF and sick sinus syndrome requiring pacemaker implantation, an alternative atrial pacing site at the RA septum or continuous atrial overdrive pacing did not prevent the development of persistent AF. URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00419640.

Progress of Diabetic Severity and Risk of Dementia.

PubMed

Chiu, Wei-Che; Ho, Wen-Chao; Liao, Ding-Lieh; Lin, Meng-Hung; Chiu, Chih-Chiang; Su, Yu-Ping; Chen, Pau-Chung

2015-08-01

Diabetes is a risk factor for dementia, but the effects of diabetic severity on dementia are unclear. The purpose of this study was to investigate the association between the severity and progress of diabetes and the risk of dementia. We conducted a 12-year population-based cohort study of new-onset diabetic patients from the Taiwan National Health Insurance Research Database. The diabetic severity was evaluated by the adapted Diabetes Complications Severity Index (aDCSI) from the prediabetic period to the end of follow-up. Cox proportional hazard regressions were used to calculate the hazard ratios (HRs) of the scores and change in the aDCSI. Participants were 431,178 new-onset diabetic patients who were older than 50 years and had to receive antidiabetic medications. Dementia cases were identified by International Classification of Diseases, ninth revision, code (International Classification of Diseases, ninth revision, codes 290.0, 290.1, 290.2, 290.3, 290.4, 294.1, 331.0), and the date of the initial dementia diagnosis was used as the index date. The scores and change in the aDCSI were associated with the risk of dementia when adjusting for patient factors, comorbidity, antidiabetic drugs, and drug adherence. At the end of the follow-up, the risks for dementia were 1.04, 1.40, 1.54, and 1.70 (P < .001 for trend) in patients with an aDCSI score of 1, 2, 3, and greater than 3, respectively. Compared with the mildly progressive patients, the adjusted HRs increased as the aDCSI increased (2 y HRs: 1.30, 1.53, and 1.97; final HRs: 2.38, 6.95, and 24.0 with the change in the aDCSI score per year: 0.51-1.00, 1.01-2.00, and > 2.00 vs < 0.50 with P < .001 for trend). The diabetic severity and progression reflected the risk of dementia, and the early change in the aDCSI could predict the risk of dementia in new-onset diabetic patients.

Current and future trends of Volcanology in Italy and abroad

NASA Astrophysics Data System (ADS)

Papale, P.

2010-12-01

Volcanology in Italy and in the world has rapidly developed during last decades. In the Seventies, stratigraphy and petrology provided the basic knowledge on the volcanic activities that still forms the root for modern volcano research. During the Eighties and Nineties the interest was more on the quantitative description of the volcanic processes, with enormous progresses in different but complementary fields including laboratory measurements and experiments, physico-mathematical modeling and numerical simulations, geophysical surveys and inverse analysis, and volcano monitoring and surveillance. In year 2000 a large number of magma properties and magmatic and volcanic processes was characterized at a first or higher order. Volcano research in Italy during the first decade of the new millennium has further developed along those lines. To-date, the very high risk Campi Flegrei and Vesuvius volcanoes, and the less risky but permanently active Etna and Stromboli volcanoes, are among the best monitored and more deeply investigated worldwide. The last decade has also seen coordinated efforts aimed at exploring exploitation of knowledge and skills for the benefit of the society. A series of projects focused on volcanic hazard and risk have joined >1000 researchers from Italian and foreign (Europe, US, Japan) Universities and Research Centers, on themes and objectives jointly defined by scientists from INGV and end-users from the national Civil Protection Department. These projects provide a global picture of volcano research in year 2010, that appears to be evolving through i) further rapid developments in the fields of investigation listed above, ii) their merging into effective multidisciplinary approaches, and iii) the full inclusion of the concepts of uncertainty and probabilities in volcanic scenario predictions and hazard forecast. The latter reflects the large inaccessibility of the volcanic systems, the extreme non-linear behaviour of volcanic processes put in light by the numerical studies, and the need of communicating in a formal and structured way the uncertain nature of volcanic predictions to emergency management authorities. Projections to year 2020 suggest a progressive relevance of structured volcano databases, that will provide large-scale sharing of basic knowledge and data for statistical analyses as for epidemiological databases in medicine; full coverage of the frequency range of geophysical and geochemical signals at active volcanoes, today not yet fully achieved; the development of standard volcano models and of global volcano simulator resources and tools, allowing separate sets of observations to be organized in a consistent global picture of the volcano dynamics; the further development of methods for the evaluation of probabilistic scenarios and their organization in event tree systems and hazard forecasting tools; the creation of large-scale volcano infrastructures for sharing of laboratory and computational resources; and the definition of international best practices for volcanic hazard and risk evaluation and for emergency preparedness and response activities. Recent initiatives in Italy and Europe (e.g., EPOS, DIVO, INGV-DPC, Exploris, and others) are developing largely along those lines, providing a view of the expected progresses in volcanology in the next decade.

Using hazard maps to identify and eliminate workplace hazards: a union-led health and safety training program.

PubMed

Anderson, Joe; Collins, Michele; Devlin, John; Renner, Paul

2012-01-01

The Institute for Sustainable Work and Environment and the Utility Workers Union of America worked with a professional evaluator to design, implement, and evaluate the results of a union-led system of safety-based hazard identification program that trained workers to use hazard maps to identify workplace hazards and target them for elimination. The evaluation documented program implementation and impact using data collected from both qualitative interviews and an on-line survey from worker trainers, plant managers, and health and safety staff. Managers and workers reported that not only were many dangerous hazards eliminated as a result of hazard mapping, some of which were long-standing, difficult-to-resolve issues, but the evaluation also documented improved communication between union members and management that both workers and managers agreed resulted in better, more sustainable hazard elimination.

a model based on crowsourcing for detecting natural hazards

NASA Astrophysics Data System (ADS)

Duan, J.; Ma, C.; Zhang, J.; Liu, S.; Liu, J.

2015-12-01

Remote Sensing Technology provides a new method for the detecting,early warning,mitigation and relief of natural hazards. Given the suddenness and the unpredictability of the location of natural hazards as well as the actual demands for hazards work, this article proposes an evaluation model for remote sensing detecting of natural hazards based on crowdsourcing. Firstly, using crowdsourcing model and with the help of the Internet and the power of hundreds of millions of Internet users, this evaluation model provides visual interpretation of high-resolution remote sensing images of hazards area and collects massive valuable disaster data; secondly, this evaluation model adopts the strategy of dynamic voting consistency to evaluate the disaster data provided by the crowdsourcing workers; thirdly, this evaluation model pre-estimates the disaster severity with the disaster pre-evaluation model based on regional buffers; lastly, the evaluation model actuates the corresponding expert system work according to the forecast results. The idea of this model breaks the boundaries between geographic information professionals and the public, makes the public participation and the citizen science eventually be realized, and improves the accuracy and timeliness of hazards assessment results.

Coffee and tea consumption in relation to prostate cancer prognosis

PubMed Central

Geybels, Milan S.; Neuhouser, Marian L.; Wright, Jonathan L.; Stott-Miller, Marni; Stanford, Janet L.

2013-01-01

Background Bioactive compounds found in coffee and tea may delay the progression of prostate cancer. Methods We investigated associations of pre-diagnostic coffee and tea consumption with risk of prostate cancer recurrence/progression. Study participants were men diagnosed with prostate cancer in 2002–2005 in King County, Washington, USA. We assessed the usual pattern of coffee and tea consumption two years before diagnosis date. Prostate cancer outcome events were identified using a detailed follow-up survey. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results The analysis of coffee intake in relation to prostate cancer recurrence/progression included 630 patients with a median follow-up of 6.4 years, during which 140 prostate cancer recurrence/progression events were recorded. Approximately 61% of patients consumed at least one cup of coffee per day. Coffee consumption was associated with a reduced risk of prostate cancer recurrence/progression; the adjusted HR for ≥4 cups/day versus ≤1 cup/week was 0.41 (95% CI: 0.20, 0.81; P for trend = 0.01). Approximately 14% of patients consumed one or more cups of tea per day, and tea consumption was unrelated to prostate cancer recurrence/progression. Conclusion Results indicate that pre-diagnostic coffee consumption is associated with a lower risk of prostate cancer recurrence/progression. This finding will require replication in larger studies. PMID:23907772

Diabetes mellitus and Parkinson disease.

PubMed

Pagano, Gennaro; Polychronis, Sotirios; Wilson, Heather; Giordano, Beniamino; Ferrara, Nicola; Niccolini, Flavia; Politis, Marios

2018-05-08

To investigate whether diabetes mellitus is associated with Parkinson-like pathology in people without Parkinson disease and to evaluate the effect of diabetes mellitus on markers of Parkinson pathology and clinical progression in drug-naive patients with early-stage Parkinson disease. We compared 25 patients with Parkinson disease and diabetes mellitus to 25 without diabetes mellitus, and 14 patients with diabetes mellitus and no Parkinson disease to 14 healthy controls (people with no diabetes mellitus or Parkinson disease). The clinical diagnosis of diabetes mellitus was confirmed by 2 consecutive fasting measurements of serum glucose levels >126 mL/dL. Over a 36-month follow-up period, we then investigated in the population with Parkinson disease whether the presence of diabetes mellitus was associated with faster motor progression or cognitive decline. The presence of diabetes mellitus was associated with higher motor scores ( p < 0.01), lower striatal dopamine transporter binding ( p < 0.05), and higher tau CSF levels ( p < 0.05) in patients with Parkinson disease. In patients with diabetes but without Parkinson disease, the presence of diabetes mellitus was associated with lower striatal dopamine transporter binding ( p < 0.05) and higher tau ( p < 0.05) and α-synuclein ( p < 0.05) CSF levels compared to healthy controls. At the Cox survival analysis in the population of patients with Parkinson disease, the presence of diabetes mellitus was associated with faster motor progression (hazard ratio = 4.521, 95% confidence interval = 1.468-13.926; p < 0.01) and cognitive decline (hazard ratio = 9.314, 95% confidence interval = 1.164-74.519; p < 0.05). Diabetes mellitus may predispose toward a Parkinson-like pathology, and when present in patients with Parkinson disease, can induce a more aggressive phenotype. © 2018 American Academy of Neurology.

Calcium-Sensing Receptor Tumor Expression and Lethal Prostate Cancer Progression.

PubMed

Ahearn, Thomas U; Tchrakian, Nairi; Wilson, Kathryn M; Lis, Rosina; Nuttall, Elizabeth; Sesso, Howard D; Loda, Massimo; Giovannucci, Edward; Mucci, Lorelei A; Finn, Stephen; Shui, Irene M

2016-06-01

Prostate cancer metastases preferentially target bone, and the calcium-sensing receptor (CaSR) may play a role in promoting this metastatic progression. We evaluated the association of prostate tumor CaSR expression with lethal prostate cancer. A validated CaSR immunohistochemistry assay was performed on tumor tissue microarrays. Vitamin D receptor (VDR) expression and phosphatase and tensin homolog tumor status were previously assessed in a subset of cases by immunohistochemistry. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and pathological tumor node metastasis stage were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of CaSR expression with lethal prostate cancer. The investigation was conducted in the Health Professionals Follow-up Study and Physicians' Health Study. We studied 1241 incident prostate cancer cases diagnosed between 1983 and 2009. Participants were followed up or cancer-specific mortality or development of metastatic disease. On average, men were followed up 13.6 years, during which there were 83 lethal events. High CaSR expression was associated with lethal prostate cancer independent of clinical and pathological variables (HR 2.0; 95% CI 1.2-3.3). Additionally, there was evidence of effect modification by VDR expression; CaSR was associated with lethal progression among men with low tumor VDR expression (HR 3.2; 95% CI 1.4-7.3) but not in cases with high tumor VDR expression (HR 0.8; 95% CI 0.2-3.0). Tumor CaSR expression is associated with an increased risk of lethal prostate cancer, particularly in tumors with low VDR expression. These results support further investigating the mechanism linking CaSR with metastases.

Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration.

PubMed

Merle, Bénédicte M J; Silver, Rachel E; Rosner, Bernard; Seddon, Johanna M

2017-09-01

There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but no prospective studies have explored the impact of vitamin D. We evaluated the association between vitamin D intake and progression to advanced AMD. Among 2146 participants (3965 eyes), 541 (777 eyes) progressed from early or intermediate AMD to advanced disease (mean follow-up: 9.4 years) based on ocular imaging. Nutrients were log transformed and calorie adjusted. Survival analysis was used to assess associations between incident advanced disease and vitamin D intake. Neovascular disease (NV) and geographic atrophy (GA) were evaluated separately. Combined effects of dietary vitamin D and calcium were assessed based on high or low consumption of each nutrient. There was a lower risk of progression to advanced AMD in the highest versus lowest quintile of dietary vitamin D intake after adjustment for demographic, behavioral, ocular, and nutritional factors (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43-0.83; P trend = 0.0007). Similar results were observed for NV (HR: 0.59; 95% CI: 0.39-0.89; P trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53-1.30; P trend = 0.35). A protective effect was observed for advanced AMD among participants with high vitamin D and low calcium compared to the group with low levels for each nutrient (HR: 0.67; 95% CI: 0.50-0.88; P = 0.005). When supplement use was considered, the effect was in the protective direction but was not significant. A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially NV. Additional exploration is needed to elucidate the potential protective role of vitamin D and its contribution to reducing visual loss.

Progression rate from new-onset pre-hypertension to hypertension in Korean adults.

PubMed

Kim, Soo Jeong; Lee, Jakyoung; Nam, Chung Mo; Jee, Sun Ha; Park, Il Soo; Lee, Kyung Jong; Lee, Soon Young

2011-01-01

There are limited studies conducted in Asia to investigate the progression rate to hypertension (HTN). This study was done to estimate the progression rate of new-onset pre-HTN (PreHTN) to HTN during an 8-year follow-up period, and to compare the impact of PreHTN on progression to HTN. A total of 49,228 participants, aged 30 to 54 years with new-onset PreHTN at baseline (1994-1996) from a biennial national medical exam were enrolled and followed up every 2 years until 2004. The incidence rate recorded at each interval and the cumulative incidence rate of HTN were analyzed. Hazard ratio of high-normal and high blood pressure (BP) in men and women was calculated. The cumulative incidence rate for high-normal BP was 27.6% and 26.4% at 2-year follow-up, increased to respectively 64.1% and 55.8% in men and women at the 8-year follow-up. Compared to optimal BP, hazard ratios for men with high-normal BP across all age groups were 3- to 4-fold higher at 2-year, and 2- to 3-fold higher at 8-year follow-up. Hazard ratios for women were about 6-fold higher at 2-year and around 4-fold higher at 8-year follow-up. New PreHTN was a significant predisposing factor for future HTN, in young adults and the effect is more prominent in women.

Environmental hazards assessment program. Annual report, July 1, 1994--June 30, 1995

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

NONE

1995-07-31

This report describes activities and reports on progress for the third year of the DOE grant to support the Environmental Hazards Assessment Program (EHAP). It reports progress against grant objectives and the Program Implementation Plan published at the end of the first year of the grant. As the program has evolved, more projects have been funded and many existing projects have become more complex. Thus, to accomplish better the objectives over the years and retain a solid focus on the total mission, we have reorganized the grant effort from three to five majoe elements: Public and professional outreach; Clinical programs;more » Science programs; Information systems; and, Program management.« less

Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal.

PubMed

Mocroft, Amanda; Sterne, Jonathan A C; Egger, Matthias; May, Margaret; Grabar, Sophie; Furrer, Hansjakob; Sabin, Caroline; Fatkenheuer, Gerd; Justice, Amy; Reiss, Peter; d'Arminio Monforte, Antonella; Gill, John; Hogg, Robert; Bonnet, Fabrice; Kitahata, Mari; Staszewski, Schlomo; Casabona, Jordi; Harris, Ross; Saag, Michael

2009-04-15

The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of antiretroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a "rare ADEs" category. During a median follow-up period of 43 months (interquartile range, 19-70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin's lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84-22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70-14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin's lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55-9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76-3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08-2.00]). In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management.

The influence of background diabetic retinopathy in the second eye on rates of progression of diabetic retinopathy between 2005 and 2010.

PubMed

Scanlon, Peter H; Stratton, Irene M; Histed, Mark; Chave, Steve J; Aldington, Stephen J

2013-08-01

The Gloucestershire Diabetic Eye Screening Programme offers annual digital photographic screening for diabetic retinopathy to a countywide population of people with diabetes. This study was designed to investigate progression of diabetic retinopathy in this programme of the English NHS Diabetic Eye Screening Programme. Mydriatic digital retinal photographs of people with diabetes screened on at least 2 occasions between 2005 and 2010 were graded and included in this study if the classification at first screening was no DR (R0), background DR in one (R1a) or both eyes (R1b). Times to detection of referable diabetic retinopathy (RDR) comprising maculopathy (M1), preproliferative (R2) or proliferative retinopathy (R3) were analysed using survival models. Data were available on 19 044 patients, 56% men, age at screening 66 (57-74) years (median, 25th, 75th centile). A total of 8.3% of those with R1a and 28.2% of those with R1b progressed to any RDR, hazard ratios 2.9 [2.5-3.3] and 11.3 [10.0-12.8]. Similarly 7.1% and 0.11% of those with R1a progressed to M1 and R3, hazard ratios 2.7 [2.3-3.2] and 1.6 [0.5-5.0], compared to 21.8% and 1.07% of those with R1b, hazard ratio 9.1 [7.8-10.4] and 15.0 [7.1-31.5]. The risk of progression is significantly higher for those with background DR in both eyes than those with background retinopathy in only one or in neither eye. © 2013 The Authors Acta Ophthalmologica © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by Blackwell Publishing Ltd.

The international workshop on wave hindcasting and forecasting and the coastal hazards symposium

NASA Astrophysics Data System (ADS)

Breivik, Øyvind; Swail, Val; Babanin, Alexander V.; Horsburgh, Kevin

2015-05-01

Following the 13th International Workshop on Wave Hindcasting and Forecasting and 4th Coastal Hazards Symposium in October 2013 in Banff, Canada, a topical collection has appeared in recent issues of Ocean Dynamics. Here, we give a brief overview of the history of the conference since its inception in 1986 and of the progress made in the fields of wind-generated ocean waves and the modelling of coastal hazards before we summarize the main results of the papers that have appeared in the topical collection.

40 CFR 161.108 - Relationship of Pesticide Assessment Guidelines to data requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... - 161.190 E Hazard Evaluation: Wildlife and Aquatic Organisms PB83-153908 161.490 F Hazard Evaluation... Use Permits PB83-153932 161.20 - 161.640 J Hazard Evaluation: Nontarget Plants PB83-153940 161.540 K...

New Elements To Consider When Modeling the Hazards Associated with Botulinum Neurotoxin in Food.

PubMed

Ihekwaba, Adaoha E C; Mura, Ivan; Malakar, Pradeep K; Walshaw, John; Peck, Michael W; Barker, G C

2016-01-15

Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the most potent biological substances known to mankind. BoNTs are the agents responsible for botulism, a rare condition affecting the neuromuscular junction and causing a spectrum of diseases ranging from mild cranial nerve palsies to acute respiratory failure and death. BoNTs are a potential biowarfare threat and a public health hazard, since outbreaks of foodborne botulism are caused by the ingestion of preformed BoNTs in food. Currently, mathematical models relating to the hazards associated with C. botulinum, which are largely empirical, make major contributions to botulinum risk assessment. Evaluated using statistical techniques, these models simulate the response of the bacterium to environmental conditions. Though empirical models have been successfully incorporated into risk assessments to support food safety decision making, this process includes significant uncertainties so that relevant decision making is frequently conservative and inflexible. Progression involves encoding into the models cellular processes at a molecular level, especially the details of the genetic and molecular machinery. This addition drives the connection between biological mechanisms and botulism risk assessment and hazard management strategies. This review brings together elements currently described in the literature that will be useful in building quantitative models of C. botulinum neurotoxin production. Subsequently, it outlines how the established form of modeling could be extended to include these new elements. Ultimately, this can offer further contributions to risk assessments to support food safety decision making. Copyright © 2015 Ihekwaba et al.

Topical Hazard Evaluation Program of Candidate Insect Repellent AI3-20816-a, US Department of Agriculture Proprietary Compound, September 1978-November 1980.

DTIC Science & Technology

1981-02-11

GROUND, MD 21010 TOPICAL HAZARD EVALUATION PROGRAM OF CANDIDATE INSECT REPELLENT AI 3- 20816 -aUS DEPARTMENT OF AGRICULTURE PROPRIETARY COMPOUND STUDY NO...irritation A13- 20816 -a Photochemical irritation Topical Hazard Evaluation Sensitization Candidate repellent ALD Skin irritation 20. ABSTRACT (Continue an...reverse e e if necessary and identify by block number) A hazard evaluation of candidate insect repellent A13- 20816 -a was performed by means of laboratory

Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC.

PubMed

Socinski, Mark A; Jotte, Robert M; Cappuzzo, Federico; Orlandi, Francisco; Stroyakovskiy, Daniil; Nogami, Naoyuki; Rodríguez-Abreu, Delvys; Moro-Sibilot, Denis; Thomas, Christian A; Barlesi, Fabrice; Finley, Gene; Kelsch, Claudia; Lee, Anthony; Coleman, Shelley; Deng, Yu; Shen, Yijing; Kowanetz, Marcin; Lopez-Chavez, Ariel; Sandler, Alan; Reck, Martin

2018-06-04

Background The cancer-cell-killing property of atezolizumab may be enhanced by the blockade of vascular endothelial growth factor-mediated immunosuppression with bevacizumab. This open-label, phase 3 study evaluated atezolizumab plus bevacizumab plus chemotherapy in patients with metastatic nonsquamous non-small-cell lung cancer (NSCLC) who had not previously received chemotherapy. Methods We randomly assigned patients to receive atezolizumab plus carboplatin plus paclitaxel (ACP), bevacizumab plus carboplatin plus paclitaxel (BCP), or atezolizumab plus BCP (ABCP) every 3 weeks for four or six cycles, followed by maintenance therapy with atezolizumab, bevacizumab, or both. The two primary end points were investigator-assessed progression-free survival both among patients in the intention-to-treat population who had a wild-type genotype (WT population; patients with EGFR or ALK genetic alterations were excluded) and among patients in the WT population who had high expression of an effector T-cell (Teff) gene signature in the tumor (Teff-high WT population) and overall survival in the WT population. The ABCP group was compared with the BCP group before the ACP group was compared with the BCP group. Results In the WT population, 356 patients were assigned to the ABCP group, and 336 to the BCP group. The median progression-free survival was longer in the ABCP group than in the BCP group (8.3 months vs. 6.8 months; hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.52 to 0.74; P<0.001); the corresponding values in the Teff-high WT population were 11.3 months and 6.8 months (hazard ratio, 0.51 [95% CI, 0.38 to 0.68]; P<0.001). Progression-free survival was also longer in the ABCP group than in the BCP group in the entire intention-to-treat population (including those with EGFR or ALK genetic alterations) and among patients with low or negative programmed death ligand 1 (PD-L1) expression, those with low Teff gene-signature expression, and those with liver metastases. Median overall survival among the patients in the WT population was longer in the ABCP group than in the BCP group (19.2 months vs. 14.7 months; hazard ratio for death, 0.78; 95% CI, 0.64 to 0.96; P=0.02). The safety profile of ABCP was consistent with previously reported safety risks of the individual medicines. Conclusions The addition of atezolizumab to bevacizumab plus chemotherapy significantly improved progression-free survival and overall survival among patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression and EGFR or ALK genetic alteration status. (Funded by F. Hoffmann-La Roche/Genentech; IMpower150 ClinicalTrials.gov number, NCT02366143 .).

Weapons of Mass Destruction Technology Evaluation and Training Range

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

Kevin Larry Young

2009-05-01

The Idaho National Laboratory (INL) has a long history for providing technology evaluation and training for military and other federal level Weapons of Mass Destruction (WMD) response agencies. Currently there are many federal organizations and commercial companies developing technologies related to detecting, assessing, mitigating and protecting against hazards associated with a WMD event. Unfortunately, very few locations exist within the United States where WMD response technologies are realistically field tested and evaluated using real chemical, biological, radiological, nuclear and explosive materials. This is particularly true with biological and radiological hazards. Related to this lack of adequate WMD, multi-hazard technology testingmore » capability is the shortage of locations where WMD response teams can train using actual chemical, biological, and radiological material or highly realistic simulates. In response to these technology evaluation and training needs, the INL has assembled a consortium of subject matter experts from existing programs and identified dedicated resources for the purpose of establishing an all-hazards, WMD technology evaluation and training range. The author describes the challenges associated with creating the all-hazards WMD technology evaluation and training range and lists the technical, logistical and financial benefits of an all-hazards technology evaluation and training range. Current resources and capabilities for conducting all-hazard technology evaluation and training at the INL are identified. Existing technology evaluation and training programs at the INL related to radiological, biological and chemical hazards are highlighted, including successes and lessons learned. Finally, remaining gaps in WMD technology evaluation and training capabilities are identified along with recommendations for closing those gaps.« less

Prediction of time to delivery by transperineal ultrasound in second stage of labor.

PubMed

Yonetani, N; Yamamoto, R; Murata, M; Nakajima, E; Taguchi, T; Ishii, K; Mitsuda, N

2017-02-01

To investigate whether the transperineal sonographic (TPS) parameters angle of progression (AoP) and midline angle (MLA) can predict the time remaining in the second stage of labor. We evaluated prospectively women with a singleton pregnancy in cephalic presentation at term between October 2013 and September 2014. TPS volumes were obtained immediately after confirmation by digital vaginal examination of a fully dilated cervix. AoP and MLA were measured offline by analyzing the ultrasound volumes. Progression of labor was evaluated every hour during the second stage. The associations of AoP and MLA with the interval between TPS assessment and delivery were evaluated using multivariable Cox proportional hazards analyses in nulliparous and parous women separately. A total of 557 women were evaluated. An AoP ≥ 160° (adjusted hazard ratio (aHR), 2.52 (95% CI, 1.98-3.19)) and MLA ≤ 10° (aHR, 1.79 (95% CI, 1.35-2.34)) in nulliparous women and an AoP ≥ 150° (aHR, 1.86 (95% CI, 1.34-2.57)) and MLA ≤ 20° (aHR, 1.69 (95% CI, 1.21-2.34)) in parous women were significantly associated with the remaining time in labor. The positive/negative likelihood ratios of AoP, MLA, clinical station (fetal head descent as observed by digital examination) and clinical rotation (fetal head rotation as observed by digital examination) at these cut-off points were 3.6/0.6, 2.0/0.6, 1.6/0.6 and 1.6/0.8, respectively, in nulliparous women, and 2.4/0.6, 1.3/0.7, 7.6/0.5 and 5.2/0.7, respectively, in parous women. TPS assessment of AoP and MLA in the second stage of labor was useful for predicting the time remaining in labor and had higher predictive value than did digital vaginal examination in nulliparous women. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer.

PubMed

Carducci, Michael A; Saad, Fred; Abrahamsson, Per-Anders; Dearnaley, David P; Schulman, Claude C; North, Scott A; Sleep, Darryl J; Isaacson, Jeffrey D; Nelson, Joel B

2007-11-01

The objective of this study was to evaluate the efficacy and safety of atrasentan (Xinlay), a selective endothelin-A receptor antagonist, in patients with metastatic hormone-refractory prostate cancer (HRPC). This multinational, double-blind, placebo-controlled trial enrolled 809 men with metastatic HRPC. Patients were randomized 1:1 to receive either atrasentan 10 mg per day or placebo. The primary endpoint was time to disease progression (TTP), which was determined according to radiographic and clinical measures. Analyses of overall survival and changes in biomarkers also were performed. Atrasentan did not reduce the risk of disease progression relative to placebo (hazards ratio, 0.89; 95% confidence interval, 0.76-1.04; P = .136). Most patients progressed radiographically at the first 12-week bone scan without concomitant clinical progression. In exploratory analyses, increases from baseline to final bone alkaline phosphatase (BAP) and prostate-specific antigen (PSA) levels were significantly lower with atrasentan treatment (P < .05 for each). The median time to BAP progression (>/=50% increase from nadir) was twice as long with atrasentan treatment (505 days vs 254 days; P < .01). The delay in time to PSA progression did not reach statistical significance. Atrasentan generally was tolerated well, and the most common adverse events associated with treatment were headache, rhinitis, and peripheral edema, reflecting the vasodilatory and fluid-retention properties of endothelin-A receptor antagonism. Atrasentan did not delay disease progression in men with metastatic HRPC despite evidence of biologic effects on PSA and BAP as markers of disease burden.

Design and evaluation guidelines for Department of Energy facilities subjected to natural phenomena hazards

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

Kennedy, R.P.; Short, S.A.; McDonald, J.R.

1990-06-01

The Department of Energy (DOE) and the DOE Natural Phenomena Hazards Panel have developed uniform design and evaluation guidelines for protection against natural phenomena hazards at DOE sites throughout the United States. The goal of the guidelines is to assure that DOE facilities can withstand the effects of natural phenomena such as earthquakes, extreme winds, tornadoes, and flooding. The guidelines apply to both new facilities (design) and existing facilities (evaluation, modification, and upgrading). The intended audience is primarily the civil/structural or mechanical engineers conducting the design or evaluation of DOE facilities. The likelihood of occurrence of natural phenomena hazards atmore » each DOE site has been evaluated by the DOE Natural Phenomena Hazard Program. Probabilistic hazard models are available for earthquake, extreme wind/tornado, and flood. Alternatively, site organizations are encouraged to develop site-specific hazard models utilizing the most recent information and techniques available. In this document, performance goals and natural hazard levels are expressed in probabilistic terms, and design and evaluation procedures are presented in deterministic terms. Design/evaluation procedures conform closely to common standard practices so that the procedures will be easily understood by most engineers. Performance goals are expressed in terms of structure or equipment damage to the extent that: (1) the facility cannot function; (2) the facility would need to be replaced; or (3) personnel are endangered. 82 refs., 12 figs., 18 tabs.« less

A GHS-consistent approach to health hazard classification of petroleum substances, a class of UVCB substances.

PubMed

Clark, Charles R; McKee, Richard H; Freeman, James J; Swick, Derek; Mahagaokar, Suneeta; Pigram, Glenda; Roberts, Linda G; Smulders, Chantal J; Beatty, Patrick W

2013-12-01

The process streams refined from petroleum crude oil for use in petroleum products are among those designated by USEPA as UVCB substances (unknown or variable composition, complex reaction products and biological materials). They are identified on global chemical inventories with unique Chemical Abstract Services (CAS) numbers and names. The chemical complexity of most petroleum substances presents challenges when evaluating their hazards and can result in differing evaluations due to the varying level of hazardous constituents and differences in national chemical control regulations. Global efforts to harmonize the identification of chemical hazards are aimed at promoting the use of consistent hazard evaluation criteria. This paper discusses a systematic approach for the health hazard evaluation of petroleum substances using chemical categories and the United Nations (UN) Globally Harmonized System (GHS) of classification and labeling. Also described are historical efforts to characterize the hazard of these substances and how they led to the development of categories, the identification of potentially hazardous constituents which should be considered, and a summary of the toxicology of the major petroleum product groups. The use of these categories can increase the utility of existing data, provide better informed hazard evaluations, and reduce the amount of animal testing required. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Predicting the onset of hazardous alcohol drinking in primary care: development and validation of a simple risk algorithm.

PubMed

Bellón, Juan Ángel; de Dios Luna, Juan; King, Michael; Nazareth, Irwin; Motrico, Emma; GildeGómez-Barragán, María Josefa; Torres-González, Francisco; Montón-Franco, Carmen; Sánchez-Celaya, Marta; Díaz-Barreiros, Miguel Ángel; Vicens, Catalina; Moreno-Peral, Patricia

2017-04-01

Little is known about the risk of progressing to hazardous alcohol use in abstinent or low-risk drinkers. To develop and validate a simple brief risk algorithm for the onset of hazardous alcohol drinking (HAD) over 12 months for use in primary care. Prospective cohort study in 32 health centres from six Spanish provinces, with evaluations at baseline, 6 months, and 12 months. Forty-one risk factors were measured and multilevel logistic regression and inverse probability weighting were used to build the risk algorithm. The outcome was new occurrence of HAD during the study, as measured by the AUDIT. From the lists of 174 GPs, 3954 adult abstinent or low-risk drinkers were recruited. The 'predictAL-10' risk algorithm included just nine variables (10 questions): province, sex, age, cigarette consumption, perception of financial strain, having ever received treatment for an alcohol problem, childhood sexual abuse, AUDIT-C, and interaction AUDIT-C*Age. The c-index was 0.886 (95% CI = 0.854 to 0.918). The optimal cutoff had a sensitivity of 0.83 and specificity of 0.80. Excluding childhood sexual abuse from the model (the 'predictAL-9'), the c-index was 0.880 (95% CI = 0.847 to 0.913), sensitivity 0.79, and specificity 0.81. There was no statistically significant difference between the c-indexes of predictAL-10 and predictAL-9. The predictAL-10/9 is a simple and internally valid risk algorithm to predict the onset of hazardous alcohol drinking over 12 months in primary care attendees; it is a brief tool that is potentially useful for primary prevention of hazardous alcohol drinking. © British Journal of General Practice 2017.

Predicting the onset of hazardous alcohol drinking in primary care: development and validation of a simple risk algorithm

PubMed Central

Bellón, Juan Ángel; de Dios Luna, Juan; King, Michael; Nazareth, Irwin; Motrico, Emma; GildeGómez-Barragán, María Josefa; Torres-González, Francisco; Montón-Franco, Carmen; Sánchez-Celaya, Marta; Díaz-Barreiros, Miguel Ángel; Vicens, Catalina; Moreno-Peral, Patricia

2017-01-01

Background Little is known about the risk of progressing to hazardous alcohol use in abstinent or low-risk drinkers. Aim To develop and validate a simple brief risk algorithm for the onset of hazardous alcohol drinking (HAD) over 12 months for use in primary care. Design and setting Prospective cohort study in 32 health centres from six Spanish provinces, with evaluations at baseline, 6 months, and 12 months. Method Forty-one risk factors were measured and multilevel logistic regression and inverse probability weighting were used to build the risk algorithm. The outcome was new occurrence of HAD during the study, as measured by the AUDIT. Results From the lists of 174 GPs, 3954 adult abstinent or low-risk drinkers were recruited. The ‘predictAL-10’ risk algorithm included just nine variables (10 questions): province, sex, age, cigarette consumption, perception of financial strain, having ever received treatment for an alcohol problem, childhood sexual abuse, AUDIT-C, and interaction AUDIT-C*Age. The c-index was 0.886 (95% CI = 0.854 to 0.918). The optimal cutoff had a sensitivity of 0.83 and specificity of 0.80. Excluding childhood sexual abuse from the model (the ‘predictAL-9’), the c-index was 0.880 (95% CI = 0.847 to 0.913), sensitivity 0.79, and specificity 0.81. There was no statistically significant difference between the c-indexes of predictAL-10 and predictAL-9. Conclusion The predictAL-10/9 is a simple and internally valid risk algorithm to predict the onset of hazardous alcohol drinking over 12 months in primary care attendees; it is a brief tool that is potentially useful for primary prevention of hazardous alcohol drinking. PMID:28360074

32 CFR 179.6 - Procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Chemical Warfare Materiel Hazard Evaluation (CHE) module. (1) The CHE module provides an evaluation of the chemical hazards associated with the physiological effects of CWM. The CHE module is used only when CWM are... used for evaluating the potential hazards posed by MC and other chemical contaminants. The HHE module...

Evaluation of pseudoprogression rates and tumor progression patterns in a phase III trial of bevacizumab plus radiotherapy/temozolomide for newly diagnosed glioblastoma.

PubMed

Wick, Wolfgang; Chinot, Olivier L; Bendszus, Martin; Mason, Warren; Henriksson, Roger; Saran, Frank; Nishikawa, Ryo; Revil, Cedric; Kerloeguen, Yannick; Cloughesy, Timothy

2016-10-01

Evaluation of glioblastoma disease status may be complicated by treatment-induced changes and discordance between enhancing and nonenhancing MRI. Exploratory analyses are presented (prospectively assessed pseudoprogression and therapy-related tumor pattern changes) from the AVAglio trial (bevacizumab or placebo plus radiotherapy/temozolomide for newly diagnosed glioblastoma). MRI was done every 8 weeks (beginning 4 wk after chemoradiotherapy) using prespecified and standardized T1 and T2 protocols. Progressive disease (PD) at 10 weeks was reconfirmed at 18 weeks to distinguish pseudoprogression. Progression-free survival (PFS), excluding cases of confirmed pseudoprogression, was assessed (post-hoc/exploratory). Tumor progression patterns were determined at each disease assessment/PD (prespecified/exploratory). Of patients with PD in the bevacizumab and placebo arms, 143/354 (40.4%) and 155/387 (40.1%), respectively, had PD due to contrast-enhancing lesions, and 51/354 (14.4%) and 53/387 (13.7%) had PD due to nonenhancing lesions. Of all patients in the bevacizumab arm (n = 458), 2.2% had confirmed pseudoprogression versus 9.3% in the placebo arm (n = 463). Baseline characteristics did not differ between patients with/without pseudoprogression (including for MGMT status). Excluding confirmed pseudoprogression, PFS (hazard ratio: 0.65, 95% CI: 0.56-0.75; P < .0001, bevacizumab vs placebo) was comparable to the intent-to-treat population. At PD, most patients had the same tumor focus (local/multifocal, >84%) and infiltrative profile (>88%) as at baseline; no shift to a diffuse or multifocal phenotype was observed. Pseudoprogression complicated progression assessment in a small but relevant number of patients but had negligible impact on PFS. Bevacizumab did not appear to adversely impact tumor progression patterns. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Health-Related Quality of Life in a Randomized Phase III Study of Bevacizumab, Temozolomide, and Radiotherapy in Newly Diagnosed Glioblastoma.

PubMed

Taphoorn, Martin J B; Henriksson, Roger; Bottomley, Andrew; Cloughesy, Timothy; Wick, Wolfgang; Mason, Warren P; Saran, Frank; Nishikawa, Ryo; Hilton, Magalie; Theodore-Oklota, Christina; Ravelo, Arliene; Chinot, Olivier L

2015-07-01

As glioblastoma progresses, patients experience a decline in health-related quality of life (HRQoL). Delaying this decline is an important treatment goal. In newly diagnosed glioblastoma, progression-free survival was prolonged when bevacizumab was added to radiotherapy plus temozolomide (RT/TMZ) versus placebo plus RT/TMZ (phase III AVAglio study; hazard ratio, 0.64; 95% CI, 0.55 to 0.74; P < .001). To ensure that addition of bevacizumab to standard-of-care therapy was not associated with HRQoL detriment, HRQoL assessment was a secondary objective. Patients completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BN20 at each tumor assessment (Appendix Table A1, online only). Raw scores were converted to a 100-point scale and mean changes from baseline scores were evaluated (stable: < 10-point change; clinically relevant deterioration/improvement: ≥ 10-point change). Deterioration-free survival was the time to deterioration/progression/death; time to deterioration was the time to deterioration/death. Most evaluable patients who had not progressed (> 74%) completed all HRQoL assessments for at least 1 year of treatment, and almost all completed at least one HRQoL assessment at baseline (98.3% and 97.6%, bevacizumab and placebo arms, respectively). Mean changes from baseline did not reach a clinically relevant difference between arms for most items. HRQoL declined at progression in both arms. The addition of bevacizumab to RT/TMZ resulted in statistically longer (P < .001) deterioration-free survival across all items. Time to deterioration was not statistically longer in the placebo plus RT/TMZ arm (v bevacizumab) for any HRQoL item. The addition of bevacizumab to standard-of-care treatment for newly diagnosed glioblastoma had no impact on HRQoL during the progression-free period. © 2015 by American Society of Clinical Oncology.

Low-Risk Lifestyle, Coronary Calcium, Cardiovascular Events, and Mortality: Results From MESA

PubMed Central

Ahmed, Haitham M.; Blaha, Michael J.; Nasir, Khurram; Jones, Steven R.; Rivera, Juan J.; Agatston, Arthur; Blankstein, Ron; Wong, Nathan D.; Lakoski, Susan; Budoff, Matthew J.; Burke, Gregory L.; Sibley, Christopher T.; Ouyang, Pamela; Blumenthal, Roger S.

2013-01-01

Unhealthy lifestyle habits are a major contributor to coronary artery disease. The purpose of the present study was to investigate the associations of smoking, weight maintenance, physical activity, and diet with coronary calcium, cardiovascular events, and mortality. US participants who were 44–84 years of age (n = 6,229) were followed in the Multi-Ethnic Study of Atherosclerosis from 2000 to 2010. A lifestyle score ranging from 0 to 4 was created using diet, exercise, body mass index, and smoking status. Coronary calcium was measured at baseline and a mean of 3.1 (standard deviation, 1.3) years later to assess calcium progression. Participants who experienced coronary events or died were followed for a median of 7.6 (standard deviation, 1.5) years. Participants with lifestyle scores of 1, 2, 3, and 4 were found to have mean adjusted annual calcium progressions that were 3.5 (95% confidence interval (CI): 0.0, 7.0), 4.2 (95% CI: 0.6, 7.9), 6.8 (95% CI: 2.0, 11.5), and 11.1 (95% CI: 2.2, 20.1) points per year slower, respectively, relative to the reference group (P = 0.003). Unadjusted hazard ratios for death by lifestyle score were as follows: for a score of 1, the hazard ratio was 0.79 (95% CI: 0.61, 1.03); for a score of 2, the hazard ratio was 0.61 (95% CI: 0.46, 0.81); for a score of 3, the hazard ratio was 0.49 (95% CI: 0.32, 0.75); and for a score of 4, the hazard ratio was 0.19 (95% CI: 0.05, 0.75) (P < 0.001 by log-rank test). In conclusion, a combination of regular exercise, healthy diet, smoking avoidance, and weight maintenance was associated with lower coronary calcium incidence, slower calcium progression, and lower all-cause mortality over 7.6 years. PMID:23733562

Monitoring and forecasting local landslide hazard in the area of Longyearbyen, Svalbard - early progress and experiences from the Autumn 2016 events

NASA Astrophysics Data System (ADS)

Wang, Thea; Krøgli, Ingeborg; Boje, Søren; Colleuille, Hervé

2017-04-01

Since 2013 the Norwegian Water Resources and Energy Directorate (NVE) has operated a landslide early warning system (LEWS) for mainland Norway. The Svalbard islands, situated 800 km north of the Norwegian mainland, and 1200 km from the North Pole, are not part of the conventional early warning service. However, following the fatal snow avalanche event 19 Dec. 2015 in the settlement of Longyearbyen (78° north latitude), local authorities and the NVE have initiated monitoring of the hydro-meteorological conditions for the area of Longyearbyen, as an extraordinary precaution. Two operational forecasting teams from the NVE; the snow avalanche and the landslide hazard forecasters, perform hazard assessment related to snow avalanches, slush flows, debris flows, shallow slides and local flooding. This abstract will focus on recent experiences made by the landslide hazard team during the autumn 2016 landslide events, caused by a record setting wet and warm summer and autumn of 2016. The general concept of the Norwegian LEWS is based on frequency intervals of extreme hydro-meteorological conditions. This general concept has been transposed to the Longyearbyen area. Although the climate is considerably colder and drier than mainland Norway, experiences so far are positive and seem useful to the local authorities. Initially, the landslide hazard evaluation was intended to consider only slush flow hazard during the snow covered season. However, due to the extraordinary warm and wet summer and autumn 2016, the landslide hazard forecasters unexpectedly had to issue warnings for the local authorities due to increased risk of shallow landslides and debris flows. This was done in close cooperation with the Norwegian Meteorological Institute, who provided weather forecasts from the recently developed weather prediction model, AROME-Arctic. Two examples, from 14-15 Oct and 8-9 Nov 2016, will be given to demonstrate how the landslide hazard assessment for the Longyearbyen area is carried out. Several aspects contrast hazard monitoring and forecasting on the mainland, such as the challenges that transpire with sparse observations of hydrometeorologial variables, landslide inventories and hydrological simulations. Particular challenges that are faced on Svalbard, are the even greater remoteness of the settlements and the strong effect permafrost has on the soil structure. The planned development for improving the monitoring of slush avalanches and landslide hazards in the Longyearbyen area will also be presented.

Achievements and challenges of Space Station Freedom's safety review process

NASA Technical Reports Server (NTRS)

Robinson, David W.

1993-01-01

The most complex space vehicle in history, Space Station Freedom, is well underway to completion, and System Safety is a vital part of the program. The purpose is to summarize and illustrate the progress that over one-hundred System Safety engineers have made in identifying, documenting, and controlling the hazards inherent in the space station. To date, Space Station Freedom has been reviewed by NASA's safety panels through the first six assembly flights, when Freedom achieves a configuration known as Man Tended Capability. During the eight weeks of safety reviews spread out over a year and a half, over 200 preliminary hazard reports were presented. Along the way NASA and its contractors faced many challenges, made much progress, and even learned a few lessons.

Achievements and challenges of Space Station Freedom's safety review process

NASA Astrophysics Data System (ADS)

Robinson, David W.

1993-07-01

The most complex space vehicle in history, Space Station Freedom, is well underway to completion, and System Safety is a vital part of the program. The purpose is to summarize and illustrate the progress that over one-hundred System Safety engineers have made in identifying, documenting, and controlling the hazards inherent in the space station. To date, Space Station Freedom has been reviewed by NASA's safety panels through the first six assembly flights, when Freedom achieves a configuration known as Man Tended Capability. During the eight weeks of safety reviews spread out over a year and a half, over 200 preliminary hazard reports were presented. Along the way NASA and its contractors faced many challenges, made much progress, and even learned a few lessons.

Comparing counselling models for the hazardous use of alcohol at the Swedish National Alcohol Helpline: study protocol for a randomised controlled trial.

PubMed

Säfsten, Eleonor; Forsell, Yvonne; Ramstedt, Mats; Galanti, Maria Rosaria

2017-06-06

Hazardous and harmful consumption of alcohol is a leading cause of preventable disease and premature deaths. Modifying the amount and pattern of risky alcohol consumption conveys substantial benefits to individuals and to society at large. Telephone helplines provide a feasible alternative to face-to-face counselling in order to increase the reach of brief interventions aiming at modifying the hazardous and harmful use of alcohol. However, there is a lack of studies on the implementation and evaluation of population-based telephone services for the prevention and treatment of alcohol misuse. A randomised controlled trial was designed to compare a brief, structured intervention to usual care within the Swedish National Alcohol Helpline (SAH), concerning their effectiveness on decreasing the hazardous use of alcohol. Between May 2015 and December 2017, about 300 callers are to be individually randomised with a 1:1 ratio to a brief, structured intervention (n = 150) or to usual care (n = 150). The brief, structured intervention consists of the delivery of a self-help booklet followed by one proactive call from SAH counsellors to monitor and give feedback about the client's progression. Callers assigned to usual care receive telephone counselling according to existing practice, i.e., motivational interviewing in a tailored and client-driven combination of proactive and reactive calls. The primary outcome is defined as a change from a higher to a lower AUDIT risk-level category between baseline and follow-up. General linear modeling will be used to calculate risk ratios of the outcome events. The primary analysis will follow an intention-to-treat (ITT) approach. The trial is designed to evaluate the effectiveness in decreasing the hazardous and harmful consumption of alcohol of a brief, structured intervention compared to usual care when delivered at the SAH. The results of the study will be used locally to improve the effectiveness of the service provided at the SAH. Additionally, they will expand the evidence base about optimal counselling models in population-based telephone services for alcohol misuse prevention and treatment. ISRCNT.com, ID: ISRCTN13160878 . Retrospectively registered on 18 January 2016.

Development and Evaluation of Reproductive and Developmental Toxicity Tests for Assessing the Hazards of Environmental Contaminants

DTIC Science & Technology

1997-08-01

AL/EQ-TR-1997-0050 DEVELOPMENT AND EVALUATION OF REPRODUCTIVE AND DEVELOPMENT TOXICITY TESTS FOR ASSESSING THE HAZARDS OF ENVIRONMENTAL...SUBTITLE Development and Evaluation of Reproductive and Developmental Toxicity Tests for Assessing the Hazards of Environmental Contaminants 6...pd in testing toxicity in surface waters, ground waters and H- ™t™j£J^^^M hazard assessment when used in conjunction in sediments. FETAX can be usea

Assessing the Current Status of Atmospheric Radiation Modelling: Progress, Challenges and the Needs for the Next Generation of Models

NASA Astrophysics Data System (ADS)

Joyce, C. J.; Tobiska, W. K.; Copeland, K.; Smart, D. F.; Shea, M. A.; Nowicki, S.; Atwell, W.; Benton, E. R.; Wilkins, R.; Hands, A.; Gronoff, G.; Meier, M. M.; Schwadron, N.

2017-12-01

Despite its potential for causing a wide range of harmful effects, including health hazards to airline passengers and damage to aircraft and satellite electronics, atmospheric radiation remains a relatively poorly defined risk, lacking sufficient measurements and modelling to fully evaluate the dangers posed. While our reliance on airline travel has increased dramatically over time, there remains an absence of international guidance and standards to protect aircraft passengers from potential health impacts due to radiation exposure. This subject has been gaining traction within the scientific community in recent years, with an expanding number of models with increasing capabilities being made available to evaluate atmospheric radiation hazards. We provide a general description of these modelling efforts, including the physics and methods used by the models, as well as their data inputs and outputs. We also discuss the current capacity for model validation via measurements and discuss the needs for the next generation of models, both in terms of their capabilities and the measurements required to validate them. This review of the status of atmospheric radiation modelling is part of a larger series of studies made as part of the SAFESKY program, with other efforts focusing on the underlying physics and implications, measurements and regulations/standards of atmospheric radiation.

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

Smith, Curtis L.; Prescott, Steven; Coleman, Justin

This report describes the current progress and status related to the Industry Application #2 focusing on External Hazards. For this industry application within the Light Water Reactor Sustainability (LWRS) Program Risk-Informed Safety Margin Characterization (RISMC) R&D Pathway, we will create the Risk-Informed Margin Management (RIMM) approach to represent meaningful (i.e., realistic facility representation) event scenarios and consequences by using an advanced 3D facility representation that will evaluate external hazards such as flooding and earthquakes in order to identify, model and analyze the appropriate physics that needs to be included to determine plant vulnerabilities related to external events; manage the communicationmore » and interactions between different physics modeling and analysis technologies; and develop the computational infrastructure through tools related to plant representation, scenario depiction, and physics prediction. One of the unique aspects of the RISMC approach is how it couples probabilistic approaches (the scenario) with mechanistic phenomena representation (the physics) through simulation. This simulation-based modeling allows decision makers to focus on a variety of safety, performance, or economic metrics. In this report, we describe the evaluation of various physics toolkits related to flooding representation. Ultimately, we will be coupling the flooding representation with other events such as earthquakes in order to provide coupled physics analysis for scenarios where interactions exist.« less

Urinary Liver-Type Fatty Acid–Binding Protein and Progression of Diabetic Nephropathy in Type 1 Diabetes

PubMed Central

Panduru, Nicolae M.; Forsblom, Carol; Saraheimo, Markku; Thorn, Lena; Bierhaus, Angelika; Humpert, Per M.; Groop, Per-Henrik

2013-01-01

OBJECTIVE Diabetic nephropathy (DN) has mainly been considered a glomerular disease, although tubular dysfunction may also play a role. This study assessed the predictive value for progression of a tubular marker, urinary liver-type fatty acid–binding protein (L-FABP), at all stages of DN. RESEARCH DESIGN AND METHODS At baseline, 1,549 patients with type 1 diabetes had an albumin excretion rate (AER) within normal reference ranges, 334 had microalbuminuria, and 363 had macroalbuminuria. Patients were monitored for a median of 5.8 years (95% CI 5.7–5.9). In addition, 208 nondiabetic subjects were studied. L-FABP was measured by ELISA and normalized with urinary creatinine. Different Cox proportional hazard models for the progression at every stage of DN were used to evaluate the predictive value of L-FABP. The potential benefit of using L-FABP alone or together with AER was assessed by receiver operating characteristic curve analyses. RESULTS L-FABP was an independent predictor of progression at all stages of DN. As would be expected, receiver operating characteristic curves for the prediction of progression were significantly larger for AER than for L-FABP, except for patients with baseline macroalbuminuria, in whom the areas were similar. Adding L-FABP to AER in the models did not significantly improve risk prediction of progression in favor of the combination of L-FABP plus AER compared with AER alone. CONCLUSIONS L-FABP is an independent predictor of progression of DN irrespective of disease stage. L-FABP used alone or together with AER may not improve the risk prediction of DN progression in patients with type 1 diabetes, but further studies are needed in this regard. PMID:23378622

21 CFR 7.41 - Health hazard evaluation and recall classification.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Health hazard evaluation and recall classification. 7.41 Section 7.41 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., and Industry Responsibilities § 7.41 Health hazard evaluation and recall classification. (a) An...

Hazards to Early Development: The Biological Embedding of Early Life Adversity.

PubMed

Nelson, Charles A

2017-10-11

The number of children under 18 years of age has increased worldwide over the past decade. This growth spurt is due, in part, to remarkable progress in child survival. Alas, surviving early hazards, like prematurity or infectious disease, does not guarantee that children's development will not be compromised by other hazards as they grow older. Throughout the world, children continue to be confronted with a large number of biological and psychosocial challenges that greatly limit their developmental potential. The focus of this article is how such adverse experiences impact the developing brain. Copyright © 2017 Elsevier Inc. All rights reserved.

(Hydrogeology of hazardous waste, Sede Boker Campus, Ben-Gurion University, Israel)

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

Stow, S.H.

1990-03-29

This trip report describes progress made by the International Commission on the Hydrogeology of Hazardous Waste in preparing a document on hydrogeologic and environmental issues associated with siting of hazardous waste disposal facilities. This document follows the successful completion of a commission report on siting of facilities for subsurface disposal of liquid wastes. Also contained in this trip report are descriptions of water and waste management activities throughout the southern part of Israel. Water availability and the need to protect the country's limited water supplies from contamination resulting from waste disposal are issues of paramount importance to Israel.

Association of Dual-Task Gait With Incident Dementia in Mild Cognitive Impairment: Results From the Gait and Brain Study.

PubMed

Montero-Odasso, Manuel M; Sarquis-Adamson, Yanina; Speechley, Mark; Borrie, Michael J; Hachinski, Vladimir C; Wells, Jennie; Riccio, Patricia M; Schapira, Marcelo; Sejdic, Ervin; Camicioli, Richard M; Bartha, Robert; McIlroy, William E; Muir-Hunter, Susan

2017-07-01

Gait performance is affected by neurodegeneration in aging and has the potential to be used as a clinical marker for progression from mild cognitive impairment (MCI) to dementia. A dual-task gait test evaluating the cognitive-motor interface may predict dementia progression in older adults with MCI. To determine whether a dual-task gait test is associated with incident dementia in MCI. The Gait and Brain Study is an ongoing prospective cohort study of community-dwelling older adults that enrolled 112 older adults with MCI. Participants were followed up for 6 years, with biannual visits including neurologic, cognitive, and gait assessments. Data were collected from July 2007 to March 2016. Incident all-cause dementia was the main outcome measure, and single- and dual-task gait velocity and dual-task gait costs were the independent variables. A neuropsychological test battery was used to assess cognition. Gait velocity was recorded under single-task and 3 separate dual-task conditions using an electronic walkway. Dual-task gait cost was defined as the percentage change between single- and dual-task gait velocities: ([single-task gait velocity - dual-task gait velocity]/ single-task gait velocity) × 100. Cox proportional hazard models were used to estimate the association between risk of progression to dementia and the independent variables, adjusted for age, sex, education, comorbidities, and cognition. Among 112 study participants with MCI, mean (SD) age was 76.6 (6.9) years, 55 were women (49.1%), and 27 progressed to dementia (24.1%), with an incidence rate of 121 per 1000 person-years. Slow single-task gait velocity (<0.8 m/second) was not associated with progression to dementia (hazard ratio [HR], 3.41; 95% CI, 0.99-11.71; P = .05)while high dual-task gait cost while counting backward (HR, 3.79; 95% CI, 1.57-9.15; P = .003) and naming animals (HR, 2.41; 95% CI, 1.04-5.59; P = .04) were associated with dementia progression (incidence rate, 155 per 1000 person-years). The models remained robust after adjusting by baseline cognition except for dual-task gait cost when dichotomized. Dual-task gait is associated with progression to dementia in patients with MCI. Dual-task gait testing is easy to administer and may be used by clinicians to decide further biomarker testing, preventive strategies, and follow-up planning in patients with MCI. clinicaltrials.gov: NCT03020381.

Statistical analysis of the uncertainty related to flood hazard appraisal

NASA Astrophysics Data System (ADS)

Notaro, Vincenza; Freni, Gabriele

2015-12-01

The estimation of flood hazard frequency statistics for an urban catchment is of great interest in practice. It provides the evaluation of potential flood risk and related damage and supports decision making for flood risk management. Flood risk is usually defined as function of the probability, that a system deficiency can cause flooding (hazard), and the expected damage, due to the flooding magnitude (damage), taking into account both the exposure and the vulnerability of the goods at risk. The expected flood damage can be evaluated by an a priori estimation of potential damage caused by flooding or by interpolating real damage data. With regard to flood hazard appraisal several procedures propose to identify some hazard indicator (HI) such as flood depth or the combination of flood depth and velocity and to assess the flood hazard corresponding to the analyzed area comparing the HI variables with user-defined threshold values or curves (penalty curves or matrixes). However, flooding data are usually unavailable or piecemeal allowing for carrying out a reliable flood hazard analysis, therefore hazard analysis is often performed by means of mathematical simulations aimed at evaluating water levels and flow velocities over catchment surface. As results a great part of the uncertainties intrinsic to flood risk appraisal can be related to the hazard evaluation due to the uncertainty inherent to modeling results and to the subjectivity of the user defined hazard thresholds applied to link flood depth to a hazard level. In the present work, a statistical methodology was proposed for evaluating and reducing the uncertainties connected with hazard level estimation. The methodology has been applied to a real urban watershed as case study.

Net endogenous acid production is associated with a faster decline in GFR in African Americans

PubMed Central

Scialla, Julia J.; Appel, Lawrence J.; Astor, Brad C.; Miller, Edgar R.; Beddhu, Srinivasan; Woodward, Mark; Parekh, Rulan S.; Anderson, Cheryl A. M.

2012-01-01

Increased acid excretion may promote renal injury. To evaluate this in African Americans with hypertensive nephrosclerosis, we studied the association between the net endogenous acid production and progression of kidney disease in 632 patients in the AASK trial. Protein and potassium intakes were estimated from 24-hour urea nitrogen and potassium excretion, and used to estimate net endogenous acid production, averaged over 2 years, approximating routine intake. The link between net endogenous acid production and the I125iothalamate glomerular filtration rate (iGFR) and time to end stage renal disease or doubling of serum creatinine was analyzed using mixed models and Cox proportional hazards regressions. The trend in higher net endogenous acid production was significantly associated with a faster decline in iGFR over a median of 3.2 years. After adjustment for age, body mass index, baseline iGFR, urine protein to creatinine ratio and randomized treatment group, the trend in higher net endogenous acid production remained significantly associated with a faster decline in iGFR at a rate 1.01 mL/min/1.73 m2 per year faster in the highest to the lowest quartile. However, in time to event analyses over a median of 7.7 years, the adjusted hazard ratio (1.10) for composite renal events per 25 mEq/day higher net endogenous acid production was not significant. Hence, our findings implicate endogenous acid production as a potential modifiable risk factor for progressive kidney disease. PMID:22475819

Comparison of smoothing methods for the development of a smoothed seismicity model for Alaska and the implications for seismic hazard

NASA Astrophysics Data System (ADS)

Moschetti, M. P.; Mueller, C. S.; Boyd, O. S.; Petersen, M. D.

2013-12-01

In anticipation of the update of the Alaska seismic hazard maps (ASHMs) by the U. S. Geological Survey, we report progress on the comparison of smoothed seismicity models developed using fixed and adaptive smoothing algorithms, and investigate the sensitivity of seismic hazard to the models. While fault-based sources, such as those for great earthquakes in the Alaska-Aleutian subduction zone and for the ~10 shallow crustal faults within Alaska, dominate the seismic hazard estimates for locations near to the sources, smoothed seismicity rates make important contributions to seismic hazard away from fault-based sources and where knowledge of recurrence and magnitude is not sufficient for use in hazard studies. Recent developments in adaptive smoothing methods and statistical tests for evaluating and comparing rate models prompt us to investigate the appropriateness of adaptive smoothing for the ASHMs. We develop smoothed seismicity models for Alaska using fixed and adaptive smoothing methods and compare the resulting models by calculating and evaluating the joint likelihood test. We use the earthquake catalog, and associated completeness levels, developed for the 2007 ASHM to produce fixed-bandwidth-smoothed models with smoothing distances varying from 10 to 100 km and adaptively smoothed models. Adaptive smoothing follows the method of Helmstetter et al. and defines a unique smoothing distance for each earthquake epicenter from the distance to the nth nearest neighbor. The consequence of the adaptive smoothing methods is to reduce smoothing distances, causing locally increased seismicity rates, where seismicity rates are high and to increase smoothing distances where seismicity is sparse. We follow guidance from previous studies to optimize the neighbor number (n-value) by comparing model likelihood values, which estimate the likelihood that the observed earthquake epicenters from the recent catalog are derived from the smoothed rate models. We compare likelihood values from all rate models to rank the smoothing methods. We find that adaptively smoothed seismicity models yield better likelihood values than the fixed smoothing models. Holding all other (source and ground motion) models constant, we calculate seismic hazard curves for all points across Alaska on a 0.1 degree grid, using the adaptively smoothed and fixed smoothed seismicity models separately. Because adaptively smoothed models concentrate seismicity near the earthquake epicenters where seismicity rates are high, the corresponding hazard values are higher, locally, but reduced with distance from observed seismicity, relative to the hazard from fixed-bandwidth models. We suggest that adaptively smoothed seismicity models be considered for implementation in the update to the ASHMs because of their improved likelihood estimates relative to fixed smoothing methods; however, concomitant increases in seismic hazard will cause significant changes in regions of high seismicity, such as near the subduction zone, northeast of Kotzebue, and along the NNE trending zone of seismicity in the Alaskan interior.

Comparison of smoothing methods for the development of a smoothed seismicity model for Alaska and the implications for seismic hazard

USGS Publications Warehouse

Moschetti, Morgan P.; Mueller, Charles S.; Boyd, Oliver S.; Petersen, Mark D.

2014-01-01

In anticipation of the update of the Alaska seismic hazard maps (ASHMs) by the U. S. Geological Survey, we report progress on the comparison of smoothed seismicity models developed using fixed and adaptive smoothing algorithms, and investigate the sensitivity of seismic hazard to the models. While fault-based sources, such as those for great earthquakes in the Alaska-Aleutian subduction zone and for the ~10 shallow crustal faults within Alaska, dominate the seismic hazard estimates for locations near to the sources, smoothed seismicity rates make important contributions to seismic hazard away from fault-based sources and where knowledge of recurrence and magnitude is not sufficient for use in hazard studies. Recent developments in adaptive smoothing methods and statistical tests for evaluating and comparing rate models prompt us to investigate the appropriateness of adaptive smoothing for the ASHMs. We develop smoothed seismicity models for Alaska using fixed and adaptive smoothing methods and compare the resulting models by calculating and evaluating the joint likelihood test. We use the earthquake catalog, and associated completeness levels, developed for the 2007 ASHM to produce fixed-bandwidth-smoothed models with smoothing distances varying from 10 to 100 km and adaptively smoothed models. Adaptive smoothing follows the method of Helmstetter et al. and defines a unique smoothing distance for each earthquake epicenter from the distance to the nth nearest neighbor. The consequence of the adaptive smoothing methods is to reduce smoothing distances, causing locally increased seismicity rates, where seismicity rates are high and to increase smoothing distances where seismicity is sparse. We follow guidance from previous studies to optimize the neighbor number (n-value) by comparing model likelihood values, which estimate the likelihood that the observed earthquake epicenters from the recent catalog are derived from the smoothed rate models. We compare likelihood values from all rate models to rank the smoothing methods. We find that adaptively smoothed seismicity models yield better likelihood values than the fixed smoothing models. Holding all other (source and ground motion) models constant, we calculate seismic hazard curves for all points across Alaska on a 0.1 degree grid, using the adaptively smoothed and fixed smoothed seismicity models separately. Because adaptively smoothed models concentrate seismicity near the earthquake epicenters where seismicity rates are high, the corresponding hazard values are higher, locally, but reduced with distance from observed seismicity, relative to the hazard from fixed-bandwidth models. We suggest that adaptively smoothed seismicity models be considered for implementation in the update to the ASHMs because of their improved likelihood estimates relative to fixed smoothing methods; however, concomitant increases in seismic hazard will cause significant changes in regions of high seismicity, such as near the subduction zone, northeast of Kotzebue, and along the NNE trending zone of seismicity in the Alaskan interior.

Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.

PubMed

Mok, Tony S; Wu, Yi-Long; Thongprasert, Sumitra; Yang, Chih-Hsin; Chu, Da-Tong; Saijo, Nagahiro; Sunpaweravong, Patrapim; Han, Baohui; Margono, Benjamin; Ichinose, Yukito; Nishiwaki, Yutaka; Ohe, Yuichiro; Yang, Jin-Ji; Chewaskulyong, Busyamas; Jiang, Haiyi; Duffield, Emma L; Watkins, Claire L; Armour, Alison A; Fukuoka, Masahiro

2009-09-03

Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer. In this phase 3, open-label study, we randomly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib (250 mg per day) (609 patients) or carboplatin (at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute) plus paclitaxel (200 mg per square meter of body-surface area) (608 patients). The primary end point was progression-free survival. The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin-paclitaxel. The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority, as compared with carboplatin-paclitaxel, with respect to progression-free survival in the intention-to-treat population (hazard ratio for progression or death, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001), whereas in the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly longer among those who received carboplatin-paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 3.98; P<0.001). The most common adverse events were rash or acne (in 66.2% of patients) and diarrhea (46.6%) in the gefitinib group and neurotoxic effects (69.9%), neutropenia (67.1%), and alopecia (58.4%) in the carboplatin-paclitaxel group. Gefitinib is superior to carboplatin-paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia. The presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib. (ClinicalTrials.gov number, NCT00322452.) 2009 Massachusetts Medical Society

An evaluation of the relative fire hazards of jet A and jet B for commercial flight

NASA Technical Reports Server (NTRS)

Hibbard, R. R.; Hacker, P. T.

1973-01-01

The relative fire hazards of Jet A and Jet B aircraft fuels are evaluated. The evaluation is based on a consideration of the presence of and/or the generation of flammable mixtures in fuel systems, the ignition characteristics, and the flame propagation rates for the two fuel types. Three distinct aircraft operating regimes where fuel type may be a factor in fire hazards are considered. These are: (1) ground handling and refueling, (2) flight, and (3) crash. The evaluation indicates that the overall fire hazards for Jet A are less than for Jet B fuel.

Software for occupational health and safety risk analysis based on a fuzzy model.

PubMed

Stefanovic, Miladin; Tadic, Danijela; Djapan, Marko; Macuzic, Ivan

2012-01-01

Risk and safety management are very important issues in healthcare systems. Those are complex systems with many entities, hazards and uncertainties. In such an environment, it is very hard to introduce a system for evaluating and simulating significant hazards. In this paper, we analyzed different types of hazards in healthcare systems and we introduced a new fuzzy model for evaluating and ranking hazards. Finally, we presented a developed software solution, based on the suggested fuzzy model for evaluating and monitoring risk.

Monitoring of Serum DNA Methylation as an Early Independent Marker of Response and Survival in Metastatic Breast Cancer: TBCRC 005 Prospective Biomarker Study

PubMed Central

Fackler, MaryJo S.; Zhang, Zhe; Lopez-Bujanda, Zoila A.; Jeter, Stacie C.; Sokoll, Lori J.; Garrett-Mayer, Elizabeth; Cope, Leslie M.; Umbricht, Christopher B.; Euhus, David M.; Forero, Andres; Storniolo, Anna M.; Nanda, Rita; Lin, Nancy U.; Carey, Lisa A.; Ingle, James N.; Sukumar, Saraswati; Wolff, Antonio C.

2017-01-01

Purpose Epigenetic alterations measured in blood may help guide breast cancer treatment. The multisite prospective study TBCRC 005 was conducted to examine the ability of a novel panel of cell-free DNA methylation markers to predict survival outcomes in metastatic breast cancer (MBC) using a new quantitative multiplex assay (cMethDNA). Patients and Methods Ten genes were tested in duplicate serum samples from 141 women at baseline, at week 4, and at first restaging. A cumulative methylation index (CMI) was generated on the basis of six of the 10 genes tested. Methylation cut points were selected to maximize the log-rank statistic, and cross-validation was used to obtain unbiased point estimates. Logistic regression or Cox proportional hazard models were used to test associations between the CMI and progression-free survival (PFS), overall survival (OS), and disease status at first restaging. The added value of the CMI in predicting survival outcomes was evaluated and compared with circulating tumor cells (CellSearch). Results Median PFS and OS were significantly shorter in women with a high CMI (PFS, 2.1 months; OS, 12.3 months) versus a low CMI (PFS, 5.8 months; OS, 21.7 months). In multivariable models, among women with MBC, a high versus low CMI at week 4 was independently associated with worse PFS (hazard ratio, 1.79; 95% CI, 1.23 to 2.60; P = .002) and OS (hazard ratio, 1.75; 95% CI, 1.21 to 2.54; P = .003). An increase in the CMI from baseline to week 4 was associated with worse PFS (P < .001) and progressive disease at first restaging (P < .001). Week 4 CMI was a strong predictor of PFS, even in the presence of circulating tumor cells (P = .004). Conclusion Methylation of this gene panel is a strong predictor of survival outcomes in MBC and may have clinical usefulness in risk stratification and disease monitoring. PMID:27870562

Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis.

PubMed

Shirani, Afsaneh; Zhao, Yinshan; Karim, Mohammad Ehsanul; Evans, Charity; Kingwell, Elaine; van der Kop, Mia L; Oger, Joel; Gustafson, Paul; Petkau, John; Tremlett, Helen

2012-07-18

Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.

The relationship between BMI and insulin resistance and progression from single to multiple autoantibody positivity and type 1 diabetes among TrialNet Pathway to Prevention participants.

PubMed

Meah, Farah A; DiMeglio, Linda A; Greenbaum, Carla J; Blum, Janice S; Sosenko, Jay M; Pugliese, Alberto; Geyer, Susan; Xu, Ping; Evans-Molina, Carmella

2016-06-01

The incidence of type 1 diabetes is increasing at a rate of 3-5% per year. Genetics cannot fully account for this trend, suggesting an influence of environmental factors. The accelerator hypothesis proposes an effect of metabolic factors on type 1 diabetes risk. To test this in the TrialNet Pathway to Prevention (PTP) cohort, we analysed the influence of BMI, weight status and insulin resistance on progression from single to multiple islet autoantibodies (Aab) and progression from normoglycaemia to diabetes. HOMA1-IR was used to estimate insulin resistance in Aab-positive PTP participants. Cox proportional hazards models were used to evaluate the effects of BMI, BMI percentile (BMI%), weight status and HOMA1-IR on the progression of autoimmunity or the development of diabetes. Data from 1,310 single and 1,897 multiple Aab-positive PTP participants were included. We found no significant relationships between BMI, BMI%, weight status or HOMA1-IR and the progression from one to multiple Aabs. Similarly, among all Aab-positive participants, no significant relationships were found between BMI, weight status or HOMA1-IR and progression to diabetes. Diabetes risk was modestly increased with increasing BMI% among the entire cohort, in obese participants 13-20 years of age and with increasing HOMA1-IR in adult Aab-positive participants. Analysis of the accelerator hypothesis in the TrialNet PTP cohort does not suggest a broad influence of metabolic variables on diabetes risk. Efforts to identify other potentially modifiable environmental factors should continue.

Reduced volatile organic compound (VOC) ammunition coatings. Progress report, October 1994-September 1995

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

Duncan, J.L.

1996-05-01

Production requirements and film thickness limitations typically require that ammunition coating systems consist of a single film. This single film must provide the corrosion resistance of a primer plus such properties as color, gloss, and solvent resistance that are required of a topcoat, a compromise at best. Federal and local regulations resulting from the Clean Air Act and its amendments restrict the amount of VOC emitted during the application of protective coatings, and regulations on worker safety restrict exposure to hazardous materials such as chromates. These materials also generate hazardous wastes and the associated high disposal costs. This report summarizesmore » progress in developing ammunition coatings that perform as well as or better than current systems, but at reduced VOC levels with chromate-free pigmentation.« less

Threshold determination and hazard evaluation of the disaster about drought/flood sudden alternation in Huaihe River basin, China

NASA Astrophysics Data System (ADS)

Ji, Zhonghui; Li, Ning; Wu, Xianhua

2017-08-01

Based on the related impact factors of precipitation anomaly referred in previous research, eight atmospheric circulation indicators in pre-winter and spring picked out by correlation analysis as the independent variables and the hazard levels of drought/flood sudden alternation index (DFSAI) as the dependent variables were used to construct the nonlinear and nonparametric classification and regression tree (CART) for the threshold determination and hazard evaluation on bimonthly and monthly scales in Huaihe River basin. Results show that the spring indicators about Arctic oscillation index (AOI_S), Asia polar vortex area index (APVAI_S), and Asian meridional circulation index (AMCI_S) were extracted as the three main impact factors, which were proved to be suitable for the hazard levels assessment of the drought/flood sudden alternation (DFSA) disaster based on bimonthly scale. On monthly scale, AOI_S, northern hemisphere polar vortex intensity index in pre-winter (NHPVII_PW), and AMCI_S are the three primary variables in hazard level prediction of DFSA in May and June; NHPVII_PW, AMCI_PW, and AMCI_S are for that in June and July; NHPVII_PW and EASMI are for that in July and August. The type of the disaster (flood to drought/drought to flood/no DFSA) and hazard level under different conditions also can be obtained from each model. The hazard level and type were expressed by the integer from - 3 to 3, which change from the high level of disaster that flood to drought (level - 3) to the high level of the reverse type (level 3). The middle number 0 represents no DFSA. The high levels of the two sides decrease progressively to the neutralization (level 0). When AOI_S less than - 0.355, the disaster of the quick turn from drought to flood is more apt to happen (level 1) on bimonthly scale; when AOI_S less than - 1.32, the same type disaster may occur (level 2) in May and June on monthly scale. When NHPVII_PW less than 341.5, the disaster of the quick turn from flood to drought will occur (level - 1) in June and July on monthly scale. By this analogy, different hazard types and levels all can be judged from the optimal models. The corresponding data from 2011 to 2015 were selected to verify the final models through the comparison between the predicted and actual levels, and the models of M1 (bimonthly scale), M2, and M3 (monthly scale) were proved to be acceptable by the prediction accuracy rate (compared the predicted with the observed levels, 73%, 11/15). The proposed CART method in this research is a new try for the short-term climate prediction.

Rail-highway crossing hazard prediction : research results

DOT National Transportation Integrated Search

1979-12-01

This document presents techniques for constructing and evaluating railroad grade : crossing hazard indexes. Hazard indexes are objective formulas for comparing or ranking : crossings according to relative hazard or for calculating absolute hazard (co...

The need for sustained and integrated high-resolution mapping of dynamic coastal environments

USGS Publications Warehouse

Stockdon, Hilary F.; Lillycrop, Jeff W.; Howd, Peter A.; Wozencraft, Jennifer M.

2007-01-01

The evolution of the United States' coastal zone response to both human activities and natural processes is dynamic. Coastal resource and population protection requires understanding, in detail, the processes needed for change as well as the physical setting. Sustained coastal area mapping allows change to be documented and baseline conditions to be established, as well as future behavior to be predicted in conjunction with physical process models. Hyperspectral imagers and airborne lidars, as well as other recent mapping technology advances, allow rapid national scale land use information and high-resolution elevation data collection. Coastal hazard risk evaluation has critical dependence on these rich data sets. A fundamental storm surge model parameter in predicting flooding location, for example, is coastal elevation data, and a foundation in identifying the most vulnerable populations and resources is land use maps. A wealth of information for physical change process study, coastal resource and community management and protection, and coastal area hazard vulnerability determination, is available in a comprehensive national coastal mapping plan designed to take advantage of recent mapping technology progress and data distribution, management, and collection.

Cytoplasmatic and Nuclear YAP1 and pYAP1 Staining in Urothelial Bladder Cancer.

PubMed

Latz, Stefan; Umbach, Tine; Goltz, Diane; Kristiansen, Glen; Müller, Stephan C; Ellinger, Jörg

2016-01-01

Yes-associated protein 1 (YAP1), the nuclear effector of the Hippo pathway, plays an important role in many tumor entities. We evaluated staining and clinical significance of YAP1 and phosphorylated YAP1 (pYAP1) in urothelial bladder cancer (BCA). We used a tissue micorarray with samples of patients with muscle-invasive bladder cancer (MIBC, n = 192), non-muscle-invasive bladder cancer (NMIBC, n = 192) and normal urothelial bladder tissue (CTRL, n = 38) to determine the immunhistochemical staining of YAP1 and pYAP1. Cytoplasmatic and nuclear levels were evaluated. The t test was used for comparative analysis. Overall survival and progression-free survival were evaluated by Kaplan-Meier estimates and the Cox proportional hazard regression model. Nuclear YAP1 as well as cytoplasmatic pYAP1 levels were higher in CTRL than in BCA, whereby both--NMIBC and MIBC--had lower levels than CTRL. Among patients with MIBC, cytoplasmatic YAP1 and pYAP1 staining decreased with advanced stage. YAP1 and pYAP1 staining did not correlate with the recurrence rate, progression-free, cancer-specific or overall survival. Immunhistochemical staining and subcellular localization of YAP1 and pYAP1 are different for BCA, NMIBC, MIBC and CTRL, indicating that the Hippo pathway is involved in urothelial carcinogenesis. © 2015 S. Karger AG, Basel.

Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL

PubMed Central

Bryce, A H; Alumkal, J J; Armstrong, A; Higano, C S; Iversen, P; Sternberg, C N; Rathkopf, D; Loriot, Y; de Bono, J; Tombal, B; Abhyankar, S; Lin, P; Krivoshik, A; Phung, D; Beer, T M

2017-01-01

Background: Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested. Methods: Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups. Results: Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26–2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar. Conclusions: Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression. PMID:28117385

Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL.

PubMed

Bryce, A H; Alumkal, J J; Armstrong, A; Higano, C S; Iversen, P; Sternberg, C N; Rathkopf, D; Loriot, Y; de Bono, J; Tombal, B; Abhyankar, S; Lin, P; Krivoshik, A; Phung, D; Beer, T M

2017-06-01

Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested. Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups. Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26-2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar. Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.

Effects of CCR5-delta32 and CCR2-64I alleles on disease progression of perinatally HIV-1-infected children: an international meta-analysis.

PubMed

Ioannidis, John P A; Contopoulos-Ioannidis, Despina G; Rosenberg, Philip S; Goedert, James J; De Rossi, Anita; Espanol, Teresa; Frenkel, Lisa; Mayaux, Marie-Jeanne; Newell, Marie-Louise; Pahwa, Savita G; Rousseau, Christine; Scarlatti, Gabriella; Sei, Shizuko; Sen, Luisa; O'Brien, Thomas R

2003-07-25

Among perinatally infected children, the effects of certain alleles of the CCR5 and CCR2 genes on the rate of disease progression remain unclear. We addressed the effects of CCR5-delta32 and CCR2-64I in an international meta-analysis. Genotype data were contributed from 10 studies with 1317 HIV-1-infected children (7263 person-years of follow-up). Time-to-event analyses were performed stratified by study and racial group. Endpoints included progression to clinical AIDS, death, and death after the diagnosis of clinical AIDS. The time-dependence of the genetic effects was specifically investigated. There was large heterogeneity in the observed rates of disease progression between different cohorts. For progression to clinical AIDS, both CCR5-delta32 and CCR2-64I showed overall non-significant trends for protection [hazard ratios 0.84, 95% confidence interval (CI) 0.58-1.23; and 0.87, 95% CI 0.67-1.14, respectively]. However, analyses of survival showed statistically significant time-dependence. No deaths occurred among CCR5-delta32 carriers in the first 3 years of life, whereas there was no protective effect (hazard ratio 0.95; 95% CI 0.43-2.10) in later years (P=0.01 for the time-dependent model). For CCR2-64I, the hazard ratio for death was 0.69 (95% CI 0.39-1.21) in the first 6 years of life and 2.56 (95% CI 1.26-5.20) in subsequent years (P<0.01 for the time-dependent model). CCR5-delta32 and CCR2-64I offered no clear protection after clinical AIDS had developed. The CCR5-delta32 and CCR2-64I alleles are associated with a decreased risk of death among perinatally infected children, but only for the first years of life.

Aberrant Expression of the Cell Polarity Regulator aPKCλ/ι is Associated With Disease Progression in Cervical Intraepithelial Neoplasia (CIN): A Possible Marker for Predicting CIN Prognosis.

PubMed

Mizushima, Taichi; Asai-Sato, Mikiko; Akimoto, Kazunori; Nagashima, Yoji; Taguri, Masataka; Sasaki, Kazunori; Nakaya, Masa-aki; Asano, Ryoko; Tokinaga, Aya; Kiyono, Tohru; Hirahara, Fumiki; Ohno, Shigeo; Miyagi, Etsuko

2016-03-01

Atypical protein kinase C λ/ι (aPKCλ/ι) is a regulator of epithelial cellular polarity. It is also overexpressed in several cancers and functions in cell proliferation and invasion. Therefore, we hypothesized that aPKCλ/ι may be involved in development and progression of cervical intraepithelial neoplasia (CIN), the precancerous disease of cervical cancer induced by human papillomavirus. To do this, we investigated the relationship between aPKCλ/ι expression and CIN. aPKCλ/ι expression level and subcellular localization were assessed in 192 CIN biopsy samples and 13 normal epithelial samples using immunohistochemistry. aPKCλ/ι overexpression (normal epithelium, 7.7%; CIN1, 41.7%; CIN2/3, 76.4%) and aPKCλ/ι nuclear localization (normal epithelium, 0.0%; CIN1, 36.9%; CIN2/3, 78.7%) were higher in CIN samples than normal samples (P<0.05), suggesting that CIN grade is related to aPKCλ/ι overexpression and nuclear localization. Then, 140 CIN cases were retrospectively analyzed for 4-yr cumulative disease progression and regression rates using the Cox proportional hazards model. CIN1 cases with aPKCλ/ι overexpression or aPKCλ/ι nuclear localization had a higher progression rate than CIN1 cases with normal aPKCλ/ι expression levels or cytoplasmic localization (62.5% vs. 9.7% and 63.1% vs. 9.4%, respectively; P<0.001). Multivariate analysis indicated that human papillomavirus types 16 and 18, aPKCλ/ι overexpression (hazard ratio=4.26; 95% confidence interval, 1.50-12.1; P=0.007), and aPKCλ/ι nuclear localization (hazard ratio=3.59; 95% confidence interval, 1.24-10.4; P=0.019) were independent risk factors for CIN1 progression. In conclusion, aPKCλ/ι could be useful for the therapeutic management of patients with CIN, particularly those with non-human papillomavirus 16/18 types.

Conceptual Development of a National Volcanic Hazard Model for New Zealand

NASA Astrophysics Data System (ADS)

Stirling, Mark; Bebbington, Mark; Brenna, Marco; Cronin, Shane; Christophersen, Annemarie; Deligne, Natalia; Hurst, Tony; Jolly, Art; Jolly, Gill; Kennedy, Ben; Kereszturi, Gabor; Lindsay, Jan; Neall, Vince; Procter, Jonathan; Rhoades, David; Scott, Brad; Shane, Phil; Smith, Ian; Smith, Richard; Wang, Ting; White, James D. L.; Wilson, Colin J. N.; Wilson, Tom

2017-06-01

We provide a synthesis of a workshop held in February 2016 to define the goals, challenges and next steps for developing a national probabilistic volcanic hazard model for New Zealand. The workshop involved volcanologists, statisticians, and hazards scientists from GNS Science, Massey University, University of Otago, Victoria University of Wellington, University of Auckland, and University of Canterbury. We also outline key activities that will develop the model components, define procedures for periodic update of the model, and effectively articulate the model to end-users and stakeholders. The development of a National Volcanic Hazard Model is a formidable task that will require long-term stability in terms of team effort, collaboration and resources. Development of the model in stages or editions that are modular will make the process a manageable one that progressively incorporates additional volcanic hazards over time, and additional functionalities (e.g. short-term forecasting). The first edition is likely to be limited to updating and incorporating existing ashfall hazard models, with the other hazards associated with lahar, pyroclastic density currents, lava flow, ballistics, debris avalanche, and gases/aerosols being considered in subsequent updates.

Evansville Area Earthquake Hazards Mapping Project (EAEHMP) - Progress Report, 2008

USGS Publications Warehouse

Boyd, Oliver S.; Haase, Jennifer L.; Moore, David W.

2009-01-01

Maps of surficial geology, deterministic and probabilistic seismic hazard, and liquefaction potential index have been prepared by various members of the Evansville Area Earthquake Hazard Mapping Project for seven quadrangles in the Evansville, Indiana, and Henderson, Kentucky, metropolitan areas. The surficial geologic maps feature 23 types of surficial geologic deposits, artificial fill, and undifferentiated bedrock outcrop and include alluvial and lake deposits of the Ohio River valley. Probabilistic and deterministic seismic hazard and liquefaction hazard mapping is made possible by drawing on a wealth of information including surficial geologic maps, water well logs, and in-situ testing profiles using the cone penetration test, standard penetration test, down-hole shear wave velocity tests, and seismic refraction tests. These data were compiled and collected with contributions from the Indiana Geological Survey, Kentucky Geological Survey, Illinois State Geological Survey, United States Geological Survey, and Purdue University. Hazard map products are in progress and are expected to be completed by the end of 2009, with a public roll out in early 2010. Preliminary results suggest that there is a 2 percent probability that peak ground accelerations of about 0.3 g will be exceeded in much of the study area within 50 years, which is similar to the 2002 USGS National Seismic Hazard Maps for a firm rock site value. Accelerations as high as 0.4-0.5 g may be exceeded along the edge of the Ohio River basin. Most of the region outside of the river basin has a low liquefaction potential index (LPI), where the probability that LPI is greater than 5 (that is, there is a high potential for liquefaction) for a M7.7 New Madrid type event is only 20-30 percent. Within the river basin, most of the region has high LPI, where the probability that LPI is greater than 5 for a New Madrid type event is 80-100 percent.

Main natural hazards and vulnerability studies for some historical constructions and urban sectors of Valparaiso City (Chile)

NASA Astrophysics Data System (ADS)

Romanelli, F.

2009-04-01

The Project "MAR VASTO" ("Risk Management in Valparaíso/Manejo de Riesgos en Valparaíso, Servicios Técnicos", 2007) started in March 2007, with coordination of ENEA (Italian Agency for New Technologies, Energy and Environment), participation of several partners (Italy: University of Ferrara, Faculties of Architecture and Engineering; University of Padua, Faculty of Engineering; Abdus Salam International Centre for Theoretical Physics of Trieste; Chile: Valparaíso Technical University Federico Santa Maria, Civil Works Department; Santiago University of Chile, Division Structures Constructions Geotechnics), and support of local stakeholders. Being Valparaíso included since 2003 in the UNESCO Word Heritage List of protected sites, the project main goals are the following: to collect, analyze and elaborate the existing information, with a satisfying evaluation of main hazards; to develop a GIS digital archive, well organized, user-friendly and easy to be implemented in the future, providing maps and scenarios of specific and multiple risk; to provide a vulnerability analysis for three historical churches (San Francisco del Baron, Las Hermanitas de la Providencia, La Matríz, made by various materials - masonry, concrete, wood and adobe - and located in different city sites) and for a building stock in the Cerro Cordillera (partially inside the UNESCO area), analyzing more than 200 constructions; to suggest guidelines for future urban planning and strengthening interventions. In the framework of the MAR VASTO Project, the most important hazards have been investigated carried out. With regard to seismic hazard, "state-of-the-art" information has been provided by Chilean partners and stakeholders, using materials of several studies and stored in original earthquake reports, local newspapers and magazines. The activities performed by the Italian team regarded the definition, for the city of Valparaiso, of earthquake scenarios and maps based on the neo-deterministic approach. With regard to tsunami, the information has been provided by SHOA (Servicio Hidrografico y Oceanografico de la Armada de Chile). Tsunami scenarios and inundation maps (for both the 1906 and 1985 earthquakes) have been evaluated by the Italian team, taking into account also worse scenarios (namely the 1730 seismic event). Landslide hazard (identifying main flow areas and pointing out most affected zones, with a deeper investigation in the Cerro Cordillera, pilot area for the MAR VASTO Project) and fire hazard have been also evaluated. Finally, a GIS database has been developed, to store the hazard maps produced in the project. In addition, the GIS database has been verified by using the data obtained by a DGPS survey, performed during the in situ work in Valparaiso. In the framework of the MAR VASTO Project a building stock located in the Cerro Cordillera, partially inside the UNESCO area, has been investigated. The work done in the above said Cerro Cordillera sector by the Italian team can be considered a pilot experience which would be enlarged to all the Valparaiso City area in the framework of the town planning, actually in progress.

Serial changes and prognostic implications of CT findings in combined pulmonary fibrosis and emphysema: comparison with fibrotic idiopathic interstitial pneumonias alone.

PubMed

Lee, Geewon; Kim, Ki Uk; Lee, Ji Won; Suh, Young Ju; Jeong, Yeon Joo

2017-05-01

Background Although fibrotic idiopathic interstitial pneumonias (IIPs) alone and those combined with pulmonary emphysema are naturally progressive diseases, the process of deterioration and outcomes are variable. Purpose To evaluate and compare serial changes of computed tomography (CT) abnormalities and prognostic predictive factors in fibrotic IIPs alone and those combined with pulmonary emphysema. Material and Methods A total of 148 patients with fibrotic IIPs alone (82 patients) and those combined with pulmonary emphysema (66 patients) were enrolled. Semi-quantitative CT analysis was used to assess the extents of CT characteristics which were evaluated on initial and follow-up CT images. Univariate and multivariate analyses were performed to assess the effects of clinical and CT variables on survival. Results Significant differences were noted between fibrotic scores, as determined using initial CT scans, in the fibrotic IIPs alone (21.22 ± 9.83) and those combined with pulmonary emphysema groups (14.70 ± 7.28) ( P < 0.001). At follow-up CT scans, changes in the extent of ground glass opacities (GGO) were greater ( P = 0.031) and lung cancer was more prevalent ( P = 0.001) in the fibrotic IIPs combined with pulmonary emphysema group. Multivariate Cox proportional hazards analysis showed changes in the extent of GGO (hazard ratio, 1.056) and the presence of lung cancer (hazard ratio, 4.631) were predictive factors of poor survivals. Conclusion Although patients with fibrotic IIPs alone and those combined with pulmonary emphysema have similar mortalities, lung cancer was more prevalent in patients with fibrotic IIPs combined with pulmonary emphysema. Furthermore, changes in the extent of GGO and the presence of lung cancer were independent prognostic factors of poor survivals.

Lactation and Progression to Type 2 Diabetes Mellitus After Gestational Diabetes Mellitus: A Prospective Cohort Study.

PubMed

Gunderson, Erica P; Hurston, Shanta R; Ning, Xian; Lo, Joan C; Crites, Yvonne; Walton, David; Dewey, Kathryn G; Azevedo, Robert A; Young, Stephen; Fox, Gary; Elmasian, Cathie C; Salvador, Nora; Lum, Michael; Sternfeld, Barbara; Quesenberry, Charles P

2015-12-15

Lactation improves glucose metabolism, but its role in preventing type 2 diabetes mellitus (DM) after gestational diabetes mellitus (GDM) remains uncertain. To evaluate lactation and the 2-year incidence of DM after GDM pregnancy. Prospective, observational cohort of women with recent GDM. (ClinicalTrials.gov: NCT01967030). Integrated health care system. 1035 women diagnosed with GDM who delivered singletons at 35 weeks' gestation or later and enrolled in the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy from 2008 to 2011. Three in-person research examinations from 6 to 9 weeks after delivery (baseline) and annual follow-up for 2 years that included 2-hour, 75-g oral glucose tolerance testing; anthropometry; and interviews. Multivariable Weibull regression models evaluated independent associations of lactation measures with incident DM adjusted for potential confounders. Of 1010 women without diabetes at baseline, 959 (95%) were evaluated up to 2 years later; 113 (11.8%) developed incident DM. There were graded inverse associations for lactation intensity at baseline with incident DM and adjusted hazard ratios of 0.64, 0.54, and 0.46 for mostly formula or mixed/inconsistent, mostly lactation, and exclusive lactation versus exclusive formula feeding, respectively (P trend = 0.016). Time-dependent lactation duration showed graded inverse associations with incident DM and adjusted hazard ratios of 0.55, 0.50, and 0.43 for greater than 2 to 5 months, greater than 5 to 10 months, and greater than 10 months, respectively, versus 0 to 2 months (P trend = 0.007). Weight change slightly attenuated hazard ratios. Randomized design is not feasible or desirable for clinical studies of lactation. Higher lactation intensity and longer duration were independently associated with lower 2-year incidences of DM after GDM pregnancy. Lactation may prevent DM after GDM delivery. National Institute of Child Health and Human Development.

Institutional Oversight of Occupational Health and Safety for Research Programs Involving Biohazards

PubMed Central

Dyson, Melissa C; Carpenter, Calvin B; Colby, Lesley A

2017-01-01

Research with hazardous biologic materials (biohazards) is essential to the progress of medicine and science. The field of microbiology has rapidly advanced over the years, partially due to the development of new scientific methods such as recombinant DNA technology, synthetic biology, viral vectors, and the use of genetically modified animals. This research poses a potential risk to personnel as well as the public and the environment. Institutions must have appropriate oversight and take appropriate steps to mitigate the risks of working with these biologic hazards. This article will review responsibilities for institutional oversight of occupational health and safety for research involving biologic hazards. PMID:28662748

Institutional Oversight of Occupational Health and Safety for Research Programs Involving Biohazards.

PubMed

Dyson, Melissa C; Carpenter, Calvin B; Colby, Lesley A

2017-06-01

Research with hazardous biologic materials (biohazards) is essential to the progress of medicine and science. The field of microbiology has rapidly advanced over the years, partially due to the development of new scientific methods such as recombinant DNA technology, synthetic biology, viral vectors, and the use of genetically modified animals. This research poses a potential risk to personnel as well as the public and the environment. Institutions must have appropriate oversight and take appropriate steps to mitigate the risks of working with these biologic hazards. This article will review responsibilities for institutional oversight of occupational health and safety for research involving biologic hazards.

Hazardous materials in aquatic environments of the Mississippi River Basin. Quarterly progress report, July 1, 1995--September 30, 1995

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

NONE

1995-12-01

This report is the quarterly progress report for July through September 1995 for work done by Tulane and Xavier Universities under DOE contract number DE-FG01-93-EW53023. Accomplishments for various tasks including administrative activities, collaborative cluster projects, education projects, initiation projects, coordinated instrumentation facility, and an investigators` retreat are detailed in the report.

Self-reported levels of education and disability progression in multiple sclerosis.

PubMed

D'hooghe, M B; Haentjens, P; Van Remoortel, A; De Keyser, J; Nagels, G

2016-12-01

The purpose of our study is to investigate whether socioeconomic indicators such as education, financial concerns, employment, and living status are associated with disease progression in relapsing-onset and progressive-onset Multiple Sclerosis (MS). We performed a cross-sectional survey among individuals with MS, registered by the Flemish MS society and included socioeconomic indicators. A Cox proportional hazard regression was performed with the time from MS onset and from birth to reach an ambulatory disability milestone corresponding to Expanded Disability Status Scale (EDSS) 6 (requiring a cane) as outcome measure, adjusted for gender, age at MS onset, and immunomodulatory treatment. Among the participants with relapsing-onset MS, subjects reporting education for more than 12 years had a reduced risk of reaching EDSS 6 compared to subjects reporting education for less than 12 years [HR from onset 0.68 (95% CI 0.49-0.95); HR from birth 0.71 (95% CI 0.51-0.99)]. In progressive-onset MS, longer education was associated with an increased hazard to reach EDSS 6 [HR from onset 1.25 (95% CI 0.91-1.70); HR from birth 1.39 (95% CI 1.02-1.90)]. Our study shows an association of self-reported levels of education with disability progression in MS, with the highest level being protective in relapsing-onset MS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hazard avoidance via descent images for safe landing

NASA Astrophysics Data System (ADS)

Yan, Ruicheng; Cao, Zhiguo; Zhu, Lei; Fang, Zhiwen

2013-10-01

In planetary or lunar landing missions, hazard avoidance is critical for landing safety. Therefore, it is very important to correctly detect hazards and effectively find a safe landing area during the last stage of descent. In this paper, we propose a passive sensing based HDA (hazard detection and avoidance) approach via descent images to lower the landing risk. In hazard detection stage, a statistical probability model on the basis of the hazard similarity is adopted to evaluate the image and detect hazardous areas, so that a binary hazard image can be generated. Afterwards, a safety coefficient, which jointly utilized the proportion of hazards in the local region and the inside hazard distribution, is proposed to find potential regions with less hazards in the binary hazard image. By using the safety coefficient in a coarse-to-fine procedure and combining it with the local ISD (intensity standard deviation) measure, the safe landing area is determined. The algorithm is evaluated and verified with many simulated descent downward looking images rendered from lunar orbital satellite images.

Environmental and economic solutions: Pollution prevention technical assistance and the City of Los Angeles Hazardous and Toxic Materials Office

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

Toy-Chen, D.; Joyce, M.M.

1994-12-31

The City of Los Angeles faces a challenge to assist industrial facilities to minimize and manage hazardous materials in order to sustain the local economy and natural environment. Industrial facilities in Los Angeles County released into the environment or transferred off-site 103,442,074 tons of hazardous materials and waste in 1988. This enormous quantity of hazardous waste requires generators to be in compliance with several environmental regulatory agencies. The City of Los Angeles Hazardous and Toxic Materials (HTM) Office has increased the awareness, commitments, and implementation of hazardous waste at the source, the amount of toxic pollutants discharged into the City`smore » publicly owned treatment works, surface and groundwaters, soils and atmosphere can be substantially reduced. Quantifying hazardous waste minimization progress is extremely difficult and complex. However, the HTM Office anticipates that if the challenge of pollution prevention is successful, more businesses will decide to remain in the region and Los Angeles residents will feel convinced that industry is making good faith efforts to protect the environment. Pollution prevention is a long term solution for the hazardous waste crisis that society has only recently recognized.« less

Gestational age-dependent risk factors for preterm birth: associations with maternal education and age early in gestation.

PubMed

Auger, Nathalie; Abrahamowicz, Michal; Wynant, Willy; Lo, Ernest

2014-05-01

Preterm birth (PTB) before 37 weeks can occur over a wide range of gestational ages, but few studies have assessed if associations between risk factors and PTB vary over the duration of gestation. We sought to evaluate if associations between two major risk factors (maternal education and age) and PTB depend on gestational age at delivery. We estimated hazard ratios of PTB for education and age in a time-to-event analysis using a retrospective cohort of 223,756 live singleton births from the province of Québec, Canada for the years 2001-2005. Differences in hazards of maternal education and age with PTB were assessed over gestational age in a Cox proportional hazards model using linear and nonlinear time interaction terms, adjusting for maternal characteristics. Associations of PTB with lower (vs. higher) education and older (vs. younger) age strengthened progressively at earlier gestational ages, such that the risk of PTB for maternal education and age was not constant over the course of gestation. Associations of PTB with risk factors such as maternal low education and older age may be stronger early in gestation. Models that capture the time-dependent nature of PTB may be useful when the goal is to assess associations at low gestational ages, and to avoid masked or biased associations early in gestation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Health hazard evaluation report HETA 84-437-1532, Perry Nuclear Power Plant, Perry, Ohio

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

Moseley, C.L.

1984-11-01

Breathing-zone samples were analyzed for iron, zinc, lead, nickel, and chromium fumes, quartz, cristobalite, and respirable particulates during construction of the Perry Nuclear Power facility, Perry, Ohio in August, 1984. The survey was requested by Local 210 of the Pipefitters Union to evaluate exposure of airborne contaminants to construction workers at the facility. All metal fume and respirable particulates were well below the relevant standards. The author notes that NIOSH conducted two previous surveys at the site and the concentrations of all contaminants have decreased since work has progressed at the facility. The quartz overexposure is due to residual constructionmore » dust. Each contractor should assume responsibility for the health and safety of his employees. Break areas should be vacuumed daily. Good housekeeping practices should be maintained in all areas to prevent exposure to quartz dust.« less

Disaster Risk Reduction in Myanmar: A Need for Focus on Community Preparedness and Improved Evaluation of Initiatives.

PubMed

Smith, Andrew D; Chan, Emily Y Y

2017-11-20

Myanmar is a country in political and economic transition. Facing a wide-variety of natural hazards and ongoing conflict, the country's under-developed infrastructure has resulted in high disaster risk. Following the devastation of Cyclone Nargis in 2008 and increased global focus on disaster management and risk reduction, Myanmar has begun development of national disaster policies. Myanmar's Action Plan for Disaster Risk Reduction addressed multiple stages of disaster development and has made progress towards national projects, however, has struggled to implement community-based preparedness and response initiatives. This article analyses Myanmar's disaster strategy, though the use of a disaster development framework and suggests areas for possible improvement. In particular, the article aims to generate discussion regarding methods of supporting objective evaluation of risk reduction initiatives in developing countries. (Disaster Med Public Health Preparedness. 2017;page 1 of 5).

Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration

PubMed Central

Merle, Bénédicte M. J.; Silver, Rachel E.; Rosner, Bernard; Seddon, Johanna M.

2017-01-01

Purpose There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but no prospective studies have explored the impact of vitamin D. We evaluated the association between vitamin D intake and progression to advanced AMD. Methods Among 2146 participants (3965 eyes), 541 (777 eyes) progressed from early or intermediate AMD to advanced disease (mean follow-up: 9.4 years) based on ocular imaging. Nutrients were log transformed and calorie adjusted. Survival analysis was used to assess associations between incident advanced disease and vitamin D intake. Neovascular disease (NV) and geographic atrophy (GA) were evaluated separately. Combined effects of dietary vitamin D and calcium were assessed based on high or low consumption of each nutrient. Results There was a lower risk of progression to advanced AMD in the highest versus lowest quintile of dietary vitamin D intake after adjustment for demographic, behavioral, ocular, and nutritional factors (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43–0.83; P trend = 0.0007). Similar results were observed for NV (HR: 0.59; 95% CI: 0.39–0.89; P trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53–1.30; P trend = 0.35). A protective effect was observed for advanced AMD among participants with high vitamin D and low calcium compared to the group with low levels for each nutrient (HR: 0.67; 95% CI: 0.50–0.88; P = 0.005). When supplement use was considered, the effect was in the protective direction but was not significant. Conclusions A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially NV. Additional exploration is needed to elucidate the potential protective role of vitamin D and its contribution to reducing visual loss. PMID:28892825

FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study†

PubMed Central

Iwamoto, S.; Takahashi, T.; Tamagawa, H.; Nakamura, M.; Munemoto, Y.; Kato, T.; Hata, T.; Denda, T.; Morita, Y.; Inukai, M.; Kunieda, K.; Nagata, N.; Kurachi, K.; Ina, K.; Ooshiro, M.; Shimoyama, T.; Baba, H.; Oba, K.; Sakamoto, J.; Mishima, H.

2015-01-01

Background A targeted agent combined with chemotherapy is the standard treatment in patients with metastatic colorectal cancer (mCRC). The present phase III study was conducted to compare two doses of bevacizumab combined with irinotecan, 5-fluorouracil/leucovorin (FOLFIRI) in the second-line setting after first-line therapy with bevacizumab plus oxaliplatin-based therapy. Patients and methods Patients were randomly assigned to receive FOLFIRI plus bevacizumab 5 or 10 mg/kg in 2-week cycles until disease progression. The primary end point was progression-free survival (PFS), and secondary end points included overall survival (OS), time to treatment failure (TTF), and safety. Results Three hundred and eighty-seven patients were randomized between September 2009 and January 2012 from 100 institutions in Japan. Baseline patient characteristics were well balanced between the two groups. Efficacy was evaluated in 369 patients (5 mg/kg, n = 181 and 10 mg/kg, n = 188). Safety was evaluated in 365 patients (5 mg/kg, n = 180 and 10 mg/kg, n = 185). The median PFS was 6.1 versus 6.4 months (hazard ratio, 0.95; 95% confidence interval [CI] 0.75–1.21; P = 0.676), and median TTF was 5.2 versus 5.2 months (hazard ratio, 1.01; 95% CI 0.81–1.25; P = 0.967), respectively, for the bevacizumab 5 and 10 mg/kg groups. Follow-up of OS is currently ongoing. Adverse events, including hypertension and hemorrhage, occurred at similar rates in both groups. Conclusion Bevacizumab 10 mg/kg plus FOLFIRI as the second-line treatment did not prolong PFS compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC. If bevacizumab is continued after first-line therapy in mCRC, a dose of 5 mg/kg is appropriate for use as second-line treatment. Clinical trial identifier UMIN000002557. PMID:25908603

Salvage stereotactic radiosurgery for breast cancer brain metastases: outcomes and prognostic factors.

PubMed

Kelly, Paul J; Lin, Nancy U; Claus, Elizabeth B; Quant, Eudocia C; Weiss, Stephanie E; Alexander, Brian M

2012-04-15

Salvage stereotactic radiosurgery (SRS) is often considered in breast cancer patients previously treated for brain metastases. The goal of this study was to analyze clinical outcomes and prognostic factors for survival in the salvage setting. The authors retrospectively examined 79 consecutive breast cancer patients who received salvage SRS (interval of >3 months after initial therapy), 76 of whom (96%) received prior whole-brain radiation therapy. Overall survival (OS) and central nervous system (CNS) progression-free survival rates were calculated from the date of SRS using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Median age was 50.5 years. Fifty-eight percent of this population was estrogen receptor positive, 62% was HER2 positive, and 10% was triple negative. At the time of SRS, 95% had extracranial metastases, with 81% of extracranial metastases at other visceral sites (lung/pleura/liver). Forty-eight percent had stable extracranial disease. Median interval from initial brain metastases therapy to SRS was 8.4 months. Median CNS progression-free survival after SRS was 5.7 months (interquartile range [IQR], 3.6-11 months), and median OS was 9.8 months (IQR, 3.8-18 months). Eighty-two percent of evaluable patients received further systemic therapy after SRS. HER2 status (adjusted hazard ratio [HR], 2.4; P = .008) and extracranial disease status (adjusted HR, 2.7; P = .004) were significant prognostic factors for survival on multivariate analysis. In patients with good Karnofsky performance status, salvage SRS for breast cancer brain metastases is a reasonable treatment option, given an associated median survival in excess of 9 months. Furthermore, patients with HER2-positive tumors at diagnosis or stable extracranial disease at the time of SRS have an improved clinical course, with median survival of >1 year. Copyright © 2011 American Cancer Society.

Serum Wisteria floribunda Agglutinin-Positive Mac-2-Binding Protein Level Predicts Liver Fibrosis and Prognosis in Primary Biliary Cirrhosis.

PubMed

Umemura, Takeji; Joshita, Satoru; Sekiguchi, Tomohiro; Usami, Yoko; Shibata, Soichiro; Kimura, Takefumi; Komatsu, Michiharu; Matsumoto, Akihiro; Ota, Masao; Tanaka, Eiji

2015-06-01

Noninvasive markers of liver fibrosis in patients with primary biliary cirrhosis (PBC) are needed for predicting disease progression. As the Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA(+)-M2BP) was recently established as a liver fibrosis glycobiomarker in chronic hepatitis C, we assessed its efficacy in evaluating liver fibrosis stage and disease progression in PBC. A total of 137 patients with PBC who underwent liver biopsy and serological tests for WFA(+)-M2BP were enrolled. All patients were treated with ursodeoxycholic acid. Clinical data were compared with those for other noninvasive markers (aspartate aminotransferase-to-platelet ratio, FIB-4 index, aspartate aminotransferase/alanine aminotransferase ratio, Forn's index, and Mayo score) for estimating liver fibrosis using receiver operating characteristic analysis. The association between WFA(+)-M2BP and clinical outcome (liver decompensation, liver transplantation, or death) was evaluated using the Cox proportional hazards model with stepwise method. WFA(+)-M2BP was independently associated with liver fibrosis stage as determined by liver biopsy. The cutoff values of WFA(+)-M2BP for fibrosis stages ≥F1, ≥F2, ≥F3, and F4 were 0.7, 1.0, 1.4, and 2.0, respectively. The area under the receiver operating characteristic curve values for significant fibrosis, severe fibrosis, and cirrhosis were 0.979, 0.933, and 0.965, respectively. WFA(+)-M2BP was significantly superior to the other indices for the determination of significant and severe fibrosis stages. Furthermore, the WFA(+)-M2BP level at enrollment was strongly and independently associated with clinical outcome (hazard ratio 18.59, P=0.021). Baseline measurements of WFA(+)-M2BP represent a simple and reliable noninvasive surrogate marker of liver fibrosis and prognosis in patients with PBC.

A RULE-BASED SYSTEM FOR EVALUATING FINAL COVERS FOR HAZARDOUS WASTE LANDFILLS

EPA Science Inventory

This chapter examines how rules are used as a knowledge representation formalism in the domain of hazardous waste management. A specific example from this domain involves performance evaluation of final covers used to close hazardous waste landfills. Final cover design and associ...

Natural phenomena hazards design and evaluation criteria for Department of Energy Facilities

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

NONE

1996-01-01

The Department of Energy (DOE) has issued an Order 420.1 which establishes policy for its facilities in the event of natural phenomena hazards (NPH) along with associated NPH mitigation requirements. This DOE Standard gives design and evaluation criteria for NPH effects as guidance for implementing the NPH mitigation requirements of DOE Order 420.1 and the associated implementation Guides. These are intended to be consistent design and evaluation criteria for protection against natural phenomena hazards at DOE sites throughout the United States. The goal of these criteria is to assure that DOE facilities can withstand the effects of natural phenomena suchmore » as earthquakes, extreme winds, tornadoes, and flooding. These criteria apply to the design of new facilities and the evaluation of existing facilities. They may also be used for modification and upgrading of existing facilities as appropriate. The design and evaluation criteria presented herein control the level of conservatism introduced in the design/evaluation process such that earthquake, wind, and flood hazards are treated on a consistent basis. These criteria also employ a graded approach to ensure that the level of conservatism and rigor in design/evaluation is appropriate for facility characteristics such as importance, hazards to people on and off site, and threat to the environment. For each natural phenomena hazard covered, these criteria consist of the following: Performance Categories and target performance goals as specified in the DOE Order 420.1 NPH Implementation Guide, and DOE-STD-1 021; specified probability levels from which natural phenomena hazard loading on structures, equipment, and systems is developed; and design and evaluation procedures to evaluate response to NPH loads and criteria to assess whether or not computed response is permissible.« less

Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer.

PubMed

Gandhi, Leena; Rodríguez-Abreu, Delvys; Gadgeel, Shirish; Esteban, Emilio; Felip, Enriqueta; De Angelis, Flávia; Domine, Manuel; Clingan, Philip; Hochmair, Maximilian J; Powell, Steven F; Cheng, Susanna Y-S; Bischoff, Helge G; Peled, Nir; Grossi, Francesco; Jennens, Ross R; Reck, Martin; Hui, Rina; Garon, Edward B; Boyer, Michael; Rubio-Viqueira, Belén; Novello, Silvia; Kurata, Takayasu; Gray, Jhanelle E; Vida, John; Wei, Ziwen; Yang, Jing; Raftopoulos, Harry; Pietanza, M Catherine; Garassino, Marina C

2018-04-16

Background First-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial. Methods In this double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations who had received no previous treatment for metastatic disease to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy. Crossover to pembrolizumab monotherapy was permitted among the patients in the placebo-combination group who had verified disease progression. The primary end points were overall survival and progression-free survival, as assessed by blinded, independent central radiologic review. Results After a median follow-up of 10.5 months, the estimated rate of overall survival at 12 months was 69.2% (95% confidence interval [CI], 64.1 to 73.8) in the pembrolizumab-combination group versus 49.4% (95% CI, 42.1 to 56.2) in the placebo-combination group (hazard ratio for death, 0.49; 95% CI, 0.38 to 0.64; P<0.001). Improvement in overall survival was seen across all PD-L1 categories that were evaluated. Median progression-free survival was 8.8 months (95% CI, 7.6 to 9.2) in the pembrolizumab-combination group and 4.9 months (95% CI, 4.7 to 5.5) in the placebo-combination group (hazard ratio for disease progression or death, 0.52; 95% CI, 0.43 to 0.64; P<0.001). Adverse events of grade 3 or higher occurred in 67.2% of the patients in the pembrolizumab-combination group and in 65.8% of those in the placebo-combination group. Conclusions In patients with previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum-based drug resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by Merck; KEYNOTE-189 ClinicalTrials.gov number, NCT02578680 .).

Comparative hazard evaluation of near-infrared diode lasers.

PubMed

Marshall, W J

1994-05-01

Hazard evaluation methods from various laser protection standards differ when applied to extended-source, near-infrared lasers. By way of example, various hazard analyses are applied to laser training systems, which incorporate diode lasers, specifically those that assist in training military or law enforcement personnel in the proper use of weapons by simulating actual firing by the substitution of a beam of near-infrared energy for bullets. A correct hazard evaluation of these lasers is necessary since simulators are designed to be directed toward personnel during normal use. The differences among laser standards are most apparent when determining the hazard class of a laser. Hazard classification is based on a comparison of the potential exposures with the maximum permissible exposures in the 1986 and 1993 versions of the American National Standard for the Safe Use of Lasers, Z136.1, and the accessible emission limits of the federal laser product performance standard. Necessary safety design features of a particular system depend on the hazard class. The ANSI Z136.1-1993 standard provides a simpler and more accurate hazard assessment of low-power, near-infrared, diode laser systems than the 1986 ANSI standard. Although a specific system is evaluated, the techniques described can be readily applied to other near-infrared lasers or laser training systems.

Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909

PubMed Central

Liu, Hongtao; Johnson, Jeffrey L.; Koval, Greg; Malnassy, Greg; Sher, Dorie; Damon, Lloyd E.; Hsi, Eric D.; Bucci, Donna Marie; Linker, Charles A.; Cheson, Bruce D.; Stock, Wendy

2012-01-01

Background In the present study, the prognostic impact of minimal residual disease during treatment on time to progression and overall survival was analyzed prospectively in patients with mantle cell lymphoma treated on the Cancer and Leukemia Group B 59909 clinical trial. Design and Methods Peripheral blood and bone marrow samples were collected during different phases of the Cancer and Leukemia Group B 59909 study for minimal residual disease analysis. Minimal residual disease status was determined by quantitative polymerase chain reaction of IgH and/or BCL-1/JH gene rearrangement. Correlation of minimal residual disease status with time to progression and overall survival was determined. In multivariable analysis, minimal residual disease, and other risk factors were correlated with time to progression. Results Thirty-nine patients had evaluable, sequential peripheral blood and bone marrow samples for minimal residual disease analysis. Using peripheral blood monitoring, 18 of 39 (46%) achieved molecular remission following induction therapy. The molecular remission rate increased from 46 to 74% after one course of intensification therapy. Twelve of 21 minimal residual disease positive patients (57%) progressed within three years of follow up compared to 4 of 18 (22%) molecular remission patients (P=0.049). Detection of minimal residual disease following induction therapy predicted disease progression with a hazard ratio of 3.7 (P=0.016). The 3-year probability of time to progression among those who were in molecular remission after induction chemotherapy was 82% compared to 48% in patients with detectable minimal residual disease. The prediction of time to progression by post-induction minimal residual disease was independent of other prognostic factors in multivariable analysis. Conclusions Detection of minimal residual disease following induction immunochemotherapy was an independent predictor of time to progression following immunochemotherapy and autologous stem cell transplantation for mantle cell lymphoma. The clinical trial was registered at ClinicalTrials.gov: NCT00020943. PMID:22102709

Perspectives on the Application of Mechanistic Information in Chemical Hazard and Dose-Response Assessments

EPA Science Inventory

This overview summarizes several EPA Assessment publications reviewing approaches for applying mechanistic information in human health risk assessment and exploring opportunities for progress in this area.

Use of Flutemetamol F 18-Labeled Positron Emission Tomography and Other Biomarkers to Assess Risk of Clinical Progression in Patients With Amnestic Mild Cognitive Impairment.

PubMed

Wolk, David A; Sadowsky, Carl; Safirstein, Beth; Rinne, Juha O; Duara, Ranjan; Perry, Richard; Agronin, Marc; Gamez, Jose; Shi, Jiong; Ivanoiu, Adrian; Minthon, Lennart; Walker, Zuzana; Hasselbalch, Steen; Holmes, Clive; Sabbagh, Marwan; Albert, Marilyn; Fleisher, Adam; Loughlin, Paul; Triau, Eric; Frey, Kirk; Høgh, Peter; Bozoki, Andrea; Bullock, Roger; Salmon, Eric; Farrar, Gillian; Buckley, Christopher J; Zanette, Michelle; Sherwin, Paul F; Cherubini, Andrea; Inglis, Fraser

2018-05-14

Patients with amnestic mild cognitive impairment (aMCI) may progress to clinical Alzheimer disease (AD), remain stable, or revert to normal. Earlier progression to AD among patients who were β-amyloid positive vs those who were β-amyloid negative has been previously observed. Current research now accepts that a combination of biomarkers could provide greater refinement in the assessment of risk for clinical progression. To evaluate the ability of flutemetamol F 18 and other biomarkers to assess the risk of progression from aMCI to probable AD. In this multicenter cohort study, from November 11, 2009, to January 16, 2014, patients with aMCI underwent positron emission tomography (PET) at baseline followed by local clinical assessments every 6 months for up to 3 years. Patients with aMCI (365 screened; 232 were eligible) were recruited from 28 clinical centers in Europe and the United States. Physicians remained strictly blinded to the results of PET, and the standard of truth was an independent clinical adjudication committee that confirmed or refuted local assessments. Flutemetamol F 18-labeled PET scans were read centrally as either negative or positive by 5 blinded readers with no knowledge of clinical status. Statistical analysis was conducted from February 19, 2014, to January 26, 2018. Flutemetamol F 18-labeled PET at baseline followed by up to 6 clinical visits every 6 months, as well as magnetic resonance imaging and multiple cognitive measures. Time from PET to probable AD or last follow-up was plotted as a Kaplan-Meier survival curve; PET scan results, age, hippocampal volume, and aMCI stage were entered into Cox proportional hazards logistic regression analyses to identify variables associated with progression to probable AD. Of 232 patients with aMCI (118 women and 114 men; mean [SD] age, 71.1 [8.6] years), 98 (42.2%) had positive results detected on PET scan. By 36 months, the rates of progression to probable AD were 36.2% overall (81 of 224 patients), 53.6% (52 of 97) for patients with positive results detected on PET scan, and 22.8% (29 of 127) for patients with negative results detected on PET scan. Hazard ratios for association with progression were 2.51 (95% CI, 1.57-3.99; P < .001) for a positive β-amyloid scan alone (primary outcome measure), 5.60 (95% CI, 3.14-9.98; P < .001) with additional low hippocampal volume, and 8.45 (95% CI, 4.40-16.24; P < .001) when poorer cognitive status was added to the model. A combination of positive results of flutemetamol F 18-labeled PET, low hippocampal volume, and cognitive status corresponded with a high probability of risk of progression from aMCI to probable AD within 36 months.

Real-world effectiveness of everolimus-based therapy versus fulvestrant monotherapy in HR(+)/HER2(-) metastatic breast cancer.

PubMed

Hao, Yanni; Lin, Peggy L; Xie, Jipan; Li, Nanxin; Koo, Valerie; Ohashi, Erika; Wu, Eric Q; Rogerio, Jaqueline

2015-08-01

Assessing real-world effectiveness of everolimus-based therapy (EVE) versus fulvestrant monotherapy (FUL) among postmenopausal women with hormone receptor-positive (HR(+))/HER2(-) metastatic breast cancer (mBC) after progression on nonsteroidal aromatase inhibitor (NSAI). Medical charts of community-based patients who received EVE or FUL for mBC after NSAI were examined. Progression-free survival (PFS), time on treatment and time to chemotherapy were compared using Kaplan-Meier curves and Cox proportional hazards models adjusting for line of therapy and patient characteristics. 192 patients received EVE and 156 FUL. After adjusting for patient characteristics, EVE was associated with significantly longer PFS than FUL (hazard ratio: 0.71; p = 0.045). EVE was associated with better PFS than FUL among NSAI-refractory postmenopausal HR(+)/HER2(-) mBC patients.

An epigenetic signature of adhesion molecules predicts poor prognosis of ovarian cancer patients

PubMed Central

Chang, Ping-Ying; Liao, Yu-Ping; Wang, Hui-Chen; Chen, Yu-Chih; Huang, Rui-Lan; Wang, Yu-Chi; Yuan, Chiou-Chung; Lai, Hung-Cheng

2017-01-01

DNA methylation is a promising biomarker for cancer. The epigenetic effects of cell adhesion molecules may affect the therapeutic outcome and the present study examined their effects on survival in ovarian cancer. We integrated methylomics and genomics datasets in The Cancer Genome Atlas (n = 391) and identified 106 highly methylated adhesion-related genes in ovarian cancer tissues. Univariate analysis revealed the methylation status of eight genes related to progression-free survival. In multivariate Cox regression analysis, four highly methylated genes (CD97, CTNNA1, DLC1, HAPLN2) and three genes (LAMA4, LPP, MFAP4) with low methylation were significantly associated with poor progression-free survival. Low methylation of VTN was an independent poor prognostic factor for overall survival after adjustment for age and stage. Patients who carried any two of CTNNA1, DLC1 or MFAP4 were significantly associated with poor progression-free survival (hazard ratio: 1.59; 95% confidence interval: 1.23, 2.05). This prognostic methylation signature was validated in a methylomics dataset generated in our lab (n = 37, hazard ratio: 16.64; 95% confidence interval: 2.68, 103.14) and in another from the Australian Ovarian Cancer Study (n = 91, hazard ratio: 2.43; 95% confidence interval: 1.11, 5.36). Epigenetics of cell adhesion molecules is related to ovarian cancer prognosis. A more comprehensive methylomics of cell adhesion molecules is needed and may advance personalized treatment with adhesion molecule-related drugs. PMID:28881822

Prognostic value of the pretreatment neutrophil-to-lymphocyte ratio in cervical cancer: a meta-analysis and systematic review.

PubMed

Wu, Jiayuan; Chen, Manyu; Liang, Caixia; Su, Wenmei

2017-02-21

The prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR) in cervical cancer remains controversial. We conducted a meta-analysis based on the data from 13 studies with 3729 patients to evaluate the association between the pretreatment NLR and the clinical outcomes of overall survival and progression-free survival in patients with cervical cancer. The relationship between NLR and clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis indicated that elevated pretreatment NLR was a poor prognostic marker for patients with cervical cancer because it predicted unfavorable overall survival (HR = 1.375, 95% CI: 1.200-1.576) and progression-free survival (HR = 1.646, 95% CI: 1.313-2.065). Increased NLR is also significantly associated with the larger tumor size (OR = 1.780, 95% CI: 1.090-2.908), advanced clinical stage (OR = 2.443, 95% CI: 1.730-3.451), and positive lymph node metastasis (OR = 2.380, 95% CI: 1.775-3.190). By these results, high pretreatment NLR predicted a shorter survival period for patients with cervical cancer, and it could be served as a novel index of prognostic evaluation in patients with cervical cancer.

State of the art in non-animal approaches for skin sensitization testing: from individual test methods towards testing strategies.

PubMed

Ezendam, Janine; Braakhuis, Hedwig M; Vandebriel, Rob J

2016-12-01

The hazard assessment of skin sensitizers relies mainly on animal testing, but much progress is made in the development, validation and regulatory acceptance and implementation of non-animal predictive approaches. In this review, we provide an update on the available computational tools and animal-free test methods for the prediction of skin sensitization hazard. These individual test methods address mostly one mechanistic step of the process of skin sensitization induction. The adverse outcome pathway (AOP) for skin sensitization describes the key events (KEs) that lead to skin sensitization. In our review, we have clustered the available test methods according to the KE they inform: the molecular initiating event (MIE/KE1)-protein binding, KE2-keratinocyte activation, KE3-dendritic cell activation and KE4-T cell activation and proliferation. In recent years, most progress has been made in the development and validation of in vitro assays that address KE2 and KE3. No standardized in vitro assays for T cell activation are available; thus, KE4 cannot be measured in vitro. Three non-animal test methods, addressing either the MIE, KE2 or KE3, are accepted as OECD test guidelines, and this has accelerated the development of integrated or defined approaches for testing and assessment (e.g. testing strategies). The majority of these approaches are mechanism-based, since they combine results from multiple test methods and/or computational tools that address different KEs of the AOP to estimate skin sensitization potential and sometimes potency. Other approaches are based on statistical tools. Until now, eleven different testing strategies have been published, the majority using the same individual information sources. Our review shows that some of the defined approaches to testing and assessment are able to accurately predict skin sensitization hazard, sometimes even more accurate than the currently used animal test. A few defined approaches are developed to provide an estimate of the potency sub-category of a skin sensitizer as well, but these approaches need further independent evaluation with a new dataset of chemicals. To conclude, this update shows that the field of non-animal approaches for skin sensitization has evolved greatly in recent years and that it is possible to predict skin sensitization hazard without animal testing.

American Indian Substance Use: The Hazards for Substance Use Initiation and Progression for Adolescents Aged 14 to 20 Years

ERIC Educational Resources Information Center

Novins, Douglas K.; Baron, Anna E.

2004-01-01

Objective: To describe the risks and risk factors for substance use initiation and progression among a large sample of American Indian (AI) adolescents. Method: Data came from surveys completed by 2,356 AI adolescents aged 14 to 20 years who participated in two or more consecutive waves of a longitudinal study between 1993 and 1996 (response rate…

A joint frailty-copula model between tumour progression and death for meta-analysis.

PubMed

Emura, Takeshi; Nakatochi, Masahiro; Murotani, Kenta; Rondeau, Virginie

2017-12-01

Dependent censoring often arises in biomedical studies when time to tumour progression (e.g., relapse of cancer) is censored by an informative terminal event (e.g., death). For meta-analysis combining existing studies, a joint survival model between tumour progression and death has been considered under semicompeting risks, which induces dependence through the study-specific frailty. Our paper here utilizes copulas to generalize the joint frailty model by introducing additional source of dependence arising from intra-subject association between tumour progression and death. The practical value of the new model is particularly evident for meta-analyses in which only a few covariates are consistently measured across studies and hence there exist residual dependence. The covariate effects are formulated through the Cox proportional hazards model, and the baseline hazards are nonparametrically modeled on a basis of splines. The estimator is then obtained by maximizing a penalized log-likelihood function. We also show that the present methodologies are easily modified for the competing risks or recurrent event data, and are generalized to accommodate left-truncation. Simulations are performed to examine the performance of the proposed estimator. The method is applied to a meta-analysis for assessing a recently suggested biomarker CXCL12 for survival in ovarian cancer patients. We implement our proposed methods in R joint.Cox package.

HPV status and favourable outcome in vulvar squamous cancer.

PubMed

Wakeham, Katie; Kavanagh, Kim; Cuschieri, Kate; Millan, David; Pollock, Kevin G; Bell, Sarah; Burton, Kevin; Reed, Nicholas S; Graham, Sheila V

2017-03-01

It is universally accepted that high-risk human papillomavirus (HR-HPV) is the cause of cervical dysplasia and cancer. More recently, it has been shown that HPV is also a marker of clinical outcome in oropharyngeal cancer. However, contemporary information is lacking on both the prevalence of HPV infection in vulvar cancer (VSCC), its precursor lesion, vulvar intraepithelial neoplasia (VIN) and the influence of HPV-status on the prognosis of this malignancy. We have conducted a detailed population-based study to examine rates of progression of VIN to VSCC, type-specific HPV prevalence in vulvar disease and the influence of HPV status on clinical outcome in VSCC. We observed that the age at which women are diagnosed with VSCC is falling and there is a significant time gap between first diagnosis of VIN and progression to invasive disease. HR-HPV infection was detected in 87% (97/112) cases of VIN and 52% cases (32/62) of VSCC. The presence of HR-HPV in squamous intraepithelial lesion was associated with lower rates of progression to invasive cancer (hazard ratio, 0.22, p = 0.001). In the adjusted analysis, HR-HPV was associated with improved progression-free survival of VSCC compared to those with HPV negative tumours (hazard ratio, 0.32, p = 0.02). © 2016 UICC.

Sarcopenia is associated with incident albuminuria in patients with type 2 diabetes: A retrospective observational study.

PubMed

Bouchi, Ryotaro; Fukuda, Tatsuya; Takeuchi, Takato; Minami, Isao; Yoshimoto, Takanobu; Ogawa, Yoshihiro

2017-11-01

Sarcopenia, defined as age-related loss of skeletal muscle mass and function, increases the risk of albuminuria. However, it has still unknown whether sarcopenia could increase the risk for the progression of albuminuria. A total 238 patients with type 2 diabetes (mean age 64 ± 12 years; 39.2% women) were studied in the present retrospective observational study. The prevalence of sarcopenia was 17.6%. During the median follow-up period of 2.6 years, albuminuria was measured 5.8 ± 1.8 times, and progression of albuminuria was observed in 14.9% of patients with normoalbuminuria, as was 11.5% in those with microalbuminuria. Sarcopenia was significantly associated with both progression (hazard ratio 2.61, 95% confidence interval 1.08-6.31, P = 0.034) and regression (hazard ratio 0.23, 95% confidence interval 0.05-0.98, P = 0.048) of albuminuria by multivariate Cox regression analysis. The present data suggest that sarcopenia is an important determinant of both progression and regression of albuminuria in patients with type 2 diabetes. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Tobacco smoking increases the risk of high-grade dysplasia and cancer among patients with Barrett's esophagus.

PubMed

Coleman, Helen G; Bhat, Shivaram; Johnston, Brian T; McManus, Damian; Gavin, Anna T; Murray, Liam J

2012-02-01

Esophageal adenocarcinoma arises from Barrett's esophagus (BE); patients with this cancer have a poor prognosis. Identification of modifiable lifestyle factors that affect the risk of progression from BE to esophageal adenocarcinoma might prevent its development. We investigated associations among body size, smoking, and alcohol use with progression of BE to neoplasia. We analyzed data from patients with BE identified from the population-based Northern Ireland BE register, diagnosed between 1993 and 2005 with specialized intestinal metaplasia (n = 3167). Data on clinical, demographic, and lifestyle factors related to diagnosis of BE were collected from hospital case notes. We used the Northern Ireland Cancer Registry to identify which of these patients later developed esophageal adenocarcinoma, adenocarcinomas of the gastric cardia, or esophageal high-grade dysplasia. Cox proportional hazards models were used to associate lifestyle factors with risk of progression. By December 31, 2008, 117 of the patients with BE developed esophageal high-grade dysplasia or adenocarcinomas of the esophagus or gastric cardia. Current tobacco smoking was significantly associated with an increased risk of progression (hazard ratio = 2.03; 95% confidence interval, 1.29-3.17) compared with never smoking, and across all strata of smoking intensity. Alcohol consumption was not related to risk of progression. Measures of body size were infrequently reported in endoscopy reports, and body size was not associated with risk of progression. Smoking tobacco increases the risk of progression to cancer or high-grade dysplasia 2-fold among patients with BE, compared with patients with BE that have never smoked. Smoking cessation strategies should be considered for patients with BE. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Feasibility and safety of extended adjuvant temozolomide beyond six cycles for patients with glioblastoma.

PubMed

Hsieh, S Yp; Chan, D Tm; Kam, M Km; Loong, H Hf; Tsang, W K; Poon, D Mc; Ng, S Cp; Poon, W S

2017-12-01

Temozolomide is the first chemotherapeutic agent proven effective for patients with newly diagnosed glioblastoma. The drug is well tolerated for its low toxicity. The current standard practice is concomitant chemoradiotherapy for 6 weeks followed by 6 cycles of adjuvant temozolomide. Some Caucasian studies have suggested that patients might benefit from extended adjuvant cycles of temozolomide (>6 cycles) to lengthen both progression-free survival and overall survival. In the present study, we compared differences in survival and toxicity profile between patients who received conventional 6-cycle temozolomide and those who received more than 6 cycles of temozolomide. Patients with newly diagnosed glioblastoma without progressive disease and completed concomitant chemoradiotherapy during a 4-year period were studied. Progression-free survival was compared using Kaplan-Meier survival curves. t Test, U test, and correlation were chosen accordingly to examine the impact of age, extent of resection, MGMT promoter methylation status and adjuvant cycles on progression-free survival. For factors with a P value of <0.05 in univariate analyses, Cox regression hazard model was adopted to determine the strongest factors related to progression-free survival. The median progression-free survival was 17.0 months for patients who received 6 cycles of temozolomide (n=7) and 43.4 months for those who received more than 6 cycles (n=7) [P=0.007, log-rank test]. Two patients in the former group and one in the latter group encountered grade 1 toxicity and recovered following dose adjustment. Cycles of adjuvant temozolomide were correlated with progression-free survival (P=0.016, hazard ratio=0.68). Extended cycles of temozolomide are safe and feasible for Chinese patients with disease responsive to temozolomide.

Research on preventive technologies for bed-separation water hazard in China coal mines

NASA Astrophysics Data System (ADS)

Gui, Herong; Tong, Shijie; Qiu, Weizhong; Lin, Manli

2018-03-01

Bed-separation water is one of the major water hazards in coal mines. Targeted researches on the preventive technologies are of paramount importance to safe mining. This article studied the restrictive effect of geological and mining factors, such as lithological properties of roof strata, coal seam inclination, water source to bed separations, roof management method, dimensions of mining working face, and mining progress, on the formation of bed-separation water hazard. The key techniques to prevent bed-separation water-related accidents include interception, diversion, destructing the buffer layer, grouting and backfilling, etc. The operation and efficiency of each technique are corroborated in field engineering cases. The results of this study will offer reference to countries with similar mining conditions in the researches on bed-separation water burst and hazard control in coal mines.

40 CFR 265.93 - Preparation, evaluation, and response.

Code of Federal Regulations, 2010 CFR

2010-07-01

... WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT... determining: (1) Whether hazardous waste or hazardous waste constituents have entered the ground water; (2... water; and (3) The concentrations of hazardous waste or hazardous waste constituents in the ground water...

40 CFR 265.93 - Preparation, evaluation, and response.

Code of Federal Regulations, 2011 CFR

2011-07-01

... WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT... determining: (1) Whether hazardous waste or hazardous waste constituents have entered the ground water; (2... water; and (3) The concentrations of hazardous waste or hazardous waste constituents in the ground water...

Association of Host Genetic Risk Factors with the Course of Cytomegalovirus Retinitis in Patients Infected with HIV

PubMed Central

Sezgin, Efe; Van Natta, Mark L.; Ahuja, Alka; Lyon, Alice; Srivastava, Sunil; Troyer, Jennifer L.; O’Brien, Stephen J.; Jabs, Douglas A.

2010-01-01

Purpose To evaluate the effects of previously reported host genetics factors that influence cytomegalovirus (CMV) retinitis incidence, progression to AIDS, and efficacy of highly active antiretroviral therapy (HAART) for mortality, retinitis progression, and retinal detachment in patients with CMV retinitis and AIDS in the era of HAART. Design Prospective, multicenter, observational study. Methods Cox proportional hazards model based genetic association tests examined the influence of IL-10R1_S420L, CCR5Δ32, CCR2-V64I, CCR5 P1, and SDF-3`A polymorphisms among patients with mortality, retinitis progression, and retinal detachment. Participants were 203 European American and 117 African American patients with AIDS and CMV retinitis. Results European American patients with the CCR5 +.P1.+ promoter haplotype showed increased risk for mortality (HR=1.83; 95% CI: 1.00–3.40; P=0.05). Although the same haplotype also trended for increased risk for mortality in African American patients, the result was not significant (HR=2.28; 95% CI: 0.93–5.60; P=0.07). However, this haplotype was associated with faster retinitis progression in African Americans (HR=5.22; 95% CI: 1.54–17.71; P=0.007). Increased risk of retinitis progression was also evident for African American patients with the SDF1-3′A variant (HR=3.89; 95% CI: 1.42–10.60; P=0.008). In addition, the SDF1-3′A variant increased the retinal detachment risk in this patient group (HR=3.05; 95% CI: 1.01–9.16; P=0.05). Conclusion Besides overall immune health, host genetic factors influence mortality, retinitis progression, and retinal detachment in patients with AIDS and CMV retinitis that are receiving HAART. PMID:21396623

PI3K pathway mutations are associated with longer time to local progression after radioembolization of colorectal liver metastases.

PubMed

Ziv, Etay; Bergen, Michael; Yarmohammadi, Hooman; Boas, F Ed; Petre, E Nadia; Sofocleous, Constantinos T; Yaeger, Rona; Solit, David B; Solomon, Stephen B; Erinjeri, Joseph P

2017-04-04

To establish the relationship between common mutations in the MAPK and PI3K signaling pathways and local progression after radioembolization. Retrospective review of a HIPAA-compliant institutional review-board approved database identified 40 patients with chemo-refractory colorectal liver metastases treated with radioembolization who underwent tumor genotyping for hotspot mutations in 6 key genes in the MAPK/PI3K pathways (KRAS, NRAS, BRAF, MEK1, PIK3CA, and AKT1). Mutation status as well as clinical, tumor, and treatment variables were recorded. These factors were evaluated in relation to time to local progression (TTLP), which was calculated from time of radioembolization to first radiographic evidence of local progression. Predictors of outcome were identified using a proportional hazards model for both univariate and multivariate analysis with death as a competing risk. Sixteen patients (40%) had no mutations in either pathway, eighteen patients (45%) had mutations in the MAPK pathway, ten patients (25%) had mutations in the PI3K pathway and four patients (10%) had mutations in both pathways. The cumulative incidence of progression at 6 and 12 months was 33% and 55% for the PI3K mutated group compared with 76% and 92% in the PI3K wild type group. Mutation in the PI3K pathway was a significant predictor of longer TTLP in both univariate (p=0.031, sHR 0.31, 95% CI: 0.11-0.90) and multivariate (p=0.015, sHR=0.27, 95% CI: 0.096-0.77) analysis. MAPK pathway alterations were not associated with TTLP. PI3K pathway mutation predicts longer time to local progression after radioembolization of colorectal liver metastases.

Systemic treatment in advanced biliary cancers: A multicenter Australian analysis and review.

PubMed

Brungs, Daniel; Aghmesheh, Morteza; Sjoquist, Katrin; Goldstein, David

2017-10-01

While first-line palliative chemotherapy (CT1) improves survival and quality of life in advanced biliary cancer (ABC), there is no randomized evidence to support second-line chemotherapy (CT2) in ABC. We aim to explore to role of CT2 in ABC. We performed a retrospective review of all patients who received one or more lines of chemotherapy for ABC at four Australian cancer centers between 2008 and 2011. A Cox proportional hazard model was developed to determine the impact of clinicopathologic variables on overall survival (OS) from time of progression on CT1. We identified 73 patients who received palliative chemotherapy for ABC. Twenty-five patients (34%) received two or more lines of chemotherapy. Patients with a preserved performance status on progression on first-line chemotherapy (CT1) were more likely to receive second-line chemotherapy (CT2) (P < 0.001). Disease control rate with CT2 was 36%, and mean progression-free survival was 3.2 months (95% confidence interval 1.5-4.9 months). The following variables were significant in the univariate analysis of OS from time of progression on CT1: lines of chemotherapy (P = 0.0001), Eastern Cooperative Oncology Group performance status at progression on CT1 (P < 0.0001) and disease control with CT1 (P = 0.027). Lines of chemotherapy received and performance status remained significant in the multivariate analysis for OS from progression on CT1. Second-line chemotherapy is feasible in a subset of patients with ABC. Even after accounting for confounding variables, CT2 appears to increase OS in ABC, although we are unable to exclude other unmeasured factors such as tumor biology. These findings warrant further evaluation with prospective trials. © 2016 John Wiley & Sons Australia, Ltd.

The relationship between BMI and insulin resistance and progression from single to multiple autoantibody positivity and type 1 diabetes among TrialNet Pathway to Prevention participants

PubMed Central

Meah, Farah A.; DiMeglio, Linda A.; Greenbaum, Carla J.; Blum, Janice S.; Sosenko, Jay M.; Pugliese, Alberto; Geyer, Susan; Xu, Ping; Evans-Molina, Carmella

2016-01-01

Aims/hypothesis The incidence of type 1 diabetes is increasing at a rate of 3–5% per year. Genetics cannot fully account for this trend, suggesting an influence of environmental factors. The accelerator hypothesis proposes an effect of metabolic factors on type 1 diabetes risk. To test this in the TrialNet Pathway to Prevention (PTP) cohort, we analysed the influence of BMI, weight status and insulin resistance on progression from single to multiple islet autoantibodies (Aab) and progression from normoglycaemia to diabetes. Methods HOMA1-IR was used to estimate insulin resistance in Aab-positive PTP participants. Cox proportional hazards models were used to evaluate the effects of BMI, BMI percentile (BMI%), weight status and HOMA1-IR on the progression of autoimmunity or the development of diabetes. Results Data from 1,310 single and 1,897 multiple Aab-positive PTP participants were included. We found no significant relationships between BMI, BMI%, weight status or HOMA1-IR and the progression from one to multiple Aabs. Similarly, among all Aab-positive participants, no significant relationships were found between BMI, weight status or HOMA1-IR and progression to diabetes. Diabetes risk was modestly increased with increasing BMI% among the entire cohort, in obese participants 13–20 years of age, and with increasing HOMA1-IR in adult Aab-positive participants. Conclusions/interpretation Analysis of the accelerator hypothesis in the TrialNet PTP cohort does not suggest a broad influence of metabolic variables on diabetes risk. Efforts to identify other potentially modifiable environmental factors should continue. PMID:26995649

Sarcopenia as a Predictor of Future Cognitive Impairment in Older Adults.

PubMed

Moon, J H; Moon, J H; Kim, K M; Choi, S H; Lim, S; Park, K S; Kim, K W; Jang, H C

2016-01-01

We investigated the association between the indices of sarcopenia and future risk of cognitive impairment in older adults. Community-based prospective cohort study. Community. A total of 297 participants aged ≥65 years without cognitive impairment at baseline (mean age, 71.9 ± 6.6 years; men:women, 158:139) and who underwent cognitive evaluation at the 5-year follow-up. Sarcopenia parameters including appendicular lean mass (ALM), handgrip strength, and the Short Physical Performance Battery (SPPB) score at baseline were compared according to the later progression of mild cognitive impairment (MCI) and/or dementia. The operational criteria suggested by the Foundation for the National Institutes of Health Sarcopenia Project were used. We performed multivariate logistic regression analysis to identify the independent indicators of the progression of cognitive impairment. Among the 297 participants, 242 (81.5%) remained cognitively normal (nonprogression group), whereas 55 (18.5%) showed progression of cognitive impairment (50 subjects (16.8%) to MCI and 5 subjects (1.7%) to dementia) (progression group). Compared with the nonprogression group, subjects in the progression group were older, had a lower educational level, and had lower physical function as assessed by the SPPB; a higher percentage were depressed. Other baseline markers of sarcopenia, including the ALM-to-body mass index ratio and handgrip strength did not differ significantly between the groups. The association between a low SPPB score (<9) and progression of cognitive impairment was maintained after adjustment for conventional risk factors for cognitive impairment (hazard ratio 2.222, 95% confidence interval 1.047-4.716, P = 0.038). Decreased physical performance, as assessed by the SPPB, but not other markers of sarcopenia, was independently associated with the risk of later cognitive impairment in older adults.

The effects of AST-120 on chronic kidney disease progression in the United States of America: a post hoc subgroup analysis of randomized controlled trials.

PubMed

Schulman, Gerald; Berl, Tomas; Beck, Gerald J; Remuzzi, Giuseppe; Ritz, Eberhard; Shimizu, Miho; Shobu, Yuko; Kikuchi, Mami

2016-09-30

The orally administered spherical carbon adsorbent AST-120 is used on-label in Asian countries to slow renal disease progression in patients with progressive chronic kidney disease (CKD). Recently, two multinational, randomized, double-blind, placebo-controlled, phase 3 trials (Evaluating Prevention of Progression in Chronic Kidney Disease [EPPIC] trials) examined AST-120's efficacy in slowing CKD progression. This study assessed the efficacy of AST-120 in the subgroup of patients from the United States of America (USA) in the EPPIC trials. In the EPPIC trials, 2035 patients with moderate to severe CKD were studied, of which 583 were from the USA. The patients were randomly assigned to two groups of equal size that were treated with AST-120 or placebo (9 g/day). The primary end point was a composite of dialysis initiation, kidney transplantation, or serum creatinine doubling. The Kaplan-Meier curve for the time to achieve the primary end point in the placebo-treated patients from the USA was similar to that projected before the study. The per protocol subgroup analysis of the population from the USA which included patients with compliance rates of ≥67 % revealed a significant difference between the treatment groups in the time to achieve the primary end point (Hazard Ratio, 0.74; 95 % Confidence Interval, 0.56-0.97). This post hoc subgroup analysis of EPPIC study data suggests that treatment with AST-120 might delay the time to primary end point in CKD patients from the USA. A further randomized controlled trial in progressive CKD patients in the USA is necessary to confirm the beneficial effect of adding AST-120 to standard therapy regimens. ClinicalTrials.gov NCT00500682 ; NCT00501046 .

Associations between Coffee, Tea, and Caffeine Intake with Coronary Artery Calcification and Cardiovascular Events

PubMed Central

Miller, P. Elliott; Zhao, Di; Frazier-Wood, Alexis C.; Michos, Erin D.; Averill, Michelle; Sandfort, Veit; Burke, Gregory L.; Polak, Joseph F.; Lima, Joao A.C.; Post, Wendy S.; Blumenthal, Roger S.; Guallar, Eliseo; Martin, Seth S.

2016-01-01

Background Coffee and tea are two of the most commonly consumed beverages in the world. The association of coffee and tea intake with coronary artery calcium and major adverse cardiovascular events remains uncertain. Methods We examined 6,508 ethnically-diverse participants with available coffee and tea data from the Multi-Ethnic Study of Atherosclerosis. Intake for each was classified as never, occasional (<1 cup/day), and regular (≥1 cup/day). A coronary artery calcium progression ratio was derived from mixed effect regression models using loge(calcium score+1) as the outcome with coefficients exponentiated to reflect coronary artery calcium progression ratio vs. the reference. Cox proportional hazards analyses were used to evaluate the association between beverage intake and incident cardiovascular events. Results Over a median follow-up of 5.3 years for coronary artery calcium and 11.1 years for cardiovascular events, participants who regularly drank tea (≥1 cup/day) had a slower progression of coronary artery calcium compared with never drinkers after multivariable adjustment. This correlated with a statistically significant lower incidence of cardiovascular events for ≥1 cup/day tea drinkers (adjusted HR 0.71; 95% CI 0.53–0.95). Compared to never coffee drinkers, regular coffee intake (≥1 cup/day) was not statistically associated with coronary artery calcium progression or cardiovascular events (adjusted HR 0.97 [0.78, 1.20]). Caffeine intake was marginally inversely associated with coronary artery calcium progression. Conclusions Moderate tea drinkers had slower progression of coronary artery calcium and reduced risk for cardiovascular events. Future research is needed to understand the potentially protective nature of moderate tea intake. PMID:27640739

The Suitport's Progress

NASA Technical Reports Server (NTRS)

Cohen, Marc M.

1995-01-01

NASA-Ames Research Center developed the Suitport as an advanced space suit airlock to support a Space Station suit based on the AX-5 hard suit. Several third parties proposed their own variations of the Suitport on the moon and Mars. The Suitport recently found its first practical use as a terrestrial application in the NASA-Ames Hazmat vehicle for the clean-up of hazardous and toxic materials. In the Hazmat application, the Suitport offers substantial improvements over conventional hazard suits by eliminating the necessity to decontaminate before doffing the suit.

77 FR 41406 - Evaluation of In Vitro Tests for Identifying Eye Injury Hazard Potential of Chemicals and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Evaluation of In Vitro Tests for Identifying Eye Injury...-animal testing strategies proposed for identifying eye injury hazard potential of chemicals and products... Panel and submission of data from substances tested in in vitro tests for identifying eye injury hazard...

Sequencing of Local Therapy Affects the Pattern of Treatment Failure and Survival in Children With Atypical Teratoid Rhabdoid Tumors of the Central Nervous System

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

Pai Panandiker, Atmaram S., E-mail: atmaram.pai-panandiker@stjude.org; Merchant, Thomas E.; Beltran, Chris

Purpose: To assess the pattern of treatment failure associated with current therapeutic paradigms for childhood atypical teratoid rhabdoid tumors (AT/RT). Methods and Materials: Pediatric patients with AT/RT of the central nervous system treated at our institution between 1987 and 2007 were retrospectively evaluated. Overall survival (OS), progression-free survival, and cumulative incidence of local failure were correlated with age, sex, tumor location, extent of disease, and extent of surgical resection. Radiotherapy (RT) sequencing, chemotherapy, dose, timing, and volume administered after resection were also evaluated. Results: Thirty-one patients at a median age of 2.3 years at diagnosis (range, 0.45-16.87 years) were enrolledmore » into protocols that included risk- and age-stratified RT. Craniospinal irradiation with focal tumor bed boost (median dose, 54 Gy) was administered to 18 patients. Gross total resection was achieved in 16. Ten patients presented with metastases at diagnosis. RT was delayed more than 3 months in 20 patients and between 1 and 3 months in 4; 7 patients received immediate postoperative irradiation preceding high-dose alkylator-based chemotherapy. At a median follow-up of 48 months, the cumulative incidence of local treatment failure was 37.5% {+-} 9%; progression-free survival was 33.2% {+-} 10%; and OS was 53.5% {+-} 10%. Children receiving delayed RT ({>=}1 month postoperatively) were more likely to experience local failure (hazard ratio [HR] 1.23, p = 0.007); the development of distant metastases before RT increased the risk of progression (HR 3.49, p = 0.006); and any evidence of disease progressionbefore RT decreased OS (HR 20.78, p = 0.004). Disease progression occurred in 52% (11/21) of children with initially localized tumors who underwent gross total resection, and the progression rate increased proportionally with increasing delay from surgery to RT. Conclusions: Delayed RT is associated with a higher rate of local and metastatic disease progression in children with AT/RT. Current treatment regimens for pediatric patients with AT/RT are distinctly age stratified; novel protocols investigating RT volumes and sequencing are needed.« less

SUPERFUND INNOVATIVE TECHNOLOGY EVALUATION PROGRAM ANNUAL REPORT TO CONGRESS FY2000

EPA Science Inventory

The Superfund Innovative Technology Evaluation Program promotes the development, commercialization, and implementation of innovative hazardous waste treatment technologies. SITE offers a mechanism for conducting joint demonstration and evaluation projects at hazardous waste site...

Validation of International Society of Urological Pathology (ISUP) grading for prostatic adenocarcinoma in thin core biopsies using TROG 03.04 'RADAR' trial clinical data.

PubMed

Delahunt, B; Egevad, L; Srigley, J R; Steigler, A; Murray, J D; Atkinson, C; Matthews, J; Duchesne, G; Spry, N A; Christie, D; Joseph, D; Attia, J; Denham, J W

2015-10-01

In 2014 a consensus conference convened by the International Society of Urological Pathology (ISUP) adopted amendments to the criteria for Gleason grading and scoring (GS) for prostatic adenocarcinoma. The meeting defined a modified grading system based on 5 grading categories (grade 1, GS 3+3; grade 2, GS 3+4; grade 3, GS 4+3; grade 4, GS 8; grade 5, GS 9-10). In this study we have evaluated the prognostic significance of ISUP grading in 496 patients enrolled in the TROG 03.04 RADAR Trial. There were 19 grade 1, 118 grade 2, 193 grade 3, 88 grade 4 and 79 grade 5 tumours in the series, with follow-up for a minimum of 6.5 years. On follow-up 76 patients experienced distant progression of disease, 171 prostate specific antigen (PSA) progression and 39 prostate cancer deaths. In contrast to the 2005 modified Gleason system (MGS), the hazards of the distant and PSA progression endpoints, relative to grade 2, were significantly greater for grades 3, 4 and 5 of the 2014 ISUP grading scheme. Comparison of predictive ability utilising Harrell's concordance index, showed 2014 ISUP grading to significantly out-perform 2005 MGS grading for each of the three clinical endpoints.

Dynamics of EGFR Mutation Load in Plasma for Prediction of Treatment Response and Disease Progression in Patients With EGFR-Mutant Lung Adenocarcinoma.

PubMed

Taus, Álvaro; Camacho, Laura; Rocha, Pedro; Hardy-Werbin, Max; Pijuan, Lara; Piquer, Gabriel; López, Eva; Dalmases, Alba; Longarón, Raquel; Clavé, Sergi; Salido, Marta; Albanell, Joan; Bellosillo, Beatriz; Arriola, Edurne

2018-03-23

The assessment of epidermal growth factor receptor (EGFR) mutations is crucial for the management of patients with lung adenocarcinoma. Circulating tumor DNA (ctDNA)-based assessment offers advantages over tumor as a minimally invasive method able to capture tumor heterogeneity. Consecutive patients diagnosed with EGFR-mutant lung adenocarcinoma in tumor biopsy were included in this study. Plasma samples were obtained at different time points during the course of the disease. EGFR mutations in plasma were quantified using BEAMing (beads, emulsions, amplification, and magnetics) or digital PCR and were correlated with mutations in tumor and with radiologic response and progression. Two hundred twenty-one plasma samples from 33 patients were analyzed. EGFR mutations in plasma were detected in 83% of all patients and 100% of those with extrathoracic metastases. The dynamics of the EGFR mutation load predicted response in 93% and progression in 89% of cases well in advance of radiologic evaluation. Progression-free survival for patients in whom ctDNA was not detected in plasma during treatment was significantly longer than for those in whom ctDNA remained detectable (295 vs. 55 days; hazard ratio, 17.1; P < .001). The detection of EGFR mutations in ctDNA showed good correlation with that in tumor biopsy and predicted tumor response and progression in most patients. The liquid biopsy for ctDNA-based assessment of EGFR mutations is a reliable technique for diagnosis and follow-up in patients with EGFR-mutant lung adenocarcinoma in routine clinical practice. Copyright © 2018 Elsevier Inc. All rights reserved.

30 CFR 47.21 - Identifying hazardous chemicals.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Identifying hazardous chemicals. 47.21 Section... TRAINING HAZARD COMMUNICATION (HazCom) Hazard Determination § 47.21 Identifying hazardous chemicals. The operator must evaluate each chemical brought on mine property and each chemical produced on mine property...

30 CFR 47.21 - Identifying hazardous chemicals.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Identifying hazardous chemicals. 47.21 Section... TRAINING HAZARD COMMUNICATION (HazCom) Hazard Determination § 47.21 Identifying hazardous chemicals. The operator must evaluate each chemical brought on mine property and each chemical produced on mine property...

30 CFR 47.21 - Identifying hazardous chemicals.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Identifying hazardous chemicals. 47.21 Section... TRAINING HAZARD COMMUNICATION (HazCom) Hazard Determination § 47.21 Identifying hazardous chemicals. The operator must evaluate each chemical brought on mine property and each chemical produced on mine property...

30 CFR 47.21 - Identifying hazardous chemicals.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Identifying hazardous chemicals. 47.21 Section... TRAINING HAZARD COMMUNICATION (HazCom) Hazard Determination § 47.21 Identifying hazardous chemicals. The operator must evaluate each chemical brought on mine property and each chemical produced on mine property...

30 CFR 47.21 - Identifying hazardous chemicals.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Identifying hazardous chemicals. 47.21 Section... TRAINING HAZARD COMMUNICATION (HazCom) Hazard Determination § 47.21 Identifying hazardous chemicals. The operator must evaluate each chemical brought on mine property and each chemical produced on mine property...

76 FR 4823 - Hazardous Waste Management System; Identifying and Listing Hazardous Waste Exclusion

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-27

... Waste Management System; Identifying and Listing Hazardous Waste Exclusion AGENCY: Environmental... hazardous wastes. The Agency has decided to grant the petition based on an evaluation of waste-specific... excludes the petitioned waste from the requirements of hazardous waste regulations under the Resource...

INTERNAL HAZARDS ANALYSIS FOR LICENSE APPLICATION

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

R.J. Garrett

2005-02-17

The purpose of this internal hazards analysis is to identify and document the internal hazards and potential initiating events associated with preclosure operations of the repository at Yucca Mountain. Internal hazards are those hazards presented by the operation of the facility and by its associated processes that can potentially lead to a radioactive release or cause a radiological hazard. In contrast to external hazards, internal hazards do not involve natural phenomena and external man-made hazards. This internal hazards analysis was performed in support of the preclosure safety analysis and the License Application for the Yucca Mountain Project. The methodology formore » this analysis provides a systematic means to identify internal hazards and potential initiating events that may result in a radiological hazard or radiological release during the repository preclosure period. These hazards are documented in tables of potential internal hazards and potential initiating events (Section 6.6) for input to the repository event sequence categorization process. The results of this analysis will undergo further screening and analysis based on the criteria that apply to the performance of event sequence analyses for the repository preclosure period. The evolving design of the repository will be re-evaluated periodically to ensure that internal hazards that have not been previously evaluated are identified.« less

Incorporating natural hazard assessments into municipal master-plans; case-studies from Israel

NASA Astrophysics Data System (ADS)

Katz, Oded

2010-05-01

The active Dead Sea Rift (DSR) runs along the length of Israel, making the entire state susceptible to earthquake-related hazards. Current building codes generally acknowledge seismic hazards and direct engineers towards earthquake-resistant structures. However, hazard mapping on a scale fit for municipal/governmental planning is subject to local initiative and is currently not mandatory as seems necessary. In the following, a few cases of seismic-hazard evaluation made by the Geological Survey of Israel are presented, emphasizing the reasons for their initiation and the way results were incorporated (or not). The first case is a seismic hazard qualitative micro-zonation invited by the municipality of Jerusalem as part of a new master plan. This work resulted in maps (1:50,000; GIS format) identifying areas prone to (1) amplification of seismic shaking due to site characteristics (outcrops of soft rocks or steep topography) and (2) sites with earthquake induced landslide (EILS) hazard. Results were validated using reports from the 1927, M=6.2 earthquake that originated along the DSR about 30km east of Jerusalem. Although the hazard maps were accepted by municipal authorities, practical use by geotechnical engineers working within the frame of the new master-plan was not significant. The main reason for that is apparently a difference of opinion between the city-engineers responsible for implementing the new master-plan and the geologists responsible of the hazard evaluation. The second case involves evaluation of EILS hazard for two towns located further north along the DSR, Zefat and Tiberias. Both were heavily damaged more than once by strong earthquakes in past centuries. Work was carried out as part of a governmental seismic-hazard reduction program. The results include maps (1:10,000 scales) of sites with high EILS hazard identified within city limits. Maps (in GIS format) were sent to city engineers with reports explaining the methods and results. As far as we know, widespread implementation of the maps within municipal master plans never came about, and there was no open discussion between city engineers and the Geological Survey. The main reasons apparently are (1) a lack, until recently, of mandatory building codes requiring incorporation of EILS hazard; (2) budget priorities; (3) failure to involve municipality personnel in planning and executing the EILS hazard evaluation. These cases demonstrate that for seismic hazard data to be incorporated and implemented within municipal master-plans there needs to be (1) active involvement of municipal officials and engineers from the early planning stages of the evaluation campaign, and (2) a-priori dedication of funds towards implementation of evaluation results.

Influence of potential sea level rise on societal vulnerability to hurricane storm-surge hazards, Sarasota County, Florida

USGS Publications Warehouse

Frazier, T.G.; Wood, N.; Yarnal, B.; Bauer, D.H.

2010-01-01

Although the potential for hurricanes under current climatic conditions continue to threaten coastal communities, there is concern that climate change, specifically potential increases in sea level, could influence the impacts of future hurricanes. To examine the potential effect of sea level rise on community vulnerability to future hurricanes, we assess variations in socioeconomic exposure in Sarasota County, FL, to contemporary hurricane storm-surge hazards and to storm-surge hazards enhanced by sea level rise scenarios. Analysis indicates that significant portions of the population, economic activity, and critical facilities are in contemporary and future hurricane storm-surge hazard zones. The addition of sea level rise to contemporary storm-surge hazard zones effectively causes population and asset (infrastructure, natural resources, etc) exposure to be equal to or greater than what is in the hazard zone of the next higher contemporary Saffir-Simpson hurricane category. There is variability among communities for this increased exposure, with greater increases in socioeconomic exposure due to the addition of sea level rise to storm-surge hazard zones as one progresses south along the shoreline. Analysis of the 2050 comprehensive land use plan suggests efforts to manage future growth in residential, economic and infrastructure development in Sarasota County may increase societal exposure to hurricane storm-surge hazards. ?? 2010 Elsevier Ltd.

Influence of potential sea level rise on societal vulnerability to hurricane storm-surge hazards, Sarasota County, Florida

USGS Publications Warehouse

Frazier, Tim G.; Wood, Nathan; Yarnal, Brent; Bauer, Denise H.

2010-01-01

Although the potential for hurricanes under current climatic conditions continue to threaten coastal communities, there is concern that climate change, specifically potential increases in sea level, could influence the impacts of future hurricanes. To examine the potential effect of sea level rise on community vulnerability to future hurricanes, we assess variations in socioeconomic exposure in Sarasota County, FL, to contemporary hurricane storm-surge hazards and to storm-surge hazards enhanced by sea level rise scenarios. Analysis indicates that significant portions of the population, economic activity, and critical facilities are in contemporary and future hurricane storm-surge hazard zones. The addition of sea level rise to contemporary storm-surge hazard zones effectively causes population and asset (infrastructure, natural resources, etc) exposure to be equal to or greater than what is in the hazard zone of the next higher contemporary Saffir–Simpson hurricane category. There is variability among communities for this increased exposure, with greater increases in socioeconomic exposure due to the addition of sea level rise to storm-surge hazard zones as one progresses south along the shoreline. Analysis of the 2050 comprehensive land use plan suggests efforts to manage future growth in residential, economic and infrastructure development in Sarasota County may increase societal exposure to hurricane storm-surge hazards.

The SAMCO Web-platform for resilience assessment in mountainous valleys impacted by landslide risks.

NASA Astrophysics Data System (ADS)

Grandjean, Gilles; Thomas, Loic; Bernardie, Severine

2016-04-01

The ANR-SAMCO project aims to develop a proactive resilience framework enhancing the overall resilience of societies on the impacts of mountain risks. The project aims to elaborate methodological tools to characterize and measure ecosystem and societal resilience from an operative perspective on three mountain representative case studies. To achieve this objective, the methodology is split in several points: (1) the definition of the potential impacts of global environmental changes (climate system, ecosystem e.g. land use, socio-economic system) on landslide hazards, (2) the analysis of these consequences in terms of vulnerability (e.g. changes in the location and characteristics of the impacted areas and level of their perturbation) and (3) the implementation of a methodology for quantitatively investigating and mapping indicators of mountain slope vulnerability exposed to several hazard types, and the development of a GIS-based demonstration platform available on the web. The strength and originality of the SAMCO project lies in the combination of different techniques, methodologies and models (multi-hazard assessment, risk evolution in time, vulnerability functional analysis, and governance strategies) that are implemented in a user-oriented web-platform, currently in development. We present the first results of this development task, architecture and functions of the web-tools, the case studies database showing the multi-hazard maps and the stakes at risks. Risk assessment over several area of interest in Alpine or Pyrenean valleys are still in progress, but the first analyses are presented for current and future periods for which climate change and land-use (economical, geographical and social aspects) scenarios are taken into account. This tool, dedicated to stakeholders, should be finally used to evaluate resilience of mountainous regions since multiple scenarios can be tested and compared.

Transuranic solid waste management programs. Progress report, July--December 1975

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

Not Available

1976-09-01

Progress is reported for three transuranic solid waste management programs funded at the Los Alamos Scientific Laboratory (LASL) by the Energy Research and Development Administration (ERDA) Division of Fuel Cycle and Production (NFCP). Under the Transuranic Waste Research and Development Program, continued studies have shown the potential attractiveness of fiber drums as an acceptable substitute for the current mild steel storage containers. Various fire retardants have been evaluated, with one indicating significant ability to inhibit fire propagation. Continued radiolysis studies, under laboratory and field conditions, continue to reaffirm earlier LASL results indicating no significant hazard from radiolytic reactions, assuming nomore » change in current allowable loadings. Care must be exercised to differentiate between radiolytic and chemical reactions. Other efforts have identified a modification of chemical processing to reduce the amounts of plutonium requiring retrievable storage. Studies are also in progress to enhance the sensitivity of the LASL MEGAS assay system. The Transuranic-Contaminated Solid Waste Treatment Development Facility building was 72 percent complete as of December 31, 1975, which is in accord with the existing schedule. Procurement of process components is also on schedule. Certain modifications to the facility have been made, and various pre-facility experiments on waste container handling and processing have been completed. The program for the Evaluation of Transuranic-Contaminated Radioactive Waste Disposal Areas continued development of various computer modules for simulation of radionuclide transport within the biosphere. In addition, program staff contributed to an ERDA document on radioactive waste management through the preparation of a report on burial of radioactive waste at ERDA-contractor and commercial sites.« less

Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma.

PubMed

Bellmunt, Joaquim; de Wit, Ronald; Vaughn, David J; Fradet, Yves; Lee, Jae-Lyun; Fong, Lawrence; Vogelzang, Nicholas J; Climent, Miguel A; Petrylak, Daniel P; Choueiri, Toni K; Necchi, Andrea; Gerritsen, Winald; Gurney, Howard; Quinn, David I; Culine, Stéphane; Sternberg, Cora N; Mai, Yabing; Poehlein, Christian H; Perini, Rodolfo F; Bajorin, Dean F

2017-03-16

Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options. In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine. The coprimary end points were overall survival and progression-free survival, which were assessed among all patients and among patients who had a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1-expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10% or more. The median overall survival in the total population was 10.3 months (95% confidence interval [CI], 8.0 to 11.8) in the pembrolizumab group, as compared with 7.4 months (95% CI, 6.1 to 8.3) in the chemotherapy group (hazard ratio for death, 0.73; 95% CI, 0.59 to 0.91; P=0.002). The median overall survival among patients who had a tumor PD-L1 combined positive score of 10% or more was 8.0 months (95% CI, 5.0 to 12.3) in the pembrolizumab group, as compared with 5.2 months (95% CI, 4.0 to 7.4) in the chemotherapy group (hazard ratio, 0.57; 95% CI, 0.37 to 0.88; P=0.005). There was no significant between-group difference in the duration of progression-free survival in the total population (hazard ratio for death or disease progression, 0.98; 95% CI, 0.81 to 1.19; P=0.42) or among patients who had a tumor PD-L1 combined positive score of 10% or more (hazard ratio, 0.89; 95% CI, 0.61 to 1.28; P=0.24). Fewer treatment-related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group (60.9% vs. 90.2%); there were also fewer events of grade 3, 4, or 5 severity reported in the pembrolizumab group than in the chemotherapy group (15.0% vs. 49.4%). Pembrolizumab was associated with significantly longer overall survival (by approximately 3 months) and with a lower rate of treatment-related adverse events than chemotherapy as second-line therapy for platinum-refractory advanced urothelial carcinoma. (Funded by Merck; KEYNOTE-045 ClinicalTrials.gov number, NCT02256436 .).

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy.

PubMed

Sehi, M; Bhardwaj, N; Chung, Y S; Greenfield, D S

2012-12-01

The objective of this study is to assess whether baseline optic nerve head (ONH) topography and retinal nerve fiber layer thickness (RNFLT) are predictive of glaucomatous visual-field progression in glaucoma suspect (GS) and glaucomatous eyes, and to calculate the level of risk associated with each of these parameters. Participants with ≥28 months of follow-up were recruited from the longitudinal Advanced Imaging for Glaucoma Study. All eyes underwent standard automated perimetry (SAP), confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography (TDOCT), and scanning laser polarimetry using enhanced corneal compensation (SLPECC) every 6 months. Visual-field progression was assessed using pointwise linear-regression analysis of SAP sensitivity values (progressor) and defined as significant sensitivity loss of >1 dB/year at ≥2 adjacent test locations in the same hemifield at P<0.01. Cox proportional hazard ratios (HR) were calculated to determine the predictive ability of baseline ONH and RNFL parameters for SAP progression using univariate and multivariate models. Seventy-three eyes of 73 patients (43 GS and 30 glaucoma, mean age 63.2±9.5 years) were enrolled (mean follow-up 51.5±11.3 months). Four of 43 GS (9.3%) and 6 of 30 (20%) glaucomatous eyes demonstrated progression. Mean time to progression was 50.8±11.4 months. Using multivariate models, abnormal CSLO temporal-inferior Moorfields classification (HR=3.76, 95% confidence interval (CI): 1.02-6.80, P=0.04), SLPECC inferior RNFLT (per -1 μm, HR=1.38, 95% CI: 1.02-2.2, P=0.02), and TDOCT inferior RNFLT (per -1 μm, HR=1.11, 95% CI: 1.04-1.2, P=0.001) had significant HRs for SAP progression. Abnormal baseline ONH topography and reduced inferior RNFL are predictive of SAP progression in GS and glaucomatous eyes.

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy

PubMed Central

Sehi, M; Bhardwaj, N; Chung, Y S; Greenfield, D S

2012-01-01

Purpose The objective of this study is to assess whether baseline optic nerve head (ONH) topography and retinal nerve fiber layer thickness (RNFLT) are predictive of glaucomatous visual-field progression in glaucoma suspect (GS) and glaucomatous eyes, and to calculate the level of risk associated with each of these parameters. Methods Participants with ≥28 months of follow-up were recruited from the longitudinal Advanced Imaging for Glaucoma Study. All eyes underwent standard automated perimetry (SAP), confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography (TDOCT), and scanning laser polarimetry using enhanced corneal compensation (SLPECC) every 6 months. Visual-field progression was assessed using pointwise linear-regression analysis of SAP sensitivity values (progressor) and defined as significant sensitivity loss of >1 dB/year at ≥2 adjacent test locations in the same hemifield at P<0.01. Cox proportional hazard ratios (HR) were calculated to determine the predictive ability of baseline ONH and RNFL parameters for SAP progression using univariate and multivariate models. Results Seventy-three eyes of 73 patients (43 GS and 30 glaucoma, mean age 63.2±9.5 years) were enrolled (mean follow-up 51.5±11.3 months). Four of 43 GS (9.3%) and 6 of 30 (20%) glaucomatous eyes demonstrated progression. Mean time to progression was 50.8±11.4 months. Using multivariate models, abnormal CSLO temporal-inferior Moorfields classification (HR=3.76, 95% confidence interval (CI): 1.02–6.80, P=0.04), SLPECC inferior RNFLT (per −1 μm, HR=1.38, 95% CI: 1.02–2.2, P=0.02), and TDOCT inferior RNFLT (per −1 μm, HR=1.11, 95% CI: 1.04–1.2, P=0.001) had significant HRs for SAP progression. Conclusion Abnormal baseline ONH topography and reduced inferior RNFL are predictive of SAP progression in GS and glaucomatous eyes. PMID:23060026

Multi-factor evaluation indicator method for the risk assessment of atmospheric and oceanic hazard group due to the attack of tropical cyclones

NASA Astrophysics Data System (ADS)

Qi, Peng; Du, Mei

2018-06-01

China's southeast coastal areas frequently suffer from storm surge due to the attack of tropical cyclones (TCs) every year. Hazards induced by TCs are complex, such as strong wind, huge waves, storm surge, heavy rain, floods, and so on. The atmospheric and oceanic hazards cause serious disasters and substantial economic losses. This paper, from the perspective of hazard group, sets up a multi-factor evaluation method for the risk assessment of TC hazards using historical extreme data of concerned atmospheric and oceanic elements. Based on the natural hazard dynamic process, the multi-factor indicator system is composed of nine natural hazard factors representing intensity and frequency, respectively. Contributing to the indicator system, in order of importance, are maximum wind speed by TCs, attack frequency of TCs, maximum surge height, maximum wave height, frequency of gusts ≥ Scale 8, rainstorm intensity, maximum tidal range, rainstorm frequency, then sea-level rising rate. The first four factors are the most important, whose weights exceed 10% in the indicator system. With normalization processing, all the single-hazard factors are superposed by multiplying their weights to generate a superposed TC hazard. The multi-factor evaluation indicator method was applied to the risk assessment of typhoon-induced atmospheric and oceanic hazard group in typhoon-prone southeast coastal cities of China.

Prognostic significance of hyperfibrinogenemia in patients with esophageal squamous cell carcinoma.

PubMed

Suzuki, Takashi; Shimada, Hideaki; Nanami, Tatsuki; Oshima, Yoko; Yajima, Satoshi; Washizawa, Naohiro; Kaneko, Hironori

2017-06-01

Preoperative hyperfibrinogenemia is associated with inflammatory mediators and a poor prognosis in several types of cancer. However, there is no published information on the monitoring of patients with preoperative hyperfibrinogenemia after surgery. The aim of the study reported here was to assess the clinicopathological and prognostic significance of plasma fibrinogen levels in patients with esophageal squamous cell carcinoma before and after surgical treatment. Plasma fibrinogen levels were analyzed before surgical treatment (endoscopic submucosal dissection and surgery) in 82 patients with esophageal squamous cell carcinoma. The clinicopathological significance of plasma fibrinogen levels and the relationship of plasma fibrinogen levels with several biomarkers were evaluated. The cutoff value for hyperfibrinogenemia was 321 mg/dl. Univariate and multivariate analysis using the Cox proportional hazards model were performed to evaluate the prognostic significance of plasma fibrinogen levels. The changing patterns of plasma fibrinogen were monitored after surgical treatment to evaluate prognostic impact. Hyperfibrinogenemia was significantly associated with advanced pathological stage of cancer and high C-reactive protein levels. Plasma fibrinogen levels significantly decreased after surgical treatment in recurrence-free patients but did not decrease in patients with recurrence. The multivariate analysis indicated that preoperative hyperfibrinogenemia was an independent prognostic factor for poor survival (hazard ratio 1.005, 95% confidence interval 1.000-1.010; P = 0.039). Preoperative hyperfibrinogenemia was associated with inflammatory mediators, tumor progression, and poor survival in patients with esophageal squamous cell carcinoma. The absence of a decrease in plasma fibrinogen levels after surgical treatment may indicate the possibility of tumor recurrence.

SURF IA Conflict Detection and Resolution Algorithm Evaluation

NASA Technical Reports Server (NTRS)

Jones, Denise R.; Chartrand, Ryan C.; Wilson, Sara R.; Commo, Sean A.; Barker, Glover D.

2012-01-01

The Enhanced Traffic Situational Awareness on the Airport Surface with Indications and Alerts (SURF IA) algorithm was evaluated in a fast-time batch simulation study at the National Aeronautics and Space Administration (NASA) Langley Research Center. SURF IA is designed to increase flight crew situation awareness of the runway environment and facilitate an appropriate and timely response to potential conflict situations. The purpose of the study was to evaluate the performance of the SURF IA algorithm under various runway scenarios, multiple levels of conflict detection and resolution (CD&R) system equipage, and various levels of horizontal position accuracy. This paper gives an overview of the SURF IA concept, simulation study, and results. Runway incursions are a serious aviation safety hazard. As such, the FAA is committed to reducing the severity, number, and rate of runway incursions by implementing a combination of guidance, education, outreach, training, technology, infrastructure, and risk identification and mitigation initiatives [1]. Progress has been made in reducing the number of serious incursions - from a high of 67 in Fiscal Year (FY) 2000 to 6 in FY2010. However, the rate of all incursions has risen steadily over recent years - from a rate of 12.3 incursions per million operations in FY2005 to a rate of 18.9 incursions per million operations in FY2010 [1, 2]. The National Transportation Safety Board (NTSB) also considers runway incursions to be a serious aviation safety hazard, listing runway incursion prevention as one of their most wanted transportation safety improvements [3]. The NTSB recommends that immediate warning of probable collisions/incursions be given directly to flight crews in the cockpit [4].

Sensing Hazards with Operational Unmanned Technology

NASA Astrophysics Data System (ADS)

Hood, R. E.

2016-12-01

The Unmanned Aircraft Systems (UAS) Program of the National Oceanic and Atmospheric Administration (NOAA) is working with the National Weather Service, the National Ocean Service, other Federal agencies, private industry, and academia to evaluate the feasibility of UAS observations to provide time critical information needed for situational awareness, prediction, warning, and damage assessment of hazards. This activity is managed within a portfolio of projects entitled "Sensing Hazards with Operational Unmanned Technology (SHOUT)." The diversity of this portfolio includes evaluations of high altitude UAS observations for high impact oceanic storms prediction to low altitude UAS observations of rivers, severe storms, and coastal areas for pre-hazard situational awareness and post-hazard damage assessments. Each SHOUT evaluation project begins with a proof-of-concept field demonstration of a UAS observing strategy for a given hazard and then matures to joint studies of both scientific data impact along with cost and operational feasibility of the observing strategy for routine applications. The technology readiness and preliminary evaulation results will be presented for several UAS observing strategies designed for improved observations of oceanic storms, floods, severe storms, and coastal ecosystem hazards.

Probabilistic seismic hazard analyses for ground motions and fault displacement at Yucca Mountain, Nevada

USGS Publications Warehouse

Stepp, J.C.; Wong, I.; Whitney, J.; Quittmeyer, R.; Abrahamson, N.; Toro, G.; Young, S.R.; Coppersmith, K.; Savy, J.; Sullivan, T.

2001-01-01

Probabilistic seismic hazard analyses were conducted to estimate both ground motion and fault displacement hazards at the potential geologic repository for spent nuclear fuel and high-level radioactive waste at Yucca Mountain, Nevada. The study is believed to be the largest and most comprehensive analyses ever conducted for ground-shaking hazard and is a first-of-a-kind assessment of probabilistic fault displacement hazard. The major emphasis of the study was on the quantification of epistemic uncertainty. Six teams of three experts performed seismic source and fault displacement evaluations, and seven individual experts provided ground motion evaluations. State-of-the-practice expert elicitation processes involving structured workshops, consensus identification of parameters and issues to be evaluated, common sharing of data and information, and open exchanges about the basis for preliminary interpretations were implemented. Ground-shaking hazard was computed for a hypothetical rock outcrop at -300 m, the depth of the potential waste emplacement drifts, at the designated design annual exceedance probabilities of 10-3 and 10-4. The fault displacement hazard was calculated at the design annual exceedance probabilities of 10-4 and 10-5.

Too easily lead? Health effects of gasoline additives.

PubMed Central

Menkes, D B; Fawcett, J P

1997-01-01

Octane-enhancing constituents of gasoline pose a number of health hazards. This paper considers the relative risks of metallic (lead, manganese), aromatic (e.g., benzene), and oxygenated additives in both industrialized and developing countries. Technological advances, particularly in industrialized countries, have allowed the progressive removal of lead from gasoline and the increased control of exhaust emissions. The developing world, by contrast, has relatively lax environmental standards and faces serious public health problems from vehicle exhaust and the rapid increase in automobile use. Financial obstacles to the modernization of refineries and vehicle fleets compound this problem and the developing world continues to import large quantities of lead additives and other hazardous materials. Progress in decreasing environmental health problems depends both on the adoption of international public health standards as well as efforts to decrease dependence on the private automobile for urban transport. Images Figure 1. Figure 2. PMID:9171982

Accident hazard evaluation and control decisions on forested recreation sites

Treesearch

Lee A. Paine

1971-01-01

Accident hazard associated with trees on recreation sites is inherently concerned with probabilities. The major factors include the probabilities of mechanical failure and of target impact if failure occurs, the damage potential of the failure, and the target value. Hazard may be evaluated as the product of these factors; i.e., expected loss during the current...

The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial: a randomised double-blind placebo-controlled parallel-group multicentre trial and economic evaluation of cannabinoids to slow progression in multiple sclerosis.

PubMed

Ball, Susan; Vickery, Jane; Hobart, Jeremy; Wright, Dave; Green, Colin; Shearer, James; Nunn, Andrew; Cano, Mayam Gomez; MacManus, David; Miller, David; Mallik, Shahrukh; Zajicek, John

2015-02-01

The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial aimed to determine whether or not oral Δ(9)-tetrahydrocannabinol (Δ(9)-THC) slowed the course of progressive multiple sclerosis (MS); evaluate safety of cannabinoid administration; and, improve methods for testing treatments in progressive MS. There were three objectives in the CUPID study: (1) to evaluate whether or not Δ(9)-THC could slow the course of progressive MS; (2) to assess the long-term safety of Δ(9)-THC; and (3) to explore newer ways of conducting clinical trials in progressive MS. The CUPID trial was a randomised, double-blind, placebo-controlled, parallel-group, multicentre trial. Patients were randomised in a 2 : 1 ratio to Δ(9)-THC or placebo. Randomisation was balanced according to Expanded Disability Status Scale (EDSS) score, study site and disease type. Analyses were by intention to treat, following a pre-specified statistical analysis plan. A cranial magnetic resonance imaging (MRI) substudy, Rasch measurement theory (RMT) analyses and an economic evaluation were undertaken. Twenty-seven UK sites. Adults aged 18-65 years with primary or secondary progressive MS, 1-year evidence of disease progression and baseline EDSS 4.0-6.5. Oral Δ(9)-THC (maximum 28 mg/day) or matching placebo. Three and 6 months, and then 6-monthly up to 36 or 42 months. Primary outcomes were time to EDSS progression, and change in Multiple Sclerosis Impact Scale-29 version 2 (MSIS-29v2) 20-point physical subscale (MSIS-29phys) score. Various secondary patient- and clinician-reported outcomes and MRI outcomes were assessed. RMT analyses examined performance of MS-specific rating scales as measurement instruments and tested for a symptomatic or disease-modifying treatment effect. Economic evaluation estimated mean incremental costs and quality-adjusted life-years (QALYs). Effectiveness - recruitment targets were achieved. Of the 498 randomised patients (332 to active and 166 to placebo), 493 (329 active and 164 placebo) were analysed. no significant treatment effect; hazard ratio EDSS score progression (active : placebo) 0.92 [95% confidence interval (CI) 0.68 to 1.23]; and estimated between-group difference in MSIS-29phys score (active-placebo) -0.9 points (95% CI -2.0 to 0.2 points). Secondary clinical and MRI outcomes: no significant treatment effects. Safety - at least one serious adverse event: 35% and 28% of active and placebo patients, respectively. RMT analyses - scale evaluation: MSIS-29 version 2, MS Walking Scale-12 version 2 and MS Spasticity Scale-88 were robust measurement instruments. There was no clear symptomatic or disease-modifying treatment effect. Economic evaluation - estimated mean incremental cost to NHS over usual care, over 3 years £27,443.20 per patient. No between-group difference in QALYs. The CUPID trial failed to demonstrate a significant treatment effect in primary or secondary outcomes. There were no major safety concerns, but unwanted side effects seemed to affect compliance. Participants were more disabled than in previous studies and deteriorated less than expected, possibly reducing our ability to detect treatment effects. RMT analyses supported performance of MS-specific rating scales as measures, enabled group- and individual person-level examination of treatment effects, but did not influence study inferences. The intervention had significant additional costs with no improvement in health outcomes; therefore, it was dominated by usual care and not cost-effective. Future work should focus on determining further factors to predict clinical deterioration, to inform the development of new studies, and modifying treatments in order to minimise side effects and improve study compliance. The absence of disease-modifying treatments in progressive MS warrants further studies of the cannabinoid pathway in potential neuroprotection. Current Controlled Trials ISRCTN62942668. The National Institute for Health Research Health Technology Assessment programme, the Medical Research Council Efficacy and Mechanism Evaluation programme, Multiple Sclerosis Society and Multiple Sclerosis Trust. The report will be published in full in Health Technology Assessment; Vol. 19, No. 12. See the NIHR Journals Library website for further project information.

Evaluations in support of regulatory and research decisions by the U. S. Environmental Protection Agency for the control of toxic hazards from hazardous wastes, glyphosate, dalapon, and synthetic fuels

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

Scofield, R.

1984-01-01

This report includes toxicological and regulatory evaluations performed in support of U.S. EPA regulation of toxic materials and hazardous wastes. The first section of the report describes evaluations which support: (a) the regulation of small-volume generators of hazardous wastes, (b) the regulation of hazardous wastes from pesticide manufacturing, and (c) the disposal of the herbicide, silvex. The second section describes the environmental fate, transport, and effect of glyphosate and dalapon. The third section deals with synthetic fuels, including evaluations of synfuel-product toxicity, uncontrolled air emissions, and particular focus on the toxicity of products from several indirect coal liquefaction processes includingmore » methanol synthesis, Fischer-Tropsch, Mobil M-Gasoline, and Lurgi gasification technologies. Three direct coal liquefaction processes were examined for product toxicity and air emissions: Solvent Refined Coal (I and II) and the Exxon Donor Solvent Process. Also described in the third section is an evaluation of environmental and health hazards associated with the use of synthetic fuels from indirect coal liquefaction, direct coal liquefaction, and shale oil. Finally, the fourth section discusses some problems associated with performing, on a contractual basis, scientific and technical evaluations in support of U.S. EPA regulatory and research decisions.« less

Promoting early exposure monitoring for respirable crystalline silica: Taking the laboratory to the mine site

PubMed Central

Cauda, Emanuele; Miller, Arthur; Drake, Pamela

2017-01-01

The exposure to respirable crystalline silica (RCS) in the mining industry is a recognized occupational hazard. The assessment and monitoring of the exposure to RCS is limited by two main factors: (1) variability of the silica percent in the mining dust and (2) lengthy off-site laboratory analysis of collected samples. The monitoring of respirable dust via traditional or real-time techniques is not adequate. A solution for on-site quantification of RCS in dust samples is being investigated by the Office of Mine Safety and Health Research, a division of the National Institute for Occupational Safety and Health. The use of portable Fourier transform infrared analyzers in conjunction with a direct-on-filter analysis approach is proposed. The progress made so far, the necessary steps in progress, and the application of the monitoring solution to a small data set is presented. When developed, the solution will allow operators to estimate RCS immediately after sampling, resulting in timelier monitoring of RCS for self-assessment of compliance at the end of the shift, more effective engineering monitoring, and better evaluation of control technologies. PMID:26558490

Use of common analgesic medications and ovarian cancer survival: results from a pooled analysis in the Ovarian Cancer Association Consortium.

PubMed

Dixon, Suzanne C; Nagle, Christina M; Wentzensen, Nicolas; Trabert, Britton; Beeghly-Fadiel, Alicia; Schildkraut, Joellen M; Moysich, Kirsten B; deFazio, Anna; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Ness, Roberta B; Edwards, Robert P; Jensen, Allan; Kjær, Susanne K; Høgdall, Estrid; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Bandera, Elisa V; Paddock, Lisa E; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Pearce, Celeste Leigh; Wu, Anna H; Pike, Malcolm C; Webb, Penelope M

2017-04-25

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95% confidence intervals): aspirin 0.96 (0.88-1.04); non-aspirin NSAIDs 0.97 (0.89-1.05); acetaminophen 1.01 (0.93-1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0.89 (0.82-0.98)). Although this study did not show a clear association between analgesic use and ovarian cancer survival, further investigation with clearer definitions of use and information about post-diagnosis use is warranted.

Multivariate analysis of prognostic factors in synovial sarcoma.

PubMed

Koh, Kyoung Hwan; Cho, Eun Yoon; Kim, Dong Wook; Seo, Sung Wook

2009-11-01

Many studies have described the diversity of synovial sarcoma in terms of its biological characteristics and clinical features. Moreover, much effort has been expended on the identification of prognostic factors because of unpredictable behaviors of synovial sarcomas. However, with the exception of tumor size, published results have been inconsistent. We attempted to identify independent risk factors using survival analysis. Forty-one consecutive patients with synovial sarcoma were prospectively followed from January 1997 to March 2008. Overall and progression-free survival for age, sex, tumor size, tumor location, metastasis at presentation, histologic subtype, chemotherapy, radiation therapy, and resection margin were analyzed, and standard multivariate Cox proportional hazard regression analysis was used to evaluate potential prognostic factors. Tumor size (>5 cm), nonlimb-based tumors, metastasis at presentation, and a monophasic subtype were associated with poorer overall survival. Multivariate analysis showed metastasis at presentation and monophasic tumor subtype affected overall survival. For the progression-free survival, monophasic subtype was found to be only 1 prognostic factor. The study confirmed that histologic subtype is the single most important independent prognostic factors of synovial sarcoma regardless of tumor stage.

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

Kienhuis, Anne S., E-mail: anne.kienhuis@rivm.nl; RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen; Netherlands Toxicogenomics Centre

Hepatic systems toxicology is the integrative analysis of toxicogenomic technologies, e.g., transcriptomics, proteomics, and metabolomics, in combination with traditional toxicology measures to improve the understanding of mechanisms of hepatotoxic action. Hepatic toxicology studies that have employed toxicogenomic technologies to date have already provided a proof of principle for the value of hepatic systems toxicology in hazard identification. In the present review, acetaminophen is used as a model compound to discuss the application of toxicogenomics in hepatic systems toxicology for its potential role in the risk assessment process, to progress from hazard identification towards hazard characterization. The toxicogenomics-based parallelogram is usedmore » to identify current achievements and limitations of acetaminophen toxicogenomic in vivo and in vitro studies for in vitro-to-in vivo and interspecies comparisons, with the ultimate aim to extrapolate animal studies to humans in vivo. This article provides a model for comparison of more species and more in vitro models enhancing the robustness of common toxicogenomic responses and their relevance to human risk assessment. To progress to quantitative dose-response analysis needed for hazard characterization, in hepatic systems toxicology studies, generation of toxicogenomic data of multiple doses/concentrations and time points is required. Newly developed bioinformatics tools for quantitative analysis of toxicogenomic data can aid in the elucidation of dose-responsive effects. The challenge herein is to assess which toxicogenomic responses are relevant for induction of the apical effect and whether perturbations are sufficient for the induction of downstream events, eventually causing toxicity.« less

Occupational Attainment as Risk Factor for Progression from Mild Cognitive Impairment to Alzheimer's Disease: A CREDOS Study.

PubMed

Myung, Woojae; Lee, Chunsoo; Park, Jin Hong; Woo, Sook-Young; Kim, Seonwoo; Kim, Sangha; Chung, Jae Won; Kang, Hyo Shin; Lim, Shinn-Won; Choi, Junbae; Na, Duk L; Kim, Seong Yoon; Lee, Jae-Hong; Han, Seol-Heui; Choi, Seong Hye; Kim, Sang Yun; Carroll, Bernard J; Kim, Doh Kwan

2017-01-01

High occupational attainment has been known as a marker of cognitive reserve. Previous studies in the general population have shown that high occupational attainment is associated with reduced risk of Alzheimer's disease (AD). However, few studies have assessed the effect of occupational attainment on the clinical course of mild cognitive impairment (MCI). In this study, we evaluated whether individuals with high occupational attainment show more frequent progression from MCI to AD. Participants (n = 961) with MCI were recruited from a nationwide, hospital-based multi-center cohort, and were followed for up to 60 months (median: 17.64, interquartile range [12.36, 29.28]). We used Cox regression for competing risks to analyze the effect of occupational attainment on development of AD, treating dementia other than AD as a competing risk. Among the 961 individuals with MCI, a total of 280 (29.1%) converted to dementia during the follow-up period. The risk of progression to AD was higher in the individuals with high occupational attainment after controlling for potential confounders (hazard ratio = 1.83, 95% confidence interval = 1.25-2.69, p = 0.002). High occupational attainment in individuals with MCI is an independent risk factor for higher progression rate of MCI to AD. This result suggests that the protective effect of high occupational attainment against cognitive decline disappears in the MCI stage, and that careful assessment of occupational history can yield important clinical information for prognosis in individuals with MCI.

High serum bicarbonate level within the normal range prevents the progression of chronic kidney disease in elderly chronic kidney disease patients

PubMed Central

2013-01-01

Background Metabolic acidosis leads to chronic kidney disease (CKD) progression. The guidelines recommend a lower limit of serum bicarbonate level, but no upper limit. For serum bicarbonate level to be clinically useful as a therapeutic target marker, it is necessary to investigate the target serum bicarbonate level within the normal range to prevent CKD progression. Methods One hundred and thirteen elderly CKD patients, whose serum bicarbonate level was controlled within the normal range, were enrolled in this retrospective cohort study in Ibaraki, Japan. Outcome was defined as a decrease of 25% or more in estimated glomerular filtration rate (eGFR) or starting dialysis. We used Cox proportional hazard models adjusted for patients’ characteristics to examine the association between serum bicarbonate level and the outcome. Results Female patients were 36.3%: average age (SD), 70.4 (6.6) years; eGFR, 25.7 (13.6) ml/min/1.73 m2; serum bicarbonate level, 27.4 (3.2) mEq/l. Patients with the lowest quartile of serum bicarbonate levels [23.4 (1.8) mEq/l] showed a high risk of CKD progression compared with patients with high serum bicarbonate levels [28.8 (2.3) mEq/l]: adjusted hazard ratio (HR), 3.511 (95% CI, 1.342-9.186). A 1 mEq/l increase in serum bicarbonate level was associated with a low risk of CKD progression: adjusted HR, 0.791 [95% confidence interval (CI), 0.684-0.914]. Conclusions In elderly CKD patients, our findings suggest that serum bicarbonate level is independently associated with CKD progression, and that a high serum bicarbonate level is associated with a low risk of CKD progression. A high target serum bicarbonate level within the normal range may be effective for preventing CKD progression. PMID:23298330

Association between First Nations ethnicity and progression to kidney failure by presence and severity of albuminuria.

PubMed

Samuel, Susan M; Palacios-Derflingher, Luz; Tonelli, Marcello; Manns, Braden; Crowshoe, Lynden; Ahmed, Sofia B; Jun, Min; Saad, Nathalie; Hemmelgarn, Brenda R

2014-02-04

Despite a low prevalence of chronic kidney disease (estimated glomerular filtration rate [GFR]<60 mL/min per 1.73 m2), First Nations people have high rates of kidney failure requiring chronic dialysis or kidney transplantation. We sought to examine whether the presence and severity of albuminuria contributes to the progression of chronic kidney disease to kidney failure among First Nations people. We identified all adult residents of Alberta (age≥18 yr) for whom an outpatient serum creatinine measurement was available from May 1, 2002, to Mar. 31, 2008. We determined albuminuria using urine dipsticks and categorized results as normal (i.e., no albuminuria), mild, heavy or unmeasured. Our primary outcome was progression to kidney failure (defined as the need for chronic dialysis or kidney transplantation, or a sustained doubling of serum creatinine levels). We calculated rates of progression to kidney failure by First Nations status, by estimated GFR and by albuminuria category. We determined the relative hazard of progression to kidney failure for First Nations compared with non-First Nations participants by level of albuminuria and estimated GFR. Of the 1 816 824 participants we identified, 48 669 (2.7%) were First Nations. First Nations people were less likely to have normal albuminuria compared with non-First Nations people (38.7% v. 56.4%). Rates of progression to kidney failure were consistently 2- to 3-fold higher among First Nations people than among non-First Nations people, across all levels of albuminuria and estimated GFRs. Compared with non-First Nations people, First Nations people with an estimated GFR of 15.0-29.9 mL/min per 1.73 m2 had the highest risk of progression to kidney failure, with similar hazard ratios for those with normal and heavy albuminuria. Albuminuria confers a similar risk of progression to kidney failure for First Nations and non-First Nations people.

75 FR 67919 - Hazardous Waste Management System; Proposed Exclusion for Identifying and Listing Hazardous Waste

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-04

...-R05-RCRA-2010-0843; SW-FRL-9221-2] Hazardous Waste Management System; Proposed Exclusion for Identifying and Listing Hazardous Waste AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule... hazardous wastes. The Agency has tentatively decided to grant the petition based on an evaluation of waste...

Association of Progression of Carotid Artery Wall Volume and Recurrent Transient Ischemic Attack or Stroke: A Magnetic Resonance Imaging Study.

PubMed

Lu, Mingming; Peng, Peng; Cui, Yuanyuan; Qiao, Huiyu; Li, Dongye; Cai, Jianming; Zhao, Xihai

2018-03-01

This study aimed to investigate the association between carotid plaque progression and subsequent recurrent events using magnetic resonance imaging. Sixty-three symptomatic patients with ipsilateral carotid atherosclerotic stenosis (30%-69% stenosis) determined by ultrasound underwent first and second carotid artery magnetic resonance imaging for carotid artery at baseline and ≥6 months after the first scan, respectively. All the patients had clinical follow-up after the second magnetic resonance scan for ≤5 years until the onset of recurrent transient ischemic attack or stroke. Presence/absence of carotid plaque compositional features, particularly intraplaque hemorrhage and fibrous cap rupture was identified. The annual progression of carotid wall volume between 2 magnetic resonance scans was measured. Univariate and multivariate Cox regression was used to calculate the hazard ratio and corresponding 95% confidence interval of carotid plaque features in discriminating recurrent events. Receiver-operating-characteristic-curve analysis was conducted to determine the area-under-the-curve of carotid plaque features in predicting recurrent events. Sixty-three patients (mean age: 66.5±10.0 years old; 54 males) were eligible for final statistics analysis. During a mean follow-up duration of 55.1±13.6 months, 14.3% of patients (n=9) experienced ipsilateral recurrent transient ischemic attack/stroke. The annual progression of carotid wall volume was significantly associated with recurrent events before (hazard ratio, 1.14 per 10 mm 3 ; 95% confidence interval, 1.02-1.27; P =0.019) and after (hazard ratio, 1.19 per 10 mm3; 95% confidence interval, 1.03-1.37; P =0.022) adjusted for confounding factors. In discriminating the recurrence of transient ischemia attack/stroke, receiver-operator curve analysis indicated that combined with annual progression of wall volume, there was a significant incremental improvement in the area-under-the-curve of intraplaque hemorrhage (area-under-the-curve: 0.69-0.81) and fibrous cap rupture (area-under-the-curve: 0.73-0.84). The annual progression of carotid wall volume is independently associated with recurrent ischemic cerebrovascular events, and this measurement has added value for intraplaque hemorrhage and fibrous cap rupture in predicting future events. © 2018 American Heart Association, Inc.

Hazardous and toxic waste management in Botswana: practices and challenges.

PubMed

Mmereki, Daniel; Li, Baizhan; Meng, Liu

2014-12-01

Hazardous and toxic waste is a complex waste category because of its inherent chemical and physical characteristics. It demands for environmentally sound technologies and know-how as well as clean technologies that simultaneously manage and dispose it in an environmentally friendly way. Nevertheless, Botswana lacks a system covering all the critical steps from importation to final disposal or processing of hazardous and toxic waste owing to limited follow-up of the sources and types of hazardous and toxic waste, lack of modern and specialised treatment/disposal facilities, technical know-how, technically skilled manpower, funds and capabilities of local institutions to take lead in waste management. Therefore, because of a lack of an integrated system, there are challenges such as lack of cooperation among all the stakeholders about the safe management of hazardous and toxic waste. Furthermore, Botswana does not have a systematic regulatory framework regarding monitoring and hazardous and toxic waste management. In addition to the absence of a systematic regulatory framework, inadequate public awareness and dissemination of information about hazardous and toxic waste management, slower progress to phase-out persistent and bio-accumulative waste, and lack of reliable and accurate information on hazardous and toxic waste generation, sources and composition have caused critical challenges to effective hazardous and toxic waste management. It is, therefore, important to examine the status of hazardous and toxic waste as a waste stream in Botswana. By default; this mini-review article presents an overview of the current status of hazardous and toxic waste management and introduces the main challenges in hazardous and toxic waste management. Moreover, the article proposes the best applicable strategies to achieve effective hazardous and toxic waste management in the future. © The Author(s) 2014.

Updated hazard rate equations for dual safeguard systems.

PubMed

Rothschild, Marc

2007-04-11

A previous paper by this author [M.J. Rothschild, Updated hazard rate equation for single safeguards, J. Hazard. Mater. 130 (1-2) (2006) 15-20] showed that commonly used analytical methods for quantifying failure rates overestimates the risk in some circumstances. This can lead the analyst to mistakenly believe that a given operation presents an unacceptable risk. For a single safeguard system, a formula was presented in that paper that accurately evaluates the risk over a wide range of conditions. This paper expands on that analysis by evaluating the failure rate for dual safeguard systems. The safeguards can be activated at the same time or at staggered times, and the safeguard may provide an indication whether it was successful upon a challenge, or its status may go undetected. These combinations were evaluated using a Monte Carlo simulation. Empirical formulas for evaluating the hazard rate were developed from this analysis. It is shown that having the safeguards activate at the same time while providing positive feedback of their individual actions is the most effective arrangement in reducing the hazard rate. The hazard rate can also be reduced by staggering the testing schedules of the safeguards.

PALLADIUM/MAGNESIUM CORROSION NANO-CELLS FOR PCB DECHLORINATION

EPA Science Inventory

Polychlorinated biphenyls (PCBs) are toxic and recalcitrant environment pollutants that are prevalent in nation's submarine sediments. PCBs bioaccumulate and progressively move up the food chain to reach humans posing serious health hazards. Today, fish consumption is a major rou...

AMBIENT AIR MONITORING STRATEGY

EPA Science Inventory

The Clean Air Act requires EPA to establish national ambient air quality standards and to regulate as necessary, hazardous air pollutants. EPA uses ambient air monitoring to determine current air quality conditions, and to assess progress toward meeting these standards and relat...

A phase II randomized trial of Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE).

PubMed

Radwan, Noura; Phillips, Ryan; Ross, Ashley; Rowe, Steven P; Gorin, Michael A; Antonarakis, Emmanuel S; Deville, Curtiland; Greco, Stephen; Denmeade, Samuel; Paller, Channing; Song, Daniel Y; Diehn, Maximilian; Wang, Hao; Carducci, Michael; Pienta, Kenneth J; Pomper, Martin G; DeWeese, Theodore L; Dicker, Adam; Eisenberger, Mario; Tran, Phuoc T

2017-06-29

We describe a randomized, non-blinded Phase II interventional study to assess the safety and efficacy of stereotactic ablative radiotherapy (SABR) for hormone-sensitive oligometastatic prostate adenocarcinoma, and to describe the biology of the oligometastatic state using immunologic, cellular, molecular, and functional imaging correlates. 54 men with oligometastatic prostate adenocarcinoma will be accrued. The primary clinical endpoint will be progression at 6 months from randomization with the hypothesis that SABR to all metastases will forestall progression by disrupting the metastatic process. Secondary clinical endpoints will include local control at 6 months post-SABR, toxicity and quality of life, and androgen deprivation therapy (ADT)-free survival (ADT-FS). Further fundamental analysis of the oligometastatic state with be achieved through correlation with investigational 18 F-DCFPyL PET/CT imaging and measurement of circulating tumor cells, circulating tumor DNA, and circulating T-cell receptor repertoires, facilitating an unprecedented opportunity to characterize, in isolation, the effects of SABR on the dynamics of and immunologic response to oligometastatic disease. Patients will be randomized 2:1 to SABR or observation with minimization to balance assignment by primary intervention, prior hormonal therapy, and PSA doubling time. Progression after 6 months will be compared using Fisher's exact test. Hazard ratios and Kaplan-Meier estimates of progression free survival (PFS), ADT free survival (ADT-FS), time to locoregional progression (TTLP) and time to distant progression (TTDP) will be calculated based on an intention-to-treat. Local control will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Withdrawal from the study prior to 6 months will be counted as progression. Adverse events will be summarized by type and grade. Quality of life pre- and post- SABR will be measured by Brief Pain Inventory. The ORIOLE trial is the first randomized, non-blinded Phase II interventional study in the North America evaluating the safety and efficacy of SABR in oligometastatic hormone-sensitive prostate cancer. Leading-edge laboratory and imaging correlates will provide unique insight into the effects of SABR on the oligometastatic state. ClinicalTrials.gov Identifier: NCT02680587. URL of Registry: https://clinicaltrials.gov/show/NCT02680587 Date of Registration: 02/08/2016. Date of First Participant Enrollment: 05/23/2016.

A novel sample size formula for the weighted log-rank test under the proportional hazards cure model.

PubMed

Xiong, Xiaoping; Wu, Jianrong

2017-01-01

The treatment of cancer has progressed dramatically in recent decades, such that it is no longer uncommon to see a cure or log-term survival in a significant proportion of patients with various types of cancer. To adequately account for the cure fraction when designing clinical trials, the cure models should be used. In this article, a sample size formula for the weighted log-rank test is derived under the fixed alternative hypothesis for the proportional hazards cure models. Simulation showed that the proposed sample size formula provides an accurate estimation of sample size for designing clinical trials under the proportional hazards cure models. Copyright © 2016 John Wiley & Sons, Ltd.

Recovery of polyclonal immunoglobulins one year after autologous stem cell transplantation as a long-term predictor marker of progression and survival in multiple myeloma.

PubMed

González-Calle, Verónica; Cerdá, Seila; Labrador, Jorge; Sobejano, Eduardo; González-Mena, Beatriz; Aguilera, Carmen; Ocio, Enrique María; Vidriales, María Belén; Puig, Noemí; Gutiérrez, Norma Carmen; García-Sanz, Ramón; Alonso, José María; López, Rosa; Aguilar, Carlos; de Coca, Alfonso García; Hernández, Roberto; Hernández, José Mariano; Escalante, Fernando; Mateos, María-Victoria

2017-05-01

Immunoparesis or suppression of polyclonal immunoglobulins is a very common condition in newly diagnosed myeloma patients. However, the recovery of polyclonal immunoglobulins in the setting of immune reconstitution after autologous stem cell transplantation and its effect on outcome has not yet been explored. We conducted this study in a cohort of 295 patients who had undergone autologous transplantation. In order to explore the potential role of immunoglubulin recovery as a dynamic predictor of progression or survival after transplantation, conditional probabilities of progression-free survival and overall survival were estimated according to immunoglobulin recovery at different time points using a landmark approach. One year after transplant, when B-cell reconstitution is expected to be completed, among 169 patients alive and progression free, 88 patients (52%) showed immunoglobulin recovery and 81 (48%) did not. Interestingly, the group with immunoglobulin recovery had a significantly longer median progression-free survival than the group with persistent immunoparesis (median 60.4 vs. 27.9 months, respectively; Hazard Ratio: 0.45, 95%Confidence Interval: 0.31-0.66; P <0.001), and improved overall survival (11.3 vs. 7.3 years; Hazard Ratio: 0.45, 95%Confidence Interval: 0.27-0.74; P =0.002). Furthermore, the percentage of normal plasma cells detected by flow cytometry in the bone marrow assessed at day 100 after transplantation was associated with the immunoglobulin recovery at that time and may predict immunoglobulin recovery in the subsequent months: nine months and one year. In conclusion, the recovery of polyclonal immunoglobulins one year after autologous transplantation in myeloma patients is an independent long-term predictor marker for progression and survival. Copyright© Ferrata Storti Foundation.

Endothelial activation biomarkers increase after HIV-1 acquisition: plasma vascular cell adhesion molecule-1 predicts disease progression.

PubMed

Graham, Susan M; Rajwans, Nimerta; Jaoko, Walter; Estambale, Benson B A; McClelland, R Scott; Overbaugh, Julie; Liles, W Conrad

2013-07-17

We aimed to determine whether endothelial activation biomarkers increase after HIV-1 acquisition, and whether biomarker levels measured in chronic infection would predict disease progression and death in HIV-1 seroconverters. HIV-1-seronegative Kenyan women were monitored monthly for seroconversion, and followed prospectively after HIV-1 acquisition. Plasma levels of angiopoietin-1 and angiopoietin-2 (ANG-1, ANG-2) and soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin were tested in stored samples from pre-infection, acute infection, and two chronic infection time points. We used nonparametric tests to compare biomarkers before and after HIV-1 acquisition, and Cox proportional-hazards regression to analyze associations with disease progression (CD4 < 200 cells/μl, stage IV disease, or antiretroviral therapy initiation) or death. Soluble ICAM-1 and VCAM-1 were elevated relative to baseline in all postinfection periods assessed (P < 0.0001). Soluble E-selectin and the ANG-2:ANG-1 ratio increased in acute infection (P = 0.0001), and ANG-1 decreased in chronic infection (P = 0.0004). Among 228 participants followed over 1028 person-years, 115 experienced disease progression or death. Plasma VCAM-1 levels measured during chronic infection were independently associated with time to HIV progression or death (adjusted hazard ratio 5.36, 95% confidence interval 1.99-14.44 per log10 increase), after adjustment for set point plasma viral load, age at infection, and soluble ICAM-1 levels. HIV-1 acquisition was associated with endothelial activation, with sustained elevations of soluble ICAM-1 and VCAM-1 postinfection. Soluble VCAM-1 may be an informative biomarker for predicting the risk of HIV-1 disease progression, morbidity, and mortality.

A methodology for physically based rockfall hazard assessment

NASA Astrophysics Data System (ADS)

Crosta, G. B.; Agliardi, F.

Rockfall hazard assessment is not simple to achieve in practice and sound, physically based assessment methodologies are still missing. The mobility of rockfalls implies a more difficult hazard definition with respect to other slope instabilities with minimal runout. Rockfall hazard assessment involves complex definitions for "occurrence probability" and "intensity". This paper is an attempt to evaluate rockfall hazard using the results of 3-D numerical modelling on a topography described by a DEM. Maps portraying the maximum frequency of passages, velocity and height of blocks at each model cell, are easily combined in a GIS in order to produce physically based rockfall hazard maps. Different methods are suggested and discussed for rockfall hazard mapping at a regional and local scale both along linear features or within exposed areas. An objective approach based on three-dimensional matrixes providing both a positional "Rockfall Hazard Index" and a "Rockfall Hazard Vector" is presented. The opportunity of combining different parameters in the 3-D matrixes has been evaluated to better express the relative increase in hazard. Furthermore, the sensitivity of the hazard index with respect to the included variables and their combinations is preliminarily discussed in order to constrain as objective as possible assessment criteria.

Natural hazards knowledge and risk perception of Wujie indigenous community in Taiwan

NASA Astrophysics Data System (ADS)

Roder, Giulia; Ruljigaljig, Tjuku; Lin, Ching-Weei; Tarolli, Paolo

2015-04-01

The purpose of this work is to investigate the natural hazard knowledge and risk perception of Wujie indigenous community, located in Fazhi Village in the Central Mountain Range of Taiwan. Taiwan has encountered many different types of natural hazards (e.g. landslides and debris flows) that have increased sharply in the last century. Because of that, they are one of the most critical issues for the government and for the people living in mountainous areas. These areas are mainly populated by indigenous people that have experienced economic competition and military conflict with a series of colonizing periods causing a progressive loss of their original cultural identity. The motivation of selecting the case study of Wujie community is because (i) it has suffered, more than others, generations of devastating colonial oppression by foreign governments; (ii) the consequences of hydroelectric projects that moved a lot of water and sediment to the valley and modified the path of the river through the years; (iii) the documented landslides and debris flows occurred in the region during the last decades. Two questions appear spontaneously: How indigenous people are nowadays living with natural hazards? Have land use change or any other human footprint affected their knowledge and perception on natural hazards? This research, the first carried out in Taiwan involving an indigenous community, can offer a unique opportunity to answer these questions. The investigation utilized a variety of participatory methods conducted at the household and community level by the use of 65 face-to-face interviews. Results revealed that residents felt a higher worry about landslide and flood risks, and a slight preparedness to face them. This discrepancy may derive from an unsatisfactory level of communication and information, and the most considerable differences were found between the evaluations of individual subjects as opposed to overall communities. Results revealed also the complexity of residents' perspectives, attitudes, behaviours and decisions about risk-related issues. In addition, gender, age, education, experience and exposure to natural hazards are also found as significant predictors of this issue. Paying attention to the indigenous perception of a hazard and risk can increase the effectiveness of projects implemented by scientists who might need to communicate risks in the future, but also help governments in their possible need to order evacuations, and future researcher planning to conduct similar projects.

Accident analysis and control options in support of the sludge water system safety analysis

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

HEY, B.E.

A hazards analysis was initiated for the SWS in July 2001 (SNF-8626, K Basin Sludge and Water System Preliminary Hazard Analysis) and updated in December 2001 (SNF-10020 Rev. 0, Hazard Evaluation for KE Sludge and Water System - Project A16) based on conceptual design information for the Sludge Retrieval System (SRS) and 60% design information for the cask and container. SNF-10020 was again revised in September 2002 to incorporate new hazards identified from final design information and from a What-if/Checklist evaluation of operational steps. The process hazards, controls, and qualitative consequence and frequency estimates taken from these efforts have beenmore » incorporated into Revision 5 of HNF-3960, K Basins Hazards Analysis. The hazards identification process documented in the above referenced reports utilized standard industrial safety techniques (AIChE 1992, Guidelines for Hazard Evaluation Procedures) to systematically guide several interdisciplinary teams through the system using a pre-established set of process parameters (e.g., flow, temperature, pressure) and guide words (e.g., high, low, more, less). The teams generally included representation from the U.S. Department of Energy (DOE), K Basins Nuclear Safety, T Plant Nuclear Safety, K Basin Industrial Safety, fire protection, project engineering, operations, and facility engineering.« less

Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor–Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance)

PubMed Central

Barry, William T.; Cirrincione, Constance T.; Ellis, Matthew J.; Moynahan, Mary Ellen; Innocenti, Federico; Hurria, Arti; Rugo, Hope S.; Lake, Diana E.; Hahn, Olwen; Schneider, Bryan P.; Tripathy, Debasish; Carey, Lisa A.; Winer, Eric P.; Hudis, Clifford A.

2016-01-01

Purpose To investigate whether anti–vascular endothelial growth factor therapy with bevacizumab prolongs progression-free survival (PFS) when added to first-line letrozole as treatment of hormone receptor–positive metastatic breast cancer (MBC). Patients and Methods Women with hormone receptor–positive MBC were randomly assigned 1:1 in a multicenter, open-label, phase III trial of letrozole (2.5 mg orally per day) with or without bevacizumab (15 mg/kg intravenously once every 3 weeks) within strata defined by measurable disease and disease-free interval. This trial had 90% power to detect a 50% improvement in median PFS from 6 to 9 months. Using a one-sided α = .025, a target sample size of 352 patients was planned. Results From May 2008 to November 2011, 350 women were recruited; 343 received treatment and were observed for efficacy and safety. Median age was 58 years (range, 25 to 87 years). Sixty-two percent had measurable disease, and 45% had de novo MBC. At a median follow-up of 39 months, the addition of bevacizumab resulted in a significant reduction in the hazard of progression (hazard ratio, 0.75; 95% CI, 0.59 to 0.96; P = .016) and a prolongation in median PFS from 15.6 months with letrozole to 20.2 months with letrozole plus bevacizumab. There was no significant difference in overall survival (hazard ratio, 0.87; 95% CI, 0.65 to 1.18; P = .188), with median overall survival of 43.9 months with letrozole versus 47.2 months with letrozole plus bevacizumab. The largest increases in incidence of grade 3 to 4 treatment-related toxicities with the addition of bevacizumab were hypertension (24% v 2%) and proteinuria (11% v 0%). Conclusion The addition of bevacizumab to letrozole improved PFS in hormone receptor–positive MBC, but this benefit was associated with a markedly increased risk of grade 3 to 4 toxicities. Research on predictive markers will be required to clarify the role of bevacizumab in this setting. PMID:27138575

Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor-Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance).

PubMed

Dickler, Maura N; Barry, William T; Cirrincione, Constance T; Ellis, Matthew J; Moynahan, Mary Ellen; Innocenti, Federico; Hurria, Arti; Rugo, Hope S; Lake, Diana E; Hahn, Olwen; Schneider, Bryan P; Tripathy, Debasish; Carey, Lisa A; Winer, Eric P; Hudis, Clifford A

2016-08-01

To investigate whether anti-vascular endothelial growth factor therapy with bevacizumab prolongs progression-free survival (PFS) when added to first-line letrozole as treatment of hormone receptor-positive metastatic breast cancer (MBC). Women with hormone receptor-positive MBC were randomly assigned 1:1 in a multicenter, open-label, phase III trial of letrozole (2.5 mg orally per day) with or without bevacizumab (15 mg/kg intravenously once every 3 weeks) within strata defined by measurable disease and disease-free interval. This trial had 90% power to detect a 50% improvement in median PFS from 6 to 9 months. Using a one-sided α = .025, a target sample size of 352 patients was planned. From May 2008 to November 2011, 350 women were recruited; 343 received treatment and were observed for efficacy and safety. Median age was 58 years (range, 25 to 87 years). Sixty-two percent had measurable disease, and 45% had de novo MBC. At a median follow-up of 39 months, the addition of bevacizumab resulted in a significant reduction in the hazard of progression (hazard ratio, 0.75; 95% CI, 0.59 to 0.96; P = .016) and a prolongation in median PFS from 15.6 months with letrozole to 20.2 months with letrozole plus bevacizumab. There was no significant difference in overall survival (hazard ratio, 0.87; 95% CI, 0.65 to 1.18; P = .188), with median overall survival of 43.9 months with letrozole versus 47.2 months with letrozole plus bevacizumab. The largest increases in incidence of grade 3 to 4 treatment-related toxicities with the addition of bevacizumab were hypertension (24% v 2%) and proteinuria (11% v 0%). The addition of bevacizumab to letrozole improved PFS in hormone receptor-positive MBC, but this benefit was associated with a markedly increased risk of grade 3 to 4 toxicities. Research on predictive markers will be required to clarify the role of bevacizumab in this setting. © 2016 by American Society of Clinical Oncology.

Evaluation of rapid progressors in HIV infection as an extreme phenotype.

PubMed

Olson, Ashley D; Guiguet, Marguerite; Zangerle, Robert; Gill, John; Perez-Hoyos, Santiago; Lodi, Sara; Ghosn, Jade; Dorrucci, Maria; Johnson, Anne; Sannes, Mette; Moreno, Santiago; Porter, Kholoud

2014-09-01

Rapid CD4 cell loss represents an HIV phenotype used to identify causal variants of accelerated disease progression. The optimal rate and threshold for identifying this extreme phenotype in recently infected individuals is unclear. Using a cohort of patients with known dates of HIV-1 seroconversion (SC), CASCADE (Concerted Action on SeroConversion on AIDS and Death in Europe), we identified proportions experiencing nadir CD4 cell levels within 1 year of SC, and assessed their mean AIDS-free survival time at 10-year follow-up and hazard of AIDS/death, compared with those whose CD4 remained >500 cells per cubic millimeter. Follow-up was censored at December 31, 1996 to avoid bias due to combination antiretroviral therapy initiation. Of 4876 individuals, 2.8%, 7.3%, and 24.9% experienced ≥1 CD4 <100, 200, and 350 cells per cubic millimeter, respectively, within 1 year of SC. Minimum CD4 levels of 30, 166, 231, and 506 cells per cubic millimeter were experienced during this period by 1%, 5%, 10%, and 50% of individuals, respectively. Mean (95% confidence interval) AIDS-free survival at 10 years follow-up was 2.9 (2.3 to 3.6), 5.5 (5.0 to 6.1), 6.7 (6.5 to 7.0), 7.4 (7.2 to 7.6), and 8.1 (7.9 to 8.3), for those with minimum counts ≤100, 100-200, 200-350, 350-500, >500 cells per cubic millimeter, respectively. Using counts of >500 cells per cubic millimeter as reference, the hazard ratios (95% confidence interval) of AIDS/death were 15.0 (11.9 to 18.9), 3.6 (2.9 to 4.5), 2.1 (1.8 to 2.4), and 1.5 (1.3 to 1.7), respectively. The hazard ratio increased to 37.5 (26.5 to 53.1) when a minimum CD4 count <100 was confirmed within 1 year of SC. At least 1 CD4 ≤100 cells per cubic millimeter within the first year of SC identifies a rare group of individuals at high risk of disease progression and could form the basis for defining the rapid progressor phenotype.

Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3.

PubMed

Slamon, Dennis J; Neven, Patrick; Chia, Stephen; Fasching, Peter A; De Laurentiis, Michelino; Im, Seock-Ah; Petrakova, Katarina; Bianchi, Giulia Val; Esteva, Francisco J; Martín, Miguel; Nusch, Arnd; Sonke, Gabe S; De la Cruz-Merino, Luis; Beck, J Thaddeus; Pivot, Xavier; Vidam, Gena; Wang, Yingbo; Rodriguez Lorenc, Karen; Miller, Michelle; Taran, Tetiana; Jerusalem, Guy

2018-06-03

Purpose This phase III study evaluated ribociclib plus fulvestrant in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer who were treatment naïve or had received up to one line of prior endocrine therapy in the advanced setting. Patients and Methods Patients were randomly assigned at a two-to-one ratio to ribociclib plus fulvestrant or placebo plus fulvestrant. The primary end point was locally assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. Results A total of 484 postmenopausal women were randomly assigned to ribociclib plus fulvestrant, and 242 were assigned to placebo plus fulvestrant. Median progression-free survival was significantly improved with ribociclib plus fulvestrant versus placebo plus fulvestrant: 20.5 months (95% CI, 18.5 to 23.5 months) versus 12.8 months (95% CI, 10.9 to 16.3 months), respectively (hazard ratio, 0.593; 95% CI, 0.480 to 0.732; P < .001). Consistent treatment effects were observed in patients who were treatment naïve in the advanced setting (hazard ratio, 0.577; 95% CI, 0.415 to 0.802), as well as in patients who had received up to one line of prior endocrine therapy for advanced disease (hazard ratio, 0.565; 95% CI, 0.428 to 0.744). Among patients with measurable disease, the overall response rate was 40.9% for the ribociclib plus fulvestrant arm and 28.7% for placebo plus fulvestrant. Grade 3 adverse events reported in ≥ 10% of patients in either arm (ribociclib plus fulvestrant v placebo plus fulvestrant) were neutropenia (46.6% v 0%) and leukopenia (13.5% v 0%); the only grade 4 event reported in ≥ 5% of patients was neutropenia (6.8% v 0%). Conclusion Ribociclib plus fulvestrant might represent a new first- or second-line treatment option in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer.

Unequal exposure to ecological hazards: environmental injustices in the Commonwealth of Massachusetts.

PubMed Central

Faber, Daniel R; Krieg, Eric J

2002-01-01

This study analyzes the social and geographic distribution of ecological hazards across 368 communities in the Commonwealth of Massachusetts. Combining census data with a variety of environmental data, we tested for and identified both income-based and racially based biases to the geographic distribution of 17 different types of environmentally hazardous sites and industrial facilities. We also developed a composite measure of cumulative exposure to compare the relative overall risks characteristic of each community. To the best of our knowledge, this point system makes this the first environmental justice study to develop a means for measuring and ranking cumulative exposure for communities. The study also controls for the intensity of hazards in each community by accounting for the area across which hazards are distributed. The findings indicate that ecologically hazardous sites and facilities are disproportionately located and concentrated in communities of color and working-class communities. The implication of this research for policymakers and citizen advocates is that cumulative exposure of residents to environmentally hazardous facilities and sites should receive greater consideration regarding community demographics and environmental health indicators. We conclude that the provision of additional resources for environmental monitoring and ranking, as well as yearly progress reports, is necessary for communities and state agencies to achieve equal access to clean and healthy environments for all residents. PMID:11929739

Pyrotechnic hazards classification and evaluation program. Phase 2, segment 3: Test plan for determining hazards associated with pyrotechnic manufacturing processes

NASA Technical Reports Server (NTRS)

1971-01-01

A comprehensive test plan for determining the hazards associated with pyrotechnic manufacturing processes is presented. The rationale for each test is based on a systematic analysis of historical accounts of accidents and a detailed study of the characteristics of each manufacturing process. The most hazardous manufacturing operations have been determined to be pressing, mixing, reaming, and filling. The hazard potential of a given situation is evaluated in terms of the probabilities of initiation, communication, and transition to detonation (ICT). The characteristics which affect the ICT probabilities include the ignition mechanisms which are present either in normal or abnormal operation, the condition and properties of the pyrotechnic material, and the configuration of the processing equipment. Analytic expressions are derived which describe the physical conditions of the system, thus permitting a variety of processes to be evaluated in terms of a small number of experiments.

Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.

PubMed

Hortobagyi, Gabriel N; Stemmer, Salomon M; Burris, Howard A; Yap, Yoon-Sim; Sonke, Gabe S; Paluch-Shimon, Shani; Campone, Mario; Blackwell, Kimberly L; André, Fabrice; Winer, Eric P; Janni, Wolfgang; Verma, Sunil; Conte, Pierfranco; Arteaga, Carlos L; Cameron, David A; Petrakova, Katarina; Hart, Lowell L; Villanueva, Cristian; Chan, Arlene; Jakobsen, Erik; Nusch, Arnd; Burdaeva, Olga; Grischke, Eva-Maria; Alba, Emilio; Wist, Erik; Marschner, Norbert; Favret, Anne M; Yardley, Denise; Bachelot, Thomas; Tseng, Ling-Ming; Blau, Sibel; Xuan, Fengjuan; Souami, Farida; Miller, Michelle; Germa, Caroline; Hirawat, Samit; O'Shaughnessy, Joyce

2016-11-03

The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on January 29, 2016, after 243 patients had disease progression or died. Prespecified criteria for superiority required a hazard ratio of 0.56 or less with P<1.29×10 -5 . The duration of progression-free survival was significantly longer in the ribociclib group than in the placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10 -6 for superiority). The median duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group. In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively (P<0.001). Common grade 3 or 4 adverse events that were reported in more than 10% of the patients in either group were neutropenia (59.3% in the ribociclib group vs. 0.9% in the placebo group) and leukopenia (21.0% vs. 0.6%); the rates of discontinuation because of adverse events were 7.5% and 2.1%, respectively. Among patients receiving initial systemic treatment for HR-positive, HER2-negative advanced breast cancer, the duration of progression-free survival was significantly longer among those receiving ribociclib plus letrozole than among those receiving placebo plus letrozole, with a higher rate of myelosuppression in the ribociclib group. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT01958021 .).

Enzalutamide in Japanese patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer: A post-hoc analysis of the placebo-controlled PREVAIL trial.

PubMed

Kimura, Go; Yonese, Junji; Fukagai, Takashi; Kamba, Tomomi; Nishimura, Kazuo; Nozawa, Masahiro; Mansbach, Hank; Theeuwes, Ad; Beer, Tomasz M; Tombal, Bertrand; Ueda, Takeshi

2016-05-01

To evaluate the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients. This was a post-hoc analysis of the phase 3, double-blind, placebo-controlled PREVAIL trial. Asymptomatic or mildly symptomatic chemotherapy-naïve patients with metastatic castration-resistant prostate cancer progressing on androgen deprivation therapy were randomized one-to-one to 160 mg/day oral enzalutamide or placebo until discontinuation on radiographic progression or skeletal-related event and initiation of subsequent antineoplastic therapy. Coprimary end-points were centrally assessed radiographic progression-free survival and overall survival. Secondary end-points were investigator-assessed radiographic progression-free survival, time to initiation of chemotherapy, time to prostate-specific antigen progression, prostate-specific antigen response (≥50% decline) and time to skeletal-related event. Of 1717 patients, 61 were enrolled in Japan (enzalutamide, n = 28; placebo, n = 33); hazard ratios (95% confidence interval) of 0.30 for centrally assessed radiographic progression-free survival (0.03-2.95), 0.59 for overall survival (0.20-1.8), 0.46 for time to chemotherapy (0.22-0.96) and 0.36 for time to prostate-specific antigen progression (0.17-0.75) showed the treatment benefit of enzalutamide over the placebo. Prostate-specific antigen responses were observed in 60.7% of enzalutamide-treated men versus 21.2% of placebo-treated men. Plasma concentrations of enzalutamide were higher in Japanese patients: the geometric mean ratio of Japanese/non-Japanese patients was 1.126 (90% confidence interval 1.018-1.245) at 13 weeks. Treatment-related adverse events grade ≥3 occurred in 3.6% of enzalutamide- and 6.1% of placebo-treated Japanese patients. Treatment effects and safety in Japanese patients were generally consistent with the overall results from PREVAIL. © 2016 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.

Cholesterol import and steroidogenesis are biosignatures for gastric cancer patient survival

PubMed Central

Chang, Wei-Chun; Huang, Shang-Fen; Lee, Yang-Ming; Lai, Hsueh-Chou; Cheng, Bi-Hua; Cheng, Wei-Chung; Ho, Jason Yen-Ping; Jeng, Long-Bin; Ma, Wen-Lung

2017-01-01

Androgens, estrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or in vivo studies. This report used a web-based gene survival analyzer to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and estrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients. The AR, PR, ESR1 and ESR2 are progression promoters, as are the L/R route LDLR, LRP6, SR-B1 and LPL. It was found that CYP11A1, HSD3B1, CYP17, HSD17B1 and CYP19A1 promote progression, but dihydrotestosterone (DHT) converting enzyme SRD5A1 suppresses progression. Analyzing steroidogenic lipidome with a hazard ratio score algorithm found that CYP19A1 is the progression confounder in surgery, HER2 positive or negative patients. Finally, in the other patient cohort from TCGA, CYP19A1 was expressed higher in the tumor compared to that in normal counterparts, and also promoted progression. Lastly, exemestrane (type II aromatase inhibitor) dramatically suppress GCa cell growth in pharmacological tolerable doses in vitro. This work depicts a route-specific outside-in delivery of cholesterol to promote disease progression, implicating a host-to-tumor macroenvironmental regulation. The result indicating lipoprotein-mediated cholesterol entry and steroidogenesis are GCa progression biosignatures. And the exemestrane clinical trial in GCa patients of unmet medical needs is suggested. PMID:27893427

Cholesterol import and steroidogenesis are biosignatures for gastric cancer patient survival.

PubMed

Chang, Wei-Chun; Huang, Shang-Fen; Lee, Yang-Ming; Lai, Hsueh-Chou; Cheng, Bi-Hua; Cheng, Wei-Chung; Ho, Jason Yen-Ping; Jeng, Long-Bin; Ma, Wen-Lung

2017-01-03

Androgens, estrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or in vivo studies. This report used a web-based gene survival analyzer to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and estrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients. The AR, PR, ESR1 and ESR2 are progression promoters, as are the L/R route LDLR, LRP6, SR-B1 and LPL. It was found that CYP11A1, HSD3B1, CYP17, HSD17B1 and CYP19A1 promote progression, but dihydrotestosterone (DHT) converting enzyme SRD5A1 suppresses progression. Analyzing steroidogenic lipidome with a hazard ratio score algorithm found that CYP19A1 is the progression confounder in surgery, HER2 positive or negative patients. Finally, in the other patient cohort from TCGA, CYP19A1 was expressed higher in the tumor compared to that in normal counterparts, and also promoted progression. Lastly, exemestrane (type II aromatase inhibitor) dramatically suppress GCa cell growth in pharmacological tolerable doses in vitro. This work depicts a route-specific outside-in delivery of cholesterol to promote disease progression, implicating a host-to-tumor macroenvironmental regulation. The result indicating lipoprotein-mediated cholesterol entry and steroidogenesis are GCa progression biosignatures. And the exemestrane clinical trial in GCa patients of unmet medical needs is suggested.

Superior Treatment Response and In-field Tumor Control in Epidermal Growth Factor Receptor-mutant Genotype of Stage III Nonsquamous Non-Small cell Lung Cancer Undergoing Definitive Concurrent Chemoradiotherapy.

PubMed

Lim, Yu Jin; Chang, Ji Hyun; Kim, Hak-Jae; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong-Wan; Paeng, Jin Chul; Kang, Keon Wook; Chung, June-Key; Jeon, Yoon Kyung; Chung, Doo Hyun; Wu, Hong-Gyun

2017-05-01

Although previous in vitro data have suggested a more radio-sensitive nature of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) cell lines, the clinical behavior according to the EGFR mutational status has not been well-established. In this study, we performed a comparative outcome analysis of EGFR-mutant and wild-type locally advanced NSCLC with chemoradiotherapy (CRT). A total of 102 patients with stage III nonsquamous NSCLC undergoing primary CRT were identified. Clinicopathologic characteristics, including the degree of glucose uptake, were evaluated. Failure patterns considering the radiation field and survival outcomes were compared according to the EGFR mutational status. Pre- and post-CRT maximum standardized uptake values were significantly lower in EGFR-mutant tumors (P = .010 and .018, respectively). The overall response rate was higher in the EGFR-mutant group compared with the wild-type (89% vs. 64%, respectively; P = .023). The 3-year overall survival rate was better with the genetic alteration (68.0% vs. 47.4%, P = .046), but the statistical significance did not remain in multivariate analysis (hazard ratio, 0.68; 95% confidence interval, 0.30-1.55). Considering the tumor progression inside or outside the radiation field, the EGFR-mutant group showed longer in-field time to progression (P = .002), even after adjusting for other related baseline variables (hazard ratio, 0.27; 95% confidence interval, 0.11-0.71). The differential metabolic activity, failure patterns, and prognosis suggest the distinct nature of the EGFR-mutant tumors. EGFR mutational status needs to be considered for more precise curative-intent treatment strategies of locally advanced nonsquamous NSCLC. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship between ornithine decarboxylase levels in anaplastic gliomas and progression-free survival in patients treated with DFMO-PCV chemotherapy.

PubMed

Levin, Victor A; Jochec, Jacob L; Shantz, Lisa M; Aldape, Kenneth D

2007-11-15

The purpose of this study was to assess the relationship between progression-free survival (PFS) in patients treated with DFMO + PCV (procarbazine, CCNU, vincristine) chemotherapy for malignant gliomas with tumor cell ornithine decarboxylase (ODC) activity. Formalin-fixed slides were obtained for study patients with anaplastic gliomas (AGs) and glioblastoma treated on protocol DM92-035. ODC levels were measured using an antibody to ODC coupled to Alexa 647 dye (Ab-ODC-Alexa 647). Ab-ODC-Alexa 647 intensity in transgenic murine hearts of differing ODC activity was used to calculate ODC activity in tumor cell nucleoplasm. In total, tumor specimens for 31 of 114 (27%) patients treated on the AG strata and 10 patients from the GBM strata were obtained. We found that tumor ODC level heterogeneity increased with increasing tumor malignancy. In a Cox proportional hazards model, PFS was found to be inversely related to median tumor ODC activity, with an unadjusted hazard ratio for median ODC group (>3.3 vs. 3.3 nmol/30 min/mug protein. Of AG tumors in which ODC activity was evaluated, 26% had ODC levels > 3.3 nmol/30 min/mug protein. This study shows that Ab-ODC-Alexa 647 fluorescence intensity can be used as a surrogate marker of ODC biochemical activity in AGs and can predict PFS to DFMO-based chemotherapy. (c) 2007 Wiley-Liss, Inc.

Metabolic Tumor Volume as a Prognostic Imaging-Based Biomarker for Head-and-Neck Cancer: Pilot Results From Radiation Therapy Oncology Group Protocol 0522

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

Schwartz, David L., E-mail: david.schwartz@utsw.edu; Harris, Jonathan; Yao, Min

2015-03-15

Purpose: To evaluate candidate fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging biomarkers for head-and-neck chemoradiotherapy outcomes in the cooperative group trial setting. Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 0522 patients consenting to a secondary FDG-PET/CT substudy were serially imaged at baseline and 8 weeks after radiation. Maximum standardized uptake value (SUVmax), SUV peak (mean SUV within a 1-cm sphere centered on SUVmax), and metabolic tumor volume (MTV) using 40% of SUVmax as threshold were obtained from primary tumor and involved nodes. Results: Of 940 patients entered onto RTOG 0522, 74 were analyzable for this substudy. Neither high baselinemore » SUVmax nor SUVpeak from primary or nodal disease were associated with poor treatment outcomes. However, primary tumor MTV above the cohort median was associated with worse local-regional control (hazard ratio 4.01, 95% confidence interval 1.28-12.52, P=.02) and progression-free survival (hazard ratio 2.34, 95% confidence interval 1.02-5.37, P=.05). Although MTV and T stage seemed to correlate (mean MTV 6.4, 13.2, and 26.8 for T2, T3, and T4 tumors, respectively), MTV remained a strong independent prognostic factor for progression-free survival in bivariate analysis that included T stage. Primary MTV remained prognostic in p16-associated oropharyngeal cancer cases, although sample size was limited. Conclusion: High baseline primary tumor MTV was associated with worse treatment outcomes in this limited patient subset of RTOG 0522. Additional confirmatory work will be required to validate primary tumor MTV as a prognostic imaging biomarker for patient stratification in future trials.« less

Combined diabetes-renal multifactorial intervention in patients with advanced diabetic nephropathy: Proof-of-concept.

PubMed

Fogelfeld, Leon; Hart, Peter; Miernik, Jadwiga; Ko, Jocelyn; Calvin, Donna; Tahsin, Bettina; Adhami, Anwar; Mehrotra, Rajeev; Fogg, Louis

2017-03-01

To evaluate efficacy of a multifactorial-multidisciplinary approach in delaying CKD 3-4 progression to ESRD. Two-year proof-of-concept stratified randomized control trial conducted in an outpatient clinic of a large public hospital system. This intervention, led by a team of endocrinologists, nephrologists, nurse practitioners, and registered dietitians, integrated intensive diabetes-renal care with behavioral/dietary and pharmacological interventions. 120 low-income adults with T2DM and CKD 3-4 enrolled; 58% male, 55% African American, 23% Hispanic. Primary outcome was progression rate from CKD 3-4 to ESRD. Fewer intervention (13%) than control (28%) developed ESRD, p<0.05. Intervention had greater albumin/creatinine ratio (ACR) decrease (62% vs. 42%, p<0.05) and A1C<7% attainment (50% vs. 30%, p<0.05) and trended toward better lipid/blood pressure control (p=NS). Significant differences between 25 ESRD and 95 ESRD-free patients were baseline eGFR (28 vs. 40ml/min/1.73m 2 ), annual eGFR decline (15 vs. 3ml/min/year), baseline ACR (2362 vs. 1139mg/g), final ACR (2896 vs. 1201mg/g), and final A1C (6.9 vs. 7.8%). In multivariate Cox analysis, receiving the intervention reduced hazard ratio to develop ESRD (0.125, CI 0.029-0.54) as did higher baseline eGFR (0.69, CI 0.59-0.80). Greater annual eGFR decline increased hazard ratio (1.59, CI 1.34-1.87). The intervention delayed ESRD. Improved A1C and ACR plus not-yet-identified variables may have influenced better outcomes. Multifactorial-multidisciplinary care may serve as a CKD 3-4 treatment paradigm. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic Impact of Primary Tumor Location on Clinical Outcomes of Metastatic Colorectal Cancer Treated With Cetuximab Plus Oxaliplatin-Based Chemotherapy: A Subgroup Analysis of the JACCRO CC-05/06 Trials.

PubMed

Sunakawa, Yu; Ichikawa, Wataru; Tsuji, Akihito; Denda, Tadamichi; Segawa, Yoshihiko; Negoro, Yuji; Shimada, Ken; Kochi, Mitsugu; Nakamura, Masato; Kotaka, Masahito; Tanioka, Hiroaki; Takagane, Akinori; Tani, Satoshi; Yamaguchi, Tatsuro; Watanabe, Takanori; Takeuchi, Masahiro; Fujii, Masashi; Nakajima, Toshifusa

2017-09-01

Primary tumor location is a critical prognostic factor in metastatic colorectal cancer (mCRC); however, it remains unclear whether tumor location is a predictor of the response to cetuximab treatment. It is also uncertain if BRAF mutation contributes to the impact of tumor location on survival. We assessed the prognostic impact of tumor location on clinical outcomes in mCRC patients treated with first-line cetuximab chemotherapy. The associations of tumor location with overall survival and progression-free survival were evaluated in mCRC patients with KRAS exon 2 wild-type tumors who were enrolled onto 2 clinical trials: JACCRO CC-05 of cetuximab plus FOLFOX (n = 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n = 61, UMIN000007022). Tumors proximal or from splenic flexure to rectum were defined as right-sided or left-sided, respectively. In addition, exploratory RAS and BRAF mutation analyses were performed. A total of 110 patients were assessable for tumor location; 90 had left-sided tumors. Left-sided tumors were significantly associated with longer overall survival (36.2 vs. 12.6 months, hazard ratio = 0.28, P < .0001) and progression-free survival (11.1 vs. 5.6 months, hazard ratio = 0.47, P = .0041) than right-sided tumors; similar results were obtained in multivariate analysis. A subanalysis showed that the association was evident in the FOLFOX group and that tumor location was an independent prognostic factor irrespective of BRAF status in RAS wild-type patients. Primary tumor location might be a predictor of survival independent of BRAF status in mCRC patients who receive first-line cetuximab combined with oxaliplatin-based chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Sensing and capture of toxic and hazardous gases and vapors by metal–organic frameworks

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

Wang, Hao; Lustig, William P.; Li, Jing

This review summaries recent progress in the luminescent detection and adsorptive removal of harmful gases and vapors by metal–organic frameworks, as well as the principles and strategies guiding the design of these materials.

40 CFR Appendix 1 to Part 3 - Priority Reports

Code of Federal Regulations, 2013 CFR

2013-07-01

...). Hazardous Air Pollutants Compliance Report Reports containing results from performance test, opacity tests, and visible emissions tests. Progress reports; periodic and immediate startup, shutdown, and... Owners report emissions data from stationary sources 51.211. Report For Initial Performance Test Report...

40 CFR Appendix 1 to Part 3 - Priority Reports

Code of Federal Regulations, 2014 CFR

2014-07-01

...). Hazardous Air Pollutants Compliance Report Reports containing results from performance test, opacity tests, and visible emissions tests. Progress reports; periodic and immediate startup, shutdown, and... Owners report emissions data from stationary sources 51.211. Report For Initial Performance Test Report...

Sensing and capture of toxic and hazardous gases and vapors by metal–organic frameworks

DOE PAGES

Wang, Hao; Lustig, William P.; Li, Jing

2018-01-01

This review summaries recent progress in the luminescent detection and adsorptive removal of harmful gases and vapors by metal–organic frameworks, as well as the principles and strategies guiding the design of these materials.

Occupational hazards to health of port workers.

PubMed

Wang, Yukun; Zhan, Shuifen; Liu, Yan; Li, Yan

2017-12-01

The aim of this article is to reduce the risk of occupational hazards and improve safety conditions by enhancing hazard knowledge and identification as well as improving safety behavior for freight port enterprises. In the article, occupational hazards to health and their prevention measures of freight port enterprises have been summarized through a lot of occupational health evaluation work, experience and understanding. Workers of freight port enterprises confront an equally wide variety of chemical, physical and psychological hazards in production technology, production environment and the course of labor. Such health hazards have been identified, the risks evaluated, the dangers to health notified and effective prevention measures which should be put in place to ensure the health of the port workers summarized. There is still a long way to go for the freight port enterprises to prevent and control the occupational hazards. Except for occupational hazards and their prevention measures, other factors that influence the health of port workers should also be paid attention to, such as age, work history, gender, contraindication and even the occurrence and development rules of occupational hazards in current production conditions.

Commentary on "Abiraterone in metastatic prostate cancer without previous chemotherapy." Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE; COU-AA-302 Investigators, Genitourinary Medical Oncology Program, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA. N Engl J Med 2013;368(2):138-48 [Epub 2012 Dec 10]; N Engl J Med 2013;368(6):584.

PubMed

Trump, Donald L

2013-11-01

Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. In this double-blind study, we randomly assigned 1088 patients to receive abiraterone acetate (1000 mg) plus prednisone (5mg twice daily) or placebo plus prednisone. The coprimary end points were radiographic progression-free survival and overall survival. The study was unblinded after a planned interim analysis that was performed after 43% of the expected deaths had occurred. The median radiographic progression-free survival was 16.5 months with abiraterone-prednisone and 8.3 months with prednisone alone (hazard ratio for abiraterone-prednisone vs. prednisone alone, 0.53; 95% confidence interval [CI], 0.45 to 0.62; P<0.001). Over a median follow-up period of 22.2 months, overall survival was improved with abiraterone-prednisone (median not reached, vs. 27.2 months for prednisone alone; hazard ratio, 0.75; 95% CI, 0.61 to 0.93; P = 0.01) but did not cross the efficacy boundary. Abiraterone-prednisone showed superiority over prednisone alone with respect to time to initiation of cytotoxic chemotherapy, opiate use for cancer-related pain, prostate-specific antigen progression, and decline in performance status. Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone-prednisone. Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

Prognostic impact of serum bilirubin level on long-term renal survival in IgA nephropathy.

PubMed

Tanaka, Shigeru; Ninomiya, Toshiharu; Masutani, Kosuke; Nagata, Masaharu; Tsuchimoto, Akihiro; Tsuruya, Kazuhiko; Kitazono, Takanari

2015-12-01

Serum bilirubin has been recognized as a novel endogenous antioxidant. The aim of our study was to evaluate the impact of serum bilirubin on kidney prognosis in IgA nephropathy (IgAN). We followed retrospectively 694 patients with IgAN diagnosed by renal biopsy between 1982 and 2010. The risk factors for developing end-stage renal disease (ESRD) were estimated using a Cox proportional hazard model. Predictive performance between models with or without serum bilirubin was evaluated by calculating the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Seventy-seven patients developed ESRD during the median 4.9 years of follow-up. Estimated glomerular filtration rate, proteinuria and histological severity were inversely related to bilirubin levels. In multivariate analysis, serum bilirubin was an independent risk factor for ESRD (hazard ratio for every 0.1 mg/dL decrease in serum bilirubin, 1.18; 95 % CI, 1.04-1.33). The incidence rate of ESRD decreased linearly with the increases in bilirubin levels (P for trend <0.01). When bilirubin was incorporated into a model with conventional ESRD risk factors, the NRI and IDI were 0.281 (P = 0.02) and 0.019 (P = 0.01), respectively. We demonstrated that lower bilirubin levels were significantly associated with higher risk of ESRD in IgAN. In addition, bilirubin provided incremental predictive value in the risk assessment for progression of IgAN beyond that provided by standard risk factors.

Combining lymphovascular invasion with reactive stromal grade predicts prostate cancer mortality.

PubMed

Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

2016-09-01

Previous studies suggest that lymphovascular invasion (LVI) has a weak and variable effect on prognosis. It is uncertain whether LVI, determined by diagnostic prostate biopsy, predicts prostate cancer death. Data from experimental studies have indicated that carcinoma-associated fibroblasts in the reactive stroma could promote LVI and progression to metastasis. Thus, combining LVI with reactive stromal grade may identify prostate cancer patients at high risk of an unfavorable outcome. The purpose of the present study was to examine if LVI, determined by diagnostic biopsy, alone and in combination with reactive stromal grade could predict prostate cancer death. This population-based study included 283 patients with prostate cancer diagnosed by needle biopsy in Aust-Agder County (Norway) from 1991 to 1999. Clinical data were obtained by medical charts review. Two uropathologists evaluated LVI and reactive stromal grade. The endpoint was prostate cancer death. Patients with LVI had marginally higher risk of prostate cancer death compared to patients without LVI (hazard ratio: 1.8, P-value = 0.04). LVI had a stronger effect on prostate cancer death risk when a high reactive stromal grade was present (hazard ratio: 16.0, P-value <0.001). Therefore, patients with concomitant LVI and high reactive stromal grade were at particularly high risk for prostate cancer death. Evaluating LVI together with reactive stromal grade on diagnostic biopsies could be used to identify patients at high risk of death from prostate cancer. Prostate 76:1088-1094, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The Clinimetric Properties of Instruments Measuring Home Hazards for Older People at Risk of Falling: A Systematic Review.

PubMed

Romli, Muhammad Hibatullah; Mackenzie, Lynette; Lovarini, Meryl; Tan, Maw Pin; Clemson, Lindy

2018-03-01

Home hazards are associated with falls among older people living in the community. However, evaluating home hazards is a complex process as environmental factors vary according to geography, culture, and architectural design. As a result, many health practitioners commonly use nonstandardized assessment methods that may lead to inaccurate findings. Thus, the aim of this systematic review was to identify standardized instruments for evaluating home hazards related to falls and evaluate the clinimetric properties of these instruments for use by health practitioners. A systematic search was conducted in the Medline, CINAHL, AgeLine, Web of Science databases, and the University of Sydney Library CrossSearch Engine. Study screening, assessment, and quality ratings were conducted independently. Thirty-six studies were identified describing 19 instruments and three assessment techniques. The clinimetric properties varied between instruments. The Home Falls and Accidents Screening Tool, Home Safety Self-Assessment Tool, In-Home Occupational Performance Evaluation, and Westmead Home Safety Assessment were the instruments with high potential for evaluating home hazards associated with falls. Health practitioners can choose the most appropriate instruments for their practice, as a range of standardized instruments with established clinimetric properties are available.

Electromagnetic Spectrum Test and Evaluation Process

DTIC Science & Technology

2010-01-01

HERO , hazards of electromagnetic radiation to ordnance ; HERP, hazards of electromagnetic radiation to personnel; HERF, hazards of electromagnetic ... electromagnetic pulse (EMP); electronic protection; electrostatic dis- charge (ESD); hazards of electromagnetic radi- ation to personnel (HERP), ordnance ...including ordnance containing electrically initiated devices, to be mutually compatible in their intended

RCRA, superfund and EPCRA hotline training module. Introduction to: Hazardous waste identification (40 cfr part 261) updated July 1996

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

NONE

1996-07-01

The module introduces a specific hazardous waste identification process, which involves asking and analyzing a series of questions about any waste being evaluated. It analyzes in detail the Resource Conservation and Recovery Act (RCRA) definition of `hazardous waste.` It explains concepts that are essential to identifying a RCRA hazardous waste: hazardous waste listing, hazardous waste characteristics, the `mixture` and `derived-from` rules, the `contained-in` policy, and the hazardous waste identification rules (HWIR).

Evaluation of liquefaction hazards in Washington state.

DOT National Transportation Integrated Search

2008-12-01

This report describes the results of a detailed investigation of improved procedures for evaluation of : liquefaction hazards in Washington State, and describes the development and use of a computer : program, WSliq, that allows rapid and convenient ...

Blood neutrophil-lymphocyte ratio predicts survival in locally advanced cancer stomach treated with neoadjuvant chemotherapy FOLFOX 4.

PubMed

el Aziz, Lamiss Mohamed Abd

2014-12-01

Accurate predictors of survival for patients with advanced gastric cancer treated with neoadjuvant chemotherapy are currently lacking. In this study, we aimed to evaluate the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with stage III-IV gastric cancer who received neoadjuvant chemotherapy FOLFOX 4 as neoadjuvant chemotherapy. We enrolled 70 patients with stage III-IV cancer stomach in this study. Patients received FOLFOX 4 as neoadjuvant chemotherapy. Blood sample was collected before chemotherapy. The NLR was divided into two groups: high (>3) and low (≤ 3). Univariate analysis on progression-free survival (PFS) and overall survival (OS) was performed using the Kaplan-Meier and log-rank tests, and multivariate analysis was conducted using the Cox proportional hazards regression model. The toxicity was evaluated according to National Cancer Institute Common Toxicity Criteria. The univariate analysis showed that PFS and OS were both worse for patients with high NLR than for those with low NLR before chemotherapy (median PFS 28 and 44 months, respectively, P = 0.001; median OS 30 and 48 months, P = 0.001). Multivariate analysis showed that NLRs before chemotherapy were independent prognostic factors of OS but not for progression-free survival. NLR may serve as a potential biomarker for survival prognosis in patients with stage III-IV gastric cancer receiving neoadjuvant chemotherapy. The FOLFOX 4 demonstrated an acceptable toxicity.

The investigation of tethered satellite system dynamics

NASA Technical Reports Server (NTRS)

Lorenzini, E.

1985-01-01

Progress in tethered satellite system dynamics research is reported. A retrieval rate control law with no angular feedback to investigate the system's dynamic response was studied. The initial conditions for the computer code which simulates the satellite's rotational dynamics were extended to a generic orbit. The model of the satellite thrusters was modified to simulate a pulsed thrust, by making the SKYHOOK integrator suitable for dealing with delta functions without loosing computational efficiency. Tether breaks were simulated with the high resolution computer code SLACK3. Shuttle's maneuvers were tested. The electric potential around a severed conductive tether with insulator, in the case of a tether breakage at 20 km from the Shuttle, was computed. The electrodynamic hazards due to the breakage of the TSS electrodynamic tether in a plasma are evaluated.

Graphic products used in the evaluation of traditional and emerging remote sensing technologies for the detection of fugitive contamination at selected superfund hazardous waste sites

USGS Publications Warehouse

Slonecker, E. Terrence; Fisher, Gary B.

2011-01-01

This report presents the overhead imagery and field sampling results used to prepare U.S. Geological Survey Open-File Report 2011-1050, 'Evaluation of Traditional and Emerging Remote Sensing Technologies for the Detection of Fugitive Contamination at Selected Superfund Hazardous Waste Sites'. These graphic products were used in the evaluation of remote sensing technology in postclosure monitoring of hazardous waste sites and represent an ongoing research effort. Soil sampling results presented here were accomplished with field portable x-ray fluoresence (XRF) technology and are used as screening tools only representing the current conditions of metals and other contaminants at selected Superfund hazardous waste sites.

75 FR 64309 - Components for Evaluation of Direct-Reading Monitors for Gases and Vapors and Addendum

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-19

... Direct-Reading Monitors for Gases and Vapors: Hazard Detection in First Responder Environments.'' The.../docket/review/docket220 . The document expands the 1995 method development and evaluation experimental... evaluating direct-reading monitors for hazard detection in First Responder environments. The 1995 document...

Base-Position Error Rate Analysis of Next-Generation Sequencing Applied to Circulating Tumor DNA in Non-Small Cell Lung Cancer: A Prospective Study

PubMed Central

Zonta, Eleonora; Didelot, Audrey; Combe, Pierre; Thibault, Constance; Gibault, Laure; Lours, Camille; Taly, Valérie; Laurent-Puig, Pierre

2016-01-01

Background Circulating tumor DNA (ctDNA) is an approved noninvasive biomarker to test for the presence of EGFR mutations at diagnosis or recurrence of lung cancer. However, studies evaluating ctDNA as a noninvasive “real-time” biomarker to provide prognostic and predictive information in treatment monitoring have given inconsistent results, mainly due to methodological differences. We have recently validated a next-generation sequencing (NGS) approach to detect ctDNA. Using this new approach, we evaluated the clinical usefulness of ctDNA monitoring in a prospective observational series of patients with non-small cell lung cancer (NSCLC). Methods and Findings We recruited 124 patients with newly diagnosed advanced NSCLC for ctDNA monitoring. The primary objective was to analyze the prognostic value of baseline ctDNA on overall survival. ctDNA was assessed by ultra-deep targeted NGS using our dedicated variant caller algorithm. Common mutations were validated by digital PCR. Out of the 109 patients with at least one follow-up marker mutation, plasma samples were contributive at baseline (n = 105), at first evaluation (n = 85), and at tumor progression (n = 66). We found that the presence of ctDNA at baseline was an independent marker of poor prognosis, with a median overall survival of 13.6 versus 21.5 mo (adjusted hazard ratio [HR] 1.82, 95% CI 1.01–3.55, p = 0.045) and a median progression-free survival of 4.9 versus 10.4 mo (adjusted HR 2.14, 95% CI 1.30–3.67, p = 0.002). It was also related to the presence of bone and liver metastasis. At first evaluation (E1) after treatment initiation, residual ctDNA was an early predictor of treatment benefit as judged by best radiological response and progression-free survival. Finally, negative ctDNA at E1 was associated with overall survival independently of Response Evaluation Criteria in Solid Tumors (RECIST) (HR 3.27, 95% CI 1.66–6.40, p < 0.001). Study population heterogeneity, over-representation of EGFR-mutated patients, and heterogeneous treatment types might limit the conclusions of this study, which require future validation in independent populations. Conclusions In this study of patients with newly diagnosed NSCLC, we found that ctDNA detection using targeted NGS was associated with poor prognosis. The heterogeneity of lung cancer molecular alterations, particularly at time of progression, impairs the ability of individual gene testing to accurately detect ctDNA in unselected patients. Further investigations are needed to evaluate the clinical impact of earlier evaluation times at 1 or 2 wk. Supporting clinical decisions, such as early treatment switching based on ctDNA positivity at first evaluation, will require dedicated interventional studies. PMID:28027313

Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2- advanced breast cancer in the randomized MONALEESA-2 trial.

PubMed

O'Shaughnessy, Joyce; Petrakova, Katarina; Sonke, Gabe S; Conte, Pierfranco; Arteaga, Carlos L; Cameron, David A; Hart, Lowell L; Villanueva, Cristian; Jakobsen, Erik; Beck, Joseph T; Lindquist, Deborah; Souami, Farida; Mondal, Shoubhik; Germa, Caroline; Hortobagyi, Gabriel N

2018-02-01

Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. Postmenopausal women with HR+ , HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27-0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2- de novo advanced breast cancer.

Abiraterone and increased survival in metastatic prostate cancer.

PubMed

de Bono, Johann S; Logothetis, Christopher J; Molina, Arturo; Fizazi, Karim; North, Scott; Chu, Luis; Chi, Kim N; Jones, Robert J; Goodman, Oscar B; Saad, Fred; Staffurth, John N; Mainwaring, Paul; Harland, Stephen; Flaig, Thomas W; Hutson, Thomas E; Cheng, Tina; Patterson, Helen; Hainsworth, John D; Ryan, Charles J; Sternberg, Cora N; Ellard, Susan L; Fléchon, Aude; Saleh, Mansoor; Scholz, Mark; Efstathiou, Eleni; Zivi, Andrea; Bianchini, Diletta; Loriot, Yohann; Chieffo, Nicole; Kheoh, Thian; Haqq, Christopher M; Scher, Howard I

2011-05-26

Biosynthesis of extragonadal androgen may contribute to the progression of castration-resistant prostate cancer. We evaluated whether abiraterone acetate, an inhibitor of androgen biosynthesis, prolongs overall survival among patients with metastatic castration-resistant prostate cancer who have received chemotherapy. We randomly assigned, in a 2:1 ratio, 1195 patients who had previously received docetaxel to receive 5 mg of prednisone twice daily with either 1000 mg of abiraterone acetate (797 patients) or placebo (398 patients). The primary end point was overall survival. The secondary end points included time to prostate-specific antigen (PSA) progression (elevation in the PSA level according to prespecified criteria), progression-free survival according to radiologic findings based on prespecified criteria, and the PSA response rate. After a median follow-up of 12.8 months, overall survival was longer in the abiraterone acetate-prednisone group than in the placebo-prednisone group (14.8 months vs. 10.9 months; hazard ratio, 0.65; 95% confidence interval, 0.54 to 0.77; P<0.001). Data were unblinded at the interim analysis, since these results exceeded the preplanned criteria for study termination. All secondary end points, including time to PSA progression (10.2 vs. 6.6 months; P<0.001), progression-free survival (5.6 months vs. 3.6 months; P<0.001), and PSA response rate (29% vs. 6%, P<0.001), favored the treatment group. Mineralocorticoid-related adverse events, including fluid retention, hypertension, and hypokalemia, were more frequently reported in the abiraterone acetate-prednisone group than in the placebo-prednisone group. The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among patients with metastatic castration-resistant prostate cancer who previously received chemotherapy. (Funded by Cougar Biotechnology; COU-AA-301 ClinicalTrials.gov number, NCT00638690.).

Baseline 24-2 Central Visual Field Damage Is Predictive of Global Progressive Field Loss.

PubMed

Garg, Aakriti; De Moraes, C Gustavo; Cioffi, George A; Girkin, Christopher A; Medeiros, Felipe A; Weinreb, Robert N; Zangwill, Linda M; Liebmann, Jeffrey M

2018-03-01

Central visual field (VF) damage in glaucoma patients can significantly hinder daily activities. The present study investigates whether the presence of localized baseline damage to the central 10 degrees of the VF is predictive of faster global mean deviation (MD) progression. Prospective cohort study. Eyes from the multicenter African Descent and Glaucoma Evaluation Study (ADAGES) with established glaucoma and VF loss and a minimum of 5 24-2 VFs were eligible. Baseline central 24-2 damage was defined as any of the 12 central-most points with total deviation (TD) values at P < 0.5% on 2 consecutive examinations. Progression was determined using trend-based and event-based criteria: (1) rates of MD change significantly faster than zero and (2) >-5 dB MD loss over the entire follow-up. A total of 827 eyes of 584 patients were studied. Mean rate of MD change of the entire sample was -0.15 dB/year (95% CI: -0.19 to -0.12, P < .001). Eyes with baseline central damage progressed faster than those without (difference: β central  = -0.07 dB/year, 95% CI: -0.11 to -0.01, P = .011) and were more likely to experience MD loss greater than 5 dB (hazard ratio = 3.0 [95% CI: 2.1-4.1, P < .001]). These differences remained significant after adjusting for confounders. The presence of central VF damage at baseline is significantly associated with more rapid global progression. Detection of central VF damage aids in stratification of high-risk patients who may need intensive surveillance and aggressive treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Cohort Study on Predictors of Need for Nursing Care in Alzheimer's Disease: An Analysis of Healthcare Data.

PubMed

Brüggenjürgen, Bernd; Andersohn, Frank; Burkowitz, Jörg; Ezzat, Nadja; Gaudig, Maren; Willich, Stefan N

2016-10-18

The individual and societal burden of Alzheimer's disease (AD) is substantial. Identifying relevant factors deteriorating AD and inducing need for nursing care would be of high relevance for healthcare planning. The main objective of this study was the identification of predictors of first assignment of a level of long-term care in AD, used as an approximation for disease progression. In a retrospective cohort study using data from a large German statutory health and long-term care insurance (SHI) company, co-morbidities and drug exposure were evaluated with respect to their predictive value for disease progression (first day the amount of daily nursing care exceeded 1.5 hours). Time to disease progression was modeled using COX-proportional hazard regression with stepwise selection of predictor variables. The risk of nursing care need increased substantially with increasing age. Number of hospitalizations and number of different drugs used were significant indicators for progression, whereas outpatient visits were associated with a reduced need for care. Gender did not indicate significant influence on progression. Malignant neoplasms of ill-defined, secondary, and unspecified sites, malnutrition, renal failure, and injuries increased the risk of need for nursing care most significantly. Among prescribed drugs, significant increased risks were associated with drugs used in diabetes, preparations for treatment of wounds and ulcers, antiseptics and disinfectants, and analgesics. Physical comorbidities are relevant contributors to an increase in need for nursing care. Some medical predicting conditions may be linked to cognition, while others may be directly linked to demand for care. AD patients with these comorbidities should be monitored with special attention, as they may be under an increased risk of care dependency.

Developing a global tsunami propagation database and its application for coastal hazard assessments in China

NASA Astrophysics Data System (ADS)

Wang, N.; Tang, L.; Titov, V.; Newman, J. C.; Dong, S.; Wei, Y.

2013-12-01

The tragedies of the 2004 Indian Ocean and 2011 Japan tsunamis have increased awareness of tsunami hazards for many nations, including China. The low land level and high population density of China's coastal areas place it at high risk for tsunami hazards. Recent research (Komatsubara and Fujiwara, 2007) highlighted concerns of a magnitude 9.0 earthquake on the Nankai trench, which may affect China's coasts not only in South China Sea, but also in the East Sea and Yellow Sea. Here we present our work in progress towards developing a global tsunami propagation database that can be used for hazard assessments by many countries. The propagation scenarios are computed by using NOAA's MOST numerical model. Each scenario represents a typical Mw 7.5 earthquake with predefined earthquake parameters (Gica et al., 2008). The model grid was interpolated from ETOPO1 at 4 arc-min resolution, covering -80° to72°N and 0 to 360°E. We use this database for preliminary tsunami hazard assessment along China's coastlines.

Pyrotechnic hazards classification and evaluation program test report. Heat flux study of deflagrating pyrotechnic munitions

NASA Technical Reports Server (NTRS)

Fassnacht, P. O.

1971-01-01

A heat flux study of deflagrating pyrotechnic munitions is presented. Three tests were authorized to investigate whether heat flux measurements may be used as effective hazards evaluation criteria to determine safe quantity distances for pyrotechnics. A passive sensor study was conducted simultaneously to investigate their usefulness in recording events and conditions. It was concluded that heat flux measurements can effectively be used to evaluate hazards criteria and that passive sensors are an inexpensive tool to record certain events in the vicinity of deflagrating pyrotechnic stacks.

[Application of risk grading and classification for occupational hazards in risk management for a shipbuilding project].

PubMed

Zeng, Wenfeng; Tan, Qiang; Wu, Shihua; Deng, Yingcong; Liu, Lifen; Wang, Zhi; Liu, Yimin

2015-12-01

To investigate the application of risk grading and classification for occupational hazards in risk management for a shipbuilding project. The risk management for this shipbuilding project was performed by a comprehensive application of MES evaluation, quality assessment of occupational health management, and risk grading and classification for occupational hazards, through the methods of occupational health survey, occupational health testing, and occupational health examinations. The results of MES evaluation showed that the risk of occupational hazards in this project was grade 3, which was considered as significant risk; Q value calculated by quality assessment of occupational health management was 0.52, which was considered to be unqualified; the comprehensive evaluation with these two methods showed that the integrated risk rating for this shipbuilding project was class D, and follow- up and rectification were needed with a focus on the improvement in health management. The application of MES evaluation and quality assessment of occupational health management in risk management for occupational hazards can achieve objective and reasonable conclusions and has good applicability.

32 CFR 643.31 - Policy-Flood hazards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Policy-Flood hazards. 643.31 Section 643.31... ESTATE Policy § 643.31 Policy—Flood hazards. Each Determination of Availability Report will include an evaluation of the flood hazards, if any, relative to the property involved in the proposed outgrant action...

34 CFR 75.611 - Avoidance of flood hazards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Avoidance of flood hazards. 75.611 Section 75.611... by a Grantee? Construction § 75.611 Avoidance of flood hazards. In planning the construction, a...) Evaluate flood hazards in connection with the construction; and (b) As far as practicable, avoid uneconomic...

Design and technical evaluation of an enhanced location-awareness service enabler for spatial disorientation management of elderly with mild cognitive impairment.

PubMed

Moreno, Pedro A; Hernando, M Elena; Gómez, Enrique J

2015-01-01

The progressive ageing of population has turned the mild cognitive impairment (MCI) into a prevalent disease suffered by elderly. Consequently, the spatial disorientation has become a significant problem for older people and their caregivers. The ambient-assisted living applications are offering location-based services for empowering elderly to go outside and encouraging a greater independence. Therefore, this paper describes the design and technical evaluation of a location-awareness service enabler aimed at supporting and managing probable wandering situations of a person with MCI. Through the presence capabilities of the IP multimedia subsystem (IMS) architecture, the service will alert patient's contacts if a hazardous situation is detected depending on his location. Furthermore, information about the older person's security areas has been included in the user profile managed by IMS. In doing so, the service enabler introduced contribute to "context-awareness" paradigm allowing the adaptation and personalization of services depending on user's context and specific conditions or preferences.

High concentrations of AGE-LDL and oxidized LDL in circulating immune complexes are associated with progression of retinopathy in type 1 diabetes.

PubMed

Lopes-Virella, Maria F; Baker, Nathaniel L; Hunt, Kelly J; Lyons, Timothy J; Jenkins, Alicia J; Virella, Gabriel

2012-06-01

To determine whether immunocomplexes (ICs) containing advanced glycation end product (AGE)-LDL (AGE-LDL) and oxidized LDL (oxLDL) contribute to the development of retinopathy over a 16-year period in subjects with type 1 diabetes. Levels of AGE-LDL and oxLDL in ICs were measured in 517 patients of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. Retinopathy was assessed by stereoscopic fundus photography. Cox proportional hazards models were used to assess the effect of AGE-LDL-ICs and oxLDL-ICs on retinopathy progression. In unadjusted models, higher baseline levels of AGE-LDL-ICs and oxLDL-ICs significantly predicted progression of diabetic retinopathy outcomes. After adjustment by study-design variables (treatment group, retinopathy cohort, duration of type 1 diabetes, and baseline albumin excretion rate [AER], hemoglobin A(1c) (HbA(1c)), and Early Treatment Diabetic Retinopathy Study [ETDRS] score), one SD increase in IC levels was associated with 47% (hazard ratio [HR] 1.47 [95% CI 1.19-1.81]; AGE-LDL-IC) and 45% (1.45 [1.17-1.80]; oxLDL-IC) increased risk of developing proliferative diabetic retinopathy (PDR) and 37% (1.37 [1.12-1.66]; to both ICs) increased risk of progressing to severe nonproliferative retinopathy. Analyses were stratified by retinopathy cohort because results differed between primary and secondary cohorts. For AGE-LDL-ICs, HR for progression to PDR was 2.38 (95% CI 1.30-4.34) in the primary cohort and attenuated in the secondary cohort (1.29 [1.03-1.62]). Similar results were observed for oxLDL-ICs. Increased levels of AGE-LDL and oxLDL in ICs are associated with increased risk for progression to advanced retinopathy in patients with type 1 diabetes, indicating that the antibody response to modified LDL plays a significant role in retinopathy progression.

Applying the natural disasters vulnerability evaluation model to the March 2011 north-east Japan earthquake and tsunami.

PubMed

Ruiz Estrada, Mario Arturo; Yap, Su Fei; Park, Donghyun

2014-07-01

Natural hazards have a potentially large impact on economic growth, but measuring their economic impact is subject to a great deal of uncertainty. The central objective of this paper is to demonstrate a model--the natural disasters vulnerability evaluation (NDVE) model--that can be used to evaluate the impact of natural hazards on gross national product growth. The model is based on five basic indicators-natural hazards growth rates (αi), the national natural hazards vulnerability rate (ΩT), the natural disaster devastation magnitude rate (Π), the economic desgrowth rate (i.e. shrinkage of the economy) (δ), and the NHV surface. In addition, we apply the NDVE model to the north-east Japan earthquake and tsunami of March 2011 to evaluate its impact on the Japanese economy. © 2014 The Author(s). Disasters © Overseas Development Institute, 2014.

Prognostic Relevance of Urinary Bladder Cancer Susceptibility Loci

PubMed Central

Grotenhuis, Anne J.; Dudek, Aleksandra M.; Verhaegh, Gerald W.; Witjes, J. Alfred; Aben, Katja K.; van der Marel, Saskia L.; Vermeulen, Sita H.; Kiemeney, Lambertus A.

2014-01-01

In the last few years, susceptibility loci have been identified for urinary bladder cancer (UBC) through candidate-gene and genome-wide association studies. Prognostic relevance of most of these loci is yet unknown. In this study, we used data of the Nijmegen Bladder Cancer Study (NBCS) to perform a comprehensive evaluation of the prognostic relevance of all confirmed UBC susceptibility loci. Detailed clinical data concerning diagnosis, stage, treatment, and disease course of a population-based series of 1,602 UBC patients were collected retrospectively based on a medical file survey. Kaplan-Meier survival analyses and Cox proportional hazard regression were performed, and log-rank tests calculated, to evaluate the association between 12 confirmed UBC susceptibility variants and recurrence and progression in non-muscle invasive bladder cancer (NMIBC) patients. Among muscle-invasive or metastatic bladder cancer (MIBC) patients, association of these variants with overall survival was tested. Subgroup analyses by tumor aggressiveness and smoking status were performed in NMIBC patients. In the overall NMIBC group (n = 1,269), a statistically significant association between rs9642880 at 8q24 and risk of progression was observed (GT vs. TT: HR = 1.08 (95% CI: 0.76–1.54), GG vs. TT: HR = 1.81 (95% CI: 1.23–2.66), P for trend = 2.6×10−3). In subgroup analyses, several other variants showed suggestive, though non-significant, prognostic relevance for recurrence and progression in NMIBC and survival in MIBC. This study provides suggestive evidence that genetic loci involved in UBC etiology may influence disease prognosis. Elucidation of the causal variant(s) could further our understanding of the mechanism of disease, could point to new therapeutic targets, and might aid in improvement of prognostic tools. PMID:24586564

Validation of the EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis.

PubMed

Burgers, Leonie E; Siljehult, Filip; Ten Brinck, Robin M; van Steenbergen, Hanna W; Landewé, Robert B M; Rantapää-Dahlqvist, Solbritt; van der Helm-van Mil, Annette H M

2017-12-01

Recently a EULAR-taskforce defined arthralgia suspicious for progression to RA, in order to allow inclusion of homogeneous sets of arthralgia patients in clinical studies. This longitudinal study aimed (i) to validate this definition in arthralgia patients in whom rheumatologists felt that imminent RA was more likely than other arthralgias [clinically suspect arthralgia (CSA)], that is, the target population fulfilling the entry criterion, and (ii) to explore the performance in arthralgia patients who were referred to secondary care prior to rheumatological evaluation, hence ignoring the entry criterion. The definition was assessed in 241 Dutch patients identified with CSA by rheumatologists and 113 patients referred to the Umeå university hospital with recent-onset arthralgia in small joints. The external reference was arthritis development <2 years' follow-up. CSA patients with a positive definition (⩾3/7 parameters present) had an increased risk for developing arthritis compared with definition-negative CSA patients (hazard ratio = 2.1, 95% CI: 0.9, 4.7). The sensitivity was 84% and the positive predictive value 30%. In arthralgia patients in whom the definition was applied before rheumatological evaluation, a positive definition was neither sensitive (10%) nor predictive (positive predictive value 3%). The EULAR definition of arthralgia suspicious for progression to RA is sensitive when used to support the rheumatologist's opinion on imminent RA. This validation study shows that the definition, when used as designed, further homogenizes patients that rheumatologists consider at risk for RA. To arrive at a high specificity, the clinical definition needs to be combined with biomarkers. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Edge Contrast of the FLAIR Hyperintense Region Predicts Survival in Patients with High-Grade Gliomas following Treatment with Bevacizumab.

PubMed

Bahrami, N; Piccioni, D; Karunamuni, R; Chang, Y-H; White, N; Delfanti, R; Seibert, T M; Hattangadi-Gluth, J A; Dale, A; Farid, N; McDonald, C R

2018-04-05

Treatment with bevacizumab is standard of care for recurrent high-grade gliomas; however, monitoring response to treatment following bevacizumab remains a challenge. The purpose of this study was to determine whether quantifying the sharpness of the fluid-attenuated inversion recovery hyperintense border using a measure derived from texture analysis-edge contrast-improves the evaluation of response to bevacizumab in patients with high-grade gliomas. MRIs were evaluated in 33 patients with high-grade gliomas before and after the initiation of bevacizumab. Volumes of interest within the FLAIR hyperintense region were segmented. Edge contrast magnitude for each VOI was extracted using gradients of the 3D FLAIR images. Cox proportional hazards models were generated to determine the relationship between edge contrast and progression-free survival/overall survival using age and the extent of surgical resection as covariates. After bevacizumab, lower edge contrast of the FLAIR hyperintense region was associated with poorer progression-free survival ( P = .009) and overall survival ( P = .022) among patients with high-grade gliomas. Kaplan-Meier curves revealed that edge contrast cutoff significantly stratified patients for both progression-free survival (log-rank χ 2 = 8.3, P = .003) and overall survival (log-rank χ 2 = 5.5, P = .019). Texture analysis using edge contrast of the FLAIR hyperintense region may be an important predictive indicator in patients with high-grade gliomas following treatment with bevacizumab. Specifically, low FLAIR edge contrast may partially reflect areas of early tumor infiltration. This study adds to a growing body of literature proposing that quantifying features may be important for determining outcomes in patients with high-grade gliomas. © 2018 by American Journal of Neuroradiology.

Evaluation of Overall Response Rate and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Immunotherapy Trials.

PubMed

Mushti, Sirisha L; Mulkey, Flora; Sridhara, Rajeshwari

2018-05-15

Purpose: With the approval of immunotherapies for a variety of indications, methods to assess treatment benefit addressing the response patterns observed are important. We evaluated RECIST criteria-based overall response rate (ORR) and progression-free survival (PFS) as potential surrogate endpoints of overall survival (OS), and explored a modified definition of PFS by altering the threshold percentage determining disease progression to assess the association with survival benefit in immunotherapy trials. Experimental Design: Thirteen randomized, multicenter, active-control trials containing immunotherapeutic agents submitted to the FDA were analyzed. Associations between treatment effects of ORR, PFS, modified PFS, and OS were evaluated at individual and trial levels. Patient-level responder analysis was performed for PFS and OS. Results: The coefficient of determination ( R ²) measured the strength of associations, where values near 1 imply surrogacy and values close to 0 suggest no association. At the trial level, the association between hazard ratios (HR) of PFS and OS was R 2 = 0.1303, and between the odds ratio (OR) of ORR and HR of OS was R 2 = 0.1277. At the individual level, the Spearman rank correlation coefficient between PFS and OS was 0.61. Trial-level associations between modified PFS and OS ranged between 0.07 and 0.1, and individual-level correlations were approximately 0.6. HRs of PFS and OS for responders versus nonresponders were 0.129 [95% confidence interval (CI), 0.11-0.15] and 0.118 (95% CI, 0.11-0.13), respectively. Conclusions: Although responders exhibited longer survival and PFS than nonresponders, the trial-level and individual-level associations were weak between PFS/ORR and OS. Modifications to PFS did not improve associations. Clin Cancer Res; 24(10); 2268-75. ©2018 AACR See related commentary by Korn and Freidlin, p. 2239 . ©2018 American Association for Cancer Research.

Longitudinal follow-up of fibrosing interstitial pneumonia: relationship between physiologic testing, computed tomography changes, and survival rate.

PubMed

Hwang, Jeong-Hwa; Misumi, Shigeki; Curran-Everett, Douglas; Brown, Kevin K; Sahin, Hakan; Lynch, David A

2011-08-01

The aim of this study was to evaluate the prognostic implications of computed tomography (CT) and physiologic variables at baseline and on sequential evaluation in patients with fibrosing interstitial pneumonia. We identified 72 patients with fibrosing interstitial pneumonia (42 with idiopathic disease, 30 with collagen vascular disease). Pulmonary function tests and CT were performed at the time of diagnosis and at a median follow-up of 12 months, respectively. Two chest radiologists scored the extent of specific abnormalities and overall disease on baseline and follow-up CT. Rate of survival was estimated using the Kaplan-Meier method. Three Cox proportional hazards models were constructed to evaluate the relationship between CT and physiologic variables and rate of survival: model 1 included only baseline variables, model 2 included only serial change variables, and model 3 included both baseline and serial change variables. On follow-up CT, the extent of mixed ground-glass and reticular opacities (P<0.001), pure reticular opacity (P=0.04), honeycombing (P=0.02), and overall extent of disease (P<0.001) was increased in the idiopathic group, whereas these variables remained unchanged in the collagen vascular disease group. Patients with idiopathic disease had a shorter rate of survival than those with collagen vascular disease (P=0.03). In model 1, the extent of honeycombing on baseline CT was the only independent predictor of mortality (P=0.02). In model 2, progression in honeycombing was the only predictor of mortality (P=0.005). In model 3, baseline extent of honeycombing and progression of honeycombing were the only independent predictors of mortality (P=0.001 and 0.002, respectively). Neither baseline nor serial change physiologic variables, nor the presence of collagen vascular disease, was predictive of rate of survival. The extent of honeycombing at baseline and its progression on follow-up CT are important determinants of rate of survival in patients with fibrosing interstitial pneumonia.

3 CFR 8658 - Proclamation 8658 of April 27, 2011. Workers Memorial Day, 2011

Code of Federal Regulations, 2012 CFR

2012-01-01

... hazards. In the four decades since those landmark laws were enacted, we have seen great progress in... full force of the law is brought to bear in cases where workers are put in harm's way. Many of our...

Systems Toxicology of Embryo Development (9th Copenhagen Workshop)

EPA Science Inventory

An important consideration for predictive toxicology is to identify developmental hazards utilizing mechanism-based in vitro assays (e.g., ToxCast) and in silico multiscale models. Steady progress has been made with agent-based models that recapitulate morphogenetic drivers for a...

Hazardous Waste Cleanup: Buckeye Caribbean Terminals Incorporated in Yabucoa, Puerto Rico

EPA Pesticide Factsheets

The Buckeye Caribbean Terminals, Inc. (formerly Shell Chemical Yabucoa, Inc.) is located on Road 901 about two miles east of the town of Yabucoa, Puerto Rico. Petroleum refining operations have been in progress at the site since May 1971.

Six Strategies for Chemical Waste Minimization in Laboratories.

ERIC Educational Resources Information Center

Matteson, Gary C.; Hadley, Cheri R.

1991-01-01

Guidelines are offered to research administrators for reducing the volume of hazardous laboratory waste. Suggestions include a chemical location inventory, a chemical reuse facility, progressive contracts with chemical suppliers, internal or external chemical recycling mechanisms, a "chemical conservation" campaign, and laboratory fees for…

Hazardous Waste Cleanup: Lenox China Incorporated in Pomona, New Jersey

EPA Pesticide Factsheets

Lenox China Inc. is a 56-acre site in a rural area located on Tilton Road on the outskirts of the Town of Pomona in southeastern New Jersey. The facility manufactures china giftware and dinnerware. The manufacturing process includes the progressive

Regional danger assessment of Debris flow and its engineering mitigation practice in Sichuan-Tibet highway

NASA Astrophysics Data System (ADS)

Su, Pengcheng; Sun, Zhengchao; li, Yong

2017-04-01

Luding-Kangding highway cross the eastern edge of Qinghai-Tibet Plateau where belong to the most deep canyon area of plateau and mountains in western Sichuan with high mountain and steep slope. This area belongs to the intersection among Xianshuihe, Longmenshan and Anninghe fault zones which are best known in Sichuan province. In the region, seismic intensity is with high frequency and strength, new tectonic movement is strong, rock is cracked, there are much loose solid materials. Debris flow disaster is well developed under the multiple effects of the earthquake, strong rainfall and human activity which poses a great threat to the local people's life and property security. So this paper chooses Kangding and LuDing as the study area to do the debris flow hazard assessment through the in-depth analysis of development characteristics and formation mechanism of debris flow. Which can provide important evidence for local disaster assessment and early warning forecast. It also has the important scientific significance and practical value to safeguard the people's life and property safety and the security implementation of the national major project. In this article, occurrence mechanism of debris flow disasters in the study area is explored, factor of evaluation with high impact to debris flow hazards is identified, the database of initial evaluation factors is made by the evaluation unit of basin. The factors with high impact to hazards occurrence are selected by using the stepwise regression method of logistic regression model, at the same time the factors with low impact are eliminated, then the hazard evaluation factor system of debris flow is determined in the study area. Then every factors of evaluation factor system are quantified, and the weights of all evaluation factors are determined by using the analysis of stepwise regression. The debris flows hazard assessment and regionalization of all the whole study area are achieved eventually after establishing the hazard assessment model. In this paper, regional debris flows hazard assessment method with strong universality and reliable evaluation result is presented. The whole study area is divided into 1674 units by automatically extracting and artificial identification, and then 11 factors are selected as the initial assessment factors of debris flow hazard assessment in the study area. The factors of the evaluation index system are quantified using the method of standardized watershed unit amount ratio. The relationship between debris flow occurrence and each evaluation factor is simulated using logistic regression model. The weights of evaluation factors are determined, and the model of debris flows hazard assessment is established in the study area. Danger assessment result of debris flow was applied in line optimization and engineering disaster reduction of Sichuan-Tibet highway (section of Luding-Kangding).

Forecasting surface water flooding hazard and impact in real-time

NASA Astrophysics Data System (ADS)

Cole, Steven J.; Moore, Robert J.; Wells, Steven C.

2016-04-01

Across the world, there is increasing demand for more robust and timely forecast and alert information on Surface Water Flooding (SWF). Within a UK context, the government Pitt Review into the Summer 2007 floods provided recommendations and impetus to improve the understanding of SWF risk for both off-line design and real-time forecasting and warning. Ongoing development and trial of an end-to-end real-time SWF system is being progressed through the recently formed Natural Hazards Partnership (NHP) with delivery to the Flood Forecasting Centre (FFC) providing coverage over England & Wales. The NHP is a unique forum that aims to deliver coordinated assessments, research and advice on natural hazards for governments and resilience communities across the UK. Within the NHP, a real-time Hazard Impact Model (HIM) framework has been developed that includes SWF as one of three hazards chosen for initial trialling. The trial SWF HIM system uses dynamic gridded surface-runoff estimates from the Grid-to-Grid (G2G) hydrological model to estimate the SWF hazard. National datasets on population, infrastructure, property and transport are available to assess impact severity for a given rarity of SWF hazard. Whilst the SWF hazard footprint is calculated in real-time using 1, 3 and 6 hour accumulations of G2G surface runoff on a 1 km grid, it has been possible to associate these with the effective rainfall design profiles (at 250m resolution) used as input to a detailed flood inundation model (JFlow+) run offline to produce hazard information resolved to 2m resolution. This information is contained in the updated Flood Map for Surface Water (uFMfSW) held by the Environment Agency. The national impact datasets can then be used with the uFMfSW SWF hazard dataset to assess impacts at this scale and severity levels of potential impact assigned at 1km and for aggregated county areas in real-time. The impact component is being led by the Health and Safety Laboratory (HSL) within the NHP. Flood Guidance within the FFC employs the national Flood Risk Matrix, which categorises potential impacts into minimal, minor, significant and severe, and Likelihood, into very low, low, medium and high classes, and the matrix entries then define the Overall Flood Risk as very low, low, medium and high. Likelihood is quantified by running G2G with Met Office ensemble rainfall inputs that in turn allows a probability to be assigned to the SWF hazard and associated impact. This overall procedure is being trialled and refined off-line by CEH and HSL using case study data, and at the same time implemented as a pre-operational test system at the Met Office for evaluation by FFC (a joint Environment Agency and Met Office centre for flood forecasting) in 2016.

Measuring disease progression in early Parkinson disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) experience.

PubMed

Parashos, Sotirios A; Luo, Sheng; Biglan, Kevin M; Bodis-Wollner, Ivan; He, Bo; Liang, Grace S; Ross, G Webster; Tilley, Barbara C; Shulman, Lisa M

2014-06-01

Optimizing assessments of rate of progression in Parkinson disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents. To examine the value of measures of impairment, disability, and quality of life in assessing progression in early PD. Inception cohort analysis of data from 413 patients with early, untreated PD who were enrolled in 2 multicenter, randomized, double-blind clinical trials. Participants were randomly assigned to 1 of 5 treatments (67 received creatine, 66 received minocycline, 71 received coenzyme Q10, 71 received GPI-1485, and 138 received placebo). We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment. Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression. After adjusting for baseline confounding variables with regard to the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score, the UPDRS Part III score, the modified Rankin Scale score, level of education, and treatment group, we assessed the rate of change for the following measurements: the UPDRS Part II score; the UPDRS Part III score; the Schwab and England Independence Scale score (which measures activities of daily living); the Total Functional Capacity scale; the 39-item Parkinson's Disease Questionnaire, summary index, and activities of daily living subscale; and version 2 of the 12-item Short Form Health Survey Physical Summary and Mental Summary. Variables reaching the statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid change (ie, worsening) in the UPDRS Part II score (hazard ratio, 1.15 [95% CI, 1.08-1.22] for 1 scale unit change per 6 months), the UPDRS Part III score (hazard ratio, 1.09 [95% CI, 1.06-1.13] for 1 scale unit change per 6 months), and the Schwab and England Independence Scale score (hazard ratio, 1.29 [95% CI, 1.12-1.48] for 5 percentage point change per 6 months) was associated with earlier need for symptomatic therapy. AND RELEVANCE In early PD, the UPDRS Part II score and Part III score and the Schwab and England Independence Scale score can be used to measure disease progression, whereas the 39-item Parkinson's Disease Questionnaire and summary index, Total Functional Capacity scale, and the 12-item Short Form Health Survey Physical Summary and Mental Summary are not sensitive to change. clinicaltrials.gov Identifiers: NCT00063193 and NCT00076492.

Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma

PubMed Central

Bellmunt, J.; de Wit, R.; Vaughn, D.J.; Fradet, Y.; Lee, J.-L.; Fong, L.; Vogelzang, N.J.; Climent, M.A.; Petrylak, D.P.; Choueiri, T.K.; Necchi, A.; Gerritsen, W.; Gurney, H.; Quinn, D.I.; Culine, S.; Sternberg, C.N.; Mai, Y.; Poehlein, C.H.; Perini, R.F.; Bajorin, D.F.

2017-01-01

BACKGROUND Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options. METHODS In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator’s choice of chemotherapy with paclitaxel, docetaxel, or vinflunine. The coprimary end points were overall survival and progression-free survival, which were assessed among all patients and among patients who had a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1–expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10% or more. RESULTS The median overall survival in the total population was 10.3 months (95% confidence interval [CI], 8.0 to 11.8) in the pembrolizumab group, as compared with 7.4 months (95% CI, 6.1 to 8.3) in the chemotherapy group (hazard ratio for death, 0.73; 95% CI, 0.59 to 0.91; P=0.002). The median overall survival among patients who had a tumor PD-L1 combined positive score of 10% or more was 8.0 months (95% CI, 5.0 to 12.3) in the pembrolizumab group, as compared with 5.2 months (95% CI, 4.0 to 7.4) in the chemotherapy group (hazard ratio, 0.57; 95% CI, 0.37 to 0.88; P=0.005). There was no significant between-group difference in the duration of progression-free survival in the total population (hazard ratio for death or disease progression, 0.98; 95% CI, 0.81 to 1.19; P=0.42) or among patients who had a tumor PD-L1 combined positive score of 10% or more (hazard ratio, 0.89; 95% CI, 0.61 to 1.28; P =0.24). Fewer treatment-related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group (60.9% vs. 90.2%); there were also fewer events of grade 3, 4, or 5 severity reported in the pembrolizumab group than in the chemotherapy group (15.0% vs. 49.4%). CONCLUSIONS Pembrolizumab was associated with significantly longer overall survival (by approximately 3 months) and with a lower rate of treatment-related adverse events than chemotherapy as second-line therapy for platinum-refractory advanced urothelial carcinoma. (Funded by Merck; KEYNOTE-045 ClinicalTrials.gov number, NCT02256436.) PMID:28212060

Seismic Hazard Assessment for a Characteristic Earthquake Scenario: Probabilistic-Deterministic Method

NASA Astrophysics Data System (ADS)

mouloud, Hamidatou

2016-04-01

The objective of this paper is to analyze the seismic activity and the statistical treatment of seismicity catalog the Constantine region between 1357 and 2014 with 7007 seismic event. Our research is a contribution to improving the seismic risk management by evaluating the seismic hazard in the North-East Algeria. In the present study, Earthquake hazard maps for the Constantine region are calculated. Probabilistic seismic hazard analysis (PSHA) is classically performed through the Cornell approach by using a uniform earthquake distribution over the source area and a given magnitude range. This study aims at extending the PSHA approach to the case of a characteristic earthquake scenario associated with an active fault. The approach integrates PSHA with a high-frequency deterministic technique for the prediction of peak and spectral ground motion parameters in a characteristic earthquake. The method is based on the site-dependent evaluation of the probability of exceedance for the chosen strong-motion parameter. We proposed five sismotectonique zones. Four steps are necessary: (i) identification of potential sources of future earthquakes, (ii) assessment of their geological, geophysical and geometric, (iii) identification of the attenuation pattern of seismic motion, (iv) calculation of the hazard at a site and finally (v) hazard mapping for a region. In this study, the procedure of the earthquake hazard evaluation recently developed by Kijko and Sellevoll (1992) is used to estimate seismic hazard parameters in the northern part of Algeria.

Preliminary volcanic hazards evaluation for Los Alamos National Laboratory Facilities and Operations : current state of knowledge and proposed path forward

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

Keating, Gordon N.; Schultz-Fellenz, Emily S.; Miller, Elizabeth D.

2010-09-01

The integration of available information on the volcanic history of the region surrounding Los Alamos National Laboratory indicates that the Laboratory is at risk from volcanic hazards. Volcanism in the vicinity of the Laboratory is unlikely within the lifetime of the facility (ca. 50–100 years) but cannot be ruled out. This evaluation provides a preliminary estimate of recurrence rates for volcanic activity. If further assessment of the hazard is deemed beneficial to reduce risk uncertainty, the next step would be to convene a formal probabilistic volcanic hazards assessment.

Efficacy and safety of third-line molecular-targeted therapy in metastatic renal cell carcinoma resistant to first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor and second-line therapy.

PubMed

Ishihara, Hiroki; Takagi, Toshio; Kondo, Tsunenori; Tachibana, Hidekazu; Yoshida, Kazuhiko; Omae, Kenji; Iizuka, Junpei; Kobayashi, Hirohito; Tanabe, Kazunari

2018-06-01

The number of studies evaluating the efficacy and safety of third-line molecular-targeted therapy for metastatic renal cell carcinoma (mRCC) is limited. The data for 48 patients with disease progression after first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI) and second-line targeted therapy were evaluated. Patients with prior cytokine therapy were excluded. Overall survival (OS) after first- and second-line therapy initiation was compared between patients with and without third-line therapy. In addition, dose-limiting toxicities (DLTs) were evaluated. Twenty-two of 48 patients (45.8%) received third-line therapy, and TKI and mammalian target of rapamycin inhibitor were each administered in 11 patients (50%). Patients with third-line therapy had significantly longer median OS after first-line therapy (26.6 vs. 14.6 months, p = 0.0010) and second-line therapy (18.2 vs. 7.4 months, p < 0.0001) compared to those without third-line therapy. Multivariate analysis showed that the use of third-line therapy following second-line therapy was an independent prognosticator for longer OS (hazard ratio 0.29, 95% confidence interval 0.14-0.58, p = 0.0005). The median progression-free survival and OS after third-line therapy was 2.76 and 8.71 months, respectively. Although a high frequency of DLTs was observed (n = 10, 45.5%), the frequencies were similar among the sequential therapies. Third-line therapy has a beneficial therapeutic effect in patients with mRCC that is resistant to previous therapies. However, there is a need to evaluate in detail the high frequency of adverse events, including DLTs.

Near surface geophysics techniques and geomorphological approach to reconstruct the hazard cave map in historical and urban areas

NASA Astrophysics Data System (ADS)

Lazzari, M.; Loperte, A.; Perrone, A.

2010-03-01

This work, carried out with an integrated methodological approach, focuses on the use of near surface geophysics techniques, such as ground penetrating radar and electrical resistivity tomography (ERT), and geomorphological analysis, in order to reconstruct the cave distribution and geometry in a urban context and, in particular, in historical centres. The interaction during recent centuries between human activity (caves excavation, birth and growth of an urban area) and the characters of the natural environment were the reasons of a progressive increase in hazard and vulnerability levels of several sites. The reconstruction of a detailed cave map distribution is the first step to define the anthropic and geomorphological hazard in urban areas, fundamental basis for planning and assessing the risk.

An Integrative Research Framework to Unravel the Interplay of Natural Hazards and Vulnerabilities

NASA Astrophysics Data System (ADS)

Di Baldassarre, Giuliano; Nohrstedt, Daniel; Mârd, Johanna; Burchardt, Steffi; Albin, Cecilia; Bondesson, Sara; Breinl, Korbinian; Deegan, Frances M.; Fuentes, Diana; Lopez, Marc Girons; Granberg, Mikael; Nyberg, Lars; Nyman, Monika Rydstedt; Rhodes, Emma; Troll, Valentin; Young, Stephanie; Walch, Colin; Parker, Charles F.

2018-03-01

Climate change, globalization, urbanization, social isolation, and increased interconnectedness between physical, human, and technological systems pose major challenges to disaster risk reduction (DRR). Subsequently, economic losses caused by natural hazards are increasing in many regions of the world, despite scientific progress, persistent policy action, and international cooperation. We argue that these dramatic figures call for novel scientific approaches and new types of data collection to integrate the two main approaches that still dominate the science underpinning DRR: the hazard paradigm and the vulnerability paradigm. Building from these two approaches, here we propose a research framework that specifies the scope of enquiry, concepts, and general relations among phenomena. We then discuss the essential steps to advance systematic empirical research and evidence-based DRR policy action.

A 3-Month Jump-Landing Training Program: A Feasibility Study Using the RE-AIM Framework

PubMed Central

Aerts, Inne; Cumps, Elke; Verhagen, Evert; Mathieu, Niels; Van Schuerbeeck, Sander; Meeusen, Romain

2013-01-01

Context: Evaluating the translatability and feasibility of an intervention program has become as important as determining the effectiveness of the intervention. Objective: To evaluate the applicability of a 3-month jump-landing training program in basketball players, using the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework. Design: Randomized controlled trial. Setting: National and regional basketball teams. Patients or Other Participants: Twenty-four teams of the second highest national division and regional basketball divisions in Flanders, Belgium, were randomly assigned (1:1) to a control group and intervention group. A total of 243 athletes (control group = 129, intervention group = 114), ages 15 to 41 years, volunteered. Intervention(s): All exercises in the intervention program followed a progressive development, emphasizing lower extremity alignment during jump-landing activities. Main Outcome Measure(s): The results of the process evaluation of the intervention program were based on the 5 dimensions of the RE-AIM framework. The injury incidence density, hazard ratios, and 95% confidence intervals were determined. Results: The participation rate of the total sample was 100% (reach). The hazard ratio was different between the intervention group and the control group (0.40 [95% confidence interval = 0.16, 0.99]; effectiveness). Of the 12 teams in the intervention group, 8 teams (66.7%) agreed to participate in the study (adoption). Eight of the participating coaches (66.7%) felt positively about the intervention program and stated that they had implemented the training sessions of the program as intended (implementation). All coaches except 1 (87.5%) intended to continue the intervention program the next season (maintenance). Conclusions: Compliance of the coaches in this coach-supervised jump-landing training program was high. In addition, the program was effective in preventing lower extremity injuries. PMID:23675788

A 3-month jump-landing training program: a feasibility study using the RE-AIM framework.

PubMed

Aerts, Inne; Cumps, Elke; Verhagen, Evert; Mathieu, Niels; Van Schuerbeeck, Sander; Meeusen, Romain

2013-01-01

Evaluating the translatability and feasibility of an intervention program has become as important as determining the effectiveness of the intervention. To evaluate the applicability of a 3-month jump-landing training program in basketball players, using the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework. Randomized controlled trial. National and regional basketball teams. Twenty-four teams of the second highest national division and regional basketball divisions in Flanders, Belgium, were randomly assigned (1:1) to a control group and intervention group. A total of 243 athletes (control group = 129, intervention group = 114), ages 15 to 41 years, volunteered. All exercises in the intervention program followed a progressive development, emphasizing lower extremity alignment during jump-landing activities. The results of the process evaluation of the intervention program were based on the 5 dimensions of the RE-AIM framework. The injury incidence density, hazard ratios, and 95% confidence intervals were determined. The participation rate of the total sample was 100% (reach). The hazard ratio was different between the intervention group and the control group (0.40 [95% confidence interval = 0.16, 0.99]; effectiveness). Of the 12 teams in the intervention group, 8 teams (66.7%) agreed to participate in the study (adoption). Eight of the participating coaches (66.7%) felt positively about the intervention program and stated that they had implemented the training sessions of the program as intended (implementation). All coaches except 1 (87.5%) intended to continue the intervention program the next season (maintenance). Compliance of the coaches in this coach-supervised jump-landing training program was high. In addition, the program was effective in preventing lower extremity injuries.

Prechemotherapy neutrophil : lymphocyte ratio is superior to the platelet : lymphocyte ratio as a prognostic indicator for locally advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy.

PubMed

Ji, W H; Jiang, Y H; Ji, Y L; Li, B; Mao, W M

2016-07-01

The study aimed to evaluate the prognostic significance of prechemotherapy neutrophil to lymphocyte ratio and platelet to lymphocyte ratio, and preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in locally advanced esophageal squamous cell cancer. We analyzed retrospectively locally advanced esophageal squamous cell cancer patients who had received neoadjuvant chemotherapy before undergoing a radical esophagectomy between 2009 and 2012. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio before chemotherapy and before the surgery were calculated. Univariate analyses showed that prechemotherapy neutrophil to lymphocyte ratio >5 (P = 0.048, hazard ratio = 2.86; 95% confidence interval: 1.01-8.12) and prechemotherapy platelet to lymphocyte ratio >130 (P = 0.025, hazard ratio = 5.50; 95% confidence interval: 1.23-24.55) were associated significantly with overall survival (OS), and prechemotherapy platelet to lymphocyte ratio >130 (P = 0.026, hazard ratio = 3.18; 95% confidence interval: 1.15-8.85) was associated significantly with progression-free survival. However, only prechemotherapy neutrophil to lymphocyte ratio >5 (P = 0.024, hazard ratio = 3.50; 95% confidence interval: 1.18-10.40) remained significantly associated with OS in multivariate analyses. Neither preoperative neutrophil to lymphocyte ratio nor platelet to lymphocyte ratio was associated with OS or progression-free survival. The prechemotherapy neutrophil to lymphocyte ratio >5 to preoperative neutrophil to lymphocyte ratio ≤5 group showed significantly worse OS than the prechemotherapy neutrophil to lymphocyte ratio ≤5 to preoperative neutrophil to lymphocyte ratio ≤5 group (P = 0.050). The prechemotherapy platelet to lymphocyte ratio >130 to preoperative platelet to lymphocyte ratio ≤130 group (P = 0.016) and platelet to lymphocyte ratio >130 to preoperative platelet to lymphocyte ratio >130 group (P = 0.042) showed significantly worse OS than the prechemotherapy platelet to lymphocyte ratio ≤30 to preoperative platelet to lymphocyte ratio ≤130 group. In conclusions, prechemotherapy neutrophil to lymphocyte ratio is an independent prognostic factor for OS in patients with advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy, and, as an adverse prognostic predictor, increased prechemotherapy neutrophil to lymphocyte ratio is superior to platelet to lymphocyte ratio. Maintaining a low neutrophil to lymphocyte ratio and platelet to lymphocyte ratio throughout treatment is a predictor of better OS. © 2015 International Society for Diseases of the Esophagus.

Seventeen-year follow-up of the prospective randomized Nordic CIS study: BCG monotherapy versus alternating therapy with mitomycin C and BCG in patients with carcinoma in situ of the urinary bladder.

PubMed

Kaasinen, Eero; Wijkström, Hans; Rintala, Erkki; Mestad, Oddvar; Jahnson, Staffan; Malmström, Per-Uno

2016-10-01

The aim of this study was to compare the long-term efficacy of BCG monotherapy to alternating therapy of mitomycin C (MMC) and BCG in patients with carcinoma in situ (CIS). Between 1992 and 1997, 321 patients with CIS were randomized from Finland, Norway and Sweden in a prospective multicenter trial into two treatment groups. The alternating therapy comprised six weekly instillations of MMC 40 mg followed by 10 instillations of BCG (Connaught 120 mg) or MMC alternating monthly for 1 year. BCG monotherapy followed the same 6 + 10 schedule. Stratification was done by nationality and CIS category. Primary endpoints were time to first recurrence and time to progression. Secondary endpoints were disease-specific mortality and overall survival. The main statistical methods were the proportional subdistribution hazards model and Cox proportional hazards model with the cumulative incidence and Kaplan-Meier analyses. The median follow-up time was 9.9 years (maximum 19.9 years) in the BCG group and 8.9 years (maximum 20.3 years) in the alternating group. The risk of recurrence was significantly lower in the BCG group than in the alternating group (49 vs 59% at 15 years, respectively; hazard ratio 0.74, 95% confidence interval 0.54-1.00, p = 0.048). There were no significant differences in the other endpoints. Patients who progressed after 2 years were particularly prone to dying from bladder carcinoma. Younger patients performed worse than older ones. BCG monotherapy including monthly maintenance was effective and better than the alternating therapy. The risk of dying from bladder carcinoma after progression was high.

Association of Pulse Wave Velocity With Chronic Kidney Disease Progression and Mortality: Findings From the CRIC Study (Chronic Renal Insufficiency Cohort).

PubMed

Townsend, Raymond R; Anderson, Amanda Hyre; Chirinos, Julio A; Feldman, Harold I; Grunwald, Juan E; Nessel, Lisa; Roy, Jason; Weir, Matthew R; Wright, Jackson T; Bansal, Nisha; Hsu, Chi-Yuan

2018-06-01

Patients with chronic kidney diseases (CKDs) are at risk for further loss of kidney function and death, which occur despite reasonable blood pressure treatment. To determine whether arterial stiffness influences CKD progression and death, independent of blood pressure, we conducted a prospective cohort study of CKD patients enrolled in the CRIC study (Chronic Renal Insufficiency Cohort). Using carotid-femoral pulse wave velocity (PWV), we examined the relationship between PWV and end-stage kidney disease (ESRD), ESRD or halving of estimated glomerular filtration rate, or death from any cause. The 2795 participants we enrolled had a mean age of 60 years, 56.4% were men, 47.3% had diabetes mellitus, and the average estimated glomerular filtration rate at entry was 44.4 mL/min per 1.73 m 2 During follow-up, there were 504 ESRD events, 628 ESRD or halving of estimated glomerular filtration rate events, and 394 deaths. Patients with the highest tertile of PWV (>10.3 m/s) were at higher risk for ESRD (hazard ratio [95% confidence interval], 1.37 [1.05-1.80]), ESRD or 50% decline in estimated glomerular filtration rate (hazard ratio [95% confidence interval], 1.25 [0.98-1.58]), or death (hazard ratio [95% confidence interval], 1.72 [1.24-2.38]). PWV is a significant predictor of CKD progression and death in people with impaired kidney function. Incorporation of PWV measurements may help define better the risks for these important health outcomes in patients with CKDs. Interventions that reduce aortic stiffness deserve study in people with CKD. © 2018 American Heart Association, Inc.

Occupational characteristics and the progression of carotid artery intima-media thickness and plaque over 9 years: the Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Fujishiro, Kaori; Diez Roux, Ana V; Landsbergis, Paul; Kaufman, Joel D; Korcarz, Claudia E; Stein, James H

2015-01-01

Objectives The role of occupation in the development of cardiovascular disease (CVD) remains a topic of research because few studies have examined longitudinal associations, and because occupation can be an indicator of socioeconomic position (SEP) and a proxy for hazard exposure. This study examines associations of occupational category as an SEP marker and selected occupational exposures with progression of the subclinical carotid artery disease. Methods A community-based, multiethnic sample (n=3109, mean age=60.2) provided subclinical CVD measures at least twice at three data collection points (mean follow-up=9.4 years). After accounting for demographic characteristics, SEP, and traditional CVD risk factors, we modelled common carotid intima-media thickness, carotid plaque scores, and carotid plaque shadowing as a function of occupational category, physical hazard exposure, physical activity on the job, interpersonal stress, job control and job demands. These job characteristics were derived from the Occupational Resource Network (O*NET). Random coefficient models were used to account for repeated measures and time-varying covariates. Results There were a few statistically significant associations at baseline. After all covariates were included in the model, men in management, office/sales, service and blue-collar jobs had 28–44% higher plaque scores than professionals at baseline (p=0.001). Physically hazardous jobs were positively associated with plaque scores among women (p=0.014). However, there were no significant longitudinal associations between any of the occupational characteristics and any of the subclinical CVD measures. Conclusions There was little evidence that the occupational characteristics examined in this study accelerated the progression of subclinical CVD. PMID:25217203

Outcome and prognostic factors for osteosarcoma of the maxilla, mandible, or calvarium in dogs: 183 cases (1986-2012).

PubMed

Selmic, Laura E; Lafferty, Mary H; Kamstock, Debra A; Garner, Alana; Ehrhart, Nicole P; Worley, Deanna R; Withrow, Stephen J; Lana, Susan E

2014-10-15

To describe the biological behavior, clinical outcome, and prognostic factors of osteosarcoma of the maxilla, mandible, or calvarium in dogs. Retrospective case series. 183 client-owned dogs with osteosarcoma of the maxilla, mandible, or calvarium. Medical records for dogs treated for osteosarcoma of the maxilla, mandible, or calvarium from 1986 through 2012 were reviewed. Dogs with a histopathologic diagnosis of osteosarcoma and treated for a primary tumor arising from these bones of the head were included. Mean age was 9.3 years, and body weight was 31.8 kg (70.0 lb). Most dogs (124/183 [67.8%]) were purebred, and the most common primary tumor site was the maxilla (80 [43.7%]). Treatments included palliative medical treatment only (11/183 [6.0%]), coarsely fractionated radiation therapy (RT; 12 [6.6%]), fractionated or stereotactic RT (18 [9.8%]), surgery (135 [73.8%]), and both surgery and fractionated RT (7 [3.8%]). Eighty-three (45.4%) dogs received adjuvant chemotherapy. Local recurrence or progression occurred in 80 of 156 (51.3%) dogs, and 60 of 156 (38.5%) dogs developed distant metastases. Median survival time for all dogs was 239 days. Dogs that underwent surgery had a median survival time of 329 days. Histologically tumor-free surgical margins were associated with significantly decreased hazards of progression or recurrence (hazard ratio [HR], 0.4) and death (HR, 0.5). Dogs with osteosarcoma of the calvarium had a significantly greater hazard of local recurrence or progression (HR, 2.0). In this study, tumor excision in dogs with histologically tumor-free margins resulted in better local control and longer survival time than did other treatment types.

RCRA/UST, superfund and EPCRA hotline training module. Introduction to: Hazardous waste identification (40 CFR part 261) updated as of July 1995

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

NONE

1995-11-01

This module introduces a specific hazardous waste identification process, which involves asking and analyzing a series of questions about any waste being evaluated. Analyzes in detail the Resource Conservation and Recovery Act (RCRA) definition of hazardous waste. It explains the following concepts that are essential to identifying a RCRA hazardous waste: hazardous waste listing, hazardous waste characteristics, the mixture and derived-from rules, the contained-in policy, and the Hazardous Waste Identification Rule (HWIR).

Method and apparatus for identification of hazards along an intended travel route

NASA Technical Reports Server (NTRS)

Kronfeld, Kevin M. (Inventor); Lapis, Mary Beth (Inventor); Walling, Karen L. (Inventor); Chackalackal, Mathew S. (Inventor)

2003-01-01

Targets proximate to a travel route plan were evaluated to determine hazardousness. Projected geometric representation of a vehicle determines intrusion of hazardous targets along travel route plan. Geometric representation of hazardous targets projected along motion vector to determine intrusion upon travel route plan. Intrusion assessment presented on user display.

75 FR 60689 - Hazardous Waste Management System; Identification and Listing of Hazardous Waste; Proposed Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-01

... exclude (or delist) a certain solid waste generated by its Beaumont, Texas, facility from the lists of hazardous wastes. EPA used the Delisting Risk Assessment Software (DRAS) Version 3.0 in the evaluation of... Waste Management System; Identification and Listing of Hazardous Waste; Proposed Rule AGENCY...

A strategic assessment of crown fire hazard in Montana: potential effectiveness and costs of hazard reduction treatments.

Treesearch

Carl E. Fiedler; Charles E. Keegan; Christopher W. Woodall; Todd A. Morgan

2004-01-01

Estimates of crown fire hazard are presented for existing forest conditions in Montana by density class, structural class, forest type, and landownership. Three hazard reduction treatments were evaluated for their effectiveness in treating historically fire-adapted forests (ponderosa pine (Pinus ponderosa Dougl. ex Laws.), Douglas-fir (...

Development of a Probabilistic Tsunami Hazard Analysis in Japan

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

Toshiaki Sakai; Tomoyoshi Takeda; Hiroshi Soraoka

2006-07-01

It is meaningful for tsunami assessment to evaluate phenomena beyond the design basis as well as seismic design. Because once we set the design basis tsunami height, we still have possibilities tsunami height may exceeds the determined design tsunami height due to uncertainties regarding the tsunami phenomena. Probabilistic tsunami risk assessment consists of estimating for tsunami hazard and fragility of structures and executing system analysis. In this report, we apply a method for probabilistic tsunami hazard analysis (PTHA). We introduce a logic tree approach to estimate tsunami hazard curves (relationships between tsunami height and probability of excess) and present anmore » example for Japan. Examples of tsunami hazard curves are illustrated, and uncertainty in the tsunami hazard is displayed by 5-, 16-, 50-, 84- and 95-percentile and mean hazard curves. The result of PTHA will be used for quantitative assessment of the tsunami risk for important facilities located on coastal area. Tsunami hazard curves are the reasonable input data for structures and system analysis. However the evaluation method for estimating fragility of structures and the procedure of system analysis is now being developed. (authors)« less

Evaluation of hazard and integrity monitor functions for integrated alerting and notification using a sensor simulation framework

NASA Astrophysics Data System (ADS)

Bezawada, Rajesh; Uijt de Haag, Maarten

2010-04-01

This paper discusses the results of an initial evaluation study of hazard and integrity monitor functions for use with integrated alerting and notification. The Hazard and Integrity Monitor (HIM) (i) allocates information sources within the Integrated Intelligent Flight Deck (IIFD) to required functionality (like conflict detection and avoidance) and determines required performance of these information sources as part of that function; (ii) monitors or evaluates the required performance of the individual information sources and performs consistency checks among various information sources; (iii) integrates the information to establish tracks of potential hazards that can be used for the conflict probes or conflict prediction for various time horizons including the 10, 5, 3, and <3 minutes used in our scenario; (iv) detects and assesses the class of the hazard and provide possible resolutions. The HIM monitors the operation-dependent performance parameters related to the potential hazards in a manner similar to the Required Navigation Performance (RNP). Various HIM concepts have been implemented and evaluated using a previously developed sensor simulator/synthesizer. Within the simulation framework, various inputs to the IIFD and its subsystems are simulated, synthesized from actual collected data, or played back from actual flight test sensor data. The framework and HIM functions are implemented in SimulinkR, a modeling language developed by The MathworksTM. This modeling language allows for test and evaluation of various sensor and communication link configurations as well as the inclusion of feedback from the pilot on the performance of the aircraft.

Landslide and Land Subsidence Hazards to Pipelines

USGS Publications Warehouse

Baum, Rex L.; Galloway, Devin L.; Harp, Edwin L.

2008-01-01

Landslides and land subsidence pose serious hazards to pipelines throughout the world. Many existing pipeline corridors and more and more new pipelines cross terrain that is affected by either landslides, land subsidence, or both. Consequently the pipeline industry recognizes a need for increased awareness of methods for identifying and evaluating landslide and subsidence hazard for pipeline corridors. This report was prepared in cooperation with the U.S. Department of Transportation Pipeline and Hazardous Materials Safety Administration, and Pipeline Research Council International through a cooperative research and development agreement (CRADA) with DGH Consulting, Inc., to address the need for up-to-date information about current methods to identify and assess these hazards. Chapters in this report (1) describe methods for evaluating landslide hazard on a regional basis, (2) describe the various types of land subsidence hazard in the United States and available methods for identifying and quantifying subsidence, and (3) summarize current methods for investigating individual landslides. In addition to the descriptions, this report provides information about the relative costs, limitations and reliability of various methods.

Directing driver attention with augmented reality cues

PubMed Central

Rusch, Michelle L.; Schall, Mark C.; Gavin, Patrick; Lee, John D.; Dawson, Jeffrey D.; Vecera, Shaun; Rizzo, Matthew

2013-01-01

This simulator study evaluated the effects of augmented reality (AR) cues designed to direct the attention of experienced drivers to roadside hazards. Twenty-seven healthy middle-aged licensed drivers with a range of attention capacity participated in a 54 mile (1.5 hour) drive in an interactive fixed-base driving simulator. Each participant received AR cues to potential roadside hazards in six simulated straight (9 mile long) rural roadway segments. Drivers were evaluated on response time for detecting a potentially hazardous event, detection accuracy for target (hazard) and non-target objects, and headway with respect to the hazards. Results showed no negative outcomes associated with interference. AR cues did not impair perception of non-target objects, including for drivers with lower attentional capacity. Results showed near significant response time benefits for AR cued hazards. AR cueing increased response rate for detecting pedestrians and warning signs but not vehicles. AR system false alarms and misses did not impair driver responses to potential hazards. PMID:24436635

Outcome of Molecular Targeted Agents Plus Chemotherapy for Second-Line Therapy of Metastatic Colorectal Cancer: A Meta-Analysis of Randomized Trials.

PubMed

Pei, Xueqing; Liu, Yu; Sun, Liwei; Zhang, Jun; Fang, Yuanyuan; Liao, Xin; Liu, Jian; Zhang, Cuntai; Yin, Tiejun

2016-12-01

The aim of this study was to evaluate the efficacy and toxicity of molecular targeted agents plus chemotherapy compared with chemotherapy alone as second-line therapy for patients with metastatic colorectal cancer (mCRC). We identified randomized controlled trials that compared molecular targeted agents plus chemotherapy with chemotherapy alone by searching the PubMed and Embase databases for articles published between January 2000 and September 2015. The outcome measures included progression-free survival, overall survival, objective response rate, and adverse events. Two investigators independently performed the information retrieval, screening, and data extraction. Stata 10.0 software was used to statistically analyze the extracted data. In accordance with our inclusion criteria, 11 trials, with a total of 7440 patients, were included in this meta-analysis through rounds of selection. We divided the biologic agents used into 3 subgroups based on the type of biologic agents-vascular endothelial growth factor (VEGF) inhibitor, epidermal growth factor receptor inhibitor, and other pathway inhibitors. Our results suggested that the regimen of a molecular targeted agent plus chemotherapy had a significant advantage in progression-free survival, overall survival, and objective response rate over chemotherapy alone (hazard ratio, 0.74; 95% confidence interval [CI], 0.70-0.78; hazard ratio, 0.88; 95% CI, 0.83-0.93; risk ratio, 2.24; 95% CI: 1.58-3.17, respectively). However, the rate of grade ≥ 3 adverse events was also higher in the combination therapy arm (risk ratio, 1.25; 95% CI, 1.17-1.33). Subgroup analysis showed that the combination of VEGF inhibitor with chemotherapy had a significant advantage in PFS, OS, and ORR over chemotherapy alone, but there was also a higher risk ratio in adverse events for this combination compared with the control group. In conclusion, a molecular targeted agent, especially VEGF inhibitor, plus chemotherapy is a worthwhile combination for patients with metastatic colorectal cancer as second-line therapy. However, more randomized controlled trials on a larger scale are needed for evaluating the value of epidermal growth factor receptor and other pathway inhibitors. Copyright © 2016 Elsevier Inc. All rights reserved.

Computed Tomography-Based Anatomic Assessment Overestimates Local Tumor Recurrence in Patients With Mass-like Consolidation After Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer

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

Dunlap, Neal E.; Yang Wensha; McIntosh, Alyson

Purpose: To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. Methods and Materials: Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET)more » CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. Results: Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade {>=}2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). Conclusion: Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will increase the likelihood of correctly identifying patients with progressive disease after lung SBRT.« less

Randomized Phase II Evaluation of Bevacizumab Versus Bevacizumab Plus Fosbretabulin in Recurrent Ovarian, Tubal, or Peritoneal Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study

PubMed Central

Sill, Michael W.; Walker, Joan L.; Darus, Christopher J.; Sutton, Gregory; Tewari, Krishnansu S.; Martin, Lainie P.; Schilder, Jeanne M.; Coleman, Robert L.; Balkissoon, Jai; Aghajanian, Carol

2016-01-01

Purpose The vascular disrupting agent fosbretabulin tromethamine selectively targets pre-existing tumor vasculature, which causes vascular shutdown and leads to cancer cell death and necrosis. Antiangiogenesis agents such as bevacizumab, a humanized antivascular endothelial growth factor monoclonal antibody, might prevent revascularization during and after treatment with a vascular disrupting agent. Patients and Methods Patients with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma, measurable or detectable disease, and three or fewer prior regimens were randomly assigned to bevacizumab (15 mg/kg intravenously once every 3 weeks) or the combination of bevacizumab (15 mg/kg) plus fosbretabulin (60 mg/m2) intravenously once every 3 weeks until disease progression or toxicity. Randomization was stratified by disease status (measurable v nonmeasurable), prior bevacizumab, and platinum-free interval. The primary end point was progression-free survival (PFS). The study was designed with 80% power for a one-sided alternative at a 10% level of significance to detect a reduction in the hazard by 37.5%. Results The study enrolled 107 patients. Median PFS was 4.8 months for bevacizumab and 7.3 months for bevacizumab plus fosbretabulin (hazard ratio, 0.69; 90% two-sided CI, 0.47 to 1.00; one-sided P = .05). The proportion responding (overall response rate) to bevacizumab was 28.2% among 39 patients with measurable disease and 35.7% among 42 patients treated with the combination. The relative probability of responding was 1.27 (90% CI, 0.74 to 2.17; one-sided P = .24). Adverse events greater than grade 3 were more common in the combination regimen than in bevacizumab only for hypertension (35% v 20%). There was one grade 3 thromboembolic event in the combination arm and one intestinal fistula in the bevacizumab only arm. Conclusion On the basis of the PFS, overall response rate, and tolerability of these two antivascular therapies, further evaluation is warranted for this chemotherapy-free regimen. Fosbretabulin in combination with bevacizumab increases the risk of hypertension. PMID:27217446

Randomized Phase II Evaluation of Bevacizumab Versus Bevacizumab Plus Fosbretabulin in Recurrent Ovarian, Tubal, or Peritoneal Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study.

PubMed

Monk, Bradley J; Sill, Michael W; Walker, Joan L; Darus, Christopher J; Sutton, Gregory; Tewari, Krishnansu S; Martin, Lainie P; Schilder, Jeanne M; Coleman, Robert L; Balkissoon, Jai; Aghajanian, Carol

2016-07-01

The vascular disrupting agent fosbretabulin tromethamine selectively targets pre-existing tumor vasculature, which causes vascular shutdown and leads to cancer cell death and necrosis. Antiangiogenesis agents such as bevacizumab, a humanized antivascular endothelial growth factor monoclonal antibody, might prevent revascularization during and after treatment with a vascular disrupting agent. Patients with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma, measurable or detectable disease, and three or fewer prior regimens were randomly assigned to bevacizumab (15 mg/kg intravenously once every 3 weeks) or the combination of bevacizumab (15 mg/kg) plus fosbretabulin (60 mg/m(2)) intravenously once every 3 weeks until disease progression or toxicity. Randomization was stratified by disease status (measurable v nonmeasurable), prior bevacizumab, and platinum-free interval. The primary end point was progression-free survival (PFS). The study was designed with 80% power for a one-sided alternative at a 10% level of significance to detect a reduction in the hazard by 37.5%. The study enrolled 107 patients. Median PFS was 4.8 months for bevacizumab and 7.3 months for bevacizumab plus fosbretabulin (hazard ratio, 0.69; 90% two-sided CI, 0.47 to 1.00; one-sided P = .05). The proportion responding (overall response rate) to bevacizumab was 28.2% among 39 patients with measurable disease and 35.7% among 42 patients treated with the combination. The relative probability of responding was 1.27 (90% CI, 0.74 to 2.17; one-sided P = .24). Adverse events greater than grade 3 were more common in the combination regimen than in bevacizumab only for hypertension (35% v 20%). There was one grade 3 thromboembolic event in the combination arm and one intestinal fistula in the bevacizumab only arm. On the basis of the PFS, overall response rate, and tolerability of these two antivascular therapies, further evaluation is warranted for this chemotherapy-free regimen. Fosbretabulin in combination with bevacizumab increases the risk of hypertension. © 2016 by American Society of Clinical Oncology.

Association Between Breast Cancer Disease Progression and Workplace Productivity in the United States.

PubMed

Yin, Wesley; Horblyuk, Ruslan; Perkins, Julia Jane; Sison, Steve; Smith, Greg; Snider, Julia Thornton; Wu, Yanyu; Philipson, Tomas J

2017-02-01

Determine workplace productivity losses attributable to breast cancer progression. Longitudinal analysis linking 2005 to 2012 medical and pharmacy claims and workplace absence data in the US patients were commercially insured women aged 18 to 64 diagnosed with breast cancer. Productivity was measured as employment status and total quarterly workplace hours missed, and valued using average US wages. Six thousand four hundred and nine women were included. Breast cancer progression was associated with a lower probability of employment (hazard ratio [HR] = 0.65, P < 0.01) and increased workplace hours missed. The annual value of missed work was $24,166 for non-metastatic and $30,666 for metastatic patients. Thus, progression to metastatic disease is associated with an additional $6500 in lost work time (P < 0.05), or 14% of average US wages. Breast cancer progression leads to diminished likelihood of employment, increased workplace hours missed, and increased cost burden.

Mechanistic modeling of developmental defects through computational embryology (WC10th)

EPA Science Inventory

Abstract: An important consideration for 3Rs is to identify developmental hazards utilizing mechanism-based in vitro assays (e.g., ToxCast) and in silico predictive models. Steady progress has been made with agent-based models that recapitulate morphogenetic drivers for angiogen...

DEVELOPMENT OF QUANTITATIVE COMPARATIVE CYTOTOXICITY AND GENOTOXICITY ASSAYS FOR ENVIRONMENTAL HAZARDOUS CHEMICALS (R825956)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

33 CFR 334.230 - Potomac River.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 334.230 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.230 Potomac River. (a) Naval Surface Warfare... manned or unmanned watercraft. (ii) When hazardous operations are in progress, no person, or fishing or...

33 CFR 334.230 - Potomac River.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 334.230 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.230 Potomac River. (a) Naval Surface Warfare... manned or unmanned watercraft. (ii) When hazardous operations are in progress, no person, or fishing or...

33 CFR 334.230 - Potomac River.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 334.230 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.230 Potomac River. (a) Naval Surface Warfare... manned or unmanned watercraft. (ii) When hazardous operations are in progress, no person, or fishing or...

33 CFR 334.230 - Potomac River.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 334.230 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.230 Potomac River. (a) Naval Surface Warfare... manned or unmanned watercraft. (ii) When hazardous operations are in progress, no person, or fishing or...

LOCAL EM ESTIMATION OF THE HAZARD FUNCTION FOR INTERVAL CENSORED DATA. (R824757)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

21 CFR 7.41 - Health hazard evaluation and recall classification.

Code of Federal Regulations, 2011 CFR

2011-04-01

... exposed to the product being considered, with particular attention paid to the hazard to those individuals....e., Class I, Class II, or Class III, to indicate the relative degree of health hazard of the product...

A Competence-Based Science Learning Framework Illustrated Through the Study of Natural Hazards and Disaster Risk Reduction

NASA Astrophysics Data System (ADS)

Oyao, Sheila G.; Holbrook, Jack; Rannikmäe, Miia; Pagunsan, Marmon M.

2015-09-01

This article proposes a competence-based learning framework for science teaching, applied to the study of 'big ideas', in this case to the study of natural hazards and disaster risk reduction (NH&DRR). The framework focuses on new visions of competence, placing emphasis on nurturing connectedness and behavioral actions toward resilience and sustainability. The framework draws together competences familiarly expressed as cognitive knowledge and skills, plus dispositions and adds connectedness and action-related behaviors, and applies this by means of a progression shift associated with NH&DRR from abilities to capabilities. The target is enhanced scientific literacy approached through an education through science focus, amplified through the study of a big idea, promotion of sustained resilience in the face of disaster and the taking of responsibilities for behavioral actions. The framework is applied to a learning progression for each interrelated education dimension, thus serving as a guide for both the development of abilities and as a platform for stimulating student capabilities within instruction and assessment.

Application of a hazard and operability study method to hazard evaluation of a chemical unit of the power station.

PubMed

Habibi, E; Zare, M; Barkhordari, A; Mirmohammadi, Sj; Halvani, Ghh

2008-12-28

The aim of this study was to identify the hazards, evaluate their risk factors and determine the measure for promotion of the process and reduction of accidents in the chemical unit of the power station. In this case and qualitative study, HAZOP technique was used to recognize the hazards and problems of operations on the chemical section at power station. Totally, 126 deviations were documented with various causes and consequences. Ranking and evaluation of identified risks indicate that the majority of deviations were categorized as "acceptable" and less than half of that were "unacceptable". The highest calculated risk level (1B) related to both the interruption of acid entry to the discharge pumps and an increased density of the acid. About 27% of the deviations had the lowest risk level (4B). The identification of hazards by HAZOP indicates that it could, systemically, assess and criticize the process of consumption or production of acid and alkali in the chemical unit of power plant.

Volcanic hazards and their mitigation: progress and problems

USGS Publications Warehouse

Tilling, R.I.

1989-01-01

A review of hazards mitigation approaches and techniques indicates that significant advances have been made in hazards assessment, volcano monioring, and eruption forecasting. For example, the remarkable accuracy of the predictions of dome-building events at Mount St. Helens since June 1980 is unprecedented. Yet a predictive capability for more voluminous and explosive eruptions still has not been achieved. Studies of magma-induced seismicity and ground deformation continue to provide the most systematic and reliable data for early detection of precursors to eruptions and shallow intrusions. In addition, some other geophysical monitoring techniques and geochemical methods have been refined and are being more widely applied and tested. Comparison of the four major volcanic disasters of the 1980s (Mount St. Helens, U.S.A. (1980), El Chichon, Mexico (1982); Galunggung, Indonesia (1982); and Nevado del Ruiz, Colombia (1985)) illustrates the importance of predisaster geoscience studies, volcanic hazards assessments, volcano monitoring, contingency planning, and effective communications between scientists and authorities. -from Author

Evaluation of an active learning module to teach hazard and risk in Hazard Analysis and Critical Control Points (HACCP) classes.

PubMed

Oyarzabal, Omar A; Rowe, Ellen

2017-04-01

The terms hazard and risk are significant building blocks for the organization of risk-based food safety plans. Unfortunately, these terms are not clear for some personnel working in food manufacturing facilities. In addition, there are few examples of active learning modules for teaching adult participants the principles of hazard analysis and critical control points (HACCP). In this study, we evaluated the effectiveness of an active learning module to teach hazard and risk to participants of HACCP classes provided by the University of Vermont Extension in 2015 and 2016. This interactive module is comprised of a questionnaire; group playing of a dice game that we have previously introduced in the teaching of HACCP; the discussion of the terms hazard and risk; and a self-assessment questionnaire to evaluate the teaching of hazard and risk. From 71 adult participants that completed this module, 40 participants (56%) provided the most appropriate definition of hazard, 19 participants (27%) provided the most appropriate definition of risk, 14 participants (20%) provided the most appropriate definitions of both hazard and risk, and 23 participants (32%) did not provide an appropriate definition for hazard or risk. Self-assessment data showed an improvement in the understanding of these terms (P < 0.05). Thirty participants (42%) stated that the most valuable thing they learned with this interactive module was the difference between hazard and risk, and 40 participants (65%) responded that they did not attend similar presentations in the past. The fact that less than one third of the participants answered properly to the definitions of hazard and risk at baseline is not surprising. However, these results highlight the need for the incorporation of modules to discuss these important food safety terms and include more active learning modules to teach food safety classes. This study suggests that active learning helps food personnel better understand important food safety terms that serve as building blocks for the understanding of more complex food safety topics.

SUPERFUND INNOVATIVE TECHNOLOGY EVALUATION PROGRAM: TECHNOLOGY WITH AN IMPACT

EPA Science Inventory

SITE promotes the development and implementation of innovative technologies for remediating hazardous waste sites and for evaluating the nature and extent of hazardous waste site contamination through four component segments. The SITE Program is a key element in EPA's efforts...

Progress Towards the Remote Sensing of Aircraft Icing Hazards

NASA Technical Reports Server (NTRS)

Reehorst, Andrew; Brinker, David; Politovich, Marcia; Serke, David; Ryerson, Charles; Pazmany, Andrew; Solheim, Fredrick

2009-01-01

NASA has teamed with the FAA, DoD, industry, and academia for research into the remote detection and measurement of atmospheric conditions leading to aircraft icing hazards. The ultimate goal of this effort is to provide pilots, controllers, and dispatchers sufficient information to allow aircraft to avoid or minimize their exposure to the hazards of in-flight icing. Since the hazard of in-flight icing is the outcome of aircraft flight through clouds containing supercooled liquid water and strongly influenced by the aircraft s speed and configuration and by the length of exposure, the hazard cannot be directly detected, but must be inferred based upon the measurement of conducive atmospheric conditions. Therefore, icing hazard detection is accomplished through the detection and measurement of liquid water in regions of measured sub-freezing air temperatures. The icing environment is currently remotely measured from the ground with a system fusing radar, lidar, and multifrequency microwave radiometer sensors. Based upon expected ice accretion severity for the measured environment, a resultant aircraft hazard is then calculated. Because of the power, size, weight, and view angle constraints of airborne platforms, the current ground-based solution is not applicable for flight. Two current airborne concepts are based upon the use of either multifrequency radiometers or multifrequency radar. Both ground-based and airborne solutions are required for the future since groundbased systems can provide hazard detection for all aircraft in airport terminal regions while airborne systems will be needed to provide equipped aircraft with flight path coverage between terminal regions.

Driver Vigilance in Automated Vehicles: Hazard Detection Failures Are a Matter of Time.

PubMed

Greenlee, Eric T; DeLucia, Patricia R; Newton, David C

2018-06-01

The primary aim of the current study was to determine whether monitoring the roadway for hazards during automated driving results in a vigilance decrement. Although automated vehicles are relatively novel, the nature of human-automation interaction within them has the classic hallmarks of a vigilance task. Drivers must maintain attention for prolonged periods of time to detect and respond to rare and unpredictable events, for example, roadway hazards that automation may be ill equipped to detect. Given the similarity with traditional vigilance tasks, we predicted that drivers of a simulated automated vehicle would demonstrate a vigilance decrement in hazard detection performance. Participants "drove" a simulated automated vehicle for 40 minutes. During that time, their task was to monitor the roadway for roadway hazards. As predicted, hazard detection rate declined precipitously, and reaction times slowed as the drive progressed. Further, subjective ratings of workload and task-related stress indicated that sustained monitoring is demanding and distressing and it is a challenge to maintain task engagement. Monitoring the roadway for potential hazards during automated driving results in workload, stress, and performance decrements similar to those observed in traditional vigilance tasks. To the degree that vigilance is required of automated vehicle drivers, performance errors and associated safety risks are likely to occur as a function of time on task. Vigilance should be a focal safety concern in the development of vehicle automation.

Progress and challenges with Warn-on-Forecast

NASA Astrophysics Data System (ADS)

Stensrud, David J.; Wicker, Louis J.; Xue, Ming; Dawson, Daniel T.; Yussouf, Nusrat; Wheatley, Dustan M.; Thompson, Therese E.; Snook, Nathan A.; Smith, Travis M.; Schenkman, Alexander D.; Potvin, Corey K.; Mansell, Edward R.; Lei, Ting; Kuhlman, Kristin M.; Jung, Youngsun; Jones, Thomas A.; Gao, Jidong; Coniglio, Michael C.; Brooks, Harold E.; Brewster, Keith A.

2013-04-01

The current status and challenges associated with two aspects of Warn-on-Forecast-a National Oceanic and Atmospheric Administration research project exploring the use of a convective-scale ensemble analysis and forecast system to support hazardous weather warning operations-are outlined. These two project aspects are the production of a rapidly-updating assimilation system to incorporate data from multiple radars into a single analysis, and the ability of short-range ensemble forecasts of hazardous convective weather events to provide guidance that could be used to extend warning lead times for tornadoes, hailstorms, damaging windstorms and flash floods. Results indicate that a three-dimensional variational assimilation system, that blends observations from multiple radars into a single analysis, shows utility when evaluated by forecasters in the Hazardous Weather Testbed and may help increase confidence in a warning decision. The ability of short-range convective-scale ensemble forecasts to provide guidance that could be used in warning operations is explored for five events: two tornadic supercell thunderstorms, a macroburst, a damaging windstorm and a flash flood. Results show that the ensemble forecasts of the three individual severe thunderstorm events are very good, while the forecasts from the damaging windstorm and flash flood events, associated with mesoscale convective systems, are mixed. Important interactions between mesoscale and convective-scale features occur for the mesoscale convective system events that strongly influence the quality of the convective-scale forecasts. The development of a successful Warn-on-Forecast system will take many years and require the collaborative efforts of researchers and operational forecasters to succeed.

A Concept-Wide Association Study of Clinical Notes to Discover New Predictors of Kidney Failure.

PubMed

Singh, Karandeep; Betensky, Rebecca A; Wright, Adam; Curhan, Gary C; Bates, David W; Waikar, Sushrut S

2016-12-07

Identifying predictors of kidney disease progression is critical toward the development of strategies to prevent kidney failure. Clinical notes provide a unique opportunity for big data approaches to identify novel risk factors for disease. We used natural language processing tools to extract concepts from the preceding year's clinical notes among patients newly referred to a tertiary care center's outpatient nephrology clinics and retrospectively evaluated these concepts as predictors for the subsequent development of ESRD using proportional subdistribution hazards (competing risk) regression. The primary outcome was time to ESRD, accounting for a competing risk of death. We identified predictors from univariate and multivariate (adjusting for Tangri linear predictor) models using a 5% threshold for false discovery rate (q value <0.05). We included all patients seen by an adult outpatient nephrologist between January 1, 2004 and June 18, 2014 and excluded patients seen only by transplant nephrology, with preexisting ESRD, with fewer than five clinical notes, with no follow-up, or with no baseline creatinine values. Among the 4013 patients selected in the final study cohort, we identified 960 concepts in the unadjusted analysis and 885 concepts in the adjusted analysis. Novel predictors identified included high-dose ascorbic acid (adjusted hazard ratio, 5.48; 95% confidence interval, 2.80 to 10.70; q<0.001) and fast food (adjusted hazard ratio, 4.34; 95% confidence interval, 2.55 to 7.40; q<0.001). Novel predictors of human disease may be identified using an unbiased approach to analyze text from the electronic health record. Copyright © 2016 by the American Society of Nephrology.

Studies in geophysics: Active tectonics

NASA Technical Reports Server (NTRS)

1986-01-01

Active tectonics is defined within the study as tectonic movements that are expected to occur within a future time span of concern to society. Such movements and their associated hazards include earthquakes, volcanic eruptions, and land subsidence and emergence. The entire range of geology, geophysics, and geodesy is, to some extent, pertinent to this topic. The needs for useful forecasts of tectonic activity, so that actions may be taken to mitigate hazards, call for special attention to ongoing tectonic activity. Further progress in understanding active tectonics depends on continued research. Particularly important is improvement in the accuracy of dating techniques for recent geologic materials.

Evaluating "The Safe Living Guide": A Home Hazard Checklist for Seniors

ERIC Educational Resources Information Center

Sorcinelli, Andrea; Shaw, Lynn; Freeman, Andrew; Cooper, Kim

2007-01-01

Purpose: The purpose of this study was to evaluate the utility and reliability of a home hazard checklist published in Health Canada, "The Safe Living Guide: A Guide to Home Safety for Seniors" (2003). Methods: 76 community-dwelling seniors evaluated the guide, and inter-rater reliability was determined through comparison of ratings of…

Serum cholesterol and risk of lower urinary tract symptoms progression: Results from the Reduction by Dutasteride of Prostate Cancer Events study.

PubMed

Feng, Tom; Howard, Lauren E; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

2017-02-01

To determine if cholesterol is a risk factor for the development of lower urinary tract symptoms in asymptomatic men. A post-hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study was carried out in 2323 men with baseline International Prostate Symptom Score <8 and not taking benign prostatic hyperplasia or cholesterol medications. Cox proportion models were used to test the association between cholesterol, high-density lipoprotein, low-density lipoprotein and the cholesterol : high-density lipoprotein ratio with incident lower urinary tract symptoms, defined as first report of medical treatment, surgery or two reports of an International Prostate Symptom Score >14. A total of 253 men (10.9%) developed incident lower urinary tract symptoms. On crude analysis, higher high-density lipoprotein was associated with a decreased lower urinary tract symptoms risk (hazard ratio 0.89, P = 0.024), whereas total cholesterol and low-density lipoprotein showed no association. After multivariable adjustment, the association between high-density lipoprotein and incident lower urinary tract symptoms remained significant (hazard ratio 0.89, P = 0.044), whereas no association was observed for low-density lipoprotein (P = 0.611). There was a trend for higher cholesterol to be linked with higher lower urinary tract symptoms risk, though this was not statistically significant (hazard ratio 1.04, P = 0.054). A higher cholesterol : high-density lipoprotein ratio was associated with increased lower urinary tract symptoms risk on crude (hazard ratio 1.11, P = 0.016) and adjusted models (hazard ratio 1.12, P = 0.012). Among asymptomatic men participating in the REDUCE study, higher cholesterol was associated with increased incident lower urinary tract symptoms risk, though the association was not significant. A higher cholesterol : high-density lipoprotein ratio was associated with increased incident lower urinary tract symptoms, whereas higher high-density lipoprotein was protective. These findings suggest dyslipidemia might play a role in lower urinary tract symptoms progression. © 2016 The Japanese Urological Association.

Rockfall Hazard Process Assessment : Final Project Report

DOT National Transportation Integrated Search

2017-10-01

After a decade of using the Rockfall Hazard Rating System (RHRS), the Montana Department of Transportation (MDT) sought a reassessment of their rockfall hazard evaluation process. Their prior system was a slightly modified version of the RHRS and was...

Marginal Structural Cox Models for Estimating the Association Between β-Interferon Exposure and Disease Progression in a Multiple Sclerosis Cohort

PubMed Central

Karim, Mohammad Ehsanul; Gustafson, Paul; Petkau, John; Zhao, Yinshan; Shirani, Afsaneh; Kingwell, Elaine; Evans, Charity; van der Kop, Mia; Oger, Joel; Tremlett, Helen

2014-01-01

Longitudinal observational data are required to assess the association between exposure to β-interferon medications and disease progression among relapsing-remitting multiple sclerosis (MS) patients in the “real-world” clinical practice setting. Marginal structural Cox models (MSCMs) can provide distinct advantages over traditional approaches by allowing adjustment for time-varying confounders such as MS relapses, as well as baseline characteristics, through the use of inverse probability weighting. We assessed the suitability of MSCMs to analyze data from a large cohort of 1,697 relapsing-remitting MS patients in British Columbia, Canada (1995–2008). In the context of this observational study, which spanned more than a decade and involved patients with a chronic yet fluctuating disease, the recently proposed “normalized stabilized” weights were found to be the most appropriate choice of weights. Using this model, no association between β-interferon exposure and the hazard of disability progression was found (hazard ratio = 1.36, 95% confidence interval: 0.95, 1.94). For sensitivity analyses, truncated normalized unstabilized weights were used in additional MSCMs and to construct inverse probability weight-adjusted survival curves; the findings did not change. Additionally, qualitatively similar conclusions from approximation approaches to the weighted Cox model (i.e., MSCM) extend confidence in the findings. PMID:24939980

Software System Architecture Modeling Methodology for Naval Gun Weapon Systems

DTIC Science & Technology

2010-12-01

Weapon System HAR Hazard Action Report HERO Hazards of Electromagnetic Radiation to Ordnance IOC Initial Operational Capability... radiation to ordnance ; and combinations therein. Equipment, systems, or procedures and processes whose malfunction would hazard the safe manufacturing...NDI Non-Development Item OPEVAL Operational Evaluation ORDALTS Ordnance Alterations O&SHA Operating and Support Hazard Analysis PDA

Opinion: The use of natural hazard modeling for decision making under uncertainty

Treesearch

David E. Calkin; Mike Mentis

2015-01-01

Decision making to mitigate the effects of natural hazards is a complex undertaking fraught with uncertainty. Models to describe risks associated with natural hazards have proliferated in recent years. Concurrently, there is a growing body of work focused on developing best practices for natural hazard modeling and to create structured evaluation criteria for complex...

Prognostic Value of [18F]-Fluoromethylcholine Positron Emission Tomography/Computed Tomography Before Stereotactic Body Radiation Therapy for Oligometastatic Prostate Cancer.

PubMed

Cysouw, Matthijs; Bouman-Wammes, Esther; Hoekstra, Otto; van den Eertwegh, Alfons; Piet, Maartje; van Moorselaar, Jeroen; Boellaard, Ronald; Dahele, Max; Oprea-Lager, Daniela

2018-06-01

To investigate the predictive value of [ 18 F]-fluoromethylcholine positron emission tomography/computed tomography (PET/CT)-derived parameters on progression-free survival (PFS) in oligometastatic prostate cancer patients treated with stereotactic body radiation therapy (SBRT). In [ 18 F]-fluoromethylcholine PET/CT scans of 40 consecutive patients with ≤4 metachronous metastases treated with SBRT we retrospectively measured the number of metastases, standardized uptake values (SUV mean , SUV max , SUV peak ), metabolically active tumor volume (MATV), and total lesion choline uptake. Partial-volume correction was applied using the iterative deconvolution Lucy-Richardson algorithm. Thirty-seven lymph node and 13 bone metastases were treated with SBRT. Thirty-three patients (82.5%) had 1 lesion, 4 (10%) had 2 lesions, and 3 (7.5%) had 3 lesions. After a median follow-up of 32.6 months (interquartile range, 35.5 months), the median PFS was 11.5 months (95% confidence interval 8.4-14.6 months). Having more than a single metastasis was a significant prognostic factor (hazard ratio 2.74; P = .03), and there was a trend in risk of progression for large MATV (hazard ratio 1.86; P = .10). No SUV or total lesion choline uptake was significantly predictive for PFS, regardless of partial-volume correction. All PET semiquantitative parameters were significantly correlated with each other (P ≤ .013). The number of choline-avid metastases was a significant prognostic factor for progression after [ 18 F]-fluormethylcholine PET/CT-guided SBRT for recurrent oligometastatic prostate cancer, and there seemed to be a trend in risk of progression for patients with large MATVs. The lesional level of [ 18 F]-fluoromethylcholine uptake was not prognostic for progression. Copyright © 2018 Elsevier Inc. All rights reserved.

SRD5A gene polymorphism in Japanese men predicts prognosis of metastatic prostate cancer with androgen-deprivation therapy.

PubMed

Shiota, Masaki; Fujimoto, Naohiro; Yokomizo, Akira; Takeuchi, Ario; Itsumi, Momoe; Inokuchi, Junichi; Tatsugami, Katsunori; Uchiumi, Takeshi; Naito, Seiji

2015-09-01

De novo androgen synthesis is thought to be involved in the progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT). During androgen synthesis, 5α-reductase encoded by SRD5A catalyses testosterone into more active dihydrotestosterone and may be involved in the progression to CRPC. Then, this study aimed to reveal the association between genetic variations in SRD5A and the prognosis in metastatic prostate cancer. We studied the polymorphisms rs518673 and rs166050 in SRD5A1, and rs12470143, rs523349, rs676033 and rs2208532 in SRD5A2 as well as the time to CRPC progression and overall survival in 104 patients with metastatic prostate cancer that had undergone primary ADT. The association between the polymorphisms and the progression to CRPC as well as overall survival was examined. Patients carrying the more active GG genotype in SRD5A2 rs523349 exhibited a higher risk of the progression (hazard ration [95% confidence interval], 1.93 [1.14-3.14], p=0.016) and death (hazard ration [95% confidence interval], 2.14 [1.16-3.76], p=0.016), compared with less active GC/CC genotypes in SRD5A2 rs523349. High 5α-reductase activity due to the polymorphism in SRD5A2 may contribute to resistance to ADT. Furthermore, SRD5A2 rs523349 polymorphism may be a promising biomarker for metastatic prostate cancer patients treated with primary ADT and a molecular target for advanced prostate cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis.

PubMed

Yardley, Denise A; Noguchi, Shinzaburo; Pritchard, Kathleen I; Burris, Howard A; Baselga, José; Gnant, Michael; Hortobagyi, Gabriel N; Campone, Mario; Pistilli, Barbara; Piccart, Martine; Melichar, Bohuslav; Petrakova, Katarina; Arena, Francis P; Erdkamp, Frans; Harb, Wael A; Feng, Wentao; Cahana, Ayelet; Taran, Tetiana; Lebwohl, David; Rugo, Hope S

2013-10-01

Effective treatments for hormone-receptor-positive (HR(+)) breast cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population. BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR(+) advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review, and was confirmed by independent central radiology review. Overall survival, response rate, and clinical benefit rate were secondary endpoints. Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [investigator review: 7.8 versus 3.2 months, respectively; hazard ratio = 0.45 (95% confidence interval 0.38-0.54); log-rank P < 0.0001; central review: 11.0 versus 4.1 months, respectively; hazard ratio = 0.38 (95% confidence interval 0.31-0.48); log-rank P < 0.0001] in the overall population and in all prospectively defined subgroups, including patients with visceral metastases, [corrected] and irrespective of age. The incidence and severity of adverse events were consistent with those reported at the interim analysis and in other everolimus trials. The addition of everolimus to exemestane markedly prolonged PFS in patients with HR(+) advanced BC with disease recurrence/progression following prior NSAIs. These results further support the use of everolimus plus exemestane in this patient population. ClinicalTrials.gov #NCT00863655.

Higher net acid excretion is associated with lower risk of kidney disease progression in patients with diabetes

PubMed Central

Scialla, Julia J.; Asplin, John; Dobre, Mirela; Chang, Alex; Lash, James; Hsu, Chi-yuan; Kallem, Radhakrishna R.; Hamm, L. Lee; Feldman, Harold I.; Chen, Jing; Appel, Lawrence; Anderson, Cheryl A. M.; Wolf, Myles

2017-01-01

Higher diet-dependent nonvolatile acid load is associated with faster chronic kidney disease (CKD) progression, but most studies have used estimated acid load or measured only components of the gold-standard, net acid excretion (NAE). Here we measured NAE as the sum of urine ammonium and titratable acidity in 24 hour urines from a random subset of 980 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. In multivariable models accounting for demographics, comorbidity and kidney function, higher NAE was significantly associated with lower serum bicarbonate (0.17 mEq/L lower serum bicarbonate per 10 mEq/day higher NAE), consistent with a larger acid load. Over a median of 6 years follow-up, higher NAE was independently associated with a significantly lower risk of the composite of end stage renal disease or halving of estimated glomerular filtration rate among diabetics (hazard ratio 0.88 per 10 mEq/day higher NAE), but not those without diabetes (hazard ratio 1.04 per 10 mEq/day higher NAE). For comparison, we estimated nonvolatile acid load as net endogenous acid production using self-reported food frequency questionnaires from 2,848 patients and dietary urine biomarkers from 3,385 patients. Higher net endogenous acid production based on biomarkers (urea nitrogen and potassium) was modestly associated with faster CKD progression consistent with prior reports, but only among those without diabetes. Results from the food frequency questionnaires were not associated with CKD progression in any group. Thus, disparate results obtained from analyses of nonvolatile acid load directly measured as NAE and estimated from diet, suggests a novel hypothesis, that the risk of CKD progression related to low NAE, or acid load, may be due to diet-independent changes in acid production in diabetes. PMID:27914710

Safety assessment of discharge chute isolation barrier preparation and installation. Revision 1

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

Meichle, R.H.

1994-10-10

This revision responds to RL comments and increases the discussion of the ``effective hazard categorization`` and the readiness review basis. The safety assessment is made for the activities for the preparation and installation of the discharge chute isolation barriers. The safety assessment includes a hazard assessment and comparison of potential accidents/events to those addressed by the current safety basis documentation. No significant hazards were identified. An evaluation against the USQ evaluation questions were made and the determination made that the activities do not represent a USQ. Hazard categorization techniques were used to provide a basis for readiness review classification.

Progressive and Accelerated Disability Onset by Race/Ethnicity and Education among Late Midlife and Older Adults

PubMed Central

Latham, Kenzie

2012-01-01

Objectives This study explores the pace of severe disability onset with an emphasis on the role of race/ethnicity and education. More specifically, this research examines whether race/ethnicity and educational attainment are independent predictors of progressive and accelerated disability onset. Methods Using the Health and Retirement Study (HRS) Waves 2–10 (1994–2010), a series of discrete-time Cox proportional hazards models with multiple competing events were created to ascertain whether respondents developed progressive or accelerated disability in subsequent waves. Results Black and Hispanic respondents were at an increased risk of developing progressive disability. Respondents without a high school degree were more likely to experience progressive or accelerated disability. Discussion Low educational attainment was a particularly strong predictor of accelerated disability onset and may represent an acute lack of resources over the life course. Race and ethnicity were important predictors of progressive disability onset, which may reflect racial/ethnic variations in the disabling process. PMID:22982972

Evaluation of Prototype Head Shield for Hazardous Material Tank Car

DOT National Transportation Integrated Search

1976-12-01

The structural integrity of a prototype tank car head shield for hazardous material railroad tank cars was evaluated under conditions of freight car coupling at moderate to high speeds. This is one of the most severe environments encountered in norma...

Notification: Preliminary Research to Evaluate Hazardous Waste Passing Through Publicly Owned Treatment Works

EPA Pesticide Factsheets

March 13, 2013. The EPA's OIG plans to start preliminary research to evaluate the effectiveness of the EPA’s programs in preventing and addressing contamination of surface water from hazardous wastes passing through publicly owned treatment works.

MEASUREMENT OF BIOAVAILABLE IRON AT TWO HAZARDOUS WASTE SITES

EPA Science Inventory

In the past, the concentrations of iron II in monitoring wells has been used to evaluate natural attenuation processes at hazardous waste sites. Changes in the aqueous concentrations of electron acceptors/products are important to the evaluation of natural biological attenuation...

Health hazard evaluation report HETA 81-472-1380, Pennsylvania Power and Light, Martins Creek Steam Electric Station, Martins Creek, Pennsylvania

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

Lewis, F.A.

1983-10-01

In August 1980, the National Institute for Occupational Safety and Health (NIOSH) received a request from the International Brotherhood of Electrical Workers Local 1600 for a Health Hazard Evaluation at the Pennsylvania Power and Light Company's Martins Creek Steam Electric Station in Martins Creek, Pennsylvania. The union was concerned about potential health and explosion hazards to employees from coal dust in Units 1 and 2 and the coal field. Based on environmental studies conducted at the time of the survey, NIOSH has determined that a potential health hazard may have existed due to exposure to respirable coal dust and quartz.more » Recommendations were made to ensure that potential health and explosion hazards are avoided in the future.« less

A Pilot Evaluation of On-Road Detection Performance by Drivers with Hemianopia Using Oblique Peripheral Prisms

PubMed Central

Bowers, Alex R.; Tant, Mark; Peli, Eli

2012-01-01

Aims. Homonymous hemianopia (HH), a severe visual consequence of stroke, causes difficulties in detecting obstacles on the nonseeing (blind) side. We conducted a pilot study to evaluate the effects of oblique peripheral prisms, a novel development in optical treatments for HH, on detection of unexpected hazards when driving. Methods. Twelve people with complete HH (median 49 years, range 29–68) completed road tests with sham oblique prism glasses (SP) and real oblique prism glasses (RP). A masked evaluator rated driving performance along the 25 km routes on busy streets in Ghent, Belgium. Results. The proportion of satisfactory responses to unexpected hazards on the blind side was higher in the RP than the SP drive (80% versus 30%; P = 0.001), but similar for unexpected hazards on the seeing side. Conclusions. These pilot data suggest that oblique peripheral prisms may improve responses of people with HH to blindside hazards when driving and provide the basis for a future, larger-sample clinical trial. Testing responses to unexpected hazards in areas of heavy vehicle and pedestrian traffic appears promising as a real-world outcome measure for future evaluations of HH rehabilitation interventions aimed at improving detection when driving. PMID:23316415

Vitamin D-related host genetic variants alter HIV disease progression in children.

PubMed

Moodley, Amaran; Qin, Min; Singh, Kumud K; Spector, Stephen A

2013-11-01

Vitamin D deficiency is common in HIV infection and has been associated with advanced disease. This study investigated whether vitamin D-related genetic variants were associated with disease progression in HIV-infected children. The Fok-I (C/T), Bsm-I (G/A), GC (A/C), DHCR7 (G/T) and CYP2R1 (G/A) genetic variants were detected by real-time polymerase chain reaction in HIV-infected children who participated in the Pediatric AIDS Clinical Trials Group P152 and P300 protocols, which predated the availability of effective combination antiretroviral therapy. The primary endpoints included time to progression to the first HIV-related disease endpoint (≥2 opportunistic infection, weight growth failure) or death, which constituted the progression-free survival. Analyses were performed for age>2 years and ≤2 years separately adjusting for race and treatment effect. Of the 998 children evaluated, 139 experienced HIV disease progression. For children>2 years, rapid disease progression was associated with the DHCR7 G allele compared with the T allele (G/G vs. T/T: hazard ratio [HR]=5.0, P = 0.035; G/T vs. T/T: HR=4.5, P=0.042; G/G+G/T vs. T/T: HR=4.8, P=0.036) and the Bsm-I A allele compared with the G allele (A/G vs. G/G: HR=2.2, P=0.014 and A/G+A/A vs. G/G: HR=2.0, P=0.026). In children≤2 years, the Bsm-I A allele increased the risk of disease progression in Hispanics (A/A vs. G/A+G/G: HR=2.8, P=0.03 and A/A vs. G/G: HR=2.8, P=0.046) and whites (A/A vs. G/G: HR=6.6, P=0.025 and A/A vs. G/A+G/G: HR=3.6, P=0.038). Vitamin D-related host genetic variants that alter the availability and activity of vitamin D are associated with risk of HIV disease progression in children and may vary by age and race.

Marijuana Use Is Not Associated With Progression to Advanced Liver Fibrosis in HIV/Hepatitis C Virus–coinfected Women

PubMed Central

Kelly, Erin M.; Dodge, Jennifer L.; Sarkar, Monika; French, Audrey L.; Tien, Phyllis C.; Glesby, Marshall J.; Golub, Elizabeth T.; Augenbraun, Michael; Plankey, Michael; Peters, Marion G.

2016-01-01

Background. Marijuana (hereafter “tetrahydrocannabinol [THC]”) use has been associated with liver fibrosis progression in retrospective analyses of patients with chronic hepatitis C (HCV). We studied long-term effects of THC on fibrosis progression in women coinfected with human immunodeficiency virus (HIV)/HCV enrolled in the Women's Interagency HIV Study (WIHS). Methods. Liver fibrosis was categorized according to FIB-4 scores as none, moderate, or significant. THC and alcohol use were quantified as average exposure per week. Associations between THC use and progression to significant fibrosis were assessed using Cox proportional hazards regression. Results. Among 575 HIV/HCV-coinfected women followed for a median of 11 (interquartile range, 6–17) years, 324 (56%) reported no THC use, 141 (25%) less than weekly use, 70 (12%) weekly use, and 40 (7%) daily use at WIHS entry. In univariable analysis, entry FIB-4 score (hazard ratio [HR], 2.26 [95% confidence interval {CI}, 1.88–2.73], P < .001), log HCV RNA (HR, 1.19 [95% CI, 1.02–1.38], P = .02), tobacco use (HR, 1.37 [95% CI, 1.02–1.85], P = .04), CD4+ count (risk per 100-cell increase: HR, 0.90 [95% CI, .86–.95], P < .001), and log HIV RNA (HR, 1.18 [95% CI, 1.05–1.32], P = .005) were associated with progression to significant fibrosis, as was cumulative alcohol use in follow-up (HR, 1.03 [95% CI, 1.02–1.04], P < .001). In multivariable analysis, entry FIB-4, entry CD4+ count, and cumulative alcohol use remained significant. Cumulative THC use was not associated with fibrosis progression (HR, 1.01 [95% CI, .92–1.10], P = .83). Conclusions. In this large cohort of HIV/HCV-coinfected women, THC was not associated with progression to significant liver fibrosis. Alcohol use was independently associated with liver fibrosis, and may better predict fibrosis progression in HIV/HCV-coinfected women. PMID:27225241

Survival benefit for patients with diffuse intrinsic pontine glioma (DIPG) undergoing re-irradiation at first progression: A matched-cohort analysis on behalf of the SIOP-E-HGG/DIPG working group.

PubMed

Janssens, Geert O; Gandola, Lorenza; Bolle, Stephanie; Mandeville, Henry; Ramos-Albiac, Monica; van Beek, Karen; Benghiat, Helen; Hoeben, Bianca; Morales La Madrid, Andres; Kortmann, Rolf-Dieter; Hargrave, Darren; Menten, Johan; Pecori, Emilia; Biassoni, Veronica; von Bueren, Andre O; van Vuurden, Dannis G; Massimino, Maura; Sturm, Dominik; Peters, Max; Kramm, Christof M

2017-03-01

Overall survival (OS) of patients with diffuse intrinsic pontine glioma (DIPG) is poor. The purpose of this study is to analyse benefit and toxicity of re-irradiation at first progression. At first progression, 31 children with DIPG, aged 2-16 years, underwent re-irradiation (dose 19.8-30.0 Gy) alone (n = 16) or combined with systemic therapy (n = 15). At initial presentation, all patients had typical symptoms and characteristic MRI features of DIPG, or biopsy-proven high-grade glioma. An interval of ≥3 months after upfront radiotherapy was required before re-irradiation. Thirty-nine patients fulfilling the same criteria receiving radiotherapy at diagnosis, followed by best supportive care (n = 20) or systemic therapy (n = 19) at progression but no re-irradiation, were eligible for a matched-cohort analysis. Median OS for patients undergoing re-irradiation was 13.7 months. For a similar median progression-free survival after upfront radiotherapy (8.2 versus 7.7 months; P = .58), a significant benefit in median OS (13.7 versus 10.3 months; P = .04) was observed in favour of patients undergoing re-irradiation. Survival benefit of re-irradiation increased with a longer interval between end-of-radiotherapy and first progression (3-6 months: 4.0 versus 2.7; P < .01; 6-12 months: 6.4 versus 3.3; P = .04). Clinical improvement with re-irradiation was observed in 24/31 (77%) patients. No grade 4-5 toxicity was recorded. On multivariable analysis, interval to progression (corrected hazard ratio = .27-.54; P < .01) and re-irradiation (corrected hazard ratio = .18-.22; P < .01) remained prognostic for survival. A risk score (RS), comprising 5 categories, was developed to predict survival from first progression (ROC: .79). Median survival ranges from 1.0 month (RS-1) to 6.7 months (RS-5). The majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinicopathological predictors for progression of chronic kidney disease in nephrosclerosis: a biopsy-based cohort study.

PubMed

Yamanouchi, Masayuki; Hoshino, Junichi; Ubara, Yoshifumi; Takaichi, Kenmei; Kinowaki, Keiichi; Fujii, Takeshi; Ohashi, Kenichi; Mise, Koki; Toyama, Tadashi; Hara, Akinori; Shimizu, Miho; Furuichi, Kengo; Wada, Takashi

2018-05-19

Biopsy-based studies on nephrosclerosis are lacking and the clinicopathological predictors for progression of chronic kidney disease (CKD) are not well established. We retrospectively assessed 401 patients with biopsy-proven nephrosclerosis in Japan. Progression of CKD was defined as new-onset end-stage renal disease, decrease of estimated glomerular filtration rate (eGFR) by  ≥50% or doubling of serum creatinine, and the sub-distribution hazard ratio (SHR) with 95% confidence interval (CI) for CKD progression was determined for various clinical and histological characteristics in competing risks analysis. The incremental value of pathological information for predicting CKD progression was assessed by calculating Harrell's C-statistics, the Akaike information criterion (AIC), net reclassification improvement and integrated discrimination improvement. During a median follow-up period of 5.3 years, 117 patients showed progression of CKD and 10 patients died before the defined kidney event. Multivariable sub-distribution hazards model identified serum albumin (SHR 0.48; 95% CI 0.35-0.67), hemoglobin A1c (SHR 0.71; 95% CI 0.54-0.94), eGFR (SHR 0.98; 95% CI 0.97-0.99), urinary albumin/creatinine ratio (UACR) (SHR 1.18; 95% CI 1.08-1.29), percentage of segmental/global glomerulosclerosis (%GS) (SHR 1.01; 95% CI 1.00-1.02) and interstitial fibrosis and tubular atrophy (IFTA) (SHR 1.52; 95% CI 1.20-1.92) as risk factors for CKD progression. The C-statistic of a model with only clinical variables was improved by adding %GS (0.790 versus 0.796, P < 0.01) and IFTA (0.790 versus 0.811, P < 0.01). The reclassification statistic was also improved after adding the biopsy data to the clinical data. The model including IFTA was superior, with the lowest AIC. The study implies that in addition to the traditional markers of eGFR and UACR, we may explore the markers of serum albumin and hemoglobin A1c, which are widely available but not routinely measured in patients with nephrosclerosis, and the biopsy data, especially the data on the severity of interstitial damage, for the better prediction of CKD progression in patients with nephrosclerosis.

Stereotactic Ablative Radiation Therapy for Pulmonary Metastases: Histology, Dose, and Indication Matter

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

Helou, Joelle; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario; Thibault, Isabelle

Purpose: To assess the association between colorectal cancer (CRC) histology, dose, and local failure (LF) after stereotactic ablative radiation therapy (SABR) for pulmonary metastases, and to describe subsequent cancer progression, change of systemic therapy (CST), survival, and their association with treatment indications. Methods and Materials: From a prospective SABR cohort, 180 pulmonary metastases in 120 patients were identified. Treatment indications were single metastasis, oligometastases, oligoprogression, and dominant areas of progression. Doses of 48 to 52 Gy/4 to 5 fractions were delivered. Since 2010 the dose for peripheral CRC metastases was increased to 60 Gy/4 fractions. Cumulative incidence function (CIF) was used tomore » report LF, progression probability, and CST. The Kaplan-Meier method estimated overall survival (OS). Univariate and multivariable analyses to assess variable associations were conducted. Results: Median follow-up was 22 months (interquartile range, 14-33 months). At 24 months, the CIF of LF was 23.6% (95% confidence interval [CI] 15.1%-33.3%) and 8.3% (95% CI 2.6%-18.6%), respectively, for CRC and non-CRC metastases (P<.001). This association remained significant after adjusting for confounders (subdistribution hazard ratio [SHR] 13.6, 95% CI 4.2-44.1, P<.001). Among CRC metastases, 56 and 45 received <60 Gy and 60 Gy, respectively. Delivering 60 Gy was independently associated with a lower hazard of LF (SHR 0.271, 95% CI 0.078-0.940, P=.040). At 12 months the CIF of progression was 41.67% (95% CI 21.69%-60.56%), 42.51% (95% CI 29.09%-55.29%), 62.96% (95% CI 41.25%-78.53%), and 78.57% (95% CI 42.20%-93.48%), respectively, for patients treated for single metastasis, oligometastases, oligoprogression, and dominant area of progression (P<.001). A CST was observed, respectively, in 4 (17%), 17 (31%), 12 (44%), and 10 (71%) patients with a median time of 13.1, 11.1, 8.4, and 8.4 months. Conclusion: Colorectal cancer lung metastases are associated with a higher hazard of LF and require higher SABR doses. Outcomes for patients with oligometastases and oligoprogression treated with SABR seem favorable. Prospective clinical trials are needed to confirm these benefits.« less

Prognostic Value of 68Ga-DOTANOC PET/CT SUVmax in Patients with Neuroendocrine Tumors of the Pancreas.

PubMed

Ambrosini, Valentina; Campana, Davide; Polverari, Giulia; Peterle, Chiara; Diodato, Stefania; Ricci, Claudio; Allegri, Vincenzo; Casadei, Riccardo; Tomassetti, Paola; Fanti, Stefano

2015-12-01

This study was performed to investigate the role of (68)Ga-DOTANOC SUVmax as a potential prognostic factor in patients with pancreatic neuroendocrine tumor (pNET). Among the patients who underwent (68)Ga-DOTANOC PET/CT, we retrospectively collected the data of those who had G1 or G2 pNET (2010 World Health Organization classification), presented with disease on PET/CT and CT, and had at least 6 mo of follow-up. Patients with multiple endocrine neoplasia were excluded. Overall, 43 patients were included. No significant differences in SUVmax were observed with respect to sex, tumor syndrome, stage, World Health Organization classification, or Ki-67. During follow-up (median, 20 mo), 11 patients (35.6%; median, 33 mo; interquartile range, 20-48 mo) had stable disease and 32 (74.4%; median, 19 mo; interquartile range, 14-26 mo) had progressive disease. SUVmax at 24 mo of follow-up was significantly higher (P = 0.022) in patients with stable disease than in patients with progressive disease. The best SUVmax cutoff ranged from 37.8 to 38.0. The major risk factors for progression included an SUVmax of no more than 37.8 (hazard ratio, 3.09; P = 0.003), a Ki-67 of more than 5% (hazard ratio, 2.89; P = 0.009), and medical therapy alone (hazard ratio, 2.36; P = 0.018). Advanced stage (IV) (P = 0.026), an SUVmax of less than 37.8 (P = 0.043), and medical therapy alone (P = 0.015) were also confirmed at multivariate analysis. Median progression-free survival was 23 mo. Significant differences in progression-free survival were observed in relationship to Ki-67 (median, 45 mo for Ki-67 ≤ 5% and 20 mo for Ki-67 > 5%; P = 0.005), SUVmax (<37.8 vs. >38.0: 16.0 vs. 27.0 mo; P = 0.002), and type of therapy (medical vs. peptide receptor radionuclide therapy: 16.0 vs. 26.0 mo; P = 0.014). (68)Ga-DOTANOC SUVmax is a relevant prognostic factor in patients with G1 and G2 pNET, and its routine use will improve disease characterization and management in these patients, who may present with atypical cases showing heterogeneous clinical behavior. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Hydrothermal Liquefaction Treatment Preliminary Hazard Analysis Report

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

Lowry, Peter P.; Wagner, Katie A.

A preliminary hazard assessment was completed during February 2015 to evaluate the conceptual design of the modular hydrothermal liquefaction treatment system. The hazard assessment was performed in 2 stages. An initial assessment utilizing Hazard Identification and Preliminary Hazards Analysis (PHA) techniques identified areas with significant or unique hazards (process safety-related hazards) that fall outside of the normal operating envelope of PNNL and warranted additional analysis. The subsequent assessment was based on a qualitative What-If analysis. This analysis was augmented, as necessary, by additional quantitative analysis for scenarios involving a release of hazardous material or energy with the potential for affectingmore » the public.« less

Serum 6-Bromotryptophan Levels Identified as a Risk Factor for CKD Progression.

PubMed

Tin, Adrienne; Nadkarni, Girish; Evans, Anne M; Winkler, Cheryl A; Bottinger, Erwin; Rebholz, Casey M; Sarnak, Mark J; Inker, Lesley A; Levey, Andrew S; Lipkowitz, Michael S; Appel, Lawrence J; Arking, Dan E; Coresh, Josef; Grams, Morgan E

2018-05-18

Background Metabolite levels reflect physiologic homeostasis and may serve as biomarkers of disease progression. Identifying metabolites associated with APOL1 risk alleles-genetic variants associated with CKD risk commonly present in persons of African descent-may reveal novel markers of CKD progression relevant to other populations. Methods We evaluated associations between the number of APOL1 risk alleles and 760 serum metabolites identified via untargeted profiling in participants of the African American Study of Kidney Disease and Hypertension (AASK) ( n =588; Bonferroni significance threshold P <6.5×10 -5 ) and replicated findings in 678 black participants with CKD in Bio Me , an electronic medical record-linked biobank. We tested the metabolite association with CKD progression in AASK, Bio Me , and the Modification of Diet in Renal Disease (MDRD) Study. Results One metabolite, 6-bromotryptophan, was significant in AASK ( P =4.7×10 -5 ) and replicated in Bio Me ( P =5.7×10 -3 ) participants, with lower levels associated with more APOL1 risk alleles. Lower levels of 6-bromotryptophan were associated with CKD progression in AASK and Bio Me participants and in white participants in the MDRD Study, independent of demographics and clinical characteristics, including baseline GFR (adjusted hazard ratio per two-fold higher 6-bromotryptophan level, AASK, 0.76; 95% confidence interval [95% CI], 0.64 to 0.91; Bio Me , 0.61; 95% CI, 0.43 to 0.85; MDRD, 0.52; 95% CI, 0.34 to 0.79). The interaction between the APOL1 risk alleles and 6-bromotryptophan was not significant. The identity of 6-bromotryptophan was confirmed in experiments comparing its molecular signature with that of authentic standards of other bromotryptophan isomers. Conclusions Serum 6-bromotryptophan is a consistent and novel risk factor for CKD progression. Copyright © 2018 by the American Society of Nephrology.

The efficacy of anti-PD-1/PD-L1 therapy and its comparison with EGFR-TKIs for advanced non-small-cell lung cancer.

PubMed

Sheng, Zhixin; Zhu, Xu; Sun, Yanhua; Zhang, Yanxia

2017-08-22

To better understand the efficacy and safety of anti-PD-1/PD-L1 therapy (atezolizumab, pembrolizumab, nivolumab) in patients with previously treated advanced non-small-cell lung cancer (NSCLC). The Cochrane Controlled Trial Register, Embase, Medline, and the Science Citation Index were searched for prospective published reports of atezolizumab, pembrolizumab, nivolumab in previously treated patients with advanced NSCLC. Finally, we identified 14 prospective published reports including four trials of atezolizumab covering 542 subjects, three trials of pembrolizumab covering 1566 subjects, seven trials of nivolumab covering 1678 subjects. When compared to docetaxel, anti-PD-1/PD-L1 therapy could significantly improve overall survival (hazard ratio [HR] 0.67, P<0.001) and progression-free survival (HR 0.83, P=0.002) for previously treated patients with advanced NSCLC. Anti-PD-1/PD-L1 therapy produced an overall response rate of 19% in the 2374 evaluable patients. When using docetaxel as the common comparator, indirect comparison of anti-PD-1/PD-L1 therapy versus EGFR-TKIs showed progression-free survival benefit (HR 0.62, P<0.001) and overall survival benefit (HR 0.60, P<0.001) for those patients with EGFR wild-type. Meanwhile, for those EGFR mutant patients, indirect comparison indicated that anti-PD-1/PD-L1 therapy was inferior to EGFR-TKIs therapy in terms of progression-free survival (HR 3.20, P<0.001), but no survival difference (HR 1.30, P=0.18). Anti-PD-1/PD-L1 therapy could produce progression-free survival and overall survival improvement over docetaxel for patients with previously treated NSCLC. For EGFR wild-type patients, anti-PD-1/PD-L1 therapy seemed to prolong progression-free survival and overall survival when compared to EGFR-TKIs. Meanwhile, for these EGFR mutant patients, anti-PD-1/PD-L1 therapy was inferior to EGFR-TKIs therapy in terms of progression-free survival.

NIMBY AND THE HAZARDOUS AND TOXIC WASTE SITING DILEMMA: THE NEED FOR CONCEPT CLARIFICATION. (R823191)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Occupational safety and health: progress toward the 1990 objectives for the nation.

PubMed Central

Millar, J D; Myers, M L

1983-01-01

Occupational safety and health is 1 of 15 areas addressed in the Public Health Service's Objectives for the Nation. This area represents 104 million working men and women and the deaths, diseases, and injuries that result from exposures to hazards in their work environment. Characteristics of public health practice are compared with characteristics of occupational safety and health practice. The National Institute for Occupational Safety and Health (NIOSH), created by the Occupational Safety and Health Act, is discussed. NIOSH has developed a list of 10 leading work-related diseases and injuries. The list is headed by occupational lung diseases. Twenty Objectives for the Nation in the area of occupational safety and health are reviewed, and the status of NIOSH efforts toward their attainment is discussed. Five categories of objectives are covered: (a) improved health status, (b) reduced risk factors, (c) improved public and professional awareness, (d) improved service and protection, and (e) improved surveillance and evaluation. The potential for achieving these objectives is discussed, with special attention given to the lack of a data base for monitoring progress. A major conclusion is that surveillance in occupational safety and health needs to be strengthened. PMID:6310668

Use of common analgesic medications and ovarian cancer survival: results from a pooled analysis in the Ovarian Cancer Association Consortium

PubMed Central

Dixon, Suzanne C; Nagle, Christina M; Wentzensen, Nicolas; Trabert, Britton; Beeghly-Fadiel, Alicia; Schildkraut, Joellen M; Moysich, Kirsten B; deFazio, Anna; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Ness, Roberta B; Edwards, Robert P; Jensen, Allan; Kjær, Susanne K; Høgdall, Estrid; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Bandera, Elisa V; Paddock, Lisa E; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Pearce, Celeste Leigh; Wu, Anna H; Pike, Malcolm C; Webb, Penelope M

2017-01-01

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. Methods: Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). Results: Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95% confidence intervals): aspirin 0.96 (0.88–1.04); non-aspirin NSAIDs 0.97 (0.89–1.05); acetaminophen 1.01 (0.93–1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0.89 (0.82–0.98)). Conclusions: Although this study did not show a clear association between analgesic use and ovarian cancer survival, further investigation with clearer definitions of use and information about post-diagnosis use is warranted. PMID:28350790

Science should warn people of looming disaster

NASA Astrophysics Data System (ADS)

Kossobokov, Vladimir

2014-05-01

Contemporary Science is responsible for not coping with challenging changes of Exposures and their Vulnerability inflicted by growing population, its concentration, etc., which result in a steady increase of Losses from Natural Hazards. Scientists owe to Society for lack of special knowledge, education, and communication. In fact, it appears that a few seismic hazard assessment programs and/or methodologies were tested appropriately against real observations before being endorsed for estimation of earthquake related risks. The fatal evidence and aftermath of the past decades prove that many of the existing internationally accepted methodologies are grossly misleading and are evidently unacceptable for any kind of responsible risk evaluation and knowledgeable disaster prevention. In contrast, the confirmed reliability of pattern recognition aimed at earthquake prone areas and times of increased probability, along with realistic earthquake scaling and scenario modeling, allow us to conclude that Contemporary Science can do a better job in disclosing Natural Hazards, assessing Risks, and delivering this state-of-the-art knowledge of looming disaster in advance catastrophic events. In a lieu of seismic observations long enough for a reliable probabilistic assessment or a comprehensive physical theory of earthquake recurrence, pattern recognition applied to available geophysical and/or geological data sets remains a broad avenue to follow in seismic hazard forecast/prediction. Moreover, better understanding seismic process in terms of non-linear dynamics of a hierarchical system of blocks-and-faults and deterministic chaos, progress to new approaches in assessing time-dependent seismic hazard based on multiscale analysis of seismic activity and reproducible intermediate-term earthquake prediction technique. The algorithms, which make use of multidisciplinary data available and account for fractal nature of earthquake distributions in space and time, have confirmed their reliability by durable statistical testing in the on-going regular real-time application lasted for more than 20 years. Geoscientists must initiate shifting the minds of community from pessimistic disbelieve in forecast/prediction products to optimistic challenging views on Hazard Predictability in space and time, so that not to repeat missed opportunities for disaster preparedness like it happen in advance the 2009 L'Aquila, M6.3 earthquake in Italy and the 2011, M9.0 mega-thrust off the Pacific coast of Tōhoku region in Japan.

Laboratory Safety and Chemical Hazards.

ERIC Educational Resources Information Center

Journal of Chemical Education, 1983

1983-01-01

Toxicology/chemical hazards, safety policy, legal responsibilities, adequacy of ventilation, chemical storage, evaluating experimental hazards, waste disposal, and laws governing chemical safety were among topics discussed in 10 papers presented at the Seventh Biennial Conference on Chemical Education (Stillwater, Oklahoma 1982). Several topics…

HAZBOT - A hazardous materials emergency response mobile robot

NASA Technical Reports Server (NTRS)

Stone, H. W.; Edmonds, G.

1992-01-01

The authors describe the progress that has been made towards the development of a mobile robot that can be used by hazardous materials emergency response teams to perform a variety of tasks including incident localization and characterization, hazardous material identification/classification, site surveillance and monitoring, and ultimately incident mitigation. In September of 1991, the HAZBOT II vehicle performed its first end-to-end demonstration involving a scenario in which the vehicle: navigated to the incident location from a distant (150-200 ft.) deployment site; entered a building through a door with thumb latch style handle and door closer; located and navigated to the suspected incident location (a chemical storeroom); unlocked and opened the storeroom's door; climbed over the storeroom's 12 in. high threshold to enter the storeroom; and located and identified a broken container of benzene.

HAZBOT - A hazardous materials emergency response mobile robot

NASA Astrophysics Data System (ADS)

Stone, H. W.; Edmonds, G.

The authors describe the progress that has been made towards the development of a mobile robot that can be used by hazardous materials emergency response teams to perform a variety of tasks including incident localization and characterization, hazardous material identification/classification, site surveillance and monitoring, and ultimately incident mitigation. In September of 1991, the HAZBOT II vehicle performed its first end-to-end demonstration involving a scenario in which the vehicle: navigated to the incident location from a distant (150-200 ft.) deployment site; entered a building through a door with thumb latch style handle and door closer; located and navigated to the suspected incident location (a chemical storeroom); unlocked and opened the storeroom's door; climbed over the storeroom's 12 in. high threshold to enter the storeroom; and located and identified a broken container of benzene.

77 FR 72435 - Pipeline Safety: Using Meaningful Metrics in Conducting Integrity Management Program Evaluations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-05

... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket No... Evaluations AGENCY: Pipeline and Hazardous Materials Safety Administration (PHMSA), DOT. ACTION: Notice... improve performance. For gas transmission pipelines, Sec. Sec. 192.911(i) and 192.945 define the...

42 CFR 85.3 - Procedures for requesting health hazard evaluations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES REQUESTS FOR HEALTH HAZARD EVALUATIONS § 85.3..., and Field Studies, NIOSH, 4676 Columbia Parkway, Cincinnati, OH 45226. (2) Requests from mining industry. Environmental Investigations Branch, Division of Respiratory Disease Studies, NIOSH, 944 Chestnut...

42 CFR 85.3 - Procedures for requesting health hazard evaluations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES REQUESTS FOR HEALTH HAZARD EVALUATIONS § 85.3..., and Field Studies, NIOSH, 4676 Columbia Parkway, Cincinnati, OH 45226. (2) Requests from mining industry. Environmental Investigations Branch, Division of Respiratory Disease Studies, NIOSH, 944 Chestnut...

42 CFR 85.3 - Procedures for requesting health hazard evaluations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES REQUESTS FOR HEALTH HAZARD EVALUATIONS § 85.3..., and Field Studies, NIOSH, 4676 Columbia Parkway, Cincinnati, OH 45226. (2) Requests from mining industry. Environmental Investigations Branch, Division of Respiratory Disease Studies, NIOSH, 944 Chestnut...

42 CFR 85.3 - Procedures for requesting health hazard evaluations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES REQUESTS FOR HEALTH HAZARD EVALUATIONS § 85.3..., and Field Studies, NIOSH, 4676 Columbia Parkway, Cincinnati, OH 45226. (2) Requests from mining industry. Environmental Investigations Branch, Division of Respiratory Disease Studies, NIOSH, 944 Chestnut...

42 CFR 85.3 - Procedures for requesting health hazard evaluations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES REQUESTS FOR HEALTH HAZARD EVALUATIONS § 85.3..., and Field Studies, NIOSH, 4676 Columbia Parkway, Cincinnati, OH 45226. (2) Requests from mining industry. Environmental Investigations Branch, Division of Respiratory Disease Studies, NIOSH, 944 Chestnut...

Health hazard evaluation/toxicity determination report 74-16-272, Marathon Battery Company, Waco, Texas. [Hazards to personnel from nickel and cadmium exposure

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

Thoburn, T.W.; Larsen, L.R.

1976-03-01

A health hazard evaluation investigation was conducted by NIOSH at the Marathon Battery Company in Waco, Texas, acting on a request from an authorized employee representative regarding exposure to dust and fumes in maintenance and production areas in the nickel-cadmium battery assembly factory. The prevailing symptoms among the approximately 60 affected predominantly female employees, was nausea. Environmental evaluation revealed that a potential hazard exists to employees from exposure to nickel and cadmium dusts. Workers in 4 departments showed levels of cadmium and nickel in hair and urine above those found in the control group; workers in 2 of the 4more » departments also showed excessive symptomatology and physical findings indicating upper respiratory irritation. Air samples also showed some excessive levels of cadmium and nickel particularly in these same 2 departments. However, medical evaluation of employees failed to demonstrate any apparent serious occupationally induced illness.« less

Maternal exposure to heatwave and preterm birth in Brisbane, Australia.

PubMed

Wang, J; Williams, G; Guo, Y; Pan, X; Tong, S

2013-12-01

To quantify the short-term effects of maternal exposure to heatwave on preterm birth. An ecological study. A population-based study in Brisbane, Australia. All pregnant women who had a spontaneous singleton live birth in Brisbane between November and March in 2000-2010 were studied. Daily data on pregnancy outcomes, meteorological factors, and ambient air pollutants were obtained. The Cox proportional hazards regression model with time-dependent variables was used to examine the short-term impact of heatwave on preterm birth. A series of cut-off temperatures and durations were used to define heatwave. Multivariable analyses were also performed to adjust for socio-economic factors, demographic factors, meteorological factors, and ambient air pollutants. Spontaneous preterm births. The adjusted hazard ratios (HRs) ranged from 1.13 (95% CI 1.03-1.24) to 2.00 (95% CI 1.37-2.91) by using different heatwave definitions, after controlling for demographic, socio-economic, and meteorological factors, and air pollutants. Heatwave was significantly associated with preterm birth: the associations were robust to the definitions of heatwave. The threshold temperatures, instead of duration, could be more likely to influence the evaluation of birth-related heatwaves. The findings of this study may have significant public health implications as climate change progresses. © 2013 RCOG.

Special Issue "Impact of Natural Hazards on Urban Areas and Infrastructure" in the Bulletin of Earthquake Engineering

NASA Astrophysics Data System (ADS)

Bostenaru Dan, M.

2009-04-01

This special issue includes selected papers on the topic of earthquake impact from the sessions held in 2004 in Nice, France and in 2005 in Vienna, Austria at the first and respectivelly the second European Geosciences Union General Assembly. Since its start in 1999, in the Hague, Netherlands, the hazard of earthquakes has been the most popular of the session. The respective calls in 2004 was for: Nature's forces including earthquakes, floods, landslides, high winds and volcanic eruptions can inflict losses to urban settlements and man-made structures such as infrastructure. In Europe, recent years have seen such significant losses from earthquakes in south and south-eastern Europe, floods in central Europe, and wind storms in western Europe. Meanwhile, significant progress has been made in understanding disasters. Several scientific fields contribute to a holistic approach in the evaluation of capacities, vulnerabilities and hazards, the main factors on mitigating urban disasters due to natural hazards. An important part of the session is devoted to assessment of earthquake shaking and loss scenarios, including both physical damage and human causalities. Early warning and rapid damage evaluation are of utmost importance for addressing the safety of many essential facilities, for emergency management of events and for disaster response. In case of earthquake occurrence strong motion networks, data processing and interpretation lead to preliminary estimation (scenarios) of geographical distribution of damages. Factual information on inflicted damage, like those obtained from shaking maps or aerial imagery permit a confrontation with simulation maps of damage in order to define a more accurate picture of the overall losses. Most recent developments towards quantitative and qualitative simulation of natural hazard impacts on urban areas, which provide decision-making support for urban disaster management, and success stories of and lessons learned from disaster mitigation will be presented. The session includes contributions showing methodological and modelling approaches from scientists in geophysical/seismological, hydrological, remote sensing, civil engineering, insurance, and urbanism, amongst other fields, as well as presentations from practitioners working on specific case studies, regarding analysis of recent events and their impact on cities as well as re-evaluation of past events from the point of view of long-time recovery. In 2005 it was called for: Most strategies for both preparedness and emergency management in case of disaster mitigation are related to urban planning. While natural, engineering and social sciences contribute to the evaluation of the impact of earthquakes and their secondary events (including tsunamis, earthquake triggered landslides, or fire), floods, landslides, high winds, and volcanic eruptions on urban areas, there are the instruments of urban planning which are to be employed for both visualisation as well as development and implementation of strategy concepts for pre- and postdisaster intervention. The evolution of natural systems towards extreme conditions is taken into consideration so far at it concerns the damaging impact on urban areas and infrastructure and the impact on the natural environment of interventions to reduce such damaging impact.

Volcanic Hazard Maps; the results and progress made by the IAVCEI Hazard Map working group

NASA Astrophysics Data System (ADS)

Calder, Eliza; Lindsay, Jan; Wright, Heather

2017-04-01

The IAVCEI Commission on Volcanic Hazards and Risk set up a working group on Hazard Maps in 2014. Since then, the group has led or co-organised three major workshops, and organized two thematic conference sessions. In particular we have initiated a series of workshops, named the "State of the Hazard Map" which we plan to continue (the first was held at COV8 (State of the Hazard Map 1) and second at COV9 (State of the Hazard Map 2) and the third will be held at IAVCEI General Assembly in Portland. The broad aim of these activities is to work towards an IAVCEI-endorsed considerations or guidelines document for volcanic hazard map generation. The workshops have brought together people from around the world working on volcanic hazard maps, and have had four primary objectives: 1) to review (and collect further data on) the diverse variety of methods and rationales currently used to develop maps; 2) to openly discuss approaches and experiences regarding how hazard maps are interpreted and used by different groups; 3) to discuss and prepare the IAVCEI Guidelines document; and lastly, 4) Discuss options for finalizing, publishing and disseminating the Guidelines document (e.g. wiki, report, open-source publication). This presentation will provide an update of the results and outcomes of those initiatives. This includes brief outcomes of the reviews undertaken, a survey that has been constructed in order to gather additional data, the planned structure for the guidelines documents and a summary of the key findings to date. The majority of the participants of these activities so far have come from volcano observatories or geological surveys, as these institutions commonly have primary responsibility for making operational hazard map. It is important however that others in the scientific community that work on quantification of volcanic hazard contribute to these guidelines. We therefore invite interested parties to become involved.

Radar image and data fusion for natural hazards characterisation

USGS Publications Warehouse

Lu, Zhong; Dzurisin, Daniel; Jung, Hyung-Sup; Zhang, Jixian; Zhang, Yonghong

2010-01-01

Fusion of synthetic aperture radar (SAR) images through interferometric, polarimetric and tomographic processing provides an all - weather imaging capability to characterise and monitor various natural hazards. This article outlines interferometric synthetic aperture radar (InSAR) processing and products and their utility for natural hazards characterisation, provides an overview of the techniques and applications related to fusion of SAR/InSAR images with optical and other images and highlights the emerging SAR fusion technologies. In addition to providing precise land - surface digital elevation maps, SAR - derived imaging products can map millimetre - scale elevation changes driven by volcanic, seismic and hydrogeologic processes, by landslides and wildfires and other natural hazards. With products derived from the fusion of SAR and other images, scientists can monitor the progress of flooding, estimate water storage changes in wetlands for improved hydrological modelling predictions and assessments of future flood impacts and map vegetation structure on a global scale and monitor its changes due to such processes as fire, volcanic eruption and deforestation. With the availability of SAR images in near real - time from multiple satellites in the near future, the fusion of SAR images with other images and data is playing an increasingly important role in understanding and forecasting natural hazards.

A Summary of Research and Progress on Carbon Monoxide Exposure Control Solutions on Houseboats

PubMed Central

Hall, Ronald M.; Earnest, G. Scott; Hammond, Duane R.; Dunn, Kevin H.; Garcia, Alberto

2015-01-01

Investigations of carbon monoxide (CO-related poisonings and deaths on houseboats were conducted by the Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. These investigations measured hazardous CO concentrations on and around houseboats that utilize gasoline-powered generators. Engineering control devices were developed and tested to mitigate this deadly hazard. CO emissions were measured using various sampling techniques which included exhaust emission analyzers, detector tubes, evacuated containers (grab air samples analyzed by a gas chromatograph), and direct-reading CO monitors. CO results on houseboats equipped with gasoline-powered generators without emission controls indicated hazardous CO concentrations exceeding immediately dangerous to life and health (IDLH) levels in potentially occupied areas of the houseboat. Air sample results on houseboats that were equipped with engineering controls to remove the hazard were highly effective and reduced CO levels by over 98% in potentially occupied areas. The engineering control devices used to reduce the hazardous CO emissions from gasoline-powered generators on houseboats were extremely effective at reducing CO concentrations to safe levels in potentially occupied areas on the houseboats and are now beginning to be widely used. PMID:24568306

A summary of research and progress on carbon monoxide exposure control solutions on houseboats.

PubMed

Hall, Ronald M; Earnest, G Scott; Hammond, Duane R; Dunn, Kevin H; Garcia, Alberto

2014-01-01

Investigations of carbon monoxide (CO-related poisonings and deaths on houseboats were conducted by the Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. These investigations measured hazardous CO concentrations on and around houseboats that utilize gasoline-powered generators. Engineering control devices were developed and tested to mitigate this deadly hazard. CO emissions were measured using various sampling techniques which included exhaust emission analyzers, detector tubes, evacuated containers (grab air samples analyzed by a gas chromatograph), and direct-reading CO monitors. CO results on houseboats equipped with gasoline-powered generators without emission controls indicated hazardous CO concentrations exceeding immediately dangerous to life and health (IDLH) levels in potentially occupied areas of the houseboat. Air sample results on houseboats that were equipped with engineering controls to remove the hazard were highly effective and reduced CO levels by over 98% in potentially occupied areas. The engineering control devices used to reduce the hazardous CO emissions from gasoline-powered generators on houseboats were extremely effective at reducing CO concentrations to safe levels in potentially occupied areas on the houseboats and are now beginning to be widely used.

Probabilistic wind/tornado/missile analyses for hazard and fragility evaluations

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

Park, Y.J.; Reich, M.

Detailed analysis procedures and examples are presented for the probabilistic evaluation of hazard and fragility against high wind, tornado, and tornado-generated missiles. In the tornado hazard analysis, existing risk models are modified to incorporate various uncertainties including modeling errors. A significant feature of this paper is the detailed description of the Monte-Carlo simulation analyses of tornado-generated missiles. A simulation procedure, which includes the wind field modeling, missile injection, solution of flight equations, and missile impact analysis, is described with application examples.

Resources Available for Hazards Analysis of Aerospace Fluids

NASA Technical Reports Server (NTRS)

Woods, S. S.; Stewart, W. F.; Baker, D. L.

2001-01-01

In recent years, the legislative and executive branches of the federal government have pushed to make government more efficient and responsive to the needs of the marketplace. One of these initiatives, Public Law 104-113, also known as the National Technology Transfer and Advancement Act of 1995 (NTTAA), is designed to accelerate technology transfer to industry and promote government-industry partnership. Summarized, NTTAA states that '... all Federal agencies and departments shall use technical standards that are developed or adopted by voluntary consensus standards bodies, using such technical standards as a means to carry out policy objectives or activities determined by the agencies and departments. Government agencies must now determine if their in-house requirement-setting activities are sufficiently unique that no public interest is served by having them adopted by a voluntary consensus organization (VCO), or if not, to use or develop voluntary consensus standards. The Office of Management and Budget (OMB) is chartered by the law to monitor federal agency progress and report the results to Congress. In response to NTTAA, agency-wide oxygen and hydrogen safety standards sponsored by the NASA Headquarters (HQ) Office of Safety and Mission Assurance (OSMA) were obvious choices for early adoption by VCOs. In 1996, HQ sought assistance from the Johnson Space Center (JSC) White Sands Test Facility (WSTF), the technical lead for development of these safety standards, to evaluate their adoption by VCOs. At that time, WSTF-developed propellant hazards manuals were likewise identified for possible VCO adoption. Subsequently, WSTF was asked to represent NASA for development of an international ISO safety standard for hydrogen use. Concurrent with these WSTF standards activities are related efforts to develop and publish propellant hazards analysis protocols and safety courses for the industrial, propellant use of oxygen, hydrogen, and hypergols. This paper reports on these efforts and describes WSTF's overall voluntary consensus standards program to coordinate the interchange of NASA's propellant hazards and safety information with industry.

Toward Establishing the Validity of the Transformative Optimism Construct Measurement for Tsunami Preparedness: A Structural Equation Model for Visitors of the Pacific Northwest Coast

ERIC Educational Resources Information Center

Rios-Uribe, Carlos Andres

2009-01-01

Measurements of social constructs that evaluate natural hazard preparedness are important to decrease natural hazard vulnerability. Preparedness reduces natural hazard impacts and human vulnerability. Investment in education and education research contribute to human sustainable development and natural hazard preparedness. Faced with other needs,…

RiskScape Volcano: Development of a risk assessment tool for volcanic hazards

NASA Astrophysics Data System (ADS)

Deligne, Natalia; King, Andrew; Jolly, Gill; Wilson, Grant; Wilson, Tom; Lindsay, Jan

2013-04-01

RiskScape is a multi-hazard risk assessment tool developed by GNS Science and the National Institute of Water and Atmospheric Research Ltd. (NIWA) in New Zealand that models the risk and impact of various natural hazards on a given built environment. RiskScape has a modular structure: the hazard module models hazard exposure (e.g., ash thickness at a given location), the asset module catalogues assets (built environment, infrastructure, and people) and their attributes exposed to the hazard, and the vulnerability module models the consequences of asset exposure to the hazard. Hazards presently included in RiskScape are earthquakes, river floods, tsunamis, windstorms, and ash from volcanic eruptions (specifically from Ruapehu). Here we present our framework for incorporating other volcanic hazards (e.g., pyroclastic density currents, lava flows, lahars, ground deformation) into RiskScape along with our approach for assessing asset vulnerability. We also will discuss the challenges of evaluating risk for 'point source' (e.g., stratovolcanoes) vs 'diffuse' (e.g., volcanic fields) volcanism using Ruapehu and the Auckland volcanic field as examples. Once operational, RiskScape Volcano will be a valuable resource both in New Zealand and internationally as a practical tool for evaluating risk and also as an example for how to predict the consequences of volcanic eruptions on both rural and urban environments.

Imaging growth and isocitrate dehydrogenase 1 mutation are independent predictors for diffuse low-grade gliomas

PubMed Central

Gozé, Catherine; Blonski, Marie; Le Maistre, Guillaume; Bauchet, Luc; Dezamis, Edouard; Page, Philippe; Varlet, Pascale; Capelle, Laurent; Devaux, Bertrand; Taillandier, Luc; Duffau, Hugues; Pallud, Johan

2014-01-01

Background We explored whether spontaneous imaging tumor growth (estimated by the velocity of diametric expansion) and isocitrate dehydrogenase 1 (IDH1) mutation (estimated by IDH1 immunoexpression) were independent predictors of long-term outcomes of diffuse low-grade gliomas in adults. Methods One hundred thirty-one adult patients with newly diagnosed supratentorial diffuse low-grade gliomas were retrospectively studied. Results Isocitrate dehydrogenase 1 mutations were present in 107 patients. The mean spontaneous velocity of diametric expansion was 5.40 ± 5.46 mm/y. During follow-up (mean, 70 ± 54.7 mo), 56 patients presented a malignant transformation and 23 died. The median malignant progression-free survival and the overall survival were significantly longer in cases of slow velocity of diametric expansion (149 and 198 mo, respectively) than in cases of fast velocity of diametric expansion (46 and 82 mo; P < .001 and P < .001, respectively) and in cases with IDH1 mutation (100 and 198 mo, respectively) than in cases without IDH1 mutation (72 mo and not reached; P = .028 and P = .001, respectively). In multivariate analyses, spontaneous velocity of diametric expansion and IDH1 mutation were independent prognostic factors for malignant progression-free survival (P < .001; hazard ratio, 4.23; 95% CI, 1.81–9.40 and P = .019; hazard ratio, 2.39; 95% CI, 1.19–4.66, respectively) and for overall survival (P < .001; hazard ratio, 26.3; 95% CI, 5.42–185.2 and P = .007; hazard ratio, 17.89; 95% CI, 2.15–200.1, respectively). Conclusions The spontaneous velocity of diametric expansion and IDH1 mutation status are 2 independent prognostic values that should be obtained at the beginning of the management of diffuse low-grade gliomas in adults. PMID:24847087

Screening guide for rapid assessment of liquefaction hazard at highway bridge sites

DOT National Transportation Integrated Search

1998-06-16

As an aid to seismic hazard assessment, this report provides a "screening guide" for systematic evaluation of liquefactin hazard at bridge sites and a guide for prioritizing sites for further investigation or mitigation. The guide presents a systemat...

Vemurafenib for BRAF V600 mutated advanced melanoma: results of treatment beyond progression.

PubMed

Scholtens, A; Geukes Foppen, M H; Blank, C U; van Thienen, J V; van Tinteren, H; Haanen, J B

2015-03-01

Selective BRAF inhibition (BRAFi) by vemurafenib or dabrafenib has become approved standard treatment in BRAF V600 mutated advanced stage melanoma. While the response rate is high, the response duration is limited with a progression-free survival (PFS) of 5-6months. Our observation of accelerated disease progression within some patients after stopping vemurafenib treatment has fostered the idea of treatment beyond progression (BRAFi TBP). In this retrospective study, we analysed 70 metastatic melanoma patients, treated at our institute, who experienced progression after prior objective response upon treatment with vemurafenib. Thirty-five patients that continued treatment beyond progression are compared with 35 patients who stopped BRAFi treatment at disease progression. Median overall survival beyond documented progression was found to be 5.2months versus 1.4months (95% confidence interval (CI): 3.8-7.4 versus 0.6-3.4; Log-Rank p=0.002) in favour of BRAFi TBP. In the multivariate survival analysis, stopping treatment at disease progression was significantly associated with shorter survival (hazard ratio: 1.92; 95% CI: 1.04-3.55; p=0.04). Our results suggest that continuing vemurafenib treatment beyond progression may be beneficial in advanced melanoma patients, who prior to progression responded to vemurafenib. Copyright © 2015 Elsevier Ltd. All rights reserved.

Body Mass Index in Mild Cognitive Impairment According to Age, Sex, Cognitive Intervention, and Hypertension and Risk of Progression to Alzheimer's Disease.

PubMed

Joo, Soo Hyun; Yun, Se Hee; Kang, Dong Woo; Hahn, Chang Tae; Lim, Hyun Kook; Lee, Chang Uk

2018-01-01

Introduction: Mild cognitive impairment (MCI) is a prodromal stage of dementia. The association of body mass index (BMI) and progression to Alzheimer's disease (AD) in MCI subjects according to age, sex, and cognitive intervention remains unknown. We investigated the relationship between BMI and the risk of progression to AD in subjects with MCI, as well as the effect of BMI on progression to AD depending on age, sex, cognitive intervention, and chronic diseases. Methods: Three hundred and eighty-eight MCI subjects were followed for 36.3 ± 18.4 months, prospectively. They underwent neuropsychological testing more than twice during the follow-up period. The MCI subjects were categorized into underweight, normal weight, overweight, and obese subgroups. The associations between baseline BMI and progression to AD over the follow-up period were estimated using Cox proportional hazard regression models. Data were analyzed after stratification by age, sex, cognitive intervention, and chronic diseases. Results: After adjustment for the covariates, the underweight MCI group had a higher risk of progression to AD [hazard ratio (HR): 2.38, 95% confidence interval (CI): 1.17-4.82] relative to the normal weight group. After stratifying by age, sex, cognitive intervention, and chronic diseases, this effect remained significant among females (HR: 3.15, 95% CI: 1.40-7.10), the older elderly ≥75 years old (HR: 3.52, 95% CI: 1.42-8.72), the non-intervention group (HR: 3.06, 95%CI: 1.18-7.91), and the hypertensive group (HR: 4.71, 95% CI: 1.17-18.99). Conclusion: These data indicate that underweight could be a useful marker for identifying individuals at increased risk for AD in MCI subjects. This association is even stronger in females, older elderly subjects, the non-cognitive intervention group, and the hypertensive group.

Relation of physical activity time to incident disability in community dwelling adults with or at risk of knee arthritis: prospective cohort study.

PubMed

Dunlop, Dorothy D; Song, Jing; Semanik, Pamela A; Sharma, Leena; Bathon, Joan M; Eaton, Charles B; Hochberg, Marc C; Jackson, Rebecca D; Kwoh, C Kent; Mysiw, W Jerry; Nevitt, Michael C; Chang, Rowland W

2014-04-29

To investigate whether objectively measured time spent in light intensity physical activity is related to incident disability and to disability progression. Prospective multisite cohort study from September 2008 to December 2012. Baltimore, Maryland; Columbus, Ohio; Pittsburgh, Pennsylvania; and Pawtucket, Rhode Island, USA. Disability onset cohort of 1680 community dwelling adults aged 49 years or older with knee osteoarthritis or risk factors for knee osteoarthritis; the disability progression cohort included 1814 adults. Physical activity was measured by accelerometer monitoring. Disability was ascertained from limitations in instrumental and basic activities of daily living at baseline and two years. The primary outcome was incident disability. The secondary outcome was progression of disability defined by a more severe level (no limitations, limitations to instrumental activities only, 1-2 basic activities, or ≥3 basic activities) at two years compared with baseline. Greater time spent in light intensity activities had a significant inverse association with incident disability. Less incident disability and less disability progression were each significantly related to increasing quartile categories of daily time spent in light intensity physical activities (hazard ratios for disability onset 1.00, 0.62, 0.47, and 0.58, P for trend=0.007; hazard ratios for progression 1.00, 0.59, 0.50, and 0.53, P for trend=0.003) with control for socioeconomic factors (age, sex, race/ethnicity, education, income) and health factors (comorbidities, depressive symptoms, obesity, smoking, lower extremity pain and function, and knee assessments: osteoarthritis severity, pain, symptoms, prior injury). This finding was independent of time spent in moderate-vigorous activities. These prospective data showed an association between greater daily time spent in light intensity physical activities and reduced risk of onset and progression of disability in adults with osteoarthritis of the knee or risk factors for knee osteoarthritis. An increase in daily physical activity time may reduce the risk of disability, even if the intensity of that additional activity is not increased.

Neurocognitive mechanisms underlying deceptive hazard evaluation: An event-related potentials investigation.

PubMed

Fu, Huijian; Qiu, Wenwei; Ma, Haiying; Ma, Qingguo

2017-01-01

Deceptive behavior is common in human social interactions. Researchers have been trying to uncover the cognitive process and neural basis underlying deception due to its theoretical and practical significance. We used Event-related potentials (ERPs) to investigate the neural correlates of deception when the participants completed a hazard judgment task. Pictures conveying or not conveying hazard information were presented to the participants who were then requested to discriminate the hazard content (safe or hazardous) and make a response corresponding to the cues (truthful or deceptive). Behavioral and electrophysiological data were recorded during the entire experiment. Results showed that deceptive responses, compared to truthful responses, were associated with longer reaction time (RT), lower accuracy, increased N2 and reduced late positive potential (LPP), suggesting a cognitively more demanding process to respond deceptively. The decrement in LPP correlated negatively with the increment in RT for deceptive relative to truthful responses, regardless of hazard content. In addition, hazardous information evoked larger N1 and P300 than safe information, reflecting an early processing bias and a later evaluative categorization process based on motivational significance, respectively. Finally, the interaction between honesty (truthful/deceptive) and safety (safe/hazardous) on accuracy and LPP indicated that deceptive responses towards safe information required more effort than deceptive responses towards hazardous information. Overall, these results demonstrate the neurocognitive substrates underlying deception about hazard information.

Neurocognitive mechanisms underlying deceptive hazard evaluation: An event-related potentials investigation

PubMed Central

Qiu, Wenwei; Ma, Haiying; Ma, Qingguo

2017-01-01

Deceptive behavior is common in human social interactions. Researchers have been trying to uncover the cognitive process and neural basis underlying deception due to its theoretical and practical significance. We used Event-related potentials (ERPs) to investigate the neural correlates of deception when the participants completed a hazard judgment task. Pictures conveying or not conveying hazard information were presented to the participants who were then requested to discriminate the hazard content (safe or hazardous) and make a response corresponding to the cues (truthful or deceptive). Behavioral and electrophysiological data were recorded during the entire experiment. Results showed that deceptive responses, compared to truthful responses, were associated with longer reaction time (RT), lower accuracy, increased N2 and reduced late positive potential (LPP), suggesting a cognitively more demanding process to respond deceptively. The decrement in LPP correlated negatively with the increment in RT for deceptive relative to truthful responses, regardless of hazard content. In addition, hazardous information evoked larger N1 and P300 than safe information, reflecting an early processing bias and a later evaluative categorization process based on motivational significance, respectively. Finally, the interaction between honesty (truthful/deceptive) and safety (safe/hazardous) on accuracy and LPP indicated that deceptive responses towards safe information required more effort than deceptive responses towards hazardous information. Overall, these results demonstrate the neurocognitive substrates underlying deception about hazard information. PMID:28793344

76 FR 58515 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-21

... regulations governing the NIOSH Health Hazard Evaluation program (42 CFR 85.3-1). In general, if employees are... occupational health hazards. In most on-site evaluations employees are interviewed to help further define...: requesters, employers, employee representatives; the Department of Labor (Occupational Safety and Health...

A MULTI-LEVEL APPROACH TO LONG-TERM BEHAVIOR CHANGE: TEACHING PROPER USE OF A HOUSEHOLD HAZARDOUS WASTE FACILITY. (R825827)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Adapting to wildfire: Rebuilding after home loss

Treesearch

Miranda H. Mockrin; Susan I. Stewart; Volker C. Radeloff; Roger B. Hammer; Patricia M. Alexandre

2015-01-01

Wildfire management now emphasizes fire-adapted communities that coexist with wildfires, although it is unclear how communities will progress to this goal. Hazards research suggests that response to wildfire - specifically, rebuilding after fire - may be a crucial opportunity for homeowner and community adaptation. We explore rebuilding after the 2010 Fourmile Canyon...

Removal of DNT from Wastewaters at Radford Army Ammunition Plant

DTIC Science & Technology

1991-03-31

appi~cable) U.S. Armty Corps of EngineersI ITEnvronenta Prgras, ic. ____________Toxic an’d Hazardous Material-, zec 6ý.. ADDPLSS (Crty, State. and... Peter Hartmann is RAAP’s Technical Analytical laboratory supervisor and is responsible for tracking analytical progress and ensuring timely completion

Seismic hazard assessment of Syria using seismicity, DEM, slope, active tectonic and GIS

NASA Astrophysics Data System (ADS)

Ahmad, Raed; Adris, Ahmad; Singh, Ramesh

2016-07-01

In the present work, we discuss the use of an integrated remote sensing and Geographical Information System (GIS) techniques for evaluation of seismic hazard areas in Syria. The present study is the first time effort to create seismic hazard map with the help of GIS. In the proposed approach, we have used Aster satellite data, digital elevation data (30 m resolution), earthquake data, and active tectonic maps. Many important factors for evaluation of seismic hazard were identified and corresponding thematic data layers (past earthquake epicenters, active faults, digital elevation model, and slope) were generated. A numerical rating scheme has been developed for spatial data analysis using GIS to identify ranking of parameters to be included in the evaluation of seismic hazard. The resulting earthquake potential map delineates the area into different relative susceptibility classes: high, moderate, low and very low. The potential earthquake map was validated by correlating the obtained different classes with the local probability that produced using conventional analysis of observed earthquakes. Using earthquake data of Syria and the peak ground acceleration (PGA) data is introduced to the model to develop final seismic hazard map based on Gutenberg-Richter (a and b values) parameters and using the concepts of local probability and recurrence time. The application of the proposed technique in Syrian region indicates that this method provides good estimate of seismic hazard map compared to those developed from traditional techniques (Deterministic (DSHA) and probabilistic seismic hazard (PSHA). For the first time we have used numerous parameters using remote sensing and GIS in preparation of seismic hazard map which is found to be very realistic.

Occupational risk factors in inflammatory bowel disease.

PubMed

Leso, V; Ricciardi, W; Iavicoli, I

2015-08-01

Crohn's disease and ulcerative colitis are the two main forms of inflammatory bowel disease (IBD). Although the aetiology of IBD is not completely understood, an interaction between genetic and environmental factors has been proposed. In this context, however, environmental epidemiology lacks a comprehensive evaluation of the possible role of occupational exposures in IBD development and progression. Therefore, aim of our review was to evaluate how certain occupational risk factors may affect IBD pathogenesis, clinical history and severity of disease manifestations. A critical revision of available literature concerning exposure to groups of potential workplace hazardous agents and IBD, as it appears in Medline and Web of knowledge, was performed. The role of workplace exposures to chemical and biological agents, ionizing or non-ionizing radiations, shift-works, indoor, and sedentary works as well as job strain on IBD has been critically revised. However, the limited number of studies addressing these issues prevented us from extrapolating definite conclusions. Our review pointed out some critical aspects concerning the relationship between occupational factors and IBD, in terms of causative pathways, hazardous exposure, susceptibility and consequences of IBD functional limitations on career choice and fitness for work that need future investigations. Overall, this seems a challenging public health issue, considering the strong IBD impact on patients' quality of life, work productivity and costs to society. Moreover, this review may encourage concerted actions of health care specialists, occupational physicians, employers and IBD workers to plan preventive and protective measures for "healthier patterns of work" for IBD and to develop innovative perspectives for an integrated management of "IBD at work".

Risk management study for the retired Hanford Site facilities: Qualitative risk evaluation for the retired Hanford Site facilities. Volume 3

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

Coles, G.A.; Shultz, M.V.; Taylor, W.E.

1993-09-01

This document provides a risk evaluation of the 100 and 200 Area retired, surplus facilities on the Hanford Site. Also included are the related data that were compiled by the risk evaluation team during investigations performed on the facilities. Results are the product of a major effort performed in fiscal year 1993 to produce qualitative information that characterizes certain risks associated with these facilities. The retired facilities investigated for this evaluation are located in the 100 and 200 Areas of the 1,450-km{sup 2} (570-mi{sup 2}) Hanford Site. The Hanford Site is a semiarid tract of land in southeastern Washington State.more » The nearest population center is Richland, Washington, (population 32,000) 30-km (20 mi) southeast of the 200 Area. During walkdown investigations of these facilities, data on real and potential hazards that threatened human health or safety or created potential environmental release issues were identified by the risk evaluation team. Using these findings, the team categorized the identified hazards by facility and evaluated the risk associated with each hazard. The factors contributing to each risk, and the consequence and likelihood of harm associated with each hazard also are included in this evaluation.« less

A Gis Model Application Supporting The Analysis of The Seismic Hazard For The Urban Area of Catania (italy)

NASA Astrophysics Data System (ADS)

Grasso, S.; Maugeri, M.

After the Summit held in Washington on August 20-22 2001 to plan the first World Conference on the mitigation of Natural Hazards, a Group for the analysis of Natural Hazards within the Mediterranean area has been formed. The Group has so far determined the following hazards: (1) Seismic hazard (hazard for historical buildings included); (2) Hazard linked to the quantity and quality of water; (3) Landslide hazard; (4) Volcanic hazard. The analysis of such hazards implies the creation and the management of data banks, which can only be used if the data are properly geo-settled to allow a crossed use of them. The obtained results must be therefore represented on geo-settled maps. The present study is part of a research programme, namely "Detailed Scenarios and Actions for Seismic Prevention of Damage in the Urban Area of Catania", financed by the National Department for the Civil Protection and the National Research Council-National Group for the Defence Against Earthquakes (CNR-GNDT). Nowadays the south-eastern area of Sicily, called the "Iblea" seismic area of Sicily, is considered as one of the most intense seismic zones in Italy, based on the past and current seismic history and on the typology of civil buildings. Safety against earthquake hazards has two as pects: structural safety against potentially destructive dynamic forces and site safety related to geotechnical phenomena such as amplification, land sliding and soil liquefaction. So the correct evaluation of seismic hazard is highly affected by risk factors due to geological nature and geotechnical properties of soils. The effect of local geotechnical conditions on damages suffered by buildings under seismic conditions has been widely recognized, as it is demonstrated by the Manual for Zonation on Seismic Geotechnical Hazards edited by the International Society for Soil Mechanics and Geotechnical Engineering (TC4, 1999). The evaluation of local amplification effects may be carried out by means of either rigorous complex methods of analysis or qualitative procedures. A semi quantitative procedure based on the definition of the geotechnical hazard index has been applied for the zonation of the seismic geotechnical hazard of the city of Catania. In particular this procedure has been applied to define the influence of geotechnical properties of soil in a central area of the city of Catania, where some historical buildings of great importance are sited. It was also performed an investigation based on the inspection of more than one hundred historical ecclesiastical buildings of great importance, located in the city. Then, in order to identify the amplification effects due to the site conditions, a geotechnical survey form was prepared, to allow a semi quantitative evaluation of the seismic geotechnical hazard for all these historical buildings. In addition, to evaluate the foundation soil time -history response, a 1-D dynamic soil model was employed for all these buildings, considering the non linearity of soil behaviour. Using a GIS, a map of the seismic geotechnical hazard, of the liquefaction hazard and a preliminary map of the seismic hazard for the city of Catania have been obtained. From the analysis of obtained results it may be noticed that high hazard zones are mainly clayey sites

24 CFR 35.310 - Notices and pamphlet.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Project-Based Assistance... evaluation or hazard reduction shall be provided to the occupants in accordance with § 35.125. (b) Lead hazard information pamphlet. The owner shall provide the lead hazard information pamphlet in accordance...

24 CFR 35.310 - Notices and pamphlet.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Project-Based Assistance... evaluation or hazard reduction shall be provided to the occupants in accordance with § 35.125. (b) Lead hazard information pamphlet. The owner shall provide the lead hazard information pamphlet in accordance...

24 CFR 35.310 - Notices and pamphlet.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Project-Based Assistance... evaluation or hazard reduction shall be provided to the occupants in accordance with § 35.125. (b) Lead hazard information pamphlet. The owner shall provide the lead hazard information pamphlet in accordance...

24 CFR 35.310 - Notices and pamphlet.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Project-Based Assistance... evaluation or hazard reduction shall be provided to the occupants in accordance with § 35.125. (b) Lead hazard information pamphlet. The owner shall provide the lead hazard information pamphlet in accordance...

24 CFR 35.310 - Notices and pamphlet.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Project-Based Assistance... evaluation or hazard reduction shall be provided to the occupants in accordance with § 35.125. (b) Lead hazard information pamphlet. The owner shall provide the lead hazard information pamphlet in accordance...

Progress of statistical analysis in biomedical research through the historical review of the development of the Framingham score.

PubMed

Ignjatović, Aleksandra; Stojanović, Miodrag; Milošević, Zoran; Anđelković Apostolović, Marija

2017-12-02

The interest in developing risk models in medicine not only is appealing, but also associated with many obstacles in different aspects of predictive model development. Initially, the association of biomarkers or the association of more markers with the specific outcome was proven by statistical significance, but novel and demanding questions required the development of new and more complex statistical techniques. Progress of statistical analysis in biomedical research can be observed the best through the history of the Framingham study and development of the Framingham score. Evaluation of predictive models comes from a combination of the facts which are results of several metrics. Using logistic regression and Cox proportional hazards regression analysis, the calibration test, and the ROC curve analysis should be mandatory and eliminatory, and the central place should be taken by some new statistical techniques. In order to obtain complete information related to the new marker in the model, recently, there is a recommendation to use the reclassification tables by calculating the net reclassification index and the integrated discrimination improvement. Decision curve analysis is a novel method for evaluating the clinical usefulness of a predictive model. It may be noted that customizing and fine-tuning of the Framingham risk score initiated the development of statistical analysis. Clinically applicable predictive model should be a trade-off between all abovementioned statistical metrics, a trade-off between calibration and discrimination, accuracy and decision-making, costs and benefits, and quality and quantity of patient's life.

Editor's highlight: Evaluation of a Microelectrode Array-based Assay for Neural Network Ontogeny using Training Set Chemicals

EPA Science Inventory

Thousands of compounds in the environment have not been characterized for developmental neurotoxicity (DNT) hazard. To address this issue, methods to screen compounds rapidly for DNT hazard evaluation are necessary and are being developed for key neurodevelopmental processes. In...

32 CFR 644.352 - Evaluation and reporting of flood hazards.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 4 2012-07-01 2011-07-01 true Evaluation and reporting of flood hazards. 644.352 Section 644.352 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Reports of Excess Real Property and Related Personal...

32 CFR 644.352 - Evaluation and reporting of flood hazards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 4 2013-07-01 2013-07-01 false Evaluation and reporting of flood hazards. 644.352 Section 644.352 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Reports of Excess Real Property and Related Personal...

32 CFR 644.352 - Evaluation and reporting of flood hazards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Evaluation and reporting of flood hazards. 644.352 Section 644.352 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Reports of Excess Real Property and Related Personal...

32 CFR 644.352 - Evaluation and reporting of flood hazards.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 4 2011-07-01 2011-07-01 false Evaluation and reporting of flood hazards. 644.352 Section 644.352 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Reports of Excess Real Property and Related Personal...

32 CFR 644.352 - Evaluation and reporting of flood hazards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 4 2014-07-01 2013-07-01 true Evaluation and reporting of flood hazards. 644.352 Section 644.352 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Reports of Excess Real Property and Related Personal...

Evaluation of the ToxRTool's ability to rate the reliability of toxicological data for human health hazard assessments

EPA Science Inventory

Regulatory agencies often utilize results from peer reviewed publications for hazard assessments.A problem in doing so is the lack of well-accepted tools to objectively, efficiently and systematically assess the quality of published toxicological studies. Herein, we evaluated the...

Evaluating Ecological Risk to Invertebrate Receptors from PAHs in Sediments at Hazardous Waste Sites (Final Report)

EPA Science Inventory

EPA's Ecological Risk Assessment Support Center (ERASC) announced the release of the final report, Evaluating Ecological Risk to Invertebrate Receptors from PAHs in Sediments at Hazardous Waste Sites. The report provides an overview of an approach for assessing risk to ...

PREVENTION REFERENCE MANUAL: OVERVIEWS ON PREVENTING AND CONTROLLING ACCIDENTIAL RELEASES OF SELECTED TOXIC CHEMICALS

EPA Science Inventory

The manual can be used to orient personnel involved in inspecting and otherwise evaluating potential toxic chemical release hazards to the fundamentals of release hazard control for 13 of the specific chemicals chosen for evaluation under Section 305(b) of the Superfund Amendment...

24 CFR 35.125 - Notice of evaluation and hazard reduction activities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Notice of evaluation and hazard reduction activities. 35.125 Section 35.125 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL...

2002 Report to Congress: Evaluating the Consensus Best Practices Developed through the Howard Hughes Medical Institute’s Collaborative Hazardous Waste Management Demonstration Project

EPA Pesticide Factsheets

This report discusses a collaborative project initiated by the Howard Hughes Medical Institute (HHMI) to establish and evaluate a performance-based approach to management of hazardous wastes in the laboratories of academic research institutions.

Integrating Entropy-Based Naïve Bayes and GIS for Spatial Evaluation of Flood Hazard.

PubMed

Liu, Rui; Chen, Yun; Wu, Jianping; Gao, Lei; Barrett, Damian; Xu, Tingbao; Li, Xiaojuan; Li, Linyi; Huang, Chang; Yu, Jia

2017-04-01

Regional flood risk caused by intensive rainfall under extreme climate conditions has increasingly attracted global attention. Mapping and evaluation of flood hazard are vital parts in flood risk assessment. This study develops an integrated framework for estimating spatial likelihood of flood hazard by coupling weighted naïve Bayes (WNB), geographic information system, and remote sensing. The north part of Fitzroy River Basin in Queensland, Australia, was selected as a case study site. The environmental indices, including extreme rainfall, evapotranspiration, net-water index, soil water retention, elevation, slope, drainage proximity, and density, were generated from spatial data representing climate, soil, vegetation, hydrology, and topography. These indices were weighted using the statistics-based entropy method. The weighted indices were input into the WNB-based model to delineate a regional flood risk map that indicates the likelihood of flood occurrence. The resultant map was validated by the maximum inundation extent extracted from moderate resolution imaging spectroradiometer (MODIS) imagery. The evaluation results, including mapping and evaluation of the distribution of flood hazard, are helpful in guiding flood inundation disaster responses for the region. The novel approach presented consists of weighted grid data, image-based sampling and validation, cell-by-cell probability inferring and spatial mapping. It is superior to an existing spatial naive Bayes (NB) method for regional flood hazard assessment. It can also be extended to other likelihood-related environmental hazard studies. © 2016 Society for Risk Analysis.

[Analysis and toxicological evaluation of hazardous gases in sealed cabin].

PubMed

He, Z; Shi, J; Yu, B; Liang, H; Yu, F

1998-10-01

82 volatile organic compounds (VOCs) of eight organic sorts and 3 target inorganic compounds in a sealed cabin that simulating the flying spaceship were identified and quantified for 5 d, the law of hazardous gas concentration variation was discussed, and the atmosphere toxicology was evaluated preliminarily. It provides a basis for detecting gas compounds and evaluating the atmosphere toxicology in the spaceship.

A Cascading Storm-Flood-Landslide Guidance System: Development and Application in China

NASA Astrophysics Data System (ADS)

Zeng, Ziyue; Tang, Guoqiang; Long, Di; Ma, Meihong; Hong, Yang

2016-04-01

Flash floods and landslides, triggered by storms, often interact and cause cascading effects on human lives and property. Satellite remote sensing data has significant potential use in analysis of these natural hazards. As one of the regions continuously affected by severe flash floods and landslides, Yunnan Province, located in Southwest China, has a complex mountainous hydrometeorology and suffers from frequent heavy rainfalls from May through to late September. Taking Yunnan as a test-bed, this study proposed a Cascading Storm-Flood-Landslide Guidance System to progressively analysis and evaluate the risk of the multi-hazards based on multisource satellite remote sensing data. First, three standardized rainfall amounts (average daily amount in flood seasons, maximum 1h and maximum 6h amount) from the products of Topical Rainfall Measuring Mission (TRMM) Multi-satellite Precipitation Analysis (TMPA) were used as rainfall indicators to derive the StorM Hazard Index (SMHI). In this process, an integrated approach of the Analytic Hierarchy Process (AHP) and the Information-Entropy theory was adopted to determine the weight of each indicator. Then, land cover and vegetation cover data from the Moderate Resolution Imaging Spectroradiometer (MODIS) products, soil type from the Harmonized World Soil Database (HWSD) soil map, and slope from the Shuttle Radar Topography Mission (SRTM) data were add as semi-static geo-topographical indicators to derive the Flash Flood Hazard Index (FFHI). Furthermore, three more relevant landslide-controlling indicators, including elevation, slope angle and soil text were involved to derive the LandSlide Hazard Index (LSHI). Further inclusion of GDP, population and prevention measures as vulnerability indicators enabled to consecutively predict the risk of storm to flash flood and landslide, respectively. Consequently, the spatial patterns of the hazard indices show that the southeast of Yunnan has more possibility to encounter with storms than other parts, while the northeast of Yunnan are most susceptible to floods and landslides, which agrees with the distribution of observed flood and landslide events. Moreover, risks for the multi-hazards were classified into four categories. Results show a strong correlation between the distributions of flash flood prone and landslide-prone regions and also highlight the counties with high risk of storms (e.g., Funing and Malipo), flash floods (e.g., Gongshan and Yanjing) and landslides (e.g., Zhaotong and Luxi). Compared to other approaches, the Cascading Storm-Flood-Landslide Guidance System uses a straightforward yet useful indicator-based weighted linear combination method and could be a useful prototype in mapping characteristics of storm-triggered hazards for users at different administrative levels (e.g., catchment, town, county, province and even nation) in China.

Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer.

PubMed

Peters, Solange; Camidge, D Ross; Shaw, Alice T; Gadgeel, Shirish; Ahn, Jin S; Kim, Dong-Wan; Ou, Sai-Hong I; Pérol, Maurice; Dziadziuszko, Rafal; Rosell, Rafael; Zeaiter, Ali; Mitry, Emmanuel; Golding, Sophie; Balas, Bogdana; Noe, Johannes; Morcos, Peter N; Mok, Tony

2017-08-31

Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease. In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival. During a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P<0.001); the median progression-free survival with alectinib was not reached. The results for independent review committee-assessed progression-free survival were consistent with those for the primary end point. A total of 18 patients (12%) in the alectinib group had an event of CNS progression, as compared with 68 patients (45%) in the crizotinib group (cause-specific hazard ratio, 0.16; 95% CI, 0.10 to 0.28; P<0.001). A response occurred in 126 patients in the alectinib group (response rate, 82.9%; 95% CI, 76.0 to 88.5) and in 114 patients in the crizotinib group (response rate, 75.5%; 95% CI, 67.8 to 82.1) (P=0.09). Grade 3 to 5 adverse events were less frequent with alectinib (41% vs. 50% with crizotinib). As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC. (Funded by F. Hoffmann-La Roche; ALEX ClinicalTrials.gov number, NCT02075840 .).

Investigation of hazards associated with plastic bonded starter mix manufacturing processes

NASA Technical Reports Server (NTRS)

1971-01-01

An investigation to determine the hazards potential evaluation of plastic bonded starter mix (PBSM) production processes and the application to the M18 and M7A3 grenades is reported. The investigation indicated: (1) the materials with the greatest hazards characteristics, (2) process operating stations most likely to initiate hazardous conditions, (3) the test program required to examine ignition characteristics and process hazards, and (4) the method of handling the accumulated information from testing and safety analyses.

PubMed

Di Mare, Valerio; Garramone, Gaetano; Rubbiani, Maristella; Moretto, Angelo

2017-02-15

Hazard classification of chemicals can be defined as a logic-mathematical operation aimed at identifying the type and severity of the inherent hazards of a substance or a mixture. The purpose of this study was to evaluate, in 134 safety data sheets (SDSs): i) the hazard classification and ii) its coherence with sections 9 (physical-chemical properties), 11 (toxicological properties) and 12 (ecological properties) of the SDSs. Hazard classification and the information provided in sections 9, 11 and 12 of the SDSs have been evaluated against the criteria provided in annexes VI of the Dangerous Substance Directive, II and III of the Dangerous Preparations Directive, I and VI of the Regulation (EC) n. 1272/2008. Most of the analyzed SDSs of substances (62%) was associated to non-classified chemicals (61.4%), although 19.6% of them should have been classified. By contrast, 59.4% of classified substances (representing 38.6% of analyzed ones) were wrongly classified. Fifty-four %, 54% and 67% of suggested substances hazard classification were in line with sections 9 (physical-chemical properties), 11 (toxicological properties) and 12 (ecological properties). The proportion of hazard classification mistakes in SDS was significant, suggesting the need of more qualified experts to derive classification. The introduction of an ad hoc evaluation team, managed by a single, qualified specialist, could represent a solution to ensure the needed improvement of SDSs quality.

A Review of Hazard Anticipation Training Programs for Young Drivers

PubMed Central

McDonald, Catherine C.; Goodwin, Arthur H.; Pradhan, Anuj K.; Romoser, Matthew R.E.; Williams, Allan F.

2015-01-01

Purpose Poor hazard anticipation skills are a risk factor associated with high motor vehicle crash rates of young drivers. A number of programs have been developed to improve these skills. The purpose of this review was to assess the empirical literature on hazard anticipation training for young drivers. Methods Studies were included if they: 1) included an assessment of hazard anticipation training outcomes; 2) were published between January 1, 1980 and December 31, 2013 in an English language peer-reviewed journal or conference proceeding; and 3) included at least one group that uniquely comprised a cohort of participants <21 years. Nineteen studies met inclusion criteria. Results Studies used a variety of training methods including interactive computer programs, videos, simulation, commentary driving, or a combination of approaches. Training effects were predominantly measured through computer-based testing and driving simulation with eye tracking. Four studies included an on-road evaluation. Most studies evaluated short-term outcomes (immediate or few days). In all studies, young drivers showed improvement in selected hazard anticipation outcomes, but none investigated crash effects. Conclusions Although there is promise in existing programs, future research should include long-term follow up, evaluate crash outcomes, and assess the optimal timing of hazard anticipation training taking into account the age and experience level of young drivers. PMID:26112734

10 CFR 850.21 - Hazard assessment.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Hazard assessment. 850.21 Section 850.21 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.21 Hazard... with the greatest risks of exposure are evaluated first. (b) The responsible employer must ensure that...

30 CFR 19.7 - Protection against explosion hazard.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC CAP LAMPS § 19.7 Protection against explosion hazard. Unless properly designed, electric cap lamps may present two sources of probable explosion hazards..., if the lamp is designed and constructed to prevent the ignition of explosive mixtures of methane and...

30 CFR 19.7 - Protection against explosion hazard.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC CAP LAMPS § 19.7 Protection against explosion hazard. Unless properly designed, electric cap lamps may present two sources of probable explosion hazards..., if the lamp is designed and constructed to prevent the ignition of explosive mixtures of methane and...

30 CFR 19.7 - Protection against explosion hazard.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC CAP LAMPS § 19.7 Protection against explosion hazard. Unless properly designed, electric cap lamps may present two sources of probable explosion hazards..., if the lamp is designed and constructed to prevent the ignition of explosive mixtures of methane and...

30 CFR 19.7 - Protection against explosion hazard.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC CAP LAMPS § 19.7 Protection against explosion hazard. Unless properly designed, electric cap lamps may present two sources of probable explosion hazards..., if the lamp is designed and constructed to prevent the ignition of explosive mixtures of methane and...

24 CFR 35.1330 - Interim controls.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Interim controls. 35.1330 Section... Lead-Paint Hazard Evaluation and Hazard Reduction Activities § 35.1330 Interim controls. Interim controls of lead-based paint hazards identified in a risk assessment shall be conducted in accordance with...

Development and Validation of a Novel Platform-Independent Metastasis Signature in Human Breast Cancer

PubMed Central

Speers, Corey; Liu, Meilan; Wilder-Romans, Kari; Lawrence, Theodore S.; Pierce, Lori J.; Feng, Felix Y.

2015-01-01

Purpose The molecular drivers of metastasis in breast cancer are not well understood. Therefore, we sought to identify the biological processes underlying distant progression and define a prognostic signature for metastatic potential in breast cancer. Experimental design In vivo screening for metastases was performed using Chick Chorioallantoic Membrane assays in 21 preclinical breast cancer models. Expressed genes associated with metastatic potential were identified using high-throughput analysis. Correlations with biological function were determined using the Database for Annotation, Visualization and Integrated Discovery. Results We identified a broad range of metastatic potential that was independent of intrinsic breast cancer subtypes. 146 genes were significantly associated with metastasis progression and were linked to cancer-related biological functions, including cell migration/adhesion, Jak-STAT, TGF-beta, and Wnt signaling. These genes were used to develop a platform-independent gene expression signature (M-Sig), which was trained and subsequently validated on 5 independent cohorts totaling nearly 1800 breast cancer patients with all p-values < 0.005 and hazard ratios ranging from approximately 2.5 to 3. On multivariate analysis accounting for standard clinicopathologic prognostic variables, M-Sig remained the strongest prognostic factor for metastatic progression, with p-values < 0.001 and hazard ratios > 2 in three different cohorts. Conclusion M-Sig is strongly prognostic for metastatic progression, and may provide clinical utility in combination with treatment prediction tools to better guide patient care. In addition, the platform-independent nature of the signature makes it an excellent research tool as it can be directly applied onto existing, and future, datasets. PMID:25974184

Mitigation of EMU Glove Cut Hazard by MMOD Impact Craters on Exposed ISS Handrails

NASA Technical Reports Server (NTRS)

Christiansen, Eric L.; Ryan, Shannon

2009-01-01

Recent cut damages to crewmember extravehicular mobility unit (EMU) gloves during extravehicular activity (EVA) onboard the International Space Station (ISS) has been found to result from contact with sharp edges or pinch points rather than general wear or abrasion. One possible source of cut-hazards are protruding sharp edged crater lips from impact of micrometeoroid and orbital debris (MMOD) particles on external metallic handrails along EVA translation paths. During impact of MMOD particles at hypervelocity an evacuation flow develops behind the shock wave, resulting in the formation of crater lips that can protrude above the target surface. In this study, two methods were evaluated to limit EMU glove cut-hazards due to MMOD impact craters. In the first phase, four flexible overwrap configurations are evaluated: a felt-reusable surface insulation (FRSI), polyurethane polyether foam with beta-cloth cover, double-layer polyurethane polyether foam with beta-cloth cover, and multi-layer beta-cloth with intermediate Dacron netting spacers. These overwraps are suitable for retrofitting ground equipment that has yet to be flown, and are not intended to protect the handrail from impact of MMOD particles, rather to act as a spacer between hazardous impact profiles and crewmember gloves. At the impact conditions considered, all four overwrap configurations evaluated were effective in limiting contact between EMU gloves and impact crater profiles. The multi-layer beta-cloth configuration was the most effective in reducing the height of potentially hazardous profiles in handrail-representative targets. In the second phase of the study, four material alternatives to current aluminum and stainless steel alloys were evaluated: a metal matrix composite, carbon fiber reinforced plastic (CFRP), fiberglass, and a fiber metal laminate. Alternative material handrails are intended to prevent the formation of hazardous damage profiles during MMOD impact and are suitable for flight hardware yet to be constructed. Of the four materials evaluated, only the fiberglass formed a less hazardous damage profile than the baseline metallic target. Although the CFRP laminate did not form any noticeable crater lip, brittle protruding fibers are considered a puncture risk. In parallel with EMU glove redesign efforts, modifications to metallic ISS handrails such as those evaluated in this study provide the means to significantly reduce cut-hazards from MMOD impact craters.

Robots, systems, and methods for hazard evaluation and visualization

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

Nielsen, Curtis W.; Bruemmer, David J.; Walton, Miles C.

A robot includes a hazard sensor, a locomotor, and a system controller. The robot senses a hazard intensity at a location of the robot, moves to a new location in response to the hazard intensity, and autonomously repeats the sensing and moving to determine multiple hazard levels at multiple locations. The robot may also include a communicator to communicate the multiple hazard levels to a remote controller. The remote controller includes a communicator for sending user commands to the robot and receiving the hazard levels from the robot. A graphical user interface displays an environment map of the environment proximatemore » the robot and a scale for indicating a hazard intensity. A hazard indicator corresponds to a robot position in the environment map and graphically indicates the hazard intensity at the robot position relative to the scale.« less

Pollution prevention and the use of low-VOC/HAP coatings at wood furniture manufacturing facilities

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

Marshall, A.M.; Spaight, J.L.; Jones, J.W.

1999-10-01

Midwest Research Institute, under a cooperative agreement with the Air Pollution Prevention and Control Division of the US Environmental Protection Agency`s (EPA`s) National Risk Management Research Laboratory, is conducting a study to identify wood furniture and cabinet manufacturing facilities that have converted to low-volatile organic compound/hazardous air pollutant (VOC/HAP) coatings and to develop case studies for those facilities. This paper discusses the progress of the project and pollution prevention options at wood furniture manufacturing facilities and the regulatory requirements (e.g., the National Emissions Standards for Hazardous Air Pollutants (NESHAP) for Wood Furniture Manufacturing Operations) that these facilities face.

A review on recent progress in observations, and health effects of bioaerosols.

PubMed

Humbal, Charmi; Gautam, Sneha; Trivedi, Ujwalkumar

2018-06-06

Bioaerosol is a particulate mixture of solid and semi-solid matter combined with biotic matter like pollens, microbes and their fragments. The present review stresses on a cumulative understanding of sources, components, quantification and distribution of bioaerosols with respect to size, and its significant impacts on human health. The present review will be instrumental in devising strategies to understand and manage bioaerosols and reducing their human exposure and associated health hazards. The present review aims explore the relationship between particle and associated biological agents responsible for behaviours like dispersal, total potential health hazards and toxicology level during exposure to bioaerosol. Copyright © 2018. Published by Elsevier Ltd.

An assessment of the crash fire hazard of liquid hydrogen fueled aircraft

NASA Technical Reports Server (NTRS)

1982-01-01

The crash fire hazards of liquid hydrogen fueled aircraft relative to those of mission equivalent aircraft fueled either with conventional fuel or with liquefied methane were evaluated. The aircraft evaluated were based on Lockheed Corporation design for 400 passenger, Mach 0.85, 5500 n. mile aircraft. Four crash scenarios were considered ranging from a minor incident causing some loss of fuel system integrity to a catastrophic crash. Major tasks included a review of hazardous properties of the alternate fuels and of historic crash fire data; a comparative hazard evluation for each of the three fuels under four crash scenarios a comprehensive review and analysis and an identification of areas further development work. The conclusion was that the crash fire hazards are not significantly different when compared in general for the three fuels, although some fuels showed minor advantages in one respect or another.

An evaluation of treatment strategies for head and neck cancer in an African American population.

PubMed

Ignacio, D N; Griffin, J J; Daniel, M G; Serlemitsos-Day, M T; Lombardo, F A; Alleyne, T A

2013-07-01

This study evaluated treatment strategies for head and neck cancers in a predominantly African American population. Data were collected utilizing medical records and the tumour registry at the Howard University Hospital. Kaplan-Meier method was used for survival analysis and Cox proportional hazards regression analysis predicted the hazard of death. Analysis revealed that the main treatment strategy was radiation combined with platinum for all stages except stage I. Cetuximab was employed in only 1% of cases. Kaplan-Meier analysis revealed stage II patients had poorer outcome than stage IV while Cox proportional hazard regression analysis (p = 0.4662) showed that stage I had a significantly lower hazard of death than stage IV (HR = 0.314; p = 0.0272). Contributory factors included tobacco and alcohol but body mass index (BMI) was inversely related to hazard of death. There was no difference in survival using any treatment modality for African Americans.