WorldWideScience

Sample records for randomized cumulative survival

  1. Lyapunov exponent of the random frequency oscillator: cumulant expansion approach

    International Nuclear Information System (INIS)

    Anteneodo, C; Vallejos, R O

    2010-01-01

    We consider a one-dimensional harmonic oscillator with a random frequency, focusing on both the standard and the generalized Lyapunov exponents, λ and λ* respectively. We discuss the numerical difficulties that arise in the numerical calculation of λ* in the case of strong intermittency. When the frequency corresponds to a Ornstein-Uhlenbeck process, we compute analytically λ* by using a cumulant expansion including up to the fourth order. Connections with the problem of finding an analytical estimate for the largest Lyapunov exponent of a many-body system with smooth interactions are discussed.

  2. Random survival forests for competing risks

    DEFF Research Database (Denmark)

    Ishwaran, Hemant; Gerds, Thomas A; Kogalur, Udaya B

    2014-01-01

    We introduce a new approach to competing risks using random forests. Our method is fully non-parametric and can be used for selecting event-specific variables and for estimating the cumulative incidence function. We show that the method is highly effective for both prediction and variable selection...

  3. Instrumental variables estimation of exposure effects on a time-to-event endpoint using structural cumulative survival models.

    Science.gov (United States)

    Martinussen, Torben; Vansteelandt, Stijn; Tchetgen Tchetgen, Eric J; Zucker, David M

    2017-12-01

    The use of instrumental variables for estimating the effect of an exposure on an outcome is popular in econometrics, and increasingly so in epidemiology. This increasing popularity may be attributed to the natural occurrence of instrumental variables in observational studies that incorporate elements of randomization, either by design or by nature (e.g., random inheritance of genes). Instrumental variables estimation of exposure effects is well established for continuous outcomes and to some extent for binary outcomes. It is, however, largely lacking for time-to-event outcomes because of complications due to censoring and survivorship bias. In this article, we make a novel proposal under a class of structural cumulative survival models which parameterize time-varying effects of a point exposure directly on the scale of the survival function; these models are essentially equivalent with a semi-parametric variant of the instrumental variables additive hazards model. We propose a class of recursive instrumental variable estimators for these exposure effects, and derive their large sample properties along with inferential tools. We examine the performance of the proposed method in simulation studies and illustrate it in a Mendelian randomization study to evaluate the effect of diabetes on mortality using data from the Health and Retirement Study. We further use the proposed method to investigate potential benefit from breast cancer screening on subsequent breast cancer mortality based on the HIP-study. © 2017, The International Biometric Society.

  4. Expert opinion on laparoscopic surgery for colorectal cancer parallels evidence from a cumulative meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Guillaume Martel

    Full Text Available This study sought to synthesize survival outcomes from trials of laparoscopic and open colorectal cancer surgery, and to determine whether expert acceptance of this technology in the literature has parallel cumulative survival evidence.A systematic review of randomized trials was conducted. The primary outcome was survival, and meta-analysis of time-to-event data was conducted. Expert opinion in the literature (published reviews, guidelines, and textbook chapters on the acceptability of laparoscopic colorectal cancer was graded using a 7-point scale. Pooled survival data were correlated in time with accumulating expert opinion scores.A total of 5,800 citations were screened. Of these, 39 publications pertaining to 23 individual trials were retained. As well, 414 reviews were included (28 guidelines, 30 textbook chapters, 20 systematic reviews, 336 narrative reviews. In total, 5,782 patients were randomized to laparoscopic (n = 3,031 and open (n = 2,751 colorectal surgery. Survival data were presented in 16 publications. Laparoscopic surgery was not inferior to open surgery in terms of overall survival (HR = 0.94, 95% CI 0.80, 1.09. Expert opinion in the literature pertaining to the oncologic acceptability of laparoscopic surgery for colon cancer correlated most closely with the publication of large RCTs in 2002-2004. Although increasingly accepted since 2006, laparoscopic surgery for rectal cancer remained controversial.Laparoscopic surgery for colon cancer is non-inferior to open surgery in terms of overall survival, and has been so since 2004. The majority expert opinion in the literature has considered these two techniques to be equivalent since 2002-2004. Laparoscopic surgery for rectal cancer has been increasingly accepted since 2006, but remains controversial. Knowledge translation efforts in this field appear to have paralleled the accumulation of clinical trial evidence.

  5. Cinacalcet in patients with chronic kidney disease: a cumulative meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Suetonia C Palmer

    Full Text Available BACKGROUND: Calcimimetic agents lower serum parathyroid hormone levels in people with chronic kidney disease (CKD, but treatment effects on patient-relevant outcomes are uncertain. We conducted a systematic review and meta-analysis to summarize the benefits and harms of calcimimetic therapy in adults with CKD and used cumulative meta-analysis to identify how evidence for calcimimetic treatment has developed in this clinical setting. METHODS AND FINDINGS: Cochrane and Embase databases (through February 7, 2013 were electronically searched to identify randomized trials evaluating effects of calcimimetic therapy on mortality and adverse events in adults with CKD. Two independent reviewers identified trials, extracted data, and assessed risk of bias. Eighteen trials comprising 7,446 participants compared cinacalcet plus conventional therapy with placebo or no treatment plus conventional therapy in adults with CKD. In moderate- to high-quality evidence (based on Grading of Recommendations Assessment, Development, and Evaluation criteria in adults with CKD stage 5D (dialysis, cinacalcet had little or no effect on all-cause mortality (relative risk, 0.97 [95% confidence interval, 0.89-1.05], had imprecise effect on cardiovascular mortality (0.67 [0.16-2.87], and prevented parathyroidectomy (0.49 [0.40-0.59] and hypercalcemia (0.23 [0.05-0.97], but increased hypocalcemia (6.98 [5.10-9.53], nausea (2.02 [1.45-2.81], and vomiting (1.97 [1.73-2.24]. Data for clinical outcomes were sparse in adults with CKD stages 3-5. On average, treating 1,000 people with CKD stage 5D for 1 y had no effect on survival and prevented about three patients from experiencing parathyroidectomy, whilst 60 experienced hypocalcemia and 150 experienced nausea. Analyses were limited by insufficient data in CKD stages 3-5 and kidney transplant recipients. CONCLUSIONS: Cinacalcet reduces the need for parathyroidectomy in patients with CKD stage 5D, but does not appear to improve all

  6. Killing (absorption) versus survival in random motion

    Science.gov (United States)

    Garbaczewski, Piotr

    2017-09-01

    We address diffusion processes in a bounded domain, while focusing on somewhat unexplored affinities between the presence of absorbing and/or inaccessible boundaries. For the Brownian motion (Lévy-stable cases are briefly mentioned) model-independent features are established of the dynamical law that underlies the short-time behavior of these random paths, whose overall lifetime is predefined to be long. As a by-product, the limiting regime of a permanent trapping in a domain is obtained. We demonstrate that the adopted conditioning method, involving the so-called Bernstein transition function, works properly also in an unbounded domain, for stochastic processes with killing (Feynman-Kac kernels play the role of transition densities), provided the spectrum of the related semigroup operator is discrete. The method is shown to be useful in the case, when the spectrum of the generator goes down to zero and no isolated minimal (ground state) eigenvalue is in existence, like in the problem of the long-term survival on a half-line with a sink at origin.

  7. Kaplan-Meier survival analysis overestimates cumulative incidence of health-related events in competing risk settings: a meta-analysis.

    Science.gov (United States)

    Lacny, Sarah; Wilson, Todd; Clement, Fiona; Roberts, Derek J; Faris, Peter; Ghali, William A; Marshall, Deborah A

    2018-01-01

    Kaplan-Meier survival analysis overestimates cumulative incidence in competing risks (CRs) settings. The extent of overestimation (or its clinical significance) has been questioned, and CRs methods are infrequently used. This meta-analysis compares the Kaplan-Meier method to the cumulative incidence function (CIF), a CRs method. We searched MEDLINE, EMBASE, BIOSIS Previews, Web of Science (1992-2016), and article bibliographies for studies estimating cumulative incidence using the Kaplan-Meier method and CIF. For studies with sufficient data, we calculated pooled risk ratios (RRs) comparing Kaplan-Meier and CIF estimates using DerSimonian and Laird random effects models. We performed stratified meta-analyses by clinical area, rate of CRs (CRs/events of interest), and follow-up time. Of 2,192 identified abstracts, we included 77 studies in the systematic review and meta-analyzed 55. The pooled RR demonstrated the Kaplan-Meier estimate was 1.41 [95% confidence interval (CI): 1.36, 1.47] times higher than the CIF. Overestimation was highest among studies with high rates of CRs [RR = 2.36 (95% CI: 1.79, 3.12)], studies related to hepatology [RR = 2.60 (95% CI: 2.12, 3.19)], and obstetrics and gynecology [RR = 1.84 (95% CI: 1.52, 2.23)]. The Kaplan-Meier method overestimated the cumulative incidence across 10 clinical areas. Using CRs methods will ensure accurate results inform clinical and policy decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE).

    Science.gov (United States)

    Bhakta, Nickhill; Liu, Qi; Ness, Kirsten K; Baassiri, Malek; Eissa, Hesham; Yeo, Frederick; Chemaitilly, Wassim; Ehrhardt, Matthew J; Bass, Johnnie; Bishop, Michael W; Shelton, Kyla; Lu, Lu; Huang, Sujuan; Li, Zhenghong; Caron, Eric; Lanctot, Jennifer; Howell, Carrie; Folse, Timothy; Joshi, Vijaya; Green, Daniel M; Mulrooney, Daniel A; Armstrong, Gregory T; Krull, Kevin R; Brinkman, Tara M; Khan, Raja B; Srivastava, Deo K; Hudson, Melissa M; Yasui, Yutaka; Robison, Leslie L

    2017-12-09

    Survivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity of survivors, however, has not been described. We aimed to describe the cumulative burden of curative cancer therapy in a clinically assessed ageing population of long-term survivors of childhood cancer. The St Jude Lifetime Cohort Study (SJLIFE) retrospectively collected data on CHCs in all patients treated for childhood cancer at the St Jude Children's Research Hospital who survived 10 years or longer from initial diagnosis and were 18 years or older as of June 30, 2015. Age-matched and sex-frequency-matched community controls were used for comparison. 21 treatment exposure variables were included in the analysis, with data abstracted from medical records. 168 CHCs for all participants were graded for severity using a modified Common Terminology Criteria of Adverse Events. Multiple imputation with predictive mean matching was used for missing occurrences and grades of CHCs in the survivors who were not clinically evaluable. Mean cumulative count was used for descriptive cumulative burden analysis and marked-point-process regression was used for inferential cumulative burden analysis. Of 5522 patients treated for childhood cancer at St Jude Children's Research Hospital who had complete records, survived 10 years or longer, and were 18 years or older at time of study, 3010 (54·5%) were alive, had enrolled, and had had prospective clinical assessment. 2512 (45·5%) of the 5522 patients were not clinically evaluable. The cumulative incidence of CHCs at age 50 years was 99·9% (95% CI 99·9-99·9) for grade 1-5 CHCs and 96·0% (95% CI 95·3-96·8%) for grade 3-5 CHCs. By age 50 years, a survivor had experienced, on average, 17·1 (95% CI 16·2-18·1) CHCs of any grade, of which 4·7 (4·6-4·9) were CHCs of grade 3-5. The cumulative burden in matched community controls of grade 1-5 CHCs was 9·2 (95% CI 7·9-10·6; pgrade 3-5 CHCs was 2·3 (1

  9. Long-term cumulative survival and mechanical complications of single-tooth Ankylos Implants: focus on the abutment neck fractures.

    Science.gov (United States)

    Shim, Hye Won; Yang, Byoung-Eun

    2015-12-01

    To evaluate the cumulative survival rate (CSR) and mechanical complications of single-tooth Ankylos® implants. This was a retrospective clinical study that analyzed 450 single Ankylos® implants installed in 275 patients between December 2005 and December 2012. The main outcomes were survival results CSR and implant failure) and mechanical complications (screw loosening, fracture, and cumulative fracture rate [CFR]). The main outcomes were analyzed according to age, sex, implant length or diameter, bone graft, arch, and position. The 8-year CSR was 96.9%. Thirteen (2.9%) implants failed because of early osseointegration failure in 3, marginal bone loss in 6, and abutment fracture in 4. Screw loosening occurred in 10 implants (2.2%), and 10 abutment fractures occurred. All abutment fractures were located in the neck, and concurrent screw fractures were observed. The CSR and rate of screw loosening did not differ significantly according to factors. The CFR was higher in middle-aged patients (5.3% vs 0.0% in younger and older patients); for teeth in a molar position (5.8% vs 0.0% for premolar or 1.1% for anterior position); and for larger-diameter implants (4.5% for 4.5 mm and 6.7% for 5.5 mm diameter vs 0.5% for 3.5 mm diameter) (all Pabutment fractures (2.2%) were observed and some fractures resulted in implant failures. Middle-aged patients, the molar position, and a large implant diameter were associated with a high incidence of abutment fracture.

  10. Prognostic Factors for Survival in Patients with Gastric Cancer using a Random Survival Forest

    Science.gov (United States)

    Adham, Davoud; Abbasgholizadeh, Nategh; Abazari, Malek

    2017-01-01

    Background: Gastric cancer is the fifth most common cancer and the third top cause of cancer related death with about 1 million new cases and 700,000 deaths in 2012. The aim of this investigation was to identify important factors for outcome using a random survival forest (RSF) approach. Materials and Methods: Data were collected from 128 gastric cancer patients through a historical cohort study in Hamedan-Iran from 2007 to 2013. The event under consideration was death due to gastric cancer. The random survival forest model in R software was applied to determine the key factors affecting survival. Four split criteria were used to determine importance of the variables in the model including log-rank, conversation?? of events, log-rank score, and randomization. Efficiency of the model was confirmed in terms of Harrell’s concordance index. Results: The mean age of diagnosis was 63 ±12.57 and mean and median survival times were 15.2 (95%CI: 13.3, 17.0) and 12.3 (95%CI: 11.0, 13.4) months, respectively. The one-year, two-year, and three-year rates for survival were 51%, 13%, and 5%, respectively. Each RSF approach showed a slightly different ranking order. Very important covariates in nearly all the 4 RSF approaches were metastatic status, age at diagnosis and tumor size. The performance of each RSF approach was in the range of 0.29-0.32 and the best error rate was obtained by the log-rank splitting rule; second, third, and fourth ranks were log-rank score, conservation of events, and the random splitting rule, respectively. Conclusion: Low survival rate of gastric cancer patients is an indication of absence of a screening program for early diagnosis of the disease. Timely diagnosis in early phases increases survival and decreases mortality. Creative Commons Attribution License

  11. Retrospective comparative ten-year study of cumulative survival rates of remaining teeth in large edentulism treated with implant-supported fixed partial dentures or removable partial dentures.

    Science.gov (United States)

    Yamazaki, Seiya; Arakawa, Hikaru; Maekawa, Kenji; Hara, Emilio Satoshi; Noda, Kinji; Minakuchi, Hajime; Sonoyama, Wataru; Matsuka, Yoshizo; Kuboki, Takuo

    2013-07-01

    This study aimed to compare the survival rates of remaining teeth between implant-supported fixed dentures (IFDs) and removable partial dentures (RPDs) in patients with large edentulous cases. The second goal was to assess the risk factors for remaining tooth loss. The study subjects were selected among those who received prosthodontic treatment at Okayama University Dental Hospital for their edentulous space exceeding at least four continuous missing teeth. Twenty-one patients were included in the IFD group and 82 patients were included in the RPD group. Survival rates of remaining teeth were calculated in three subcategories: (1) whole remaining teeth, (2) adjacent teeth to intended edentulous space, and (3) opposing teeth to intended edentulous space. The ten-year cumulative survival rate of the whole remaining teeth was significantly higher in the IFD group (40.0%) than in the RPD group (24.4%). On the other hand, there was no significant difference between two groups in the survival rate of teeth adjacent or opposing to intended edentulous space. A Cox proportional hazard analysis revealed that RPD restoration and gender (male) were the significant risk factors for remaining tooth loss (whole remaining teeth). These results suggest that IFD treatment can reduce the incidence of remaining tooth loss in large edentulous cases. Copyright © 2013 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  12. Association between B vitamins supplementation and risk of cardiovascular outcomes: a cumulative meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Chi Zhang

    Full Text Available BACKGROUND: Observational studies suggest that B vitamin supplementation reduces cardiovascular risk in adults, but this association remains controversial. This study aimed to summarize the evidence from randomized controlled trials (RCTs investigating B vitamin supplementation for the primary or secondary prevention of major adverse cardiovascular outcomes and to perform a cumulative meta-analysis to determine the evidence base. METHODOLOGY AND PRINCIPAL FINDINGS: In April 2013, we searched PubMed, Embase, and the Cochrane Library to identify relevant RCTs. We included RCTs investigating the effect of B vitamin supplementation on cardiovascular outcome. Relative risk (RR was used to measure the effect using a random-effect model. Statistical heterogeneity scores were assessed using the Q statistic. We included data on 57,952 individuals from 24 RCTs: 12 primary prevention trials and 12 secondary prevention trials. In 23 of these trials, 10,917 major adverse cardiovascular events (MACE occurred; in 20 trials, 7,203 deaths occurred; in 15 trials, 3,422 cardiac deaths occurred; in 19 trials, 3,623 myocardial infarctions (MI occurred; and in 18 trials, 2,465 strokes occurred. B vitamin supplementation had little or no effect on the incidence of MACE (RR, 0.98; 95% confidence interval [CI]: 0.93-1.03; P = 0.37, total mortality (RR, 1.01; 95% CI: 0.97-1.05; P = 0.77, cardiac death (RR, 0.96; 95% CI: 0.90-1.02; P = 0.21, MI (RR, 0.99; 95% CI: 0.93-1.06; P = 0.82, or stroke (RR, 0.94; 95% CI: 0.85-1.03; P = 0.18. CONCLUSION/SIGNIFICANCE: B vitamin supplementation, when used for primary or secondary prevention, is not associated with a reduction in MACE, total mortality, cardiac death, MI, or stroke.

  13. Data-Driven Lead-Acid Battery Prognostics Using Random Survival Forests

    Science.gov (United States)

    2014-10-02

    Kogalur, Blackstone , & Lauer, 2008; Ishwaran & Kogalur, 2010). Random survival forest is a sur- vival analysis extension of Random Forests (Breiman, 2001...Statistics & probability letters, 80(13), 1056–1064. Ishwaran, H., Kogalur, U. B., Blackstone , E. H., & Lauer, M. S. (2008). Random survival forests. The...and environment for sta- tistical computing [Computer software manual]. Vienna, Austria. Retrieved from http://www.R-project .org/ Wager, S., Hastie, T

  14. Impact on Medical Cost, Cumulative Survival, and Cost-Effectiveness of Adding Rituximab to First-Line Chemotherapy for Follicular Lymphoma in Elderly Patients: An Observational Cohort Study Based on SEER-Medicare

    International Nuclear Information System (INIS)

    Griffiths, R. I.; Gleeson, M. L.; Danese, M. D.; Griffiths, R. I.; Mikhael, J.

    2012-01-01

    Rituximab improves survival in follicular lymphoma (FL), but is considerably more expensive than conventional chemotherapy. We estimated the total direct medical costs, cumulative survival, and cost-effectiveness of adding rituximab to first-line chemotherapy for FL, based on a single source of data representing routine practice in the elderly. Using surveillance, epidemiology, and end results (SEER) registry data plus Medicare claims, we identified 1,117 FL patients who received first-line CHOP (cyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P)) or CVP +/− rituximab. Multivariate regression was used to estimate adjusted cumulative cost and survival differences between the two groups over four years after beginning treatment. The median age was 73 years (minimum 66 years), 56% had stage III-IV disease, and 67% received rituximab. Adding rituximab to first-line chemotherapy was associated with higher adjusted incremental total cost ($18,695; 95% Confidence Interval (CI) $9,302-$28,643) and longer adjusted cumulative survival (0.18 years; 95% CI 0.10-0.27) over four years of followup. The expected cost-effectiveness was $102,142 (95% CI $34,531-296,337) per life-year gained. In routine clinical practice, adding rituximab to first-line chemotherapy for elderly patients with FL results in higher direct medical costs to Medicare and longer cumulative survival after four years.

  15. Impact on Medical Cost, Cumulative Survival, and Cost-Effectiveness of Adding Rituximab to First-Line Chemotherapy for Follicular Lymphoma in Elderly Patients: An Observational Cohort Study Based on SEER-Medicare

    Directory of Open Access Journals (Sweden)

    Robert I. Griffiths

    2012-01-01

    Full Text Available Rituximab improves survival in follicular lymphoma (FL, but is considerably more expensive than conventional chemotherapy. We estimated the total direct medical costs, cumulative survival, and cost-effectiveness of adding rituximab to first-line chemotherapy for FL, based on a single source of data representing routine practice in the elderly. Using surveillance, epidemiology, and end results (SEER registry data plus Medicare claims, we identified 1,117 FL patients who received first-line CHOP (cyclophosphamide (C, doxorubicin, vincristine (V, and prednisone (P or CVP +/− rituximab. Multivariate regression was used to estimate adjusted cumulative cost and survival differences between the two groups over four years after beginning treatment. The median age was 73 years (minimum 66 years, 56% had stage III-IV disease, and 67% received rituximab. Adding rituximab to first-line chemotherapy was associated with higher adjusted incremental total cost ($18,695; 95% Confidence Interval (CI $9,302–$28,643 and longer adjusted cumulative survival (0.18 years; 95% CI 0.10–0.27 over four years of followup. The expected cost-effectiveness was $102,142 (95% CI $34,531–296,337 per life-year gained. In routine clinical practice, adding rituximab to first-line chemotherapy for elderly patients with FL results in higher direct medical costs to Medicare and longer cumulative survival after four years.

  16. Survival after relapse in patients with endometrial cancer : results from a randomized trial

    NARCIS (Netherlands)

    Creutzberg, CL; van Putten, WLJ; Koper, PC; Lybeert, MLM; Jobsen, JJ; Warlam-Rodenhuis, CC; De Winter, KAJ; Lutgens, LCHW; van den Bergh, ACM; van der Steen-Banasik, E; Beerman, H; van Lent, M

    Objective. The aim of this study was to determine the rates of local control and survival after relapse in patients with stage I endometrial cancer treated in the multicenter randomized PORTEC trial. Methods, The PORTEC trial included 715 patients with stage I endometrial cancer, either grade I or 2

  17. Survival behavior in the cyclic Lotka-Volterra model with a randomly switching reaction rate

    Science.gov (United States)

    West, Robert; Mobilia, Mauro; Rucklidge, Alastair M.

    2018-02-01

    We study the influence of a randomly switching reproduction-predation rate on the survival behavior of the nonspatial cyclic Lotka-Volterra model, also known as the zero-sum rock-paper-scissors game, used to metaphorically describe the cyclic competition between three species. In large and finite populations, demographic fluctuations (internal noise) drive two species to extinction in a finite time, while the species with the smallest reproduction-predation rate is the most likely to be the surviving one (law of the weakest). Here we model environmental (external) noise by assuming that the reproduction-predation rate of the strongest species (the fastest to reproduce and predate) in a given static environment randomly switches between two values corresponding to more and less favorable external conditions. We study the joint effect of environmental and demographic noise on the species survival probabilities and on the mean extinction time. In particular, we investigate whether the survival probabilities follow the law of the weakest and analyze their dependence on the external noise intensity and switching rate. Remarkably, when, on average, there is a finite number of switches prior to extinction, the survival probability of the predator of the species whose reaction rate switches typically varies nonmonotonically with the external noise intensity (with optimal survival about a critical noise strength). We also outline the relationship with the case where all reaction rates switch on markedly different time scales.

  18. Survival behavior in the cyclic Lotka-Volterra model with a randomly switching reaction rate.

    Science.gov (United States)

    West, Robert; Mobilia, Mauro; Rucklidge, Alastair M

    2018-02-01

    We study the influence of a randomly switching reproduction-predation rate on the survival behavior of the nonspatial cyclic Lotka-Volterra model, also known as the zero-sum rock-paper-scissors game, used to metaphorically describe the cyclic competition between three species. In large and finite populations, demographic fluctuations (internal noise) drive two species to extinction in a finite time, while the species with the smallest reproduction-predation rate is the most likely to be the surviving one (law of the weakest). Here we model environmental (external) noise by assuming that the reproduction-predation rate of the strongest species (the fastest to reproduce and predate) in a given static environment randomly switches between two values corresponding to more and less favorable external conditions. We study the joint effect of environmental and demographic noise on the species survival probabilities and on the mean extinction time. In particular, we investigate whether the survival probabilities follow the law of the weakest and analyze their dependence on the external noise intensity and switching rate. Remarkably, when, on average, there is a finite number of switches prior to extinction, the survival probability of the predator of the species whose reaction rate switches typically varies nonmonotonically with the external noise intensity (with optimal survival about a critical noise strength). We also outline the relationship with the case where all reaction rates switch on markedly different time scales.

  19. Prediction of 90Y Radioembolization Outcome from Pretherapeutic Factors with Random Survival Forests.

    Science.gov (United States)

    Ingrisch, Michael; Schöppe, Franziska; Paprottka, Karolin; Fabritius, Matthias; Strobl, Frederik F; De Toni, Enrico N; Ilhan, Harun; Todica, Andrei; Michl, Marlies; Paprottka, Philipp Marius

    2018-05-01

    Our objective was to predict the outcome of 90 Y radioembolization in patients with intrahepatic tumors from pretherapeutic baseline parameters and to identify predictive variables using a machine-learning approach based on random survival forests. Methods: In this retrospective study, 366 patients with primary ( n = 92) or secondary ( n = 274) liver tumors who had received 90 Y radioembolization were analyzed. A random survival forest was trained to predict individual risk from baseline values of cholinesterase, bilirubin, type of primary tumor, age at radioembolization, hepatic tumor burden, presence of extrahepatic disease, and sex. The predictive importance of each baseline parameter was determined using the minimal-depth concept, and the partial dependency of predicted risk on the continuous variables bilirubin level and cholinesterase level was determined. Results: Median overall survival was 11.4 mo (95% confidence interval, 9.7-14.2 mo), with 228 deaths occurring during the observation period. The random-survival-forest analysis identified baseline cholinesterase and bilirubin as the most important variables (forest-averaged lowest minimal depth, 1.2 and 1.5, respectively), followed by the type of primary tumor (1.7), age (2.4), tumor burden (2.8), and presence of extrahepatic disease (3.5). Sex had the highest forest-averaged minimal depth (5.5), indicating little predictive value. Baseline bilirubin levels above 1.5 mg/dL were associated with a steep increase in predicted mortality. Similarly, cholinesterase levels below 7.5 U predicted a strong increase in mortality. The trained random survival forest achieved a concordance index of 0.657, with an SE of 0.02, comparable to the concordance index of 0.652 and SE of 0.02 for a previously published Cox proportional hazards model. Conclusion: Random survival forests are a simple and straightforward machine-learning approach for prediction of overall survival. The predictive performance of the trained model

  20. Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial.

    Science.gov (United States)

    Eeles, Rosalind A; Morden, James P; Gore, Martin; Mansi, Janine; Glees, John; Wenczl, Miklos; Williams, Christopher; Kitchener, Henry; Osborne, Richard; Guthrie, David; Harper, Peter; Bliss, Judith M

    2015-12-10

    To assess the effects of adjuvant hormone therapy (AHT) on survival and disease outcome in women with epithelial ovarian cancer. Participants were premenopausal and postmenopausal women who had been diagnosed with epithelial ovarian cancer (any International Federation of Gynecology and Obstetrics stage) 9 or fewer months previously. Ineligible patients included those with deliberately preserved ovarian function, with a history of a hormone-dependent malignancy, or with any contraindications to hormone-replacement therapy. Patients were centrally randomly assigned in a 1:1 ratio to either AHT for 5 years after random assignment or no AHT (control). Main outcome measures were overall survival (OS), defined as time from random assignment to death (any cause), and relapse-free survival, defined as time from random assignment to relapse or death (any cause). Patients who continued, alive and relapse free, were censored at their last known follow-up. A total of 150 patients (n = 75, AHT; n = 75, control) were randomly assigned from 1990 to 1995 from 19 centers in the United Kingdom, Spain, and Hungary; all patients were included in intention-to-treat analyses. The median follow-up in alive patients is currently 19.1 years. Of the 75 patients with AHT, 53 (71%) have died compared with 68 (91%) of 75 patients in the control group. OS was significantly improved in patients who were receiving AHT (hazard ratio, 0.63; 95% CI, 0.44 to 0.90; P = .011). A similar effect was seen for relapse-free survival (hazard ratio, 0.67; 95% CI, 0.47 to 0.97; P = .032). Effects remained after adjustment for known prognostic factors. These results show that women who have severe menopausal symptoms after ovarian cancer treatment can safely take hormone-replacement therapy, and this may, in fact, infer benefits in terms of OS in addition to known advantages in terms of quality of life. © 2015 by American Society of Clinical Oncology.

  1. Cumulative Intracranial Tumor Volume Augments the Prognostic Value of Diagnosis-Specific Graded Prognostic Assessment Model for Survival in Patients with Melanoma Cerebral Metastases

    DEFF Research Database (Denmark)

    Hirshman, Brian R; Wilson, Bayard R; Ali, Mir Amaan

    2018-01-01

    BACKGROUND: The diagnosis-specific graded prognostic assessment scale (ds-GPA) for patients with melanoma brain metastasis (BM) utilizes only 2 key prognostic variables: Karnofsky performance status and the number of intracranial metastases. We wished to determine whether inclusion of cumulative ...

  2. Comparison of the effect of glycerol and triamcinolone acetonide on cumulative skin irritation in a randomized trial

    DEFF Research Database (Denmark)

    Andersen, Flemming; Hedegaard, Kathryn; Petersen, Thomas Kongstad

    2007-01-01

    BACKGROUND: So-called anti-irritants are added to cosmetic formulations because of their alleged beneficial effect on irritated skin. Documentation for these claims is often limited. However, glycerol has shown anti-irritant properties in experimentally induced irritation from sodium lauryl sulfate...... volunteers. METHODS: Irritation was induced by 3 daily arm washes for a week with 10% sodium lauryl sulfate on one arm and 30% NON on the other. To maintain irritation, for the next 12 days volunteers washed their arms twice daily with the irritants. Treatments were applied immediately after washing....... The treatments (including vehicle and no treatment) were randomized to sites using a Latin square design. The reactions were evaluated clinically and instrumentally. LIMITATIONS: Study was designed to only detect potent anti-irritants. CONCLUSION: Glycerol reduced the irritant effect of both sodium lauryl...

  3. Cost-effectiveness of a mild compared with a standard strategy for IVF: a randomized comparison using cumulative term live birth as the primary endpoint.

    Science.gov (United States)

    Polinder, S; Heijnen, E M E W; Macklon, N S; Habbema, J D F; Fauser, B J C M; Eijkemans, M J C

    2008-02-01

    BACKGROUND Conventional ovarian stimulation and the transfer of two embryos in IVF exhibits an inherent high probability of multiple pregnancies, resulting in high costs. We evaluated the cost-effectiveness of a mild compared with a conventional strategy for IVF. METHODS Four hundred and four patients were randomly assigned to undergo either mild ovarian stimulation/GnRH antagonist co-treatment combined with single embryo transfer, or standard stimulation/GnRH agonist long protocol and the transfer of two embryos. The main outcome measures are total costs of treatment within a 12 months period after randomization, and the relationship between total costs and proportion of cumulative pregnancies resulting in term live birth within 1 year of randomization. RESULTS Despite a significantly increased average number of IVF cycles (2.3 versus 1.7; P costs over a 12-month period (8333 versus euro10 745; P = 0.006) were observed using the mild strategy. This was mainly due to higher costs of the obstetric and post-natal period for the standard strategy, related to multiple pregnancies. The costs per pregnancy leading to term live birth were euro19 156 in the mild strategy and euro24 038 in the standard. The incremental cost-effectiveness ratio of the standard strategy compared with the mild strategy was euro185 000 per extra pregnancy leading to term live birth. CONCLUSIONS Despite an increased mean number of IVF cycles within 1 year, from an economic perspective, the mild treatment strategy is more advantageous per term live birth. It is unlikely, over a wide range of society's willingness-to-pay, that the standard treatment strategy is cost-effective, compared with the mild strategy.

  4. Risk Prediction of One-Year Mortality in Patients with Cardiac Arrhythmias Using Random Survival Forest

    Directory of Open Access Journals (Sweden)

    Fen Miao

    2015-01-01

    Full Text Available Existing models for predicting mortality based on traditional Cox proportional hazard approach (CPH often have low prediction accuracy. This paper aims to develop a clinical risk model with good accuracy for predicting 1-year mortality in cardiac arrhythmias patients using random survival forest (RSF, a robust approach for survival analysis. 10,488 cardiac arrhythmias patients available in the public MIMIC II clinical database were investigated, with 3,452 deaths occurring within 1-year followups. Forty risk factors including demographics and clinical and laboratory information and antiarrhythmic agents were analyzed as potential predictors of all-cause mortality. RSF was adopted to build a comprehensive survival model and a simplified risk model composed of 14 top risk factors. The built comprehensive model achieved a prediction accuracy of 0.81 measured by c-statistic with 10-fold cross validation. The simplified risk model also achieved a good accuracy of 0.799. Both results outperformed traditional CPH (which achieved a c-statistic of 0.733 for the comprehensive model and 0.718 for the simplified model. Moreover, various factors are observed to have nonlinear impact on cardiac arrhythmias prognosis. As a result, RSF based model which took nonlinearity into account significantly outperformed traditional Cox proportional hazard model and has great potential to be a more effective approach for survival analysis.

  5. The adverse effect of selective cyclooxygenase-2 inhibitor on random skin flap survival in rats.

    Directory of Open Access Journals (Sweden)

    Haiyong Ren

    Full Text Available BACKGROUND: Cyclooxygenase-2(COX-2 inhibitors provide desired analgesic effects after injury or surgery, but evidences suggested they also attenuate wound healing. The study is to investigate the effect of COX-2 inhibitor on random skin flap survival. METHODS: The McFarlane flap model was established in 40 rats and evaluated within two groups, each group gave the same volume of Parecoxib and saline injection for 7 days. The necrotic area of the flap was measured, the specimens of the flap were stained with haematoxylin-eosin(HE for histologic analysis. Immunohistochemical staining was performed to analyse the level of VEGF and COX-2 . RESULTS: 7 days after operation, the flap necrotic area ratio in study group (66.65 ± 2.81% was significantly enlarged than that of the control group(48.81 ± 2.33%(P <0.01. Histological analysis demonstrated angiogenesis with mean vessel density per mm(2 being lower in study group (15.4 ± 4.4 than in control group (27.2 ± 4.1 (P <0.05. To evaluate the expression of COX-2 and VEGF protein in the intermediate area II in the two groups by immunohistochemistry test .The expression of COX-2 in study group was (1022.45 ± 153.1, and in control group was (2638.05 ± 132.2 (P <0.01. The expression of VEGF in the study and control groups were (2779.45 ± 472.0 vs (4938.05 ± 123.6(P <0.01.In the COX-2 inhibitor group, the expressions of COX-2 and VEGF protein were remarkably down-regulated as compared with the control group. CONCLUSION: Selective COX-2 inhibitor had adverse effect on random skin flap survival. Suppression of neovascularization induced by low level of VEGF was supposed to be the biological mechanism.

  6. Effect of botulinum toxin A and nitroglycerin on random skin flap survival in rats.

    Science.gov (United States)

    Ghanbarzadeh, Kourosh; Tabatabaie, Omid Reza; Salehifar, Ebrahim; Amanlou, Massoud; Khorasani, Ghasemali

    2016-01-01

    A suitable pharmacological substitute for the well-established surgical delay technique for random skin flaps to increase viability has been elusive. To evaluate the effects of nitroglycerin and botulinum toxin type A on random flap survival in a rat model. The present controlled experimental study was performed in the four groups of rats. One week after intervention in each group, the flap was raised and kept in situ, and flap necrosis was evaluated through follow-up. Group 1 received intradermal botulinum toxin type A (BTX-A) and topical nitroglycerin 2%; group 2 received BTX-A and topical Vaseline (Unilever, USA); group 3 received topical nitroglycerin and intradermal normal saline; and group 4 received topical Vaseline and intradermal normal saline. BTX-A reduced the area of necrosis compared with control (24% versus 56% respectively; P<0.001). Nitroglycerin application was associated with a trend toward improved flap viability (42% versus 56%; P=0.059). The combination of topical nitroglycerin and BTX-A, compared with Vaseline and BTX-A, was associated with decreased flap necrosis (16.1% versus 24%, respectively), although it was not statistically significant (P=0.45). BTX-A was effective in reducing distal flap necrosis. The effect of BTX-A was significantly more pronounced than nitroglycerin ointment.

  7. Manuscripts as Evidence for the use of Classics in Education, c. 800–1200: Estimating the Randomness of Survival

    Directory of Open Access Journals (Sweden)

    Jaakko Tahkokallio

    2017-06-01

    Full Text Available Are the surviving copies of schooltexts representative of what was popularly used in schools in the medieval period? In other words, was the survival of these manuscripts a random or selective process? To approach this question, this article presents a series of comparisons between the numbers of manuscripts of different schooltexts. It demonstrates that the most popular schooltexts all survive in very similar numbers from each century, and that the typical number of copies varies from one century to another. The easiest explanation for such a survival pattern is to assume that the texts were produced in equal numbers and passed through a relatively random filter of losses. The article seeks to test this intuitive explanation by using a simple probability mathematical experiment. In addition, the article analyses how the numbers of surviving manuscripts relate to entries in medieval book lists and medieval library catalogues. This examination supports the interpretation that the survival of schooltexts was a relatively random process. In addition, comparison between medieval book lists and extant manuscripts advocates caution in using the book lists as evidence for the popularity of texts in the medieval centuries. Even though the catalogues provide snapshots of specific historical situations, this paper concludes that the mass of extant books is more likely to give us a realistic picture of the contemporary popularity of texts.

  8. Effect of Electroacupuncture at The Zusanli Point (Stomach-36) on Dorsal Random Pattern Skin Flap Survival in a Rat Model.

    Science.gov (United States)

    Wang, Li-Ren; Cai, Le-Yi; Lin, Ding-Sheng; Cao, Bin; Li, Zhi-Jie

    2017-10-01

    Random skin flaps are commonly used for wound repair and reconstruction. Electroacupuncture at The Zusanli point could enhance microcirculation and blood perfusion in random skin flaps. To determine whether electroacupuncture at The Zusanli point can improve the survival of random skin flaps in a rat model. Thirty-six male Sprague Dawley rats were randomly divided into 3 groups: control group (no electroacupuncture), Group A (electroacupuncture at a nonacupoint near The Zusanli point), and Group B (electroacupuncture at The Zusanli point). McFarlane flaps were established. On postoperative Day 2, malondialdehyde (MDA) and superoxide dismutase were detected. The flap survival rate was evaluated, inflammation was examined in hematoxylin and eosin-stained slices, and the expression of vascular endothelial growth factor (VEGF) was measured immunohistochemically on Day 7. The mean survival area of the flaps in Group B was significantly larger than that in the control group and Group A. Superoxide dismutase activity and VEGF expression level were significantly higher in Group B than those in the control group and Group A, whereas MDA and inflammation levels in Group B were significantly lower than those in the other 2 groups. Electroacupuncture at The Zusanli point can effectively improve the random flap survival.

  9. Survival in Malnourished Older Patients Receiving Post-Discharge Nutritional Support; Long-Term Results of a Randomized Controlled Trial.

    Science.gov (United States)

    Neelemaat, F; van Keeken, S; Langius, J A E; de van der Schueren, M A E; Thijs, A; Bosmans, J E

    2017-01-01

    Previous analyses have shown that a post-discharge individualized nutritional intervention had positive effects on body weight, lean body mass, functional limitations and fall incidents in malnourished older patients. However, the impact of this intervention on survival has not yet been studied. The objective of this randomized controlled study was to examine the effect of a post-discharge individualized nutritional intervention on survival in malnourished older patients. Malnourished older patients, aged ≥ 60 years, were randomized during hospitalization to a three-months post-discharge nutritional intervention group (protein and energy enriched diet, oral nutritional supplements, vitamin D3/calcium supplement and telephone counseling by a dietitian) or to a usual care regimen (control group). Survival data were collected 4 years after enrollment. Survival analyses were performed using intention-to-treat analysis by Log-rank tests and Cox regression adjusted for confounders. The study population consisted of 94 men (45%) and 116 women with a mean age of 74.5 (SD 9.5) years. There were no statistically significant differences in baseline characteristics. Survival data was available in 208 out of 210 patients. After 1 and 4 years of follow-up, survival rates were respectively 66% and 29% in the intervention group (n=104) and 73% and 30% in the control group (n=104). There were no statistically significant differences in survival between the two groups 1 year (HR= 0.933, 95% CI=0.675-1.289) and 4 years after enrollment (HR=0.928, 95% CI=0.671-1.283). The current study failed to show an effect of a three-months post-discharge multi-component nutritional intervention in malnourished older patients on long-term survival, despite the positive effects on short-term outcome such as functional limitations and falls.

  10. Use of Systemic Rosmarinus Officinalis to Enhance the Survival of Random-Pattern Skin Flaps

    Directory of Open Access Journals (Sweden)

    Bilsev İnce

    2016-12-01

    Full Text Available Background: Skin flaps are commonly used in soft-tissue reconstruction; however, necrosis can be a frequent complication. Several systemic and local agents have been used in attempts to improve skin flap survival, but none that can prevent flap necrosis have been identified. Aims: This study aims to determine whether the use of systemic Rosmarinus officinalis (R. officinalis extract can prevent flap necrosis and improve skin flap recovery. Study Design: Animal experimentation. Methods: Thirty-five Wistar albino rats were divided in five groups. A rectangular random-pattern flaps measuring 8×2 cm was elevated from the back of each rat. Group I was the control group. In Group II, 0.2 ml of R. officinalis oil was given orally 2h before surgery. R. officinalis oil was then applied orally twice a day for a week. In Group III, R. officinalis oil was given orally twice a day for one week before surgery. At the end of the week, 0.2 mL of R. officinalis oil was given orally 2 h before surgery. In Group IV, 0.2 mL of R. officinalis oil was injected subcutaneously 2 h before surgery. After the surgery, 0.2 mL R. officinalis oil was injected subcutaneously twice a day for one week. In Group V, 0.2 mL R. officinalis oil was injected subcutaneously twice a day for one week prior to surgery. At the end of the week, one last 0.2 mL R. officinalis oil injection was administered subcutaneously 2 h before surgery. After the surgery, 0.2 mL R. officinalis oil was injected subcutaneously twice a day for one week. Results: The mean percentage of viable surface area was significantly greater (p<0.05 in Groups II, III, IV, and V as compared to Group I. Mean vessel diameter was significantly greater (p<0.05 in Groups II, III, IV, and V as compared to Group I. Conclusion: We have determined that, in addition to its anti-inflammatory and anti-oxidant effects, R. officinalis has vasodilatory effects that contribute to increased skin flap survival.

  11. Ten-Year Survival Results of a Randomized Trial of Irradiation of Internal Mammary Nodes After Mastectomy

    International Nuclear Information System (INIS)

    Hennequin, Christophe; Bossard, Nadine; Servagi-Vernat, Stéphanie; Maingon, Philippe; Dubois, Jean-Bernard; Datchary, Jean; Carrie, Christian; Roullet, Bernard; Suchaud, Jean-Philippe; Teissier, Eric; Lucardi, Audrey; Gerard, Jean-Pierre; Belot, Aurélien

    2013-01-01

    Purpose: To evaluate the efficacy of irradiation of internal mammary nodes (IMN) on 10-year overall survival in breast cancer patients after mastectomy. Methods and Patients: This multicenter phase 3 study enrolled patients with positive axillary nodes (pN+) or central/medial tumors with or without pN+. Other inclusion criteria were age <75 and a Karnofsky index ≥70. All patients received postoperative irradiation of the chest wall and supraclavicular nodes and were randomly assigned to receive IMN irradiation or not. Randomization was stratified by tumor location (medial/central or lateral), axillary lymph node status, and adjuvant therapy (chemotherapy vs no chemotherapy). The prescribed dose of irradiation to the target volumes was 50 Gy or equivalent. The first 5 intercostal spaces were included in the IMN target volume, and two-thirds of the dose (31.5 Gy) was given by electrons. The primary outcome was overall survival at 10 years. Disease-free survival and toxicity were secondary outcomes. Results: T total of 1334 patients were analyzed after a median follow-up of 11.3 years among the survivors. No benefit of IMN irradiation on the overall survival could be demonstrated: the 10-year overall survival was 59.3% in the IMN-nonirradiated group versus 62.6% in the IMN-irradiated group (P=.8). According to stratification factors, we defined 6 subgroups (medial/central or lateral tumor, pN0 [only for medial/central] or pN+, and chemotherapy or not). In all these subgroups, IMN irradiation did not significantly improve overall survival. Conclusions: In patients treated with 2-dimensional techniques, we failed to demonstrate a survival benefit for IMN irradiation. This study cannot rule out a moderate benefit, especially with more modern, conformal techniques applied to a higher risk population

  12. Cumulative Poisson Distribution Program

    Science.gov (United States)

    Bowerman, Paul N.; Scheuer, Ernest M.; Nolty, Robert

    1990-01-01

    Overflow and underflow in sums prevented. Cumulative Poisson Distribution Program, CUMPOIS, one of two computer programs that make calculations involving cumulative Poisson distributions. Both programs, CUMPOIS (NPO-17714) and NEWTPOIS (NPO-17715), used independently of one another. CUMPOIS determines cumulative Poisson distribution, used to evaluate cumulative distribution function (cdf) for gamma distributions with integer shape parameters and cdf for X (sup2) distributions with even degrees of freedom. Used by statisticians and others concerned with probabilities of independent events occurring over specific units of time, area, or volume. Written in C.

  13. Ovarian Suppression With Triptorelin During Adjuvant Breast Cancer Chemotherapy and Long-term Ovarian Function, Pregnancies, and Disease-Free Survival: A Randomized Clinical Trial.

    Science.gov (United States)

    Lambertini, Matteo; Boni, Luca; Michelotti, Andrea; Gamucci, Teresa; Scotto, Tiziana; Gori, Stefania; Giordano, Monica; Garrone, Ornella; Levaggi, Alessia; Poggio, Francesca; Giraudi, Sara; Bighin, Claudia; Vecchio, Carlo; Sertoli, Mario Roberto; Pronzato, Paolo; Del Mastro, Lucia

    Whether the administration of luteinizing hormone-releasing hormone analogues (LHRHa) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy. To evaluate long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy. Parallel, randomized, open-label, phase 3 superiority trial conducted at 16 Italian sites. Between October 2003 and January 2008, 281 premenopausal women with stage I to III hormone receptor-positive or hormone receptor-negative breast cancer were enrolled. Last annual follow-up was June 3, 2014. Patients were randomized to receive adjuvant or neoadjuvant chemotherapy alone (control group) or chemotherapy plus triptorelin (LHRHa group). The primary planned end point was incidence of chemotherapy-induced early menopause. Post hoc end points were long-term ovarian function (evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle), pregnancies, and disease-free survival (DFS). A total of 281 women (median age, 39 [range, 24-45] years) were randomized. Median follow-up was 7.3 years (interquartile range, 6.3-8.2 years). The 5-year cumulative incidence estimate of menstrual resumption was 72.6% (95% CI, 65.7%-80.3%) among the 148 patients in the LHRHa group and 64.0% (95% CI, 56.2%-72.8%) among the 133 patients in the control group (hazard ratio [HR], 1.28 [95% CI, 0.98-1.68]; P = .07; age-adjusted HR, 1.48 [95% CI, 1.12-1.95]; P = .006). Eight pregnancies (5-year cumulative incidence estimate of pregnancy, 2.1% [95% CI, 0.7%-6.3%]) occurred in the LHRHa group and 3 (5-year cumulative incidence estimate of pregnancy, 1.6% [95% CI, 0.4%-6.2%]) in the control group (HR, 2.56 [95% CI, 0.68-9.60]; P = .14; age-adjusted HR, 2.40 [95% CI, 0

  14. Effects of Benazepril on Survival of Dogs with Chronic Kidney Disease: A Multicenter, Randomized, Blinded, Placebo-Controlled Clinical Trial.

    Science.gov (United States)

    King, J N; Font, A; Rousselot, J-F; Ash, R A; Bonfanti, U; Brovida, C; Crowe, I D; Lanore, D; Pechereau, D; Seewald, W; Strehlau, G

    2017-07-01

    Chronic kidney disease (CKD) is an important cause of morbidity and mortality in dogs. To evaluate the efficacy in prolonging survival and safety of benazepril administration to dogs with CKD. Forty-nine client-owned dogs with CKD. Dogs were randomized to benazepril (0.25 to benazepril versus placebo was detected for renal survival time in all dogs; median (95% confidence interval (CI)) survival times were 305 (53-575) days in the benazepril group and 287 (152-not available) in the placebo group (P = .53). Renal survival times were not significantly longer with benazepril compared to placebo for subgroups: hazard ratios (95% CI) were 0.50 (0.21-1.22) with P = .12 for initial urine protein-to-creatinine ratio (UPC) >0.5, and 0.38 (0.12-1.19) with P = .080 for initial UPC >0.5 plus plasma creatinine ≤440 μmol/L. Proteinuria, assessed from the UPC, was significantly (P = .0032) lower after treatment with benazepril compared to placebo. There were no significant differences between groups for clinical signs or frequencies of adverse events. Benazepril significantly reduced proteinuria in dogs with CKD. Insufficient numbers of dogs were recruited to allow conclusions on survival time. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  15. About the cumulants of periodic signals

    Science.gov (United States)

    Barrau, Axel; El Badaoui, Mohammed

    2018-01-01

    This note studies cumulants of time series. These functions originating from the probability theory being commonly used as features of deterministic signals, their classical properties are examined in this modified framework. We show additivity of cumulants, ensured in the case of independent random variables, requires here a different hypothesis. Practical applications are proposed, in particular an analysis of the failure of the JADE algorithm to separate some specific periodic signals.

  16. Statistical modelling of survival data with random effects h-likelihood approach

    CERN Document Server

    Ha, Il Do; Lee, Youngjo

    2017-01-01

    This book provides a groundbreaking introduction to the likelihood inference for correlated survival data via the hierarchical (or h-) likelihood in order to obtain the (marginal) likelihood and to address the computational difficulties in inferences and extensions. The approach presented in the book overcomes shortcomings in the traditional likelihood-based methods for clustered survival data such as intractable integration. The text includes technical materials such as derivations and proofs in each chapter, as well as recently developed software programs in R (“frailtyHL”), while the real-world data examples together with an R package, “frailtyHL” in CRAN, provide readers with useful hands-on tools. Reviewing new developments since the introduction of the h-likelihood to survival analysis (methods for interval estimation of the individual frailty and for variable selection of the fixed effects in the general class of frailty models) and guiding future directions, the book is of interest to research...

  17. Divergent Cumulative Cultural Evolution

    OpenAIRE

    Marriott, Chris; Chebib, Jobran

    2016-01-01

    Divergent cumulative cultural evolution occurs when the cultural evolutionary trajectory diverges from the biological evolutionary trajectory. We consider the conditions under which divergent cumulative cultural evolution can occur. We hypothesize that two conditions are necessary. First that genetic and cultural information are stored separately in the agent. Second cultural information must be transferred horizontally between agents of different generations. We implement a model with these ...

  18. SNRFCB: sub-network based random forest classifier for predicting chemotherapy benefit on survival for cancer treatment.

    Science.gov (United States)

    Shi, Mingguang; He, Jianmin

    2016-04-01

    Adjuvant chemotherapy (CTX) should be individualized to provide potential survival benefit and avoid potential harm to cancer patients. Our goal was to establish a computational approach for making personalized estimates of the survival benefit from adjuvant CTX. We developed Sub-Network based Random Forest classifier for predicting Chemotherapy Benefit (SNRFCB) based gene expression datasets of lung cancer. The SNRFCB approach was then validated in independent test cohorts for identifying chemotherapy responder cohorts and chemotherapy non-responder cohorts. SNRFCB involved the pre-selection of gene sub-network signatures based on the mutations and on protein-protein interaction data as well as the application of the random forest algorithm to gene expression datasets. Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer patients in the chemotherapy responder group (P = 0.008), but it was not beneficial to patients in the chemotherapy non-responder group (P = 0.657). Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer squamous cell carcinoma (SQCC) subtype patients in the chemotherapy responder cohorts (P = 0.024), but it was not beneficial to patients in the chemotherapy non-responder cohorts (P = 0.383). SNRFCB improved prediction performance as compared to the machine learning method, support vector machine (SVM). To test the general applicability of the predictive model, we further applied the SNRFCB approach to human breast cancer datasets and also observed superior performance. SNRFCB could provide recurrent probability for individual patients and identify which patients may benefit from adjuvant CTX in clinical trials.

  19. Effect of a new moisturizing lotion on immediate and cumulative skin hydration: Two randomized, intra-individual, vehicle- and comparator-controlled studies.

    Science.gov (United States)

    Nogueira, Alessandra; Sidou, Farzaneh; Brocard, Sylvie

    2011-08-01

    Moisturizers increase skin hydration and can serve as adjunctive care in dermatologic conditions such as xerosis, psoriasis vulgaris, atopic dermatitis and ichthyosis, in which dry skin is implicated. A non-irritating hydrating lotion (CDA lotion) was recently developed. We assessed the effect of CDA lotion on skin hydration in two randomized, evaluator-blind and intra-individual comparison studies. After a single application, CDA lotion induced significantly greater hydration than the non-treated control for at least 24 hours (p skin hydration up to 3 days after treatment cessation (p skin dryness score up to 7 days after treatment cessation (p hydration effects of CDA lotion were also compared to those of several currently available moisturizing products. In summary, application of CDA lotion increases skin hydration and alleviates the condition of skin dryness.

  20. Isoflurane Preconditioning Increases Survival of Rat Skin Random-Pattern Flaps by Induction of HIF-1α Expression

    Directory of Open Access Journals (Sweden)

    Yu Sun

    2013-04-01

    Full Text Available Background: Survival of random-pattern skin flaps is important for the success of plastic and reconstructive surgeries. This study investigates isoflurane-induced protection against ischemia of skin flap and the underlying molecular mechanism in this process. Methods: Human umbilical vein endothelial cells (HUVECs and human skin fibroblast cells were exposed to isoflurane for 4 h. Expression of hypoxia inducible factor-1α (HIF-1α, heme oxygenase-1 (HO-1 and vascular endothelial growth factor (VEGF were analyzed up to 24 h post isoflurane exposure using qRT-PCR and western blot, or ELISA analyses. PI3K inhibitors - LY 294002 and wortmannin, mTOR inhibitor - rapamycin, and GSK3β inhibitor - SB 216763 were used respectively to assess the effects of isoflurane treatment and HIF-1α expression. Furthermore, 40 rats were randomly divided into 5 groups (control, isoflurane, scrambled siRNA plus isoflurane, HIF-1α siRNA plus isoflurane, and DMOG and subjected to random-pattern skin flaps operation. Rats were prepared for evaluation of flap survival and full-feld laser perfusion imager (FLPI (at 7 day and microvessel density evaluation (at 10 day. Results: Isoflurane exposure induced expression of HIF-1α protein, HO-1 and VEGF mRNA and proteins in a time-dependent manner. Both LY 294002 and wortmannin inhibited phospho-Akt, phospho-mTOR, phospho-GSK 3β and HIF-1α expression after isoflurane exposure. Both wortmannin and rapamycin inhibited isoflurane-induced phospho-4E-BP1 (Ser 65 and phospho-P70s6k (Thr 389 and HIF-1α expression. SB 216763 pre-treatment could further enhance isoflurane-induced expression of phospho-GSK 3β (Ser 9 and HIF-1α protein compared to the isoflurane-alone cells. In animal experiments, isoflurane alone, scrambled siRNA plus isoflurane, or DMOG groups had significantly upregulated vascularity and increased survival of the skin flaps compared to the controls. However, HIF-1α knockdown abrogated the protective effect of

  1. Enriched enteral nutrition may improve short-term survival in stage IV gastric cancer patients: A randomized, controlled trial.

    Science.gov (United States)

    Klek, Stanislaw; Scislo, Lucyna; Walewska, Elzbieta; Choruz, Ryszard; Galas, Aleksander

    2017-04-01

    The aim of the study was to determine whether the postoperative use of enteral nutrition enriched with arginine, glutamine, and omega-3 fatty acids influences survival in patients diagnosed with stomach cancer. For the purpose of the study, the second wave of the trial performed in 2003 to 2009 was done. Ninety-nine patients who underwent surgery for gastric cancer (27 F, 72 M, mean age: 62.9 y) met the inclusion criteria. Of those, 54 were randomized to standard and 45 to enriched enteral nutrition (EEN). In all patients, short- and long-term (5 y) survival was analyzed. Analysis of the overall survival time did not reveal differences between groups (P = 0.663). Until the end of the third month, however, there were nine deaths in the standard enteral nutrition group and no deaths in the EEN group (16.7% versus 0.0%, P = 0.004). The univariate analyses suggested that the EEN group may have lower risk, especially during the first year after intervention. A significant reduction in the risk of death was seen during the early period after surgery (first 6 mo) in the EEN group in stage IV patients (hazard ratio = 0.25, P = 0.049). The use of enriched enteral diet did not influence, however, the risk of dying when patients were analyzed together. The study does not support the beneficial effect of enriched enteral nutrition in long-term survival; however, the positive impact on the stage IV patients suggests the need for further, more detailed studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The Norwegian dietary guidelines and colorectal cancer survival (CRC-NORDIET) study: a food-based multicentre randomized controlled trial.

    Science.gov (United States)

    Henriksen, Hege Berg; Ræder, Hanna; Bøhn, Siv Kjølsrud; Paur, Ingvild; Kværner, Ane Sørlie; Billington, Siv Åshild; Eriksen, Morten Tandberg; Wiedsvang, Gro; Erlund, Iris; Færden, Arne; Veierød, Marit Bragelien; Zucknick, Manuela; Smeland, Sigbjørn; Blomhoff, Rune

    2017-01-30

    Colorectal cancer survivors are not only at risk for recurrent disease but also at increased risk of comorbidities such as other cancers, cardiovascular disease, diabetes, hypertension and functional decline. In this trial, we aim at investigating whether a diet in accordance with the Norwegian food-based dietary guidelines and focusing at dampening inflammation and oxidative stress will improve long-term disease outcomes and survival in colorectal cancer patients. This paper presents the study protocol of the Norwegian Dietary Guidelines and Colorectal Cancer Survival study. Men and women aged 50-80 years diagnosed with primary invasive colorectal cancer (Stage I-III) are invited to this randomized controlled, parallel two-arm trial 2-9 months after curative surgery. The intervention group (n = 250) receives an intensive dietary intervention lasting for 12 months and a subsequent maintenance intervention for 14 years. The control group (n = 250) receives no dietary intervention other than standard clinical care. Both groups are offered equal general advice of physical activity. Patients are followed-up at 6 months and 1, 3, 5, 7, 10 and 15 years after baseline. The study center is located at the Department of Nutrition, University of Oslo, and patients are recruited from two hospitals within the South-Eastern Norway Regional Health Authority. Primary outcomes are disease-free survival and overall survival. Secondary outcomes are time to recurrence, cardiovascular disease-free survival, compliance to the dietary recommendations and the effects of the intervention on new comorbidities, intermediate biomarkers, nutrition status, physical activity, physical function and quality of life. The current study is designed to gain a better understanding of the role of a healthy diet aimed at dampening inflammation and oxidative stress on long-term disease outcomes and survival in colorectal cancer patients. Since previous research on the role of diet for

  3. Lack of evidence for a harmful effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on fracture risk among type 2 diabetes patients: a network and cumulative meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Tang, H L; Li, D D; Zhang, J J; Hsu, Y H; Wang, T S; Zhai, S D; Song, Y Q

    2016-12-01

    To evaluate the comparative effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on risk of bone fracture in patients with type 2 diabetes mellitus (T2DM). PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were systematically searched from inception to 27 January 2016 to identify randomized controlled trials (RCTs) reporting the outcome of fracture in patients with T2DM treated with SGLT2 inhibitors. Pairwise and network meta-analyses, as well as a cumulative meta-analysis, were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). A total of 38 eligible RCTs (10 canagliflozin, 15 dapagliflozin and 13 empagliflozin) involving 30 384 patients, with follow-ups ranging from 24 to 160 weeks, were included. The fracture event rates were 1.59% in the SGLT2 inhibitor groups and 1.56% in the control groups. The incidence of fracture events was similar among these three SGLT2 inhibitor groups. Compared with placebo, canagliflozin (OR 1.15; 95% CI 0.71-1.88), dapagliflozin (OR 0.68; 95% CI 0.37-1.25) and empagliflozin (OR 0.93; 95% CI 0.74-1.18) were not significantly associated with an increased risk of fracture. Our cumulative meta-analysis indicated the robustness of the null findings with regard to SGLT2 inhibitors. Our meta-analysis based on available RCT data does not support the harmful effect of SGLT2 inhibitors on fractures, although future safety monitoring from RCTs and real-world data with detailed information on bone health is warranted. © 2016 John Wiley & Sons Ltd.

  4. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial.

    Science.gov (United States)

    Mentzelopoulos, Spyros D; Malachias, Sotirios; Chamos, Christos; Konstantopoulos, Demetrios; Ntaidou, Theodora; Papastylianou, Androula; Kolliantzaki, Iosifinia; Theodoridi, Maria; Ischaki, Helen; Makris, Dimosthemis; Zakynthinos, Epaminondas; Zintzaras, Elias; Sourlas, Sotirios; Aloizos, Stavros; Zakynthinos, Spyros G

    2013-07-17

    Among patients with cardiac arrest, preliminary data have shown improved return of spontaneous circulation and survival to hospital discharge with the vasopressin-steroids-epinephrine (VSE) combination. To determine whether combined vasopressin-epinephrine during cardiopulmonary resuscitation (CPR) and corticosteroid supplementation during and after CPR improve survival to hospital discharge with a Cerebral Performance Category (CPC) score of 1 or 2 in vasopressor-requiring, in-hospital cardiac arrest. Randomized, double-blind, placebo-controlled, parallel-group trial performed from September 1, 2008, to October 1, 2010, in 3 Greek tertiary care centers (2400 beds) with 268 consecutive patients with cardiac arrest requiring epinephrine according to resuscitation guidelines (from 364 patients assessed for eligibility). Patients received either vasopressin (20 IU/CPR cycle) plus epinephrine (1 mg/CPR cycle; cycle duration approximately 3 minutes) (VSE group, n = 130) or saline placebo plus epinephrine (1 mg/CPR cycle; cycle duration approximately 3 minutes) (control group, n = 138) for the first 5 CPR cycles after randomization, followed by additional epinephrine if needed. During the first CPR cycle after randomization, patients in the VSE group received methylprednisolone (40 mg) and patients in the control group received saline placebo. Shock after resuscitation was treated with stress-dose hydrocortisone (300 mg daily for 7 days maximum and gradual taper) (VSE group, n = 76) or saline placebo (control group, n = 73). Return of spontaneous circulation (ROSC) for 20 minutes or longer and survival to hospital discharge with a CPC score of 1 or 2. Follow-up was completed in all resuscitated patients. Patients in the VSE group vs patients in the control group had higher probability for ROSC of 20 minutes or longer (109/130 [83.9%] vs 91/138 [65.9%]; odds ratio [OR], 2.98; 95% CI, 1.39-6.40; P = .005) and survival to hospital discharge with CPC

  5. Effect of Haloperidol on Survival Among Critically Ill Adults With a High Risk of Delirium: The REDUCE Randomized Clinical Trial.

    Science.gov (United States)

    van den Boogaard, Mark; Slooter, Arjen J C; Brüggemann, Roger J M; Schoonhoven, Lisette; Beishuizen, Albertus; Vermeijden, J Wytze; Pretorius, Danie; de Koning, Jan; Simons, Koen S; Dennesen, Paul J W; Van der Voort, Peter H J; Houterman, Saskia; van der Hoeven, J G; Pickkers, Peter; van der Woude, Margaretha C. E.; Besselink, Anna; Hofstra, Lieuwe S; Spronk, Peter E; van den Bergh, Walter; Donker, Dirk W; Fuchs, Malaika; Karakus, Attila; Koeman, M; van Duijnhoven, Mirella; Hannink, Gerjon

    2018-02-20

    Results of studies on use of prophylactic haloperidol in critically ill adults are inconclusive, especially in patients at high risk of delirium. To determine whether prophylactic use of haloperidol improves survival among critically ill adults at high risk of delirium, which was defined as an anticipated intensive care unit (ICU) stay of at least 2 days. Randomized, double-blind, placebo-controlled investigator-driven study involving 1789 critically ill adults treated at 21 ICUs, at which nonpharmacological interventions for delirium prevention are routinely used in the Netherlands. Patients without delirium whose expected ICU stay was at least a day were included. Recruitment was from July 2013 to December 2016 and follow-up was conducted at 90 days with the final follow-up on March 1, 2017. Patients received prophylactic treatment 3 times daily intravenously either 1 mg (n = 350) or 2 mg (n = 732) of haloperidol or placebo (n = 707), consisting of 0.9% sodium chloride. The primary outcome was the number of days that patients survived in 28 days. There were 15 secondary outcomes, including delirium incidence, 28-day delirium-free and coma-free days, duration of mechanical ventilation, and ICU and hospital length of stay. All 1789 randomized patients (mean, age 66.6 years [SD, 12.6]; 1099 men [61.4%]) completed the study. The 1-mg haloperidol group was prematurely stopped because of futility. There was no difference in the median days patients survived in 28 days, 28 days in the 2-mg haloperidol group vs 28 days in the placebo group, for a difference of 0 days (95% CI, 0-0; P = .93) and a hazard ratio of 1.003 (95% CI, 0.78-1.30, P=.82). All of the 15 secondary outcomes were not statistically different. These included delirium incidence (mean difference, 1.5%, 95% CI, -3.6% to 6.7%), delirium-free and coma-free days (mean difference, 0 days, 95% CI, 0-0 days), and duration of mechanical ventilation, ICU, and hospital length of stay (mean difference

  6. [Effects and related mechanism of bivalirudin on the survival of random skin flap on the back of rat].

    Science.gov (United States)

    Cai, L Y; Wang, T; Lin, D S; Lu, D

    2017-04-20

    Objective: To investigate the effects and related mechanism of bivalirudin on the survival of random skin flap on the back of rat. Methods: Thirty SD rats were divided into bivalirudin group and normal saline group according to the random number table, with 15 rats in each group. The random flap model with size of 9 cm×3 cm was reproduced on the back of rats in two groups. Immediately post injury, rats in bivalirudin group were intraperitoneally injected with 5 mg/mL bivalirudin (0.8 mL/kg), while rats in normal saline group were intraperitoneally injected with normal saline (0.8 mL/kg) once a day. The continuous injection lasted for 7 days. The flap was divided into distal area, middle area and proximal area averagely based on the flap blood supply. On post injury day (PID) 1, 3, and 7, the overall survival of each area of flap was observed with naked eyes. On PID 7, the survival rate of flap was calculated, and then the morphology of skin tissue at the center of the three areas of flap was observed by HE staining, the microvessel density (MVD) of the middle area of flap was calculated, and the expression of vascular endothelial growth factor (VEGF) of the middle area of flap was detected with immunohistochemical staining. Data were processed with t test. Results: (1) On PID 1, flaps of rats in two groups had different degrees of swelling, mainly concentrated in distal area, but there was no obvious necrosis. The middle area and proximal area of flaps in two groups were survived. On PID 3, the necrosis of flaps of rats in two groups was concentrated in the middle area, while the proximal area of flap was still in survival state, and most distal area of flap was necrosis with a little scab. On PID 7, the necrosis of middle area of flaps of rats in two groups was gradually fused, and the survival area of flap of rats in bivalirudin group was larger than that in normal saline group. The distal area of flap was almost necrotic, and the proximal area of flap was

  7. Meta-analysis of single-arm survival studies: a distribution-free approach for estimating summary survival curves with random effects.

    Science.gov (United States)

    Combescure, Christophe; Foucher, Yohann; Jackson, Daniel

    2014-07-10

    In epidemiologic studies and clinical trials with time-dependent outcome (for instance death or disease progression), survival curves are used to describe the risk of the event over time. In meta-analyses of studies reporting a survival curve, the most informative finding is a summary survival curve. In this paper, we propose a method to obtain a distribution-free summary survival curve by expanding the product-limit estimator of survival for aggregated survival data. The extension of DerSimonian and Laird's methodology for multiple outcomes is applied to account for the between-study heterogeneity. Statistics I(2)  and H(2) are used to quantify the impact of the heterogeneity in the published survival curves. A statistical test for between-strata comparison is proposed, with the aim to explore study-level factors potentially associated with survival. The performance of the proposed approach is evaluated in a simulation study. Our approach is also applied to synthesize the survival of untreated patients with hepatocellular carcinoma from aggregate data of 27 studies and synthesize the graft survival of kidney transplant recipients from individual data from six hospitals. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Random Linear Network Coding is Key to Data Survival in Highly Dynamic Distributed Storage

    DEFF Research Database (Denmark)

    Sipos, Marton A.; Fitzek, Frank; Roetter, Daniel Enrique Lucani

    2015-01-01

    Distributed storage solutions have become widespread due to their ability to store large amounts of data reliably across a network of unreliable nodes, by employing repair mechanisms to prevent data loss. Conventional systems rely on static designs with a central control entity to oversee...... and control the repair process. Given the large costs for maintaining and cooling large data centers, our work proposes and studies the feasibility of a fully decentralized systems that can store data even on unreliable and, sometimes, unavailable mobile devices. This imposes new challenges on the design...... as the number of available nodes varies greatly over time and keeping track of the system's state becomes unfeasible. As a consequence, conventional erasure correction approaches are ill-suited for maintaining data integrity. In this highly dynamic context, random linear network coding (RLNC) provides...

  9. A comparison of the conditional inference survival forest model to random survival forests based on a simulation study as well as on two applications with time-to-event data.

    Science.gov (United States)

    Nasejje, Justine B; Mwambi, Henry; Dheda, Keertan; Lesosky, Maia

    2017-07-28

    Random survival forest (RSF) models have been identified as alternative methods to the Cox proportional hazards model in analysing time-to-event data. These methods, however, have been criticised for the bias that results from favouring covariates with many split-points and hence conditional inference forests for time-to-event data have been suggested. Conditional inference forests (CIF) are known to correct the bias in RSF models by separating the procedure for the best covariate to split on from that of the best split point search for the selected covariate. In this study, we compare the random survival forest model to the conditional inference model (CIF) using twenty-two simulated time-to-event datasets. We also analysed two real time-to-event datasets. The first dataset is based on the survival of children under-five years of age in Uganda and it consists of categorical covariates with most of them having more than two levels (many split-points). The second dataset is based on the survival of patients with extremely drug resistant tuberculosis (XDR TB) which consists of mainly categorical covariates with two levels (few split-points). The study findings indicate that the conditional inference forest model is superior to random survival forest models in analysing time-to-event data that consists of covariates with many split-points based on the values of the bootstrap cross-validated estimates for integrated Brier scores. However, conditional inference forests perform comparably similar to random survival forests models in analysing time-to-event data consisting of covariates with fewer split-points. Although survival forests are promising methods in analysing time-to-event data, it is important to identify the best forest model for analysis based on the nature of covariates of the dataset in question.

  10. A comparison of the conditional inference survival forest model to random survival forests based on a simulation study as well as on two applications with time-to-event data

    Directory of Open Access Journals (Sweden)

    Justine B. Nasejje

    2017-07-01

    Full Text Available Abstract Background Random survival forest (RSF models have been identified as alternative methods to the Cox proportional hazards model in analysing time-to-event data. These methods, however, have been criticised for the bias that results from favouring covariates with many split-points and hence conditional inference forests for time-to-event data have been suggested. Conditional inference forests (CIF are known to correct the bias in RSF models by separating the procedure for the best covariate to split on from that of the best split point search for the selected covariate. Methods In this study, we compare the random survival forest model to the conditional inference model (CIF using twenty-two simulated time-to-event datasets. We also analysed two real time-to-event datasets. The first dataset is based on the survival of children under-five years of age in Uganda and it consists of categorical covariates with most of them having more than two levels (many split-points. The second dataset is based on the survival of patients with extremely drug resistant tuberculosis (XDR TB which consists of mainly categorical covariates with two levels (few split-points. Results The study findings indicate that the conditional inference forest model is superior to random survival forest models in analysing time-to-event data that consists of covariates with many split-points based on the values of the bootstrap cross-validated estimates for integrated Brier scores. However, conditional inference forests perform comparably similar to random survival forests models in analysing time-to-event data consisting of covariates with fewer split-points. Conclusion Although survival forests are promising methods in analysing time-to-event data, it is important to identify the best forest model for analysis based on the nature of covariates of the dataset in question.

  11. A paradox of cumulative culture.

    Science.gov (United States)

    Kobayashi, Yutaka; Wakano, Joe Yuichiro; Ohtsuki, Hisashi

    2015-08-21

    Culture can grow cumulatively if socially learnt behaviors are improved by individual learning before being passed on to the next generation. Previous authors showed that this kind of learning strategy is unlikely to be evolutionarily stable in the presence of a trade-off between learning and reproduction. This is because culture is a public good that is freely exploited by any member of the population in their model (cultural social dilemma). In this paper, we investigate the effect of vertical transmission (transmission from parents to offspring), which decreases the publicness of culture, on the evolution of cumulative culture in both infinite and finite population models. In the infinite population model, we confirm that culture accumulates largely as long as transmission is purely vertical. It turns out, however, that introduction of even slight oblique transmission drastically reduces the equilibrium level of culture. Even more surprisingly, if the population size is finite, culture hardly accumulates even under purely vertical transmission. This occurs because stochastic extinction due to random genetic drift prevents a learning strategy from accumulating enough culture. Overall, our theoretical results suggest that introducing vertical transmission alone does not really help solve the cultural social dilemma problem. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Quantification of the heterogeneity of prognostic cellular biomarkers in ewing sarcoma using automated image and random survival forest analysis.

    Directory of Open Access Journals (Sweden)

    Claudia Bühnemann

    Full Text Available Driven by genomic somatic variation, tumour tissues are typically heterogeneous, yet unbiased quantitative methods are rarely used to analyse heterogeneity at the protein level. Motivated by this problem, we developed automated image segmentation of images of multiple biomarkers in Ewing sarcoma to generate distributions of biomarkers between and within tumour cells. We further integrate high dimensional data with patient clinical outcomes utilising random survival forest (RSF machine learning. Using material from cohorts of genetically diagnosed Ewing sarcoma with EWSR1 chromosomal translocations, confocal images of tissue microarrays were segmented with level sets and watershed algorithms. Each cell nucleus and cytoplasm were identified in relation to DAPI and CD99, respectively, and protein biomarkers (e.g. Ki67, pS6, Foxo3a, EGR1, MAPK localised relative to nuclear and cytoplasmic regions of each cell in order to generate image feature distributions. The image distribution features were analysed with RSF in relation to known overall patient survival from three separate cohorts (185 informative cases. Variation in pre-analytical processing resulted in elimination of a high number of non-informative images that had poor DAPI localisation or biomarker preservation (67 cases, 36%. The distribution of image features for biomarkers in the remaining high quality material (118 cases, 104 features per case were analysed by RSF with feature selection, and performance assessed using internal cross-validation, rather than a separate validation cohort. A prognostic classifier for Ewing sarcoma with low cross-validation error rates (0.36 was comprised of multiple features, including the Ki67 proliferative marker and a sub-population of cells with low cytoplasmic/nuclear ratio of CD99. Through elimination of bias, the evaluation of high-dimensionality biomarker distribution within cell populations of a tumour using random forest analysis in quality

  13. Quantification of the heterogeneity of prognostic cellular biomarkers in ewing sarcoma using automated image and random survival forest analysis.

    Science.gov (United States)

    Bühnemann, Claudia; Li, Simon; Yu, Haiyue; Branford White, Harriet; Schäfer, Karl L; Llombart-Bosch, Antonio; Machado, Isidro; Picci, Piero; Hogendoorn, Pancras C W; Athanasou, Nicholas A; Noble, J Alison; Hassan, A Bassim

    2014-01-01

    Driven by genomic somatic variation, tumour tissues are typically heterogeneous, yet unbiased quantitative methods are rarely used to analyse heterogeneity at the protein level. Motivated by this problem, we developed automated image segmentation of images of multiple biomarkers in Ewing sarcoma to generate distributions of biomarkers between and within tumour cells. We further integrate high dimensional data with patient clinical outcomes utilising random survival forest (RSF) machine learning. Using material from cohorts of genetically diagnosed Ewing sarcoma with EWSR1 chromosomal translocations, confocal images of tissue microarrays were segmented with level sets and watershed algorithms. Each cell nucleus and cytoplasm were identified in relation to DAPI and CD99, respectively, and protein biomarkers (e.g. Ki67, pS6, Foxo3a, EGR1, MAPK) localised relative to nuclear and cytoplasmic regions of each cell in order to generate image feature distributions. The image distribution features were analysed with RSF in relation to known overall patient survival from three separate cohorts (185 informative cases). Variation in pre-analytical processing resulted in elimination of a high number of non-informative images that had poor DAPI localisation or biomarker preservation (67 cases, 36%). The distribution of image features for biomarkers in the remaining high quality material (118 cases, 104 features per case) were analysed by RSF with feature selection, and performance assessed using internal cross-validation, rather than a separate validation cohort. A prognostic classifier for Ewing sarcoma with low cross-validation error rates (0.36) was comprised of multiple features, including the Ki67 proliferative marker and a sub-population of cells with low cytoplasmic/nuclear ratio of CD99. Through elimination of bias, the evaluation of high-dimensionality biomarker distribution within cell populations of a tumour using random forest analysis in quality controlled tumour

  14. Decision analysis with cumulative prospect theory.

    Science.gov (United States)

    Bayoumi, A M; Redelmeier, D A

    2000-01-01

    Individuals sometimes express preferences that do not follow expected utility theory. Cumulative prospect theory adjusts for some phenomena by using decision weights rather than probabilities when analyzing a decision tree. The authors examined how probability transformations from cumulative prospect theory might alter a decision analysis of a prophylactic therapy in AIDS, eliciting utilities from patients with HIV infection (n = 75) and calculating expected outcomes using an established Markov model. They next focused on transformations of three sets of probabilities: 1) the probabilities used in calculating standard-gamble utility scores; 2) the probabilities of being in discrete Markov states; 3) the probabilities of transitioning between Markov states. The same prophylaxis strategy yielded the highest quality-adjusted survival under all transformations. For the average patient, prophylaxis appeared relatively less advantageous when standard-gamble utilities were transformed. Prophylaxis appeared relatively more advantageous when state probabilities were transformed and relatively less advantageous when transition probabilities were transformed. Transforming standard-gamble and transition probabilities simultaneously decreased the gain from prophylaxis by almost half. Sensitivity analysis indicated that even near-linear probability weighting transformations could substantially alter quality-adjusted survival estimates. The magnitude of benefit estimated in a decision-analytic model can change significantly after using cumulative prospect theory. Incorporating cumulative prospect theory into decision analysis can provide a form of sensitivity analysis and may help describe when people deviate from expected utility theory.

  15. CUMBIN - CUMULATIVE BINOMIAL PROGRAMS

    Science.gov (United States)

    Bowerman, P. N.

    1994-01-01

    The cumulative binomial program, CUMBIN, is one of a set of three programs which calculate cumulative binomial probability distributions for arbitrary inputs. The three programs, CUMBIN, NEWTONP (NPO-17556), and CROSSER (NPO-17557), can be used independently of one another. CUMBIN can be used by statisticians and users of statistical procedures, test planners, designers, and numerical analysts. The program has been used for reliability/availability calculations. CUMBIN calculates the probability that a system of n components has at least k operating if the probability that any one operating is p and the components are independent. Equivalently, this is the reliability of a k-out-of-n system having independent components with common reliability p. CUMBIN can evaluate the incomplete beta distribution for two positive integer arguments. CUMBIN can also evaluate the cumulative F distribution and the negative binomial distribution, and can determine the sample size in a test design. CUMBIN is designed to work well with all integer values 0 < k <= n. To run the program, the user simply runs the executable version and inputs the information requested by the program. The program is not designed to weed out incorrect inputs, so the user must take care to make sure the inputs are correct. Once all input has been entered, the program calculates and lists the result. The CUMBIN program is written in C. It was developed on an IBM AT with a numeric co-processor using Microsoft C 5.0. Because the source code is written using standard C structures and functions, it should compile correctly with most C compilers. The program format is interactive. It has been implemented under DOS 3.2 and has a memory requirement of 26K. CUMBIN was developed in 1988.

  16. Cumulation of light nuclei

    International Nuclear Information System (INIS)

    Baldin, A.M.; Bondarev, V.K.; Golovanov, L.B.

    1977-01-01

    Limit fragmentation of light nuclei (deuterium, helium) bombarded with 8,6 GeV/c protons was investigated. Fragments (pions, protons and deuterons) were detected within the emission angle 50-150 deg with regard to primary protons and within the pulse range 150-180 MeV/c. By the kinematics of collision of a primary proton with a target at rest the fragments observed correspond to a target mass upto 3 GeV. Thus, the data obtained correspond to teh cumulation upto the third order

  17. CROSSER - CUMULATIVE BINOMIAL PROGRAMS

    Science.gov (United States)

    Bowerman, P. N.

    1994-01-01

    The cumulative binomial program, CROSSER, is one of a set of three programs which calculate cumulative binomial probability distributions for arbitrary inputs. The three programs, CROSSER, CUMBIN (NPO-17555), and NEWTONP (NPO-17556), can be used independently of one another. CROSSER can be used by statisticians and users of statistical procedures, test planners, designers, and numerical analysts. The program has been used for reliability/availability calculations. CROSSER calculates the point at which the reliability of a k-out-of-n system equals the common reliability of the n components. It is designed to work well with all integer values 0 < k <= n. To run the program, the user simply runs the executable version and inputs the information requested by the program. The program is not designed to weed out incorrect inputs, so the user must take care to make sure the inputs are correct. Once all input has been entered, the program calculates and lists the result. It also lists the number of iterations of Newton's method required to calculate the answer within the given error. The CROSSER program is written in C. It was developed on an IBM AT with a numeric co-processor using Microsoft C 5.0. Because the source code is written using standard C structures and functions, it should compile correctly with most C compilers. The program format is interactive. It has been implemented under DOS 3.2 and has a memory requirement of 26K. CROSSER was developed in 1988.

  18. Identification by random forest method of HLA class I amino acid substitutions associated with lower survival at day 100 in unrelated donor hematopoietic cell transplantation.

    Science.gov (United States)

    Marino, S R; Lin, S; Maiers, M; Haagenson, M; Spellman, S; Klein, J P; Binkowski, T A; Lee, S J; van Besien, K

    2012-02-01

    The identification of important amino acid substitutions associated with low survival in hematopoietic cell transplantation (HCT) is hampered by the large number of observed substitutions compared with the small number of patients available for analysis. Random forest analysis is designed to address these limitations. We studied 2107 HCT recipients with good or intermediate risk hematological malignancies to identify HLA class I amino acid substitutions associated with reduced survival at day 100 post transplant. Random forest analysis and traditional univariate and multivariate analyses were used. Random forest analysis identified amino acid substitutions in 33 positions that were associated with reduced 100 day survival, including HLA-A 9, 43, 62, 63, 76, 77, 95, 97, 114, 116, 152, 156, 166 and 167; HLA-B 97, 109, 116 and 156; and HLA-C 6, 9, 11, 14, 21, 66, 77, 80, 95, 97, 99, 116, 156, 163 and 173. In all 13 had been previously reported by other investigators using classical biostatistical approaches. Using the same data set, traditional multivariate logistic regression identified only five amino acid substitutions associated with lower day 100 survival. Random forest analysis is a novel statistical methodology for analysis of HLA mismatching and outcome studies, capable of identifying important amino acid substitutions missed by other methods.

  19. Survival of bonded lingual retainers with chemical or photo polymerization over a 2-year period: a single-center, randomized controlled clinical trial

    NARCIS (Netherlands)

    Pandis, N.; Fleming, P.S.; Kloukos, D.; Polychronopoulou, A.; Katsaros, C.; Eliades, T.

    2013-01-01

    INTRODUCTION: The objective of this trial was to compare the survival rates of mandibular lingual retainers bonded with either chemically cured or light-cured adhesive after orthodontic treatment. METHODS: Patients having undergone orthodontic treatment at a private orthodontic office were randomly

  20. Cumulative environmental effects. Summary

    International Nuclear Information System (INIS)

    2012-01-01

    This report presents a compilation of knowledge about the state of the environment and human activity in the Norwegian part of the North Sea and Skagerrak. The report gives an overview of pressures and impacts on the environment from normal activity and in the event of accidents. This is used to assess the cumulative environmental effects, which factors have most impact and where the impacts are greatest, and to indicate which problems are expected to be most serious in the future. The report is intended to provide relevant information that can be used in the management of the marine area in the future. It also provides input for the identification of environmental targets and management measures for the North Sea and Skagerrak.(Author)

  1. Cumulative environmental effects. Summary

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-07-01

    This report presents a compilation of knowledge about the state of the environment and human activity in the Norwegian part of the North Sea and Skagerrak. The report gives an overview of pressures and impacts on the environment from normal activity and in the event of accidents. This is used to assess the cumulative environmental effects, which factors have most impact and where the impacts are greatest, and to indicate which problems are expected to be most serious in the future. The report is intended to provide relevant information that can be used in the management of the marine area in the future. It also provides input for the identification of environmental targets and management measures for the North Sea and Skagerrak.(Author)

  2. NEWTONP - CUMULATIVE BINOMIAL PROGRAMS

    Science.gov (United States)

    Bowerman, P. N.

    1994-01-01

    The cumulative binomial program, NEWTONP, is one of a set of three programs which calculate cumulative binomial probability distributions for arbitrary inputs. The three programs, NEWTONP, CUMBIN (NPO-17555), and CROSSER (NPO-17557), can be used independently of one another. NEWTONP can be used by statisticians and users of statistical procedures, test planners, designers, and numerical analysts. The program has been used for reliability/availability calculations. NEWTONP calculates the probably p required to yield a given system reliability V for a k-out-of-n system. It can also be used to determine the Clopper-Pearson confidence limits (either one-sided or two-sided) for the parameter p of a Bernoulli distribution. NEWTONP can determine Bayesian probability limits for a proportion (if the beta prior has positive integer parameters). It can determine the percentiles of incomplete beta distributions with positive integer parameters. It can also determine the percentiles of F distributions and the midian plotting positions in probability plotting. NEWTONP is designed to work well with all integer values 0 < k <= n. To run the program, the user simply runs the executable version and inputs the information requested by the program. NEWTONP is not designed to weed out incorrect inputs, so the user must take care to make sure the inputs are correct. Once all input has been entered, the program calculates and lists the result. It also lists the number of iterations of Newton's method required to calculate the answer within the given error. The NEWTONP program is written in C. It was developed on an IBM AT with a numeric co-processor using Microsoft C 5.0. Because the source code is written using standard C structures and functions, it should compile correctly with most C compilers. The program format is interactive. It has been implemented under DOS 3.2 and has a memory requirement of 26K. NEWTONP was developed in 1988.

  3. Impact of weight loss on survival after chemoradiation for locally advanced head and neck Cancer: secondary results of a randomized phase III trial (SAKK 10/94)

    International Nuclear Information System (INIS)

    Ghadjar, Pirus; Hayoz, Stefanie; Zimmermann, Frank; Bodis, Stephan; Kaul, David; Badakhshi, Harun; Bernier, Jacques; Studer, Gabriela; Plasswilm, Ludwig; Budach, Volker; Aebersold, Daniel M

    2015-01-01

    To analyze the impact of weight loss before and during chemoradiation on survival outcomes in patients with locally advanced head and neck cancer. From 07/1994-07/2000 a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to either hyperfractionated radiation therapy alone or the same radiation therapy combined with two cycles of concomitant cisplatin. The primary endpoint was time to any treatment failure (TTF); secondary endpoints were locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Patient weight was measured 6 months before treatment, at treatment start and treatment end. The proportion of patients with >5% weight loss was 32% before, and 51% during treatment, and the proportion of patients with >10% weight loss was 12% before, and 17% during treatment. After a median follow-up of 9.5 years (range, 0.1 – 15.4 years) weight loss before treatment was associated with decreased TTF, LRRFS, DMFS, cancer specific survival and OS in a multivariable analysis. However, weight loss during treatment was not associated with survival outcomes. Weight loss before and during chemoradiation was commonly observed. Weight loss before but not during treatment was associated with worse survival

  4. Cumulative radiation effect

    International Nuclear Information System (INIS)

    Kirk, J.; Gray, W.M.; Watson, E.R.

    1977-01-01

    In five previous papers, the concept of Cumulative Radiation Effect (CRE) has been presented as a scale of accumulative sub-tolerance radiation damage, with a unique value of the CRE describing a specific level of radiation effect. Simple nomographic and tabular methods for the solution of practical problems in radiotherapy are now described. An essential feature of solving a CRE problem is firstly to present it in a concise and readily appreciated form, and, to do this, nomenclature has been introduced to describe schedules and regimes as compactly as possible. Simple algebraic equations have been derived to describe the CRE achieved by multi-schedule regimes. In these equations, the equivalence conditions existing at the junctions between schedules are not explicit and the equations are based on the CREs of the constituent schedules assessed individually without reference to their context in the regime as a whole. This independent evaluation of CREs for each schedule has resulted in a considerable simplification in the calculation of complex problems. The calculations are further simplified by the use of suitable tables and nomograms, so that the mathematics involved is reduced to simple arithmetical operations which require at the most the use of a slide rule but can be done by hand. The order of procedure in the presentation and calculation of CRE problems can be summarised in an evaluation procedure sheet. The resulting simple methods for solving practical problems of any complexity on the CRE-system are demonstrated by a number of examples. (author)

  5. Cumulative trauma disorders: A review.

    Science.gov (United States)

    Iqbal, Zaheen A; Alghadir, Ahmad H

    2017-08-03

    Cumulative trauma disorder (CTD) is a term for various injuries of the musculoskeletal and nervous systems that are caused by repetitive tasks, forceful exertions, vibrations, mechanical compression or sustained postures. Although there are many studies citing incidence of CTDs, there are fewer articles about its etiology, pathology and management. The aim of our study was to discuss the etiology, pathogenesis, prevention and management of CTDs. A literature search was performed using various electronic databases. The search was limited to articles in English language pertaining to randomized clinical trials, cohort studies and systematic reviews of CTDs. A total of 180 papers were identified to be relevant published since 1959. Out of these, 125 papers reported about its incidence and 50 about its conservative treatment. Workplace environment, same task repeatability and little variability, decreased time for rest, increase in expectations are major factors for developing CTDs. Prevention of its etiology and early diagnosis can be the best to decrease its incidence and severity. For effective management of CTDs, its treatment should be divided into Primordial, Primary, Secondary and Tertiary prevention.

  6. Cumulative radiation effect

    International Nuclear Information System (INIS)

    Kirk, J.; Cain, O.; Gray, W.M.

    1977-01-01

    Cumulative Radiation Effect (CRE) represents a scale of accumulative sub-tolerance radiation damage, with a unique value of the CRE describing a specific level of radiation effect. Computer calculations have been used to simplify the evaluation of problems associated with the applications of the CRE-system in radiotherapy. In a general appraisal of the applications of computers to the CRE-system, the various problems encountered in clinical radiotherapy have been categorised into those involving the evaluation of a CRE at a point in tissue and those involving the calculation of CRE distributions. As a general guide, the computer techniques adopted at the Glasgow Institute of Radiotherapeutics for the solution of CRE problems are presented, and consist basically of a package of three interactive programs for point CRE calculations and a Fortran program which calculates CRE distributions for iso-effect treatment planning. Many examples are given to demonstrate the applications of these programs, and special emphasis has been laid on the problem of treating a point in tissue with different doses per fraction on alternate treatment days. The wide range of possible clinical applications of the CRE-system has been outlined and described under the categories of routine clinical applications, retrospective and prospective surveys of patient treatment, and experimental and theoretical research. Some of these applications such as the results of surveys and studies of time optimisation of treatment schedules could have far-reaching consequences and lead to significant improvements in treatment and cure rates with the minimum damage to normal tissue. (author)

  7. Secant cumulants and toric geometry

    NARCIS (Netherlands)

    Michalek, M.; Oeding, L.; Zwiernik, P.W.

    2012-01-01

    We study the secant line variety of the Segre product of projective spaces using special cumulant coordinates adapted for secant varieties. We show that the secant variety is covered by open normal toric varieties. We prove that in cumulant coordinates its ideal is generated by binomial quadrics. We

  8. High cumulants of conserved charges and their statistical uncertainties

    Science.gov (United States)

    Li-Zhu, Chen; Ye-Yin, Zhao; Xue, Pan; Zhi-Ming, Li; Yuan-Fang, Wu

    2017-10-01

    We study the influence of measured high cumulants of conserved charges on their associated statistical uncertainties in relativistic heavy-ion collisions. With a given number of events, the measured cumulants randomly fluctuate with an approximately normal distribution, while the estimated statistical uncertainties are found to be correlated with corresponding values of the obtained cumulants. Generally, with a given number of events, the larger the cumulants we measure, the larger the statistical uncertainties that are estimated. The error-weighted averaged cumulants are dependent on statistics. Despite this effect, however, it is found that the three sigma rule of thumb is still applicable when the statistics are above one million. Supported by NSFC (11405088, 11521064, 11647093), Major State Basic Research Development Program of China (2014CB845402) and Ministry of Science and Technology (MoST) (2016YFE0104800)

  9. Does quasi-long-range order in the two-dimensional XY model really survive weak random phase fluctuations?

    International Nuclear Information System (INIS)

    Mudry, Christopher; Wen Xiaogang

    1999-01-01

    Effective theories for random critical points are usually non-unitary, and thus may contain relevant operators with negative scaling dimensions. To study the consequences of the existence of negative-dimensional operators, we consider the random-bond XY model. It has been argued that the XY model on a square lattice, when weakly perturbed by random phases, has a quasi-long-range ordered phase (the random spin wave phase) at sufficiently low temperatures. We show that infinitely many relevant perturbations to the proposed critical action for the random spin wave phase were omitted in all previous treatments. The physical origin of these perturbations is intimately related to the existence of broadly distributed correlation functions. We find that those relevant perturbations do enter the Renormalization Group equations, and affect critical behavior. This raises the possibility that the random XY model has no quasi-long-range ordered phase and no Kosterlitz-Thouless (KT) phase transition

  10. Cluster-randomized study of intermittent preventive treatment for malaria in infants (IPTi in southern Tanzania: evaluation of impact on survival

    Directory of Open Access Journals (Sweden)

    Schellenberg Joanna

    2011-12-01

    Full Text Available Abstract Background Intermittent Preventive Treatment for malaria control in infants (IPTi consists of the administration of a treatment dose of an anti-malarial drug, usually sulphadoxine-pyrimethamine, at scheduled intervals, regardless of the presence of Plasmodium falciparum infection. A pooled analysis of individually randomized trials reported that IPTi reduced clinical episodes by 30%. This study evaluated the effect of IPTi on child survival in the context of a five-district implementation project in southern Tanzania. [Trial registration: clinical trials.gov NCT00152204]. Methods After baseline household and health facility surveys in 2004, five districts comprising 24 divisions were randomly assigned either to receive IPTi (n = 12 or not (n = 12. Implementation started in March 2005, led by routine health services with support from the research team. In 2007, a large household survey was undertaken to assess the impact of IPTi on survival in infants aged two-11 months through birth history interviews with all women aged 13-49 years. The analysis is based on an "intention-to-treat" ecological design, with survival outcomes analysed according to the cluster in which the mothers lived. Results Survival in infants aged two-11 months was comparable in IPTi and comparison areas at baseline. In intervention areas in 2007, 48% of children aged 12-23 months had documented evidence of receiving three doses of IPTi, compared to 2% in comparison areas (P P = 0.31. Conclusion The lack of evidence of an effect of IPTi on survival could be a false negative result due to a lack of power or imbalance of unmeasured confounders. Alternatively, there could be no mortality impact of IPTi due to low coverage, late administration, drug resistance, decreased malaria transmission or improvements in vector control and case management. This study raises important questions for programme evaluation design.

  11. Association between expression of random gene sets and survival is evident in multiple cancer types and may be explained by sub-classification

    Science.gov (United States)

    2018-01-01

    One of the goals of cancer research is to identify a set of genes that cause or control disease progression. However, although multiple such gene sets were published, these are usually in very poor agreement with each other, and very few of the genes proved to be functional therapeutic targets. Furthermore, recent findings from a breast cancer gene-expression cohort showed that sets of genes selected randomly can be used to predict survival with a much higher probability than expected. These results imply that many of the genes identified in breast cancer gene expression analysis may not be causal of cancer progression, even though they can still be highly predictive of prognosis. We performed a similar analysis on all the cancer types available in the cancer genome atlas (TCGA), namely, estimating the predictive power of random gene sets for survival. Our work shows that most cancer types exhibit the property that random selections of genes are more predictive of survival than expected. In contrast to previous work, this property is not removed by using a proliferation signature, which implies that proliferation may not always be the confounder that drives this property. We suggest one possible solution in the form of data-driven sub-classification to reduce this property significantly. Our results suggest that the predictive power of random gene sets may be used to identify the existence of sub-classes in the data, and thus may allow better understanding of patient stratification. Furthermore, by reducing the observed bias this may allow more direct identification of biologically relevant, and potentially causal, genes. PMID:29470520

  12. The challenge of cumulative impacts

    Energy Technology Data Exchange (ETDEWEB)

    Masden, Elisabeth

    2011-07-01

    Full text: As governments pledge to combat climate change, wind turbines are becoming a common feature of terrestrial and marine environments. Although wind power is a renewable energy source and a means of reducing carbon emissions, there is a need to ensure that the wind farms themselves do not damage the environment. There is particular concern over the impacts of wind farms on bird populations, and with increasing numbers of wind farm proposals, the concern focuses on cumulative impacts. Individually, a wind farm, or indeed any activity/action, may have minor effects on the environment, but collectively these may be significant, potentially greater than the sum of the individual parts acting alone. Cumulative impact assessment is a legislative requirement of environmental impact assessment but such assessments are rarely adequate restricting the acquisition of basic knowledge about the cumulative impacts of wind farms on bird populations. Reasons for this are numerous but a recurring theme is the lack of clear definitions and guidance on how to perform cumulative assessments. Here we present a conceptual framework and include illustrative examples to demonstrate how the framework can be used to improve the planning and execution of cumulative impact assessments. The core concept is that explicit definitions of impacts, actions and scales of assessment are required to reduce uncertainty in the process of assessment and improve communication between stake holders. Only when it is clear what has been included within a cumulative assessment, is it possible to make comparisons between developments. Our framework requires improved legislative guidance on the actions to include in assessments, and advice on the appropriate baselines against which to assess impacts. Cumulative impacts are currently considered on restricted scales (spatial and temporal) relating to individual development assessments. We propose that benefits would be gained from elevating cumulative

  13. Cumulative irritation potential of topical retinoid formulations.

    Science.gov (United States)

    Leyden, James J; Grossman, Rachel; Nighland, Marge

    2008-08-01

    Localized irritation can limit treatment success with topical retinoids such as tretinoin and adapalene. The factors that influence irritant reactions have been shown to include individual skin sensitivity, the particular retinoid and concentration used, and the vehicle formulation. To compare the cutaneous tolerability of tretinoin 0.04% microsphere gel (TMG) with that of adapalene 0.3% gel and a standard tretinoin 0.025% cream. The results of 2 randomized, investigator-blinded studies of 2 to 3 weeks' duration, which utilized a split-face method to compare cumulative irritation scores induced by topical retinoids in subjects with healthy skin, were combined. Study 1 compared TMG 0.04% with adapalene 0.3% gel over 2 weeks, while study 2 compared TMG 0.04% with tretinoin 0.025% cream over 3 weeks. In study 1, TMG 0.04% was associated with significantly lower cumulative scores for erythema, dryness, and burning/stinging than adapalene 0.3% gel. However, in study 2, there were no significant differences in cumulative irritation scores between TMG 0.04% and tretinoin 0.025% cream. Measurements of erythema by a chromameter showed no significant differences between the test formulations in either study. Cutaneous tolerance of TMG 0.04% on the face was superior to that of adapalene 0.3% gel and similar to that of a standard tretinoin cream containing a lower concentration of the drug (0.025%).

  14. A preliminary randomized clinical trial comparing diode laser and scalpel periosteal incision during implant surgery: impact on postoperative morbidity and implant survival.

    Science.gov (United States)

    Shahnaz, Aysan; Jamali, Raika; Mohammadi, Farnush; Khorsand, Afshin; Moslemi, Neda; Fekrazad, Reza

    2018-01-01

    The aim of this preliminary randomized clinical trial was to compare: (1) post-operative morbidity after application of laser or scalpel incision for flap advancement during implant surgery and bone grafting and (2) implant survival rate following flap advancement with laser or scalpel incision after 6 months of loading. Eighteen patients who were scheduled for dental implant placement and simultaneous bone grafting were randomly assigned to test or control groups. Diode laser (810 nm, 2 W, pulse interval 200 μs; pulse length 100 μs, 400-μm initiated fiber tip), or scalpel (control) was used to sever the periosteum to create a tension-free flap. Visual analogue scale (VAS) pain score, rate of nonsteroid anti-inflammatory drug (NSAID) consumption, intensity of swelling, and ecchymosis were measured for the six postsurgical days. Six months after loading, implant survival was assessed. VAS pain score (during the first four postoperative days), rate of NSAID consumption (during the first three postoperative days), and intensity of swelling (during the first five postoperative days) were significantly lower in the test group compared to the control group (All P values laser for performing periosteal releasing incision reduced the incidence and severity of postoperative morbidity of the patients undergone implant surgery in conjunction with bone augmentation procedure. We did not find any detrimental effect of laser incision on the implant survival within 6 months of loading.

  15. Spatial Random Effects Survival Models to Assess Geographical Inequalities in Dengue Fever Using Bayesian Approach: a Case Study

    Science.gov (United States)

    Astuti Thamrin, Sri; Taufik, Irfan

    2018-03-01

    Dengue haemorrhagic fever (DHF) is an infectious disease caused by dengue virus. The increasing number of people with DHF disease correlates with the neighbourhood, for example sub-districts, and the characteristics of the sub-districts are formed from individuals who are domiciled in the sub-districts. Data containing individuals and sub-districts is a hierarchical data structure, called multilevel analysis. Frequently encountered response variable of the data is the time until an event occurs. Multilevel and spatial models are being increasingly used to obtain substantive information on area-level inequalities in DHF survival. Using a case study approach, we report on the implications of using multilevel with spatial survival models to study geographical inequalities in all cause survival.

  16. Survival in Malnourished Older Patients Receiving Post-Discharge Nutritional Support; Long-Term Results of a Randomized Controlled Trial

    NARCIS (Netherlands)

    Neelemaat, F; van Keeken, S; Langius, J A E; de van der Schueren, M A E; Thijs, A; Bosmans, J E

    2017-01-01

    BACKGROUND: Previous analyses have shown that a post-discharge individualized nutritional intervention had positive effects on body weight, lean body mass, functional limitations and fall incidents in malnourished older patients. However, the impact of this intervention on survival has not yet been

  17. Robust estimation of the expected survival probabilities from high-dimensional Cox models with biomarker-by-treatment interactions in randomized clinical trials

    Directory of Open Access Journals (Sweden)

    Nils Ternès

    2017-05-01

    Full Text Available Abstract Background Thanks to the advances in genomics and targeted treatments, more and more prediction models based on biomarkers are being developed to predict potential benefit from treatments in a randomized clinical trial. Despite the methodological framework for the development and validation of prediction models in a high-dimensional setting is getting more and more established, no clear guidance exists yet on how to estimate expected survival probabilities in a penalized model with biomarker-by-treatment interactions. Methods Based on a parsimonious biomarker selection in a penalized high-dimensional Cox model (lasso or adaptive lasso, we propose a unified framework to: estimate internally the predictive accuracy metrics of the developed model (using double cross-validation; estimate the individual survival probabilities at a given timepoint; construct confidence intervals thereof (analytical or bootstrap; and visualize them graphically (pointwise or smoothed with spline. We compared these strategies through a simulation study covering scenarios with or without biomarker effects. We applied the strategies to a large randomized phase III clinical trial that evaluated the effect of adding trastuzumab to chemotherapy in 1574 early breast cancer patients, for which the expression of 462 genes was measured. Results In our simulations, penalized regression models using the adaptive lasso estimated the survival probability of new patients with low bias and standard error; bootstrapped confidence intervals had empirical coverage probability close to the nominal level across very different scenarios. The double cross-validation performed on the training data set closely mimicked the predictive accuracy of the selected models in external validation data. We also propose a useful visual representation of the expected survival probabilities using splines. In the breast cancer trial, the adaptive lasso penalty selected a prediction model with 4

  18. Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer : A systematic review

    NARCIS (Netherlands)

    Strojan, Primoz; Vermorken, Jan B.; Beitler, Jonathan J.; Saba, Nabil F.; Haigentz, Missak; Bossi, Paolo; Worden, Francis P.; Langendijk, Johannes A.; Eisbruch, Avraham; Mendenhall, William M.; Lee, Anne W. M.; Harrison, Louis B.; Bradford, Carol R.; Smee, Robert; Silver, Carl E.; Rinaldo, Alessandra; Ferlito, Alfio

    Background. The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for nonmetastatic head and neck squamous cell carcinoma (HNSCC) has not been determined. Methods. The absolute survival benefit at 5 years of concurrent chemoradiotherapy

  19. The INCA trial (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Casper, Markus; Mengel, Martin; Fuhrmann, Christine; Herrmann, Eva; Appenrodt, Beate; Schiedermaier, Peter; Reichert, Matthias; Bruns, Tony; Engelmann, Cornelius; Grünhage, Frank; Lammert, Frank

    2015-03-08

    Patients with liver cirrhosis have a highly elevated risk of developing bacterial infections that significantly decrease survival rates. One of the most relevant infections is spontaneous bacterial peritonitis (SBP). Recently, NOD2 germline variants were found to be potential predictors of the development of infectious complications and mortality in patients with cirrhosis. The aim of the INCA (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites) trial is to investigate whether survival of this genetically defined high-risk group of patients with cirrhosis defined by the presence of NOD2 variants is improved by primary antibiotic prophylaxis of SBP. The INCA trial is a double-blind, placebo-controlled clinical trial with two parallel treatment arms (arm 1: norfloxacin 400 mg once daily; arm 2: placebo once daily; 12-month treatment and observational period). Balanced randomization of 186 eligible patients with stratification for the protein content of the ascites (INCA trial is first in the field of hepatology aimed at rapidly transferring and validating information on individual genetic risk into clinical decision algorithms. German Clinical Trials Register DRKS00005616 . Registered 22 January 2014. EU Clinical Trials Register EudraCT 2013-001626-26 . Registered 26 January 2015.

  20. A randomized controlled trial of cognitive-behavioral stress management in breast cancer: survival and recurrence at 11-year follow-up.

    Science.gov (United States)

    Stagl, Jamie M; Lechner, Suzanne C; Carver, Charles S; Bouchard, Laura C; Gudenkauf, Lisa M; Jutagir, Devika R; Diaz, Alain; Yu, Qilu; Blomberg, Bonnie B; Ironson, Gail; Glück, Stefan; Antoni, Michael H

    2015-11-01

    Non-metastatic breast cancer patients often experience psychological distress which may influence disease progression and survival. Cognitive-behavioral stress management (CBSM) improves psychological adaptation and lowers distress during breast cancer treatment and long-term follow-ups. We examined whether breast cancer patients randomized to CBSM had improved survival and recurrence 8-15 years post-enrollment. From 1998 to 2005, women (N = 240) 2-10 weeks post-surgery for non-metastatic Stage 0-IIIb breast cancer were randomized to a 10-week, group-based CBSM intervention (n = 120) or a 1-day psychoeducational seminar control (n = 120). In 2013, 8-15 years post-study enrollment (11-year median), recurrence and survival data were collected. Cox Proportional Hazards Models and Weibull Accelerated Failure Time tests were used to assess group differences in all-cause mortality, breast cancer-specific mortality, and disease-free interval, controlling for biomedical confounders. Relative to the control, the CBSM group was found to have a reduced risk of all-cause mortality (HR = 0.21; 95 % CI [0.05, 0.93]; p = .040). Restricting analyses to women with invasive disease revealed significant effects of CBSM on breast cancer-related mortality (p = .006) and disease-free interval (p = .011). CBSM intervention delivered post-surgery may provide long-term clinical benefit for non-metastatic breast cancer patients in addition to previously established psychological benefits. Results should be interpreted with caution; however, the findings contribute to the limited evidence regarding physical benefits of psychosocial intervention post-surgery for non-metastatic breast cancer. Additional research is necessary to confirm these results and investigate potential explanatory mechanisms, including physiological pathways, health behaviors, and treatment adherence changes.

  1. Survival of bonded lingual retainers with chemical or photo polymerization over a 2-year period: a single-center, randomized controlled clinical trial.

    Science.gov (United States)

    Pandis, Nikolaos; Fleming, Padhraig S; Kloukos, Dimitrios; Polychronopoulou, Argy; Katsaros, Christos; Eliades, Theodore

    2013-08-01

    The objective of this trial was to compare the survival rates of mandibular lingual retainers bonded with either chemically cured or light-cured adhesive after orthodontic treatment. Patients having undergone orthodontic treatment at a private orthodontic office were randomly allocated to fixed retainers placed with chemically cured composite or light-cured composite. Eligibility criteria included no active caries, restorations, or fractures on the mandibular anterior teeth, and adequate oral hygiene. The main outcome was any type of first-time lingual retainer breakage; pattern of failure (adapted adhesive remnant index scores) was a secondary outcome. Randomization was accomplished with random permuted blocks of 20 patients with allocation concealed in sequentially numbered, opaque, sealed envelopes. Blinding was applicable for outcome assessment only. Patients were reviewed at 1, 3, and 6 months and then every 6 months after placement of the retainer until completion of the study. Data were analyzed using survival analysis including Cox regression; sensitivity analysis was carried out after data imputation for subjects lost to follow-up. Two hundred twenty patients (median age, 16 years; interquartile range, 2; range, 12-47 years) were randomized in a 1:1 ratio to either chemical or light curing. Baseline characteristics were similar between groups, the median follow-up period was 2.19 years (range, 0.003-3.64 years), and 16 patients were lost to follow-up. At a minimum follow-up of 2 years, 47 of 110 (42.7%) and 55 of 110 (50.0%) retainers had some type of failure with chemically cured and light-cured adhesive, respectively (log-rank test, P = 0.35). Data were analyzed on an intention-to-treat basis, and the hazard ratio (HR) was 1.15 (95% confidence interval [CI], 0.88-1.70; P = 0.47). There was weak evidence that age is a significant predictor for lingual retainer failures (HR, 0.96; 95% CI, 0.93-1.00; P = 0.08). Adhesive remnant index scoring was

  2. Randomized, placebo controlled study of the effect of propentofylline on survival time and quality of life of cats with feline infectious peritonitis.

    Science.gov (United States)

    Fischer, Y; Ritz, S; Weber, K; Sauter-Louis, C; Hartmann, K

    2011-01-01

    Currently there is no drug proven to effectively treat cats with feline infectious peritonitis (FIP). Propentofylline (PPF) can decrease vasculitis, and therefore prolong survival time in cats with FIP, and increase their quality of life. Twenty-three privately owned cats with FIP. Placebo-controlled double-blind trial. FIP was confirmed by histology or immunostaining of feline coronavirus (FCoV) antigen in effusion or tissue macrophages or both. The cats were randomly selected for treatment with either PPF or placebo. All cats received additional treatment with glucocorticoids, antibiotics, and low molecular weight heparin according to methods. There was no statistically significant difference in the survival time of cats treated with PPF (8 days, 95% CI 5.4-10.6) versus placebo (7.5 days, 95% CI 4.4-9.6). The median survival time of all cats was 8 days (4-36 days). There was neither a difference in quality of life (day 7, P = .892), in the amount of effusion (day 7, P = .710), the tumor necrosis factor-alpha (TNF-α) concentration (day 7, P = .355), nor in any other variable investigated in this study, including a complete blood count, and a small animal biochemistry profile. This study did not detect an effect of PPF on the survival time, the quality of life, or any clinical or laboratory parameter in cats with FIP. Therefore, PPF does not appear to be an effective treatment option in cats with a late stage of the disease FIP. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  3. Cumulative risk, cumulative outcome: a 20-year longitudinal study.

    Directory of Open Access Journals (Sweden)

    Leslie Atkinson

    Full Text Available Cumulative risk (CR models provide some of the most robust findings in the developmental literature, predicting numerous and varied outcomes. Typically, however, these outcomes are predicted one at a time, across different samples, using concurrent designs, longitudinal designs of short duration, or retrospective designs. We predicted that a single CR index, applied within a single sample, would prospectively predict diverse outcomes, i.e., depression, intelligence, school dropout, arrest, smoking, and physical disease from childhood to adulthood. Further, we predicted that number of risk factors would predict number of adverse outcomes (cumulative outcome; CO. We also predicted that early CR (assessed at age 5/6 explains variance in CO above and beyond that explained by subsequent risk (assessed at ages 12/13 and 19/20. The sample consisted of 284 individuals, 48% of whom were diagnosed with a speech/language disorder. Cumulative risk, assessed at 5/6-, 12/13-, and 19/20-years-old, predicted aforementioned outcomes at age 25/26 in every instance. Furthermore, number of risk factors was positively associated with number of negative outcomes. Finally, early risk accounted for variance beyond that explained by later risk in the prediction of CO. We discuss these findings in terms of five criteria posed by these data, positing a "mediated net of adversity" model, suggesting that CR may increase some central integrative factor, simultaneously augmenting risk across cognitive, quality of life, psychiatric and physical health outcomes.

  4. Overall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator's Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III Trial.

    Science.gov (United States)

    Larkin, James; Minor, David; D'Angelo, Sandra; Neyns, Bart; Smylie, Michael; Miller, Wilson H; Gutzmer, Ralf; Linette, Gerald; Chmielowski, Bartosz; Lao, Christopher D; Lorigan, Paul; Grossmann, Kenneth; Hassel, Jessica C; Sznol, Mario; Daud, Adil; Sosman, Jeffrey; Khushalani, Nikhil; Schadendorf, Dirk; Hoeller, Christoph; Walker, Dana; Kong, George; Horak, Christine; Weber, Jeffrey

    2018-02-01

    Purpose Until recently, limited options existed for patients with advanced melanoma who experienced disease progression while receiving treatment with ipilimumab. Here, we report the coprimary overall survival (OS) end point of CheckMate 037, which has previously shown that nivolumab resulted in more patients achieving an objective response compared with chemotherapy regimens in ipilimumab-refractory patients with advanced melanoma. Patients and Methods Patients were stratified by programmed death-ligand 1 expression, BRAF status, and best prior cytotoxic T-lymphocyte antigen-4 therapy response, then randomly assigned 2:1 to nivolumab 3 mg/kg intravenously every 2 weeks or investigator's choice chemotherapy (ICC; dacarbazine 1,000 mg/m 2 every 3 weeks or carboplatin area under the curve 6 plus paclitaxel 175 mg/m 2 every 3 weeks). Patients were treated until they experienced progression or unacceptable toxicity, with follow-up of approximately 2 years. Results Two hundred seventy-two patients were randomly assigned to nivolumab (99% treated) and 133 to ICC (77% treated). More nivolumab-treated patients had brain metastases (20% v 14%) and increased lactate dehydrogenase levels (52% v 38%) at baseline; 41% of patients treated with ICC versus 11% of patients treated with nivolumab received anti-programmed death 1 agents after randomly assigned therapy. Median OS was 16 months for nivolumab versus 14 months for ICC (hazard ratio, 0.95; 95.54% CI, 0.73 to 1.24); median progression-free survival was 3.1 months versus 3.7 months, respectively (hazard ratio, 1.0; 95.1% CI, 0.78 to 1.436). Overall response rate (27% v 10%) and median duration of response (32 months v 13 months) were notably higher for nivolumab versus ICC. Fewer grade 3 and 4 treatment-related adverse events were observed in patients on nivolumab (14% v 34%). Conclusion Nivolumab demonstrated higher, more durable responses but no difference in survival compared with ICC. OS should be interpreted with

  5. Application of random survival forests in understanding the determinants of under-five child mortality in Uganda in the presence of covariates that satisfy the proportional and non-proportional hazards assumption.

    Science.gov (United States)

    Nasejje, Justine B; Mwambi, Henry

    2017-09-07

    Uganda just like any other Sub-Saharan African country, has a high under-five child mortality rate. To inform policy on intervention strategies, sound statistical methods are required to critically identify factors strongly associated with under-five child mortality rates. The Cox proportional hazards model has been a common choice in analysing data to understand factors strongly associated with high child mortality rates taking age as the time-to-event variable. However, due to its restrictive proportional hazards (PH) assumption, some covariates of interest which do not satisfy the assumption are often excluded in the analysis to avoid mis-specifying the model. Otherwise using covariates that clearly violate the assumption would mean invalid results. Survival trees and random survival forests are increasingly becoming popular in analysing survival data particularly in the case of large survey data and could be attractive alternatives to models with the restrictive PH assumption. In this article, we adopt random survival forests which have never been used in understanding factors affecting under-five child mortality rates in Uganda using Demographic and Health Survey data. Thus the first part of the analysis is based on the use of the classical Cox PH model and the second part of the analysis is based on the use of random survival forests in the presence of covariates that do not necessarily satisfy the PH assumption. Random survival forests and the Cox proportional hazards model agree that the sex of the household head, sex of the child, number of births in the past 1 year are strongly associated to under-five child mortality in Uganda given all the three covariates satisfy the PH assumption. Random survival forests further demonstrated that covariates that were originally excluded from the earlier analysis due to violation of the PH assumption were important in explaining under-five child mortality rates. These covariates include the number of children under the

  6. A randomized trial of the effect of a plant-based dietary pattern on additional breast cancer events and survival: the Women's Healthy Eating and Living (WHEL) Study.

    Science.gov (United States)

    Pierce, John P; Faerber, Susan; Wright, Fred A; Rock, Cheryl L; Newman, Vicky; Flatt, Shirley W; Kealey, Sheila; Jones, Vicky E; Caan, Bette J; Gold, Ellen B; Haan, Mary; Hollenbach, Kathryn A; Jones, Lovell; Marshall, James R; Ritenbaugh, Cheryl; Stefanick, Marcia L; Thomson, Cynthia; Wasserman, Linda; Natarajan, Loki; Thomas, Ronald G; Gilpin, Elizabeth A

    2002-12-01

    The Women's Healthy Eating and Living (WHEL) Study is a multisite randomized controlled trial of the effectiveness of a high-vegetable, low-fat diet, aimed at markedly raising circulating carotenoid concentrations from food sources, in reducing additional breast cancer events and early death in women with early-stage invasive breast cancer (within 4 years of diagnosis). The study randomly assigned 3088 such women to an intensive diet intervention or to a comparison group between 1995 and 2000 and is expected to follow them through 2006. Two thirds of these women were under 55 years of age at randomization. This research study has a coordinating center and seven clinical sites. Randomization was stratified by age, stage of tumor and clinical site. A comprehensive intervention program that includes intensive telephone counseling, cooking classes and print materials helps shift the dietary pattern of women in the intervention. Through an innovative telephone counseling program, dietary counselors encourage women in the intervention group to meet the following daily behavioral targets: five vegetable servings, 16 ounces of vegetable juice, three fruit servings, 30 g of fiber and 15-20% energy from fat. Adherence assessments occur at baseline, 6, 12, 24 or 36, 48 and 72 months. These assessments can include dietary intake (repeated 24-hour dietary recalls and food frequency questionnaire), circulating carotenoid concentrations, physical measures and questionnaires about health symptoms, quality of life, personal habits and lifestyle patterns. Outcome assessments are completed by telephone interview every 6 months with medical record verification. We will assess evidence of effectiveness by the length of the breast cancer event-free interval, as well as by overall survival separately in all the women in the study as well as specifically in women under and over the age of 55 years.

  7. Bonded versus vacuum-formed retainers: a randomized controlled trial. Part 1: stability, retainer survival, and patient satisfaction outcomes after 12 months.

    Science.gov (United States)

    Forde, Katherine; Storey, Madeleine; Littlewood, Simon J; Scott, Paul; Luther, Friedy; Kang, Jing

    2017-10-20

    There is a shortage of evidence on the best type of retainer. Evaluate upper and lower bonded retainers (BRs) versus upper and lower vacuum-formed retainers (VFRs) over 12 months, in terms of stability, retainer survival, and patient satisfaction. Two-arm parallel group multi-centre randomized controlled clinical trial. Sixty consecutive patients completing fixed appliance therapy and requiring retainers were recruited from 3 hospital departments. They were randomly allocated to either upper and lower labial segment BRs (n = 30) or upper and lower full-arch VFRs (n = 30). Primary outcome was stability. Secondary outcomes were retainer survival and patient satisfaction. A random sequence of treatment allocation was computer-generated and implemented by sealing in sequentially numbered opaque sealed envelopes independently prepared in advance. Patients, operators and outcome could not be blinded due to the nature of the intervention. Thirty patients received BRs (median [Mdn] age 16 years, inter-quartile range [IQR] = 2) and 30 received VFRs (Mdn age 17 years, IQR = 4). Baseline characteristics were similar between groups. At 12 months, there were no statistically significant inter-group differences in post-treatment change of maxillary labial segment alignment (BR = 1.1 mm, IQR = 1.56, VFR = 0.76 mm, IQR = 1.55, P = 0.61); however, there was greater post-treatment change in the mandibular VFR group (BR = 0.77 mm, IQR = 1.46, VFR = 1.69mm, IQR = 2.00, P = 0.008). The difference in maxillary retainer survival rates were statistically non-significant, P = 0.34 (BR = 63.6%, 239.3 days, 95% confidence interval [CI] = 191.1-287.5, VFR = 73.3%, 311.1 days, 95% CI = 278.3-344.29). The mandibular BR had a lower survival rate (P = 0.01) at 12 months (BR = 50%, 239.3 days 95% CI = 191.1-287.5, VFR = 80%, 324.9 days 95% CI = 295.4-354.4). More subjects with VFRs reported discomfort (P = 0.002) and speech difficulties (P = 0.004) but found them easier to clean than those with

  8. A flexible and coherent test/estimation procedure based on restricted mean survival times for censored time-to-event data in randomized clinical trials.

    Science.gov (United States)

    Horiguchi, Miki; Cronin, Angel M; Takeuchi, Masahiro; Uno, Hajime

    2018-04-22

    In randomized clinical trials where time-to-event is the primary outcome, almost routinely, the logrank test is prespecified as the primary test and the hazard ratio is used to quantify treatment effect. If the ratio of 2 hazard functions is not constant, the logrank test is not optimal and the interpretation of hazard ratio is not obvious. When such a nonproportional hazards case is expected at the design stage, the conventional practice is to prespecify another member of weighted logrank tests, eg, Peto-Prentice-Wilcoxon test. Alternatively, one may specify a robust test as the primary test, which can capture various patterns of difference between 2 event time distributions. However, most of those tests do not have companion procedures to quantify the treatment difference, and investigators have fallen back on reporting treatment effect estimates not associated with the primary test. Such incoherence in the "test/estimation" procedure may potentially mislead clinicians/patients who have to balance risk-benefit for treatment decision. To address this, we propose a flexible and coherent test/estimation procedure based on restricted mean survival time, where the truncation time τ is selected data dependently. The proposed procedure is composed of a prespecified test and an estimation of corresponding robust and interpretable quantitative treatment effect. The utility of the new procedure is demonstrated by numerical studies based on 2 randomized cancer clinical trials; the test is dramatically more powerful than the logrank, Wilcoxon tests, and the restricted mean survival time-based test with a fixed τ, for the patterns of difference seen in these cancer clinical trials. Copyright © 2018 John Wiley & Sons, Ltd.

  9. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial.

    Science.gov (United States)

    Cortés, Javier; Rugo, Hope S; Awada, Ahmad; Twelves, Chris; Perez, Edith A; Im, Seock-Ah; Gómez-Pardo, Patricia; Schwartzberg, Lee S; Diéras, Veronique; Yardley, Denise A; Potter, David A; Mailliez, Audrey; Moreno-Aspitia, Alvaro; Ahn, Jin-Seok; Zhao, Carol; Hoch, Ute; Tagliaferri, Mary; Hannah, Alison L; O'Shaughnessy, Joyce

    2017-09-01

    Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician's choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744).

  10. Laparoscopic Complete Mesocolic Excision versus Open Complete Mesocolic Excision for Transverse Colon Cancer: Long-Term Survival Results of a Prospective Single Centre Non-Randomized Study.

    Science.gov (United States)

    Storli, Kristian Eeg; Eide, Geir Egil

    2016-01-01

    Laparoscopic complete mesocolic excision (CME) used in the treatment of transverse colon cancer has been questioned on the basis of the technical challenges. The aim of this study was to evaluate the medium- and long-term clinical and survival outcomes after laparoscopic and open CME for transverse colon cancer and to compare the 2 approaches. This study was a retrospective non-randomized study of patients with prospectively registered data on open and laparoscopic CME for transverse colon cancer tumour-node-metastasis stages I-III operated on between 2007 and 2014. This was a single-centre study in a community teaching hospital. A total of 56 patients with transverse colon cancer were included, excluding those with tumours in the colonic flexures. The outcome aims were 4-year time to recurrence (TTR) and cancer-specific survival (CSS). Morbidity was also measured. The 4-year TTR was 93.9% in the laparoscopic group and 91.3% in the open group (p = 0.71). The 4-year CSS was 97.0% in the laparoscopic group and 91.3% in the open group (p = 0.42). This was a prospective single-institution study with a small sample size. Results of the study suggest that the laparoscopic CME approach might be the preferred approach for transverse colon cancer, especially regarding its benefits in terms of short-term morbidity, length of stay and oncological outcome. © 2016 S. Karger AG, Basel.

  11. MRE11-Deficiency Associated with Improved Long-Term Disease Free Survival and Overall Survival in a Subset of Stage III Colon Cancer Patients in Randomized CALGB 89803 Trial

    Science.gov (United States)

    Pavelitz, Thomas; Renfro, Lindsay; Foster, Nathan R.; Caracol, Amber; Welsch, Piri; Lao, Victoria Valinluck; Grady, William B.; Niedzwiecki, Donna; Saltz, Leonard B.; Bertagnolli, Monica M.; Goldberg, Richard M.; Rabinovitch, Peter S.; Emond, Mary; Monnat, Raymond J.; Maizels, Nancy

    2014-01-01

    Purpose Colon cancers deficient in mismatch repair (MMR) may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer. Patients and Methods Cancer and Leukemia Group B 89803 (Alliance) randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV) or irinotecan+FU/LV (IFL), with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS), and a secondary endpoint was disease-free survival (DFS). Non-proportional hazards were addressed using time-dependent covariates in Cox analyses. Results Of 625 tumor cases examined, 70 (11.2%) exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11). In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed. Conclusions Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples. Trial Registration ClinicalTrials.gov NCT00003835 PMID:25310185

  12. MRE11-deficiency associated with improved long-term disease free survival and overall survival in a subset of stage III colon cancer patients in randomized CALGB 89803 trial.

    Directory of Open Access Journals (Sweden)

    Thomas Pavelitz

    Full Text Available Colon cancers deficient in mismatch repair (MMR may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer.Cancer and Leukemia Group B 89803 (Alliance randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV or irinotecan+FU/LV (IFL, with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS, and a secondary endpoint was disease-free survival (DFS. Non-proportional hazards were addressed using time-dependent covariates in Cox analyses.Of 625 tumor cases examined, 70 (11.2% exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11. In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed.Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples.ClinicalTrials.gov NCT00003835.

  13. The Algebra of the Cumulative Percent Operation.

    Science.gov (United States)

    Berry, Andrew J.

    2002-01-01

    Discusses how to help students avoid some pervasive reasoning errors in solving cumulative percent problems. Discusses the meaning of ."%+b%." the additive inverse of ."%." and other useful applications. Emphasizes the operational aspect of the cumulative percent concept. (KHR)

  14. Adaptive strategies for cumulative cultural learning.

    Science.gov (United States)

    Ehn, Micael; Laland, Kevin

    2012-05-21

    The demographic and ecological success of our species is frequently attributed to our capacity for cumulative culture. However, it is not yet known how humans combine social and asocial learning to generate effective strategies for learning in a cumulative cultural context. Here we explore how cumulative culture influences the relative merits of various pure and conditional learning strategies, including pure asocial and social learning, critical social learning, conditional social learning and individual refiner strategies. We replicate the Rogers' paradox in the cumulative setting. However, our analysis suggests that strategies that resolved Rogers' paradox in a non-cumulative setting may not necessarily evolve in a cumulative setting, thus different strategies will optimize cumulative and non-cumulative cultural learning. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Lymphadenectomy extent and survival of patients with gastric carcinoma: a systematic review and meta-analysis of time-to-event data from randomized trials.

    Science.gov (United States)

    Mocellin, Simone; Nitti, Donato

    2015-05-01

    The extent of lymph node dissection in patients with resectable non-metastatic primary carcinoma of the stomach is still a controversial matter of debate, with special regard to its effect on survival. We conducted a systematic review and meta-analysis of time-to-event data from randomized controlled trials (RCTs) comparing the three main types of lymphadenectomy (D1, D2, and D3) for gastric cancer. Hazard ratio (HR) was considered the effect measure for both overall (OS), disease-specific (DSS) and disease-free survival (DFS). The quality of the available evidence was assessed using the GRADE system. Eight RCTs enrolling 2515 patients were eligible. The meta-analysis of four RCTs (n=1599) showed a significant impact of D2 versus D1 lymphadenectomy on DSS (summary HR=0.807, CI: 0.705-0.924, P=0.002), the corresponding number-to-treat being equal to ten. This effect remained clinically valuable even after adjustment for postoperative mortality. However, the quality of evidence was graded as moderate due to inconsistency issues. When OS and DFS were considered, the meta-analysis of respectively five (n=1653) and three RCTs (n=1332) found no significant difference between D2 and D1 lymph node dissection (summary HR=0.911, CI: 0.708-1.172, P=0.471, and summary HR=0.946, CI: 0.840-1.066, P=0.366, respectively). However, at subgroup analysis D2 type resulted superior to D1 type lymphadenectomy in terms of OS considering the two RCTs carried out in Eastern countries (summary HR=0.627, CI: 0.396-0.994, P=0.047). As regards the D3 vs D2 comparison, the meta-analysis of the three available RCTs (n=862) showed no significant impact of more extended lymphadenectomy on OS (summary HR=0.990, CI: 0.814-1.205, P=0.924). Our findings support the superiority of D2 versus D1 lymphadenectomy in terms of survival benefit. However, this advantage is mainly limited to DSS, the level of evidence is moderate, and the interaction with other factors affecting patient survival (such as

  16. 32 CFR 651.16 - Cumulative impacts.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Cumulative impacts. 651.16 Section 651.16... § 651.16 Cumulative impacts. (a) NEPA analyses must assess cumulative effects, which are the impact on the environment resulting from the incremental impact of the action when added to other past, present...

  17. Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants.

    Science.gov (United States)

    Hehlmann, R; Lauseker, M; Saußele, S; Pfirrmann, M; Krause, S; Kolb, H J; Neubauer, A; Hossfeld, D K; Nerl, C; Gratwohl, A; Baerlocher, G M; Heim, D; Brümmendorf, T H; Fabarius, A; Haferlach, C; Schlegelberger, B; Müller, M C; Jeromin, S; Proetel, U; Kohlbrenner, K; Voskanyan, A; Rinaldetti, S; Seifarth, W; Spieß, B; Balleisen, L; Goebeler, M C; Hänel, M; Ho, A; Dengler, J; Falge, C; Kanz, L; Kremers, S; Burchert, A; Kneba, M; Stegelmann, F; Köhne, C A; Lindemann, H W; Waller, C F; Pfreundschuh, M; Spiekermann, K; Berdel, W E; Müller, L; Edinger, M; Mayer, J; Beelen, D W; Bentz, M; Link, H; Hertenstein, B; Fuchs, R; Wernli, M; Schlegel, F; Schlag, R; de Wit, M; Trümper, L; Hebart, H; Hahn, M; Thomalla, J; Scheid, C; Schafhausen, P; Verbeek, W; Eckart, M J; Gassmann, W; Pezzutto, A; Schenk, M; Brossart, P; Geer, T; Bildat, S; Schäfer, E; Hochhaus, A; Hasford, J

    2017-11-01

    Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.

  18. Hyperscaling breakdown and Ising spin glasses: The Binder cumulant

    Science.gov (United States)

    Lundow, P. H.; Campbell, I. A.

    2018-02-01

    Among the Renormalization Group Theory scaling rules relating critical exponents, there are hyperscaling rules involving the dimension of the system. It is well known that in Ising models hyperscaling breaks down above the upper critical dimension. It was shown by Schwartz (1991) that the standard Josephson hyperscaling rule can also break down in Ising systems with quenched random interactions. A related Renormalization Group Theory hyperscaling rule links the critical exponents for the normalized Binder cumulant and the correlation length in the thermodynamic limit. An appropriate scaling approach for analyzing measurements from criticality to infinite temperature is first outlined. Numerical data on the scaling of the normalized correlation length and the normalized Binder cumulant are shown for the canonical Ising ferromagnet model in dimension three where hyperscaling holds, for the Ising ferromagnet in dimension five (so above the upper critical dimension) where hyperscaling breaks down, and then for Ising spin glass models in dimension three where the quenched interactions are random. For the Ising spin glasses there is a breakdown of the normalized Binder cumulant hyperscaling relation in the thermodynamic limit regime, with a return to size independent Binder cumulant values in the finite-size scaling regime around the critical region.

  19. Radiographic Progression-Free Survival as a Clinically Meaningful End Point in Metastatic Castration-Resistant Prostate Cancer: The PREVAIL Randomized Clinical Trial.

    Science.gov (United States)

    Rathkopf, Dana E; Beer, Tomasz M; Loriot, Yohann; Higano, Celestia S; Armstrong, Andrew J; Sternberg, Cora N; de Bono, Johann S; Tombal, Bertrand; Parli, Teresa; Bhattacharya, Suman; Phung, De; Krivoshik, Andrew; Scher, Howard I; Morris, Michael J

    2018-05-01

    Drug development for metastatic castration-resistant prostate cancer has been limited by a lack of clinically relevant trial end points short of overall survival (OS). Radiographic progression-free survival (rPFS) as defined by the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) is a candidate end point that represents a clinically meaningful benefit to patients. To demonstrate the robustness of the PCWG2 definition and to examine the relationship between rPFS and OS. PREVAIL was a phase 3, randomized, double-blind, placebo-controlled multinational study that enrolled 1717 chemotherapy-naive men with metastatic castration-resistant prostate cancer from September 2010 through September 2012. The data were analyzed in November 2016. Patients were randomized 1:1 to enzalutamide 160 mg or placebo until confirmed radiographic disease progression or a skeletal-related event and initiation of either cytotoxic chemotherapy or an investigational agent for prostate cancer treatment. Sensitivity analyses (SAs) of investigator-assessed rPFS were performed using the final rPFS data cutoff (May 6, 2012; 439 events; SA1) and the interim OS data cutoff (September 16, 2013; 540 events; SA2). Additional SAs using investigator-assessed rPFS from the final rPFS data cutoff assessed the impact of skeletal-related events (SA3), clinical progression (SA4), a confirmatory scan for soft-tissue disease progression (SA5), and all deaths regardless of time after study drug discontinuation (SA6). Correlations between investigator-assessed rPFS (SA2) and OS were calculated using Spearman ρ and Kendall τ via Clayton copula. In the 1717 men (mean age, 72.0 [range, 43.0-93.0] years in enzalutamide arm and 71.0 [range, 42.0-93.0] years in placebo arm), enzalutamide significantly reduced risk of radiographic progression or death in all SAs, with hazard ratios of 0.22 (SA1; 95% CI, 0.18-0.27), 0.31 (SA2; 95% CI, 0.27-0.35), 0.21 (SA3; 95% CI, 0.18-0.26), 0.21 (SA4; 95% CI, 0.17-0.26), 0

  20. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial.

    Science.gov (United States)

    Kyriakopoulos, Christos E; Chen, Yu-Hui; Carducci, Michael A; Liu, Glenn; Jarrard, David F; Hahn, Noah M; Shevrin, Daniel H; Dreicer, Robert; Hussain, Maha; Eisenberger, Mario; Kohli, Manish; Plimack, Elizabeth R; Vogelzang, Nicholas J; Picus, Joel; Cooney, Matthew M; Garcia, Jorge A; DiPaola, Robert S; Sweeney, Christopher J

    2018-04-10

    Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m 2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.

  1. Extensions and Applications of the Cox-Aalen Survival Model

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2003-01-01

    Aalen additive risk model; competing risk; counting processes; Cox model; cumulative incidence function; goodness of fit; prediction of survival probability; time-varying effects......Aalen additive risk model; competing risk; counting processes; Cox model; cumulative incidence function; goodness of fit; prediction of survival probability; time-varying effects...

  2. Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial.

    Science.gov (United States)

    Brune, Mats; Castaigne, Sylvie; Catalano, John; Gehlsen, Kurt; Ho, Anthony D; Hofmann, Wolf-Karsten; Hogge, Donna E; Nilsson, Bo; Or, Reuven; Romero, Ana I; Rowe, Jacob M; Simonsson, Bengt; Spearing, Ruth; Stadtmauer, Edward A; Szer, Jeff; Wallhult, Elisabeth; Hellstrand, Kristoffer

    2006-07-01

    The primary objective of this phase 3 study was to determine whether postconsolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) improved the leukemia-free survival (LFS) of adult patients with acute myeloid leukemia (AML) in complete remission (CR). Three hundred twenty patients with AML (median age, 57 years; range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1) and randomly assigned to treatment with HDC/IL-2 or no treatment (control). Treatment comprised 10 21-day cycles with IL-2 (16 400 U/kg) plus HDC (0.5 mg); both compounds were administered by subcutaneous injection twice daily. Study arms were balanced for age, sex, previous treatment, leukemic karyotypes, time from CR to inclusion, and frequency of secondary leukemia. Three years after enrollment of the last patient, treatment with HDC/IL-2 was found to improve LFS over control in the study population (CR1 + CR > 1, n = 320; P < .01, log-rank test). For patients in CR1 (n = 261), treatment significantly improved LFS (P = .01) with 3-year LFS estimates of 40% (HDC/IL-2) compared with 26% (control). Side effects were typically mild to moderate. These results indicate that HDC/IL-2 treatment offers an efficacious and tolerable treatment for patients with AML in remission.

  3. Randomized study of control of the primary tumor and survival using preoperative radiation, radiation alone, or surgery alone in head and beck carcinomas

    International Nuclear Information System (INIS)

    Hintz, B.; Charyulu, K.; Chandler, J.R.; Sudarsanam, A.; Garciga, C.

    1979-01-01

    Fifty-five selected patients with previously untreated squamous cell carcinoma of the head and neck regions were studied in a randomized, prospective manner. The three treatment categories were primary radiation (Gp R), primary surgery (Gp S), and preoperative radiation of 4000 rads in four weeks (Gp R/S). The local control rates for the 44 evaluable patients with a two-year minimum followup were 24%, 39%, and 43%, respectively. Further treatment attempts in patients failing initial therapy yielded local control rates of 35%, 39%, and 43% for Gp R, Gp S, and Gp R/S, respectively. None of the local control rates nor the corresponding survival curves were significantly different at P < 0.10. However, the group sizes were sufficiently small that true differences might not have been detected. Postoperative complications were higher in the primary radiation failures subsequently operated upon compared to the primary surgery group (P = 0.07). A table is included in which the types of postoperative complications are listed and enumerated according to treatment regime

  4. Individual Patient Data Analysis of Progression-Free Survival Versus Overall Survival As a First-Line End Point for Metastatic Colorectal Cancer in Modern Randomized Trials: Findings From the Analysis and Research in Cancers of the Digestive System Database

    NARCIS (Netherlands)

    Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T.; Adams, Richard; Saltz, Leonard; Goldberg, Richard M.; Punt, Cornelis J. A.; Douillard, Jean-Yves; Hoff, Paulo M.; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C.; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F.; Heinemann, Volker; van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J.

    2015-01-01

    Purpose Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods Individual

  5. Complete cumulative index (1963-1983)

    International Nuclear Information System (INIS)

    1983-01-01

    This complete cumulative index covers all regular and special issues and supplements published by Atomic Energy Review (AER) during its lifetime (1963-1983). The complete cumulative index consists of six Indexes: the Index of Abstracts, the Subject Index, the Title Index, the Author Index, the Country Index and the Table of Elements Index. The complete cumulative index supersedes the Cumulative Indexes for Volumes 1-7: 1963-1969 (1970), and for Volumes 1-10: 1963-1972 (1972); this Index also finalizes Atomic Energy Review, the publication of which has recently been terminated by the IAEA

  6. Is There a Role for Pelvic Irradiation in Localized Prostate Adenocarcinoma? Update of the Long-Term Survival Results of the GETUG-01 Randomized Study

    Energy Technology Data Exchange (ETDEWEB)

    Pommier, Pascal, E-mail: Pascal.pommier@lyon.unicancer.fr [Department of Radiation Oncology, Centre Léon Bérard, Lyon (France); Chabaud, Sylvie [Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon (France); Lagrange, Jean-Leon [Department of Radiation Oncology, Centre Hospitalo-Universitaire H. Mondor, Créteil (France); Richaud, Pierre [Department of Radiation Oncology, Institut Bergognié, Bordeaux (France); Le Prise, Elisabeth [Department of Radiation Oncology, Centre Eugène Marquis, Rennes (France); Wagner, Jean-Philippe [Department of Radiation Oncology, Institut Andrée Dutreix, Dunkerque (France); Azria, David [Department of Radiation Oncology, Institut de Cancérologie de Montpellier, Montpellier (France); Beckendorf, Veronique [Department of Radiation Oncology, Institut de Cancérologie de Lorraine, Nancy (France); Suchaud, Jean-Philippe [Department of Radiation Oncology, Centre Hospitalier de Roanne, Roanne (France); Bernier, Valerie [Department of Radiation Oncology, Centre Oscar Lambret, Lille (France); Perol, David [Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon (France); Carrie, Christian [Department of Radiation Oncology, Centre Léon Bérard, Lyon (France)

    2016-11-15

    Purpose: To report the long-term results of the French Genitourinary Study Group (GETUG)-01 study in terms of event-free survival (EFS) and overall survival (OS) and assess the potential interaction between hormonotherapy and pelvic nodes irradiation. Patients and Methods: Between December 1998 and June 2004, 446 patients with T1b-T3, N0pNx, M0 prostate carcinoma were randomly assigned to either pelvic nodes and prostate or prostate-only radiation therapy. Patients were stratified into 2 groups: “low risk” (T1-T2 and Gleason score 6 and prostate-specific antigen <3× the upper normal limit of the laboratory) (92 patients) versus “high risk” (T3 or Gleason score >6 or prostate-specific antigen >3× the upper normal limit of the laboratory). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for high-risk patients. Radiation therapy was delivered with a 3-dimensional conformal technique, using a 4-field technique for the pelvic volume (46 Gy). The total dose recommended to the prostate moved from 66 Gy to 70 Gy during the course of the study. Criteria for EFS included biologic prostate-specific antigen recurrences and/or a local or metastatic progression. Results: With a median follow-up of 11.4 years, the 10-year OS and EFS were similar in the 2 treatment arms. A higher but nonsignificant EFS was observed in the low-risk subgroup in favor of pelvic nodes radiation therapy (77.2% vs 62.5%; P=.18). A post hoc subgroup analysis showed a significant benefit of pelvic irradiation when the risk of lymph node involvement was <15% (Roach formula). This benefit seemed to be limited to patients who did not receive hormonal therapy. Conclusion: Pelvic nodes irradiation did not statistically improve EFS or OS in the whole population but may be beneficial in selected low- and intermediate-risk prostate cancer patients treated with exclusive radiation therapy.

  7. Cost-effectiveness of invitation to food supplementation early in pregnancy combined with multiple micronutrients on infant survival: analysis of data from MINIMat randomized trial, Bangladesh.

    Science.gov (United States)

    Shaheen, Rubina; Persson, Lars Åke; Ahmed, Shakil; Streatfield, Peter Kim; Lindholm, Lars

    2015-05-28

    Absence of cost-effectiveness (CE) analyses limits the relevance of large-scale nutrition interventions in low-income countries. We analyzed if the effect of invitation to food supplementation early in pregnancy combined with multiple micronutrient supplements (MMS) on infant survival represented value for money compared to invitation to food supplementation at usual time in pregnancy combined with iron-folic acid. Outcome data, infant mortality (IM) rates, came from MINIMat trial (Maternal and Infant Nutrition Interventions, Matlab, ISRCTN16581394). In MINIMat, women were randomized to early (E around 9 weeks of pregnancy) or usual invitation (U around 20 weeks) to food supplementation and daily doses of 30 mg, or 60 mg iron with 400 μgm of folic acid, or MMS with 15 micronutrients including 30 mg iron and 400 μgm of folic acid. In MINIMat, EMMS significantly reduced IM compared to UFe60F (U plus 60 mg iron 400 μgm Folic acid). We present incremental CE ratios for incrementing UFe60F to EMMS. Costing data came mainly from a published study. By incrementing UFe60F to EMMS, one extra IM could be averted at a cost of US$907 and US$797 for NGO run and government run CNCs, respectively, and at US$1024 for a hypothetical scenario of highest cost. These comparisons generated one extra life year (LY) saved at US$30, US$27, and US$34, respectively. Incrementing UFe60F to EMMS in pregnancy seems worthwhile from health economic and public health standpoints. Maternal and Infant Nutrition Interventions, Matlab; ISRCTN16581394 ; Date of registration: Feb 16, 2009.

  8. Two-year survival analysis of twisted wire fixed retainer versus spiral wire and fiber-reinforced composite retainers: a preliminary explorative single-blind randomized clinical trial.

    Science.gov (United States)

    Sobouti, Farhad; Rakhshan, Vahid; Saravi, Mahdi Gholamrezaei; Zamanian, Ali; Shariati, Mahsa

    2016-03-01

    Traditional retainers (both metal and fiber-reinforced composite [FRC]) have limitations, and a retainer made from more flexible ligature wires might be advantageous. We aimed to compare an experimental design with two traditional retainers. In this prospective preliminary clinical trial, 150 post-treatment patients were enrolled and randomly divided into three groups of 50 patients each to receive mandibular canine-to-canine retainers made of FRC, flexible spiral wire (FSW), and twisted wire (TW). The patients were monitored monthly. The time at which the first signs of breakage/debonding were detected was recorded. The success rates of the retainers were compared using chi-squared, Kaplan-Meier, and Cox proportional-hazard regression analyses (α = 0.05). In total, 42 patients in the FRC group, 41 in the FSW group, and 45 in the TW group completed the study. The 2-year failure rates were 35.7% in the FRC group, 26.8% in the FSW group, and 17.8% in the TW group. These rates differed insignificantly (chi-squared p = 0.167). According to the Kaplan-Meier analysis, failure occurred at 19.95 months in the FRC group, 21.37 months in the FSW group, and 22.36 months in the TW group. The differences between the survival rates in the three groups were not significant (Cox regression p = 0.146). Although the failure rate of the experimental retainer was two times lower than that of the FRC retainer, the difference was not statistically significant. The experimental TW retainer was successful, and larger studies are warranted to verify these results.

  9. System-Reliability Cumulative-Binomial Program

    Science.gov (United States)

    Scheuer, Ernest M.; Bowerman, Paul N.

    1989-01-01

    Cumulative-binomial computer program, NEWTONP, one of set of three programs, calculates cumulative binomial probability distributions for arbitrary inputs. NEWTONP, CUMBIN (NPO-17555), and CROSSER (NPO-17557), used independently of one another. Program finds probability required to yield given system reliability. Used by statisticians and users of statistical procedures, test planners, designers, and numerical analysts. Program written in C.

  10. Common-Reliability Cumulative-Binomial Program

    Science.gov (United States)

    Scheuer, Ernest, M.; Bowerman, Paul N.

    1989-01-01

    Cumulative-binomial computer program, CROSSER, one of set of three programs, calculates cumulative binomial probability distributions for arbitrary inputs. CROSSER, CUMBIN (NPO-17555), and NEWTONP (NPO-17556), used independently of one another. Point of equality between reliability of system and common reliability of components found. Used by statisticians and users of statistical procedures, test planners, designers, and numerical analysts. Program written in C.

  11. Cumulative human impacts on marine predators

    DEFF Research Database (Denmark)

    Maxwell, Sara M; Hazen, Elliott L; Bograd, Steven J

    2013-01-01

    Stressors associated with human activities interact in complex ways to affect marine ecosystems, yet we lack spatially explicit assessments of cumulative impacts on ecologically and economically key components such as marine predators. Here we develop a metric of cumulative utilization and impact...

  12. Cumulative Student Loan Debt in Minnesota, 2015

    Science.gov (United States)

    Williams-Wyche, Shaun

    2016-01-01

    To better understand student debt in Minnesota, the Minnesota Office of Higher Education (the Office) gathers information on cumulative student loan debt from Minnesota degree-granting institutions. These data detail the number of students with loans by institution, the cumulative student loan debt incurred at that institution, and the percentage…

  13. Influence of complete administration of adjuvant chemotherapy cycles on overall and disease-free survival in locally advanced rectal cancer: post hoc analysis of a randomized, multicenter, non-inferiority, phase 3 trial.

    Science.gov (United States)

    Sandra-Petrescu, Flavius; Herrle, Florian; Burkholder, Iris; Kienle, Peter; Hofheinz, Ralf-Dieter

    2018-04-03

    A randomized trial demonstrated that capecitabine is at least as effective as fluorouracil in the adjuvant treatment of patients with locally advanced rectal cancer. However, not all patients receive all planned cycles of chemotherapy. Therefore it is of interest how complete or partial administration of chemotherapy influences oncological outcome. A post hoc analysis of a trial with 401 randomized patients, nine being excluded because of missing data, was performed. 392 patients (197 - capecitabine, 195 - fluorouracil) could be analyzed regarding the number of administered adjuvant chemotherapy cycles. In the subgroup of 361 patients with an overall survival of at least six months, five-year overall and disease-free survival were analyzed in respect to completion (complete vs. incomplete) of chemotherapy cycles. Survival rates and curves were calculated and compared using the log-rank test. The effect of completion of chemotherapy was adjusted for relevant confounding factors. Two hundred fifty-one (64.0%) of analyzed patients received all postoperative scheduled cycles. Five-year overall survival was significantly better in these patients compared to the incomplete group (76.0 vs. 60.6%, p cycles. Five-year overall survival was also significantly better than in the incomplete group (76.0 vs. 66.4%, p = 0.0073). Five-year disease free survival was numerically better (64.9 vs. 58.7%, p = 0.0646; HR [not all cycles vs. all cycles] = 1.42 95% CI: [0.98, 2.07]). Cox regression models show a non-significant better OS (p = 0.061) and DFS (p = 0.083), if chemotherapy cycles were administered completely. Complete administration of chemotherapy cycles was associated with improved five-year overall and disease-free survival in patients with locally advanced rectal cancer.

  14. Comparative efficacy, tolerability, and survival outcomes of various radiopharmaceuticals in castration-resistant prostate cancer with bone metastasis: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Tunio M

    2015-09-01

    Full Text Available Mutahir Tunio,1 Mushabbab Al Asiri,1 Abdulrehman Al Hadab,1 Yasser Bayoumi2 1Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 2Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt Background: A meta-analysis was conducted to assess the impact of radiopharmaceuticals (RPs in castration-resistant prostate cancer (CRPC on pain control, symptomatic skeletal events (SSEs, toxicity profile, quality of life (QoL, and overall survival (OS.Materials and methods: The PubMed/MEDLINE, CANCERLIT, EMBASE, Cochrane Library database, and other search engines were searched to identify randomized controlled trials (RCTs comparing RPs with control (placebo or radiation therapy in metastatic CRPC. Data were extracted and assessed for the risk of bias (Cochrane’s risk of bias tool. Pooled data were expressed as odds ratio (OR, with 95% confidence intervals (CIs; Mantel–Haenszel fixed-effects model.Results: Eight RCTs with a total patient population of 1,877 patients were identified. The use of RP was associated with significant reduction in pain intensity and SSE (OR: 0.63, 95% CI: 0.51–0.78, I2=27%, P<0.0001, improved QoL (OR: 0.71, 95% CI: 0.55–0.91, I2=65%, three trials, 1,178 patients, P=0.006, and a minimal improved OS (OR: 0.84, 95% CI: 0.64–1.04, I2=47%, seven trials, 1,845 patients, P=0.11. A subgroup analysis suggested an improved OS with radium-223 (OR: 0.68, 95% CI: 0.51–0.90, one trial, 921 patients and strontium-89 (OR: 0.21, 95% CI: 0.05–0.91, one trial, 49 patients. Strontium-89 (five trials was associated with increased rates of grade 3 and 4 thrombocytopenia (OR: 4.26, 95% CI: 2.22–8.18, P=0.01, leucopenia (OR: 7.98, 95% CI: 1.82–34.95, P=0.02, pain flare (OR: 6.82, 95% CI: 3.42–13.55, P=0.04, and emesis (OR: 3.61, 95% CI: 1.76–7.40, P=0.02.Conclusion: The use of RPs was associated with significant reduction in SSEs and improved QoL, while the radium-223

  15. Predictors for contrast media-induced nephropathy and long-term survival: Prospectively assessed data from the randomized controlled Dialysis-Versus-Diuresis (DVD) trial

    Science.gov (United States)

    Hölscher, Birgit; Heitmeyer, Christine; Fobker, Manfred; Breithardt, Günter; Schaefer, Roland M; Reinecke, Holger

    2008-01-01

    BACKGROUND: Among the numerous studies concerning contrast media-induced nephropathy (CIN), there was no prospective trial that provided data on the long-term outcomes. OBJECTIVES: To prospectively assess predictors of CIN and long-term outcomes of affected patients. METHODS: Four hundred twelve consecutive patients with serum creatinine levels of 115 μmol/L to 309 μmol/L (1.3 mg/dL to 3.5 mg/dL) undergoing elective coronary angiography were included. Patients were randomly assigned to periprocedural hydration alone, hydration plus onetime hemodialysis or hydration plus N-acetylcysteine. RESULTS: Multivariate logistic regression identified the following as predictors of CIN within 72 h (equivalent to an increase in creatinine 44.2 μmol/L [0.5 mg/dL] or more) : prophylactic postprocedural hemodialysis (OR 2.86, 95% CI 1.07 to 7.69), use of angiotensin-converting enzyme inhibitors (OR 6.16, 95% CI 2.01 to 18.93), baseline glomerular filtration rate (OR 0.94, 95% CI 0.90 to 0.98) and the amount of contrast media given (OR 1.01, 95% CI 1.00 to 1.01). With regard to long-term outcome (mean follow-up 649 days), multivariate Cox regression models found elevated creatinine levels at 30 days (hazard rate ratio [HRR] 5.48, 95% CI 2.85 to 10.53), but not CIN within 72 h (HRR 1.12, 95% CI 0.63 to 2.02), to be associated with increased mortality. In addition, independent predictors for death during follow-up included left ventricular ejection fraction lower than 35% (HRR 4.01, 95% CI 2.22 to 7.26), serum phosphate (HRR 1.64, 95% CI 1.10 to 2.43) and hemoglobin (HRR 0.80, 95% CI 0.67 to 0.96). CONCLUSION: From the present prospective trial, performance of post-procedural hemodialysis, use of angiotensin-converting enzyme inhibitors, reduced baseline glomerular filtration rate and amount of contrast media were independent predictors of CIN within 72 h after catheterization. Assessing renal function after 30 days, rather than within 72 h, seemed to be more predictive for

  16. The Relationship between Gender, Cumulative Adversities and ...

    African Journals Online (AJOL)

    The Relationship between Gender, Cumulative Adversities and Mental Health of Employees in ... CAs were measured in three forms (family adversities (CAFam), personal adversities ... Age of employees ranged between 18-65 years.

  17. Cumulative cultural learning: Development and diversity

    Science.gov (United States)

    2017-01-01

    The complexity and variability of human culture is unmatched by any other species. Humans live in culturally constructed niches filled with artifacts, skills, beliefs, and practices that have been inherited, accumulated, and modified over generations. A causal account of the complexity of human culture must explain its distinguishing characteristics: It is cumulative and highly variable within and across populations. I propose that the psychological adaptations supporting cumulative cultural transmission are universal but are sufficiently flexible to support the acquisition of highly variable behavioral repertoires. This paper describes variation in the transmission practices (teaching) and acquisition strategies (imitation) that support cumulative cultural learning in childhood. Examining flexibility and variation in caregiver socialization and children’s learning extends our understanding of evolution in living systems by providing insight into the psychological foundations of cumulative cultural transmission—the cornerstone of human cultural diversity. PMID:28739945

  18. Complexity and demographic explanations of cumulative culture

    NARCIS (Netherlands)

    Querbes, A.; Vaesen, K.; Houkes, W.N.

    2014-01-01

    Formal models have linked prehistoric and historical instances of technological change (e.g., the Upper Paleolithic transition, cultural loss in Holocene Tasmania, scientific progress since the late nineteenth century) to demographic change. According to these models, cumulation of technological

  19. Cumulative human impacts on marine predators.

    Science.gov (United States)

    Maxwell, Sara M; Hazen, Elliott L; Bograd, Steven J; Halpern, Benjamin S; Breed, Greg A; Nickel, Barry; Teutschel, Nicole M; Crowder, Larry B; Benson, Scott; Dutton, Peter H; Bailey, Helen; Kappes, Michelle A; Kuhn, Carey E; Weise, Michael J; Mate, Bruce; Shaffer, Scott A; Hassrick, Jason L; Henry, Robert W; Irvine, Ladd; McDonald, Birgitte I; Robinson, Patrick W; Block, Barbara A; Costa, Daniel P

    2013-01-01

    Stressors associated with human activities interact in complex ways to affect marine ecosystems, yet we lack spatially explicit assessments of cumulative impacts on ecologically and economically key components such as marine predators. Here we develop a metric of cumulative utilization and impact (CUI) on marine predators by combining electronic tracking data of eight protected predator species (n=685 individuals) in the California Current Ecosystem with data on 24 anthropogenic stressors. We show significant variation in CUI with some of the highest impacts within US National Marine Sanctuaries. High variation in underlying species and cumulative impact distributions means that neither alone is sufficient for effective spatial management. Instead, comprehensive management approaches accounting for both cumulative human impacts and trade-offs among multiple stressors must be applied in planning the use of marine resources.

  20. Cumulative cultural learning: Development and diversity.

    Science.gov (United States)

    Legare, Cristine H

    2017-07-24

    The complexity and variability of human culture is unmatched by any other species. Humans live in culturally constructed niches filled with artifacts, skills, beliefs, and practices that have been inherited, accumulated, and modified over generations. A causal account of the complexity of human culture must explain its distinguishing characteristics: It is cumulative and highly variable within and across populations. I propose that the psychological adaptations supporting cumulative cultural transmission are universal but are sufficiently flexible to support the acquisition of highly variable behavioral repertoires. This paper describes variation in the transmission practices (teaching) and acquisition strategies (imitation) that support cumulative cultural learning in childhood. Examining flexibility and variation in caregiver socialization and children's learning extends our understanding of evolution in living systems by providing insight into the psychological foundations of cumulative cultural transmission-the cornerstone of human cultural diversity.

  1. Calculating Cumulative Binomial-Distribution Probabilities

    Science.gov (United States)

    Scheuer, Ernest M.; Bowerman, Paul N.

    1989-01-01

    Cumulative-binomial computer program, CUMBIN, one of set of three programs, calculates cumulative binomial probability distributions for arbitrary inputs. CUMBIN, NEWTONP (NPO-17556), and CROSSER (NPO-17557), used independently of one another. Reliabilities and availabilities of k-out-of-n systems analyzed. Used by statisticians and users of statistical procedures, test planners, designers, and numerical analysts. Used for calculations of reliability and availability. Program written in C.

  2. Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial.

    Science.gov (United States)

    Strug, Michael R; Su, Renwei; Young, James E; Dodds, William G; Shavell, Valerie I; Díaz-Gimeno, Patricia; Ruíz-Alonso, Maria; Simón, Carlos; Lessey, Bruce A; Leach, Richard E; Fazleabas, Asgerally T

    2016-07-01

    Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation? Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival. The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1. Oocyte donors (n=15) were randomly assigned to receive an intrauterine infusion of 500 IU hCG (n=7) or embryo culture media vehicle (n=8) 3 days following oocyte retrieval during their donor stimulation cycle. Endometrial biopsies were performed 2 days later, followed by either RNA isolation or tissue fixation in formalin and paraffin embedding. Reverse transcription of total RNA from endometrial biopsies generated cDNA, which was used for analysis in the endometrial receptivity array (ERA; n = 5/group) or quantitative RT-PCR to determine relative expression of ESR1, PGR, C3 and NOTCH1. Tissue sections were stained with hematoxylin and eosin followed by blinded staging analysis for dating of endometrial glands and stroma. Immunostaining for ESR1, PGR, α-SMA, C3 and NOTCH1 was performed to determine their tissue localization. Intrauterine hCG infusion was associated with endometrial synchrony and reprograming of stromal development following ovarian stimulation. ESR1 and PGR were significantly elevated in the endometrium of hCG-treated patients, consistent with earlier staging. The ERA did not predict an overall positive impact of

  3. Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Soiffer, Robert J; Kim, Haesook T; McGuirk, Joseph; Horwitz, Mitchell E; Johnston, Laura; Patnaik, Mrinal M; Rybka, Witold; Artz, Andrew; Porter, David L; Shea, Thomas C; Boyer, Michael W; Maziarz, Richard T; Shaughnessy, Paul J; Gergis, Usama; Safah, Hana; Reshef, Ran; DiPersio, John F; Stiff, Patrick J; Vusirikala, Madhuri; Szer, Jeff; Holter, Jennifer; Levine, James D; Martin, Paul J; Pidala, Joseph A; Lewis, Ian D; Ho, Vincent T; Alyea, Edwin P; Ritz, Jerome; Glavin, Frank; Westervelt, Peter; Jagasia, Madan H; Chen, Yi-Bin

    2017-12-20

    Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days -3, -2, -1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

  4. Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

    Science.gov (United States)

    San Miguel, Jesus F.; Weisel, Katja C.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine; Renner, Christoph; Bahlis, Nizar Jacques; Yu, Xin; Teasdale, Terri; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Dimopoulos, Meletios A.

    2015-01-01

    Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30. PMID:26160879

  5. Cumulative effects assessment: Does scale matter?

    International Nuclear Information System (INIS)

    Therivel, Riki; Ross, Bill

    2007-01-01

    Cumulative effects assessment (CEA) is (or should be) an integral part of environmental assessment at both the project and the more strategic level. CEA helps to link the different scales of environmental assessment in that it focuses on how a given receptor is affected by the totality of plans, projects and activities, rather than on the effects of a particular plan or project. This article reviews how CEAs consider, and could consider, scale issues: spatial extent, level of detail, and temporal issues. It is based on an analysis of Canadian project-level CEAs and UK strategic-level CEAs. Based on a review of literature and, especially, case studies with which the authors are familiar, it concludes that scale issues are poorly considered at both levels, with particular problems being unclear or non-existing cumulative effects scoping methodologies; poor consideration of past or likely future human activities beyond the plan or project in question; attempts to apportion 'blame' for cumulative effects; and, at the plan level, limited management of cumulative effects caused particularly by the absence of consent regimes. Scale issues are important in most of these problems. However both strategic-level and project-level CEA have much potential for managing cumulative effects through better siting and phasing of development, demand reduction and other behavioural changes, and particularly through setting development consent rules for projects. The lack of strategic resource-based thresholds constrains the robust management of strategic-level cumulative effects

  6. Modelling survival

    DEFF Research Database (Denmark)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

    2016-01-01

    The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test...

  7. Predicting Cumulative Incidence Probability: Marginal and Cause-Specific Modelling

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2005-01-01

    cumulative incidence probability; cause-specific hazards; subdistribution hazard; binomial modelling......cumulative incidence probability; cause-specific hazards; subdistribution hazard; binomial modelling...

  8. Predicting Cumulative Incidence Probability by Direct Binomial Regression

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    Binomial modelling; cumulative incidence probability; cause-specific hazards; subdistribution hazard......Binomial modelling; cumulative incidence probability; cause-specific hazards; subdistribution hazard...

  9. Managing cumulative impacts: A key to sustainability?

    Energy Technology Data Exchange (ETDEWEB)

    Hunsaker, C.T.

    1994-12-31

    This paper addresses how science can be more effectively used in creating policy to manage cumulative effects on ecosystems. The paper focuses on the scientific techniques that we have to identify and to assess cumulative impacts on ecosystems. The term ``sustainable development`` was brought into common use by the World Commission on Environment and Development (The Brundtland Commission) in 1987. The Brundtland Commission report highlighted the need to simultaneously address developmental and environmental imperatives simultaneously by calling for development that ``meets the needs of the present generation without compromising the needs of future generations.`` We cannot claim to be working toward sustainable development until we can quantitatively assess cumulative impacts on the environment: The two concepts are inextricibally linked in that the elusiveness of cumulative effects likely has the greatest potential of keeping us from achieving sustainability. In this paper, assessment and management frameworks relevant to cumulative impacts are discussed along with recent literature on how to improve such assessments. When possible, examples are given for marine ecosystems.

  10. Survival analysis

    International Nuclear Information System (INIS)

    Badwe, R.A.

    1999-01-01

    The primary endpoint in the majority of the studies has been either disease recurrence or death. This kind of analysis requires a special method since all patients in the study experience the endpoint. The standard method for estimating such survival distribution is Kaplan Meier method. The survival function is defined as the proportion of individuals who survive beyond certain time. Multi-variate comparison for survival has been carried out with Cox's proportional hazard model

  11. Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials: findings from the analysis and research in cancers of the digestive system database.

    Science.gov (United States)

    Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T; Adams, Richard; Saltz, Leonard; Goldberg, Richard M; Punt, Cornelis J A; Douillard, Jean-Yves; Hoff, Paulo M; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F; Heinemann, Volker; Van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J

    2015-01-01

    Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R(2) statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R(2), 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents. © 2014 by American Society of Clinical Oncology.

  12. Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial

    International Nuclear Information System (INIS)

    Wasserman, Todd H.; Brizel, David M.; Henke, Michael; Monnier, Alain; Eschwege, Francois; Sauer, Rolf; Strnad, Vratislav

    2005-01-01

    Purpose: To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a randomized controlled trial of patients with head-and-neck cancer; at 12 months after radiotherapy (RT), amifostine had been shown to reduce xerostomia without changing tumor control. Methods and Materials: Adults with head-and-neck cancer who underwent once-daily RT for 5-7 weeks (total dose, 50-70 Gy) received either open-label amifostine (200 mg/m 2 i.v.) 15-30 min before each fraction of radiation (n = 150) or RT alone (control; n = 153). Results: Amifostine administration was associated with a reduced incidence of Grade ≥2 xerostomia over 2 years of follow-up (p = 0.002), an increase in the proportion of patients with meaningful (>0.1 g) unstimulated saliva production at 24 months (p = 0.011), and reduced mouth dryness scores on a patient benefit questionnaire at 24 months (p < 0.001). Locoregional control rate, progression-free survival, and overall survival were not significantly different between the amifostine group and the control group. Conclusions: Amifostine administration during head-and-neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates, progression-free survival, or overall survival

  13. Perspectives on cumulative risks and impacts.

    Science.gov (United States)

    Faust, John B

    2010-01-01

    Cumulative risks and impacts have taken on different meanings in different regulatory and programmatic contexts at federal and state government levels. Traditional risk assessment methodologies, with considerable limitations, can provide a framework for the evaluation of cumulative risks from chemicals. Under an environmental justice program in California, cumulative impacts are defined to include exposures, public health effects, or environmental effects in a geographic area from the emission or discharge of environmental pollution from all sources, through all media. Furthermore, the evaluation of these effects should take into account sensitive populations and socioeconomic factors where possible and to the extent data are available. Key aspects to this potential approach include the consideration of exposures (versus risk), socioeconomic factors, the geographic or community-level assessment scale, and the inclusion of not only health effects but also environmental effects as contributors to impact. Assessments of this type extend the boundaries of the types of information that toxicologists generally provide for risk management decisions.

  14. Cumulative processes and quark distribution in nuclei

    International Nuclear Information System (INIS)

    Kondratyuk, L.; Shmatikov, M.

    1984-01-01

    Assuming existence of multiquark (mainly 12q) bags in nuclei the spectra of cumulative nucleons and mesons produced in high-energy particle-nucleus collisions are discussed. The exponential form of quark momentum distribution in 12q-bag (agreeing well with the experimental data on lepton-nucleus interactions at large q 2 ) is shown to result in quasi-exponential distribution of cumulative particles over the light-cone variable αsub(B). The dependence of f(αsub(B); psub(perpendicular)) (where psub(perpendicular) is the transverse momentum of the bag) upon psub(perpendicular) is considered. The yields of cumulative resonances as well as effects related to the u- and d-quark distributions in N > Z nuclei being different are dicscussed

  15. Cumulative Culture and Future Thinking: Is Mental Time Travel a Prerequisite to Cumulative Cultural Evolution?

    Science.gov (United States)

    Vale, G. L.; Flynn, E. G.; Kendal, R. L.

    2012-01-01

    Cumulative culture denotes the, arguably, human capacity to build on the cultural behaviors of one's predecessors, allowing increases in cultural complexity to occur such that many of our cultural artifacts, products and technologies have progressed beyond what a single individual could invent alone. This process of cumulative cultural evolution…

  16. EXAFS cumulants of CdSe

    International Nuclear Information System (INIS)

    Diop, D.

    1997-04-01

    EXAFS functions had been extracted from measurements on the K edge of Se at different temperatures between 20 and 300 K. The analysis of the EXAFS of the filtered first two shells has been done in the wavevector range laying between 2 and 15.5 A -1 in terms of the cumulants of the effective distribution of distances. The cumulants C 3 and C 4 obtained from the phase difference and the amplitude ratio methods have shown the anharmonicity in the vibrations of atoms around their equilibrium position. (author). 13 refs, 3 figs

  17. Cumulative effects of wind turbines. A guide to assessing the cumulative effects of wind energy development

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    This guidance provides advice on how to assess the cumulative effects of wind energy developments in an area and is aimed at developers, planners, and stakeholders interested in the development of wind energy in the UK. The principles of cumulative assessment, wind energy development in the UK, cumulative assessment of wind energy development, and best practice conclusions are discussed. The identification and assessment of the cumulative effects is examined in terms of global environmental sustainability, local environmental quality and socio-economic activity. Supplementary guidance for assessing the principle cumulative effects on the landscape, on birds, and on the visual effect is provided. The consensus building approach behind the preparation of this guidance is outlined in the annexes of the report.

  18. Long-term survival results of a randomized trial comparing gemcitabine/cisplatin and methotrexate/vinblastine/doxorubicin/cisplatin in patients with locally advanced and metastatic bladder cancer

    DEFF Research Database (Denmark)

    Roberts, J. T.; Maase, Hans von der; Sengeløv, Lisa

    2006-01-01

    Purpose: To compare long-term survival in patients with locally advanced       and metastatic transitional cell carcinoma (TCC) of the urothelium treated       with gemcitabine plus cisplatin (GC) or       methotrexate/vinblastine/doxorubicin/cisplatin (MVAC). PATIENTS AND       METHODS: Efficacy.......       CONCLUSIONS: Long-term overall and progression-free survival following       treatment with GC or MVAC are similar. These results strengthen the role       of GC as a standard of care in patients with locally advanced and       metastatic transitional-cell carcinoma (TCC)....

  19. Multiparty correlation measure based on the cumulant

    International Nuclear Information System (INIS)

    Zhou, D. L.; Zeng, B.; Xu, Z.; You, L.

    2006-01-01

    We propose a genuine multiparty correlation measure for a multiparty quantum system as the trace norm of the cumulant of the state. The legitimacy of our multiparty correlation measure is explicitly demonstrated by proving it satisfies the five basic conditions required for a correlation measure. As an application we construct an efficient algorithm for the calculation of our measures for all stabilizer states

  20. Cumulative watershed effects: a research perspective

    Science.gov (United States)

    Leslie M. Reid; Robert R. Ziemer

    1989-01-01

    A cumulative watershed effect (CWE) is any response to multiple land-use activities that is caused by, or results in, altered watershed function. The CWE issue is politically defined, as is the significance of particular impacts. But the processes generating CWEs are the traditional focus of geomorphology and ecology, and have thus been studied for decades. The CWE...

  1. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer

    DEFF Research Database (Denmark)

    Maase, Hans von der; Sengeløv, Lisa; Roberts, James T.

    2005-01-01

    PURPOSE: To compare long-term survival in patients with locally advanced       or metastatic transitional cell carcinoma (TCC) of the urothelium treated       with gemcitabine/cisplatin (GC) or       methotrexate/vinblastine/doxorubicin/cisplatin (MVAC). PATIENTS AND       METHODS: Efficacy data...... in patients with locally advanced or       metastatic TCC...

  2. An evaluation paradigm for cumulative impact analysis

    Science.gov (United States)

    Stakhiv, Eugene Z.

    1988-09-01

    Cumulative impact analysis is examined from a conceptual decision-making perspective, focusing on its implicit and explicit purposes as suggested within the policy and procedures for environmental impact analysis of the National Environmental Policy Act of 1969 (NEPA) and its implementing regulations. In this article it is also linked to different evaluation and decision-making conventions, contrasting a regulatory context with a comprehensive planning framework. The specific problems that make the application of cumulative impact analysis a virtually intractable evaluation requirement are discussed in connection with the federal regulation of wetlands uses. The relatively familiar US Army Corps of Engineers' (the Corps) permit program, in conjunction with the Environmental Protection Agency's (EPA) responsibilities in managing its share of the Section 404 regulatory program requirements, is used throughout as the realistic context for highlighting certain pragmatic evaluation aspects of cumulative impact assessment. To understand the purposes of cumulative impact analysis (CIA), a key distinction must be made between the implied comprehensive and multiobjective evaluation purposes of CIA, promoted through the principles and policies contained in NEPA, and the more commonly conducted and limited assessment of cumulative effects (ACE), which focuses largely on the ecological effects of human actions. Based on current evaluation practices within the Corps' and EPA's permit programs, it is shown that the commonly used screening approach to regulating wetlands uses is not compatible with the purposes of CIA, nor is the environmental impact statement (EIS) an appropriate vehicle for evaluating the variety of objectives and trade-offs needed as part of CIA. A heuristic model that incorporates the basic elements of CIA is developed, including the idea of trade-offs among social, economic, and environmental protection goals carried out within the context of environmental

  3. Nonparametric Estimation of Cumulative Incidence Functions for Competing Risks Data with Missing Cause of Failure

    DEFF Research Database (Denmark)

    Effraimidis, Georgios; Dahl, Christian Møller

    In this paper, we develop a fully nonparametric approach for the estimation of the cumulative incidence function with Missing At Random right-censored competing risks data. We obtain results on the pointwise asymptotic normality as well as the uniform convergence rate of the proposed nonparametric...

  4. Family Resources and Effects on Child Behavior Problem Interventions: A Cumulative Risk Approach.

    Science.gov (United States)

    Tømmerås, Truls; Kjøbli, John

    2017-01-01

    Family resources have been associated with health care inequality in general and with social gradients in treatment outcomes for children with behavior problems. However, there is limited evidence concerning cumulative risk-the accumulation of social and economic disadvantages in a family-and whether cumulative risk moderates the outcomes of evidence-based parent training interventions. We used data from two randomized controlled trials evaluating high-intensity ( n  = 137) and low-intensity ( n  = 216) versions of Parent Management Training-Oregon (PMTO) with a 50:50 allocation between participants receiving PMTO interventions or regular care. A nine-item family cumulative risk index tapping socioeconomic resources and parental health was constructed to assess the family's exposure to risk. Autoregressive structured equation models (SEM) were run to investigate whether cumulative risk moderated child behaviors at post-treatment and follow-up (6 months). Our results showed opposite social gradients for the treatment conditions: the children exposed to cumulative risk in a pooled sample of both PMTO groups displayed lower levels of behavior problems, whereas children with identical risk exposures who received regular care experienced more problems. Furthermore, our results indicated that the social gradients differed between PMTO interventions: children exposed to cumulative risk in the low-intensity (five sessions) Brief Parent Training fared equally well as their high-resource counterparts, whereas children exposed to cumulative risk in the high-intensity PMTO (12 sessions) experienced vastly better treatment effects. Providing evidence-based parent training seem to be an effective way to counteract health care inequality, and the more intensive PMTO treatment seemed to be a particularly effective way to help families with cumulative risk.

  5. Racial Differences in CYP3A4 Genotype and Survival Among Men Treated on Radiation Therapy Oncology Group (RTOG) 9202: A Phase III Randomized Trial

    International Nuclear Information System (INIS)

    Roach, Mack; Silvio, Michelle de; Rebbick, Timothy; Grignon, David; Rotman, Marvin; Wolkov, Harvey; Fisher, Barbara; Hanks, Gerald; Shipley, William U.; Pollack, Alan; Sandler, Howard; Watkins-Bruner, Deborah Ph.D.

    2007-01-01

    Purpose: Inherited genotypes may explain the inferior outcomes of African American (AA) men with prostate cancer. To understand how variation in CYP3A4 correlated with outcomes, a retrospective examination of the CYP3A4*1B genotype was performed on men treated with Radiation Therapy Oncology Group (RTOG) 92-02. Methods and Materials: From 1,514 cases, we evaluated 56 (28.4%) of 197 AA and 54 (4.3%) of 1,274 European American (EA) patients. All patients received goserelin and flutamide for 2 months before and during RT (STAD-RT) ± 24 months of goserelin (long-term androgen deprivation plus radiation [LTAD-RT]). Events studied included overall survival and biochemical progression using American Society for Therapeutic Radiology and Oncology consensus guidelines. Results: There were no differences in outcome in patients in with or without CYP3A4 data. There was an association between race and CYP3A4 polymorphisms with 75% of EAs having the Wild Type compared to only 25% of AA men (p <0.0001). There was no association between CYP3A4 classification or race and survival or progression. Conclusions: The samples analyzed support previously reported observations about the distribution of CYP3A4*1B genotype by race, but race was not associated with poorer outcome. However, patient numbers were limited, and selection bias cannot be completely ruled out

  6. Sharing a quota on cumulative carbon emissions

    International Nuclear Information System (INIS)

    Raupach, Michael R.; Davis, Steven J.; Peters, Glen P.; Andrew, Robbie M.; Canadell, Josep G.; Ciais, Philippe

    2014-01-01

    Any limit on future global warming is associated with a quota on cumulative global CO 2 emissions. We translate this global carbon quota to regional and national scales, on a spectrum of sharing principles that extends from continuation of the present distribution of emissions to an equal per-capita distribution of cumulative emissions. A blend of these endpoints emerges as the most viable option. For a carbon quota consistent with a 2 C warming limit (relative to pre-industrial levels), the necessary long-term mitigation rates are very challenging (typically over 5% per year), both because of strong limits on future emissions from the global carbon quota and also the likely short-term persistence in emissions growth in many regions. (authors)

  7. Complexity and demographic explanations of cumulative culture.

    Science.gov (United States)

    Querbes, Adrien; Vaesen, Krist; Houkes, Wybo

    2014-01-01

    Formal models have linked prehistoric and historical instances of technological change (e.g., the Upper Paleolithic transition, cultural loss in Holocene Tasmania, scientific progress since the late nineteenth century) to demographic change. According to these models, cumulation of technological complexity is inhibited by decreasing--while favoured by increasing--population levels. Here we show that these findings are contingent on how complexity is defined: demography plays a much more limited role in sustaining cumulative culture in case formal models deploy Herbert Simon's definition of complexity rather than the particular definitions of complexity hitherto assumed. Given that currently available empirical evidence doesn't afford discriminating proper from improper definitions of complexity, our robustness analyses put into question the force of recent demographic explanations of particular episodes of cultural change.

  8. Complexity and demographic explanations of cumulative culture.

    Directory of Open Access Journals (Sweden)

    Adrien Querbes

    Full Text Available Formal models have linked prehistoric and historical instances of technological change (e.g., the Upper Paleolithic transition, cultural loss in Holocene Tasmania, scientific progress since the late nineteenth century to demographic change. According to these models, cumulation of technological complexity is inhibited by decreasing--while favoured by increasing--population levels. Here we show that these findings are contingent on how complexity is defined: demography plays a much more limited role in sustaining cumulative culture in case formal models deploy Herbert Simon's definition of complexity rather than the particular definitions of complexity hitherto assumed. Given that currently available empirical evidence doesn't afford discriminating proper from improper definitions of complexity, our robustness analyses put into question the force of recent demographic explanations of particular episodes of cultural change.

  9. Conceptual models for cumulative risk assessment.

    Science.gov (United States)

    Linder, Stephen H; Sexton, Ken

    2011-12-01

    In the absence of scientific consensus on an appropriate theoretical framework, cumulative risk assessment and related research have relied on speculative conceptual models. We argue for the importance of theoretical backing for such models and discuss 3 relevant theoretical frameworks, each supporting a distinctive "family" of models. Social determinant models postulate that unequal health outcomes are caused by structural inequalities; health disparity models envision social and contextual factors acting through individual behaviors and biological mechanisms; and multiple stressor models incorporate environmental agents, emphasizing the intermediary role of these and other stressors. The conclusion is that more careful reliance on established frameworks will lead directly to improvements in characterizing cumulative risk burdens and accounting for disproportionate adverse health effects.

  10. Childhood Cumulative Risk and Later Allostatic Load

    DEFF Research Database (Denmark)

    Doan, Stacey N; Dich, Nadya; Evans, Gary W

    2014-01-01

    State, followed for 8 years (between the ages 9 and 17). Poverty- related stress was computed using the cumulative risk approach, assessing stressors across 9 domains, including environmental, psychosocial, and demographic factors. Allostatic load captured a range of physiological responses, including......Objective: The present study investigated the long-term impact of exposure to poverty-related stressors during childhood on allostatic load, an index of physiological dysregulation, and the potential mediating role of substance use. Method: Participants (n = 162) were rural children from New York...... cardiovascular, hypothalamic pituitary adrenal axis, sympathetic adrenal medullary system, and metabolic activity. Smoking and alcohol/drug use were tested as mediators of the hypothesized childhood risk-adolescent allostatic load relationship. Results: Cumulative risk exposure at age 9 predicted increases...

  11. Fuzzy set theory for cumulative trauma prediction

    OpenAIRE

    Fonseca, Daniel J.; Merritt, Thomas W.; Moynihan, Gary P.

    2001-01-01

    A widely used fuzzy reasoning algorithm was modified and implemented via an expert system to assess the potential risk of employee repetitive strain injury in the workplace. This fuzzy relational model, known as the Priority First Cover Algorithm (PFC), was adapted to describe the relationship between 12 cumulative trauma disorders (CTDs) of the upper extremity, and 29 identified risk factors. The algorithm, which finds a suboptimal subset from a group of variables based on the criterion of...

  12. Sikap Kerja Duduk Terhadap Cumulative Trauma Disorder

    OpenAIRE

    Rahmawati, Yulita; Sugiharto, -

    2011-01-01

    Permasalahan yang diteliti adalah adakah hubungan antara sikap kerja duduk dengan kejadian Cumulative Trauma Disorder (CTD) pada pekerja bagian pengamplasan di PT. Geromar Jepara. Tujuan yang ingin dicapai adalah untuk mengetahui hubungan antara sikap kerja duduk dengan kejadian CTD pada pekerja bagian pengamplasan. Metode penelitian ini bersifat explanatory dengan menggunakan pendekatan belah lintang. Populasi dalam penelitian ini adalah pekerja bagian pengamplasan sebanyak 30 orang. Teknik ...

  13. Power Reactor Docket Information. Annual cumulation (citations)

    International Nuclear Information System (INIS)

    1977-12-01

    An annual cumulation of the citations to the documentation associated with civilian nuclear power plants is presented. This material is that which is submitted to the U.S. Nuclear Regulatory Commission in support of applications for construction and operating licenses. Citations are listed by Docket number in accession number sequence. The Table of Contents is arranged both by Docket number and by nuclear power plant name

  14. Cumulative Effect of Depression on Dementia Risk

    OpenAIRE

    Olazarán, J.; Trincado, R.; Bermejo-Pareja, F.

    2013-01-01

    Objective. To analyze a potential cumulative effect of life-time depression on dementia and Alzheimer's disease (AD), with control of vascular factors (VFs). Methods. This study was a subanalysis of the Neurological Disorders in Central Spain (NEDICES) study. Past and present depression, VFs, dementia status, and dementia due to AD were documented at study inception. Dementia status was also documented after three years. Four groups were created according to baseline data: never depression (n...

  15. Cumulative release to the accessible environment

    International Nuclear Information System (INIS)

    Kanehiro, B.

    1985-01-01

    The Containment and Isolation Working Group considered issues related to the postclosure behavior of repositories in crystalline rock. This working group was further divided into subgroups to consider the progress since the 1978 GAIN Symposium and identify research needs in the individual areas of regional ground-water flow, ground-water travel time, fractional release, and cumulative release. The analysis and findings of the Fractional Release Subgroup are presented

  16. EPA Workshop on Epigenetics and Cumulative Risk ...

    Science.gov (United States)

    Agenda Download the Workshop Agenda (PDF) The workshop included presentations and discussions by scientific experts pertaining to three topics (i.e., epigenetic changes associated with diverse stressors, key science considerations in understanding epigenetic changes, and practical application of epigenetic tools to address cumulative risks from environmental stressors), to address several questions under each topic, and included an opportunity for attendees to participate in break-out groups, provide comments and ask questions. Workshop Goals The workshop seeks to examine the opportunity for use of aggregate epigenetic change as an indicator in cumulative risk assessment for populations exposed to multiple stressors that affect epigenetic status. Epigenetic changes are specific molecular changes around DNA that alter expression of genes. Epigenetic changes include DNA methylation, formation of histone adducts, and changes in micro RNAs. Research today indicates that epigenetic changes are involved in many chronic diseases (cancer, cardiovascular disease, obesity, diabetes, mental health disorders, and asthma). Research has also linked a wide range of stressors including pollution and social factors with occurrence of epigenetic alterations. Epigenetic changes have the potential to reflect impacts of risk factors across multiple stages of life. Only recently receiving attention is the nexus between the factors of cumulative exposure to environmental

  17. Higher order cumulants in colorless partonic plasma

    Energy Technology Data Exchange (ETDEWEB)

    Cherif, S. [Sciences and Technologies Department, University of Ghardaia, Ghardaia, Algiers (Algeria); Laboratoire de Physique et de Mathématiques Appliquées (LPMA), ENS-Kouba (Bachir El-Ibrahimi), Algiers (Algeria); Ahmed, M. A. A. [Department of Physics, College of Science, Taibah University Al-Madinah Al-Mounawwarah KSA (Saudi Arabia); Department of Physics, Taiz University in Turba, Taiz (Yemen); Laboratoire de Physique et de Mathématiques Appliquées (LPMA), ENS-Kouba (Bachir El-Ibrahimi), Algiers (Algeria); Ladrem, M., E-mail: mladrem@yahoo.fr [Department of Physics, College of Science, Taibah University Al-Madinah Al-Mounawwarah KSA (Saudi Arabia); Laboratoire de Physique et de Mathématiques Appliquées (LPMA), ENS-Kouba (Bachir El-Ibrahimi), Algiers (Algeria)

    2016-06-10

    Any physical system considered to study the QCD deconfinement phase transition certainly has a finite volume, so the finite size effects are inevitably present. This renders the location of the phase transition and the determination of its order as an extremely difficult task, even in the simplest known cases. In order to identify and locate the colorless QCD deconfinement transition point in finite volume T{sub 0}(V), a new approach based on the finite-size cumulant expansion of the order parameter and the ℒ{sub m,n}-Method is used. We have shown that both cumulants of higher order and their ratios, associated to the thermodynamical fluctuations of the order parameter, in QCD deconfinement phase transition behave in a particular enough way revealing pronounced oscillations in the transition region. The sign structure and the oscillatory behavior of these in the vicinity of the deconfinement phase transition point might be a sensitive probe and may allow one to elucidate their relation to the QCD phase transition point. In the context of our model, we have shown that the finite volume transition point is always associated to the appearance of a particular point in whole higher order cumulants under consideration.

  18. Quantitative methods for analysing cumulative effects on fish migration success: a review.

    Science.gov (United States)

    Johnson, J E; Patterson, D A; Martins, E G; Cooke, S J; Hinch, S G

    2012-07-01

    It is often recognized, but seldom addressed, that a quantitative assessment of the cumulative effects, both additive and non-additive, of multiple stressors on fish survival would provide a more realistic representation of the factors that influence fish migration. This review presents a compilation of analytical methods applied to a well-studied fish migration, a more general review of quantitative multivariable methods, and a synthesis on how to apply new analytical techniques in fish migration studies. A compilation of adult migration papers from Fraser River sockeye salmon Oncorhynchus nerka revealed a limited number of multivariable methods being applied and the sub-optimal reliance on univariable methods for multivariable problems. The literature review of fisheries science, general biology and medicine identified a large number of alternative methods for dealing with cumulative effects, with a limited number of techniques being used in fish migration studies. An evaluation of the different methods revealed that certain classes of multivariable analyses will probably prove useful in future assessments of cumulative effects on fish migration. This overview and evaluation of quantitative methods gathered from the disparate fields should serve as a primer for anyone seeking to quantify cumulative effects on fish migration survival. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

  19. Clinical impact of tumor location on the colon cancer survival and recurrence: analyses of pooled data from three large phase III randomized clinical trials.

    Science.gov (United States)

    Aoyama, Toru; Kashiwabara, Kosuke; Oba, Koji; Honda, Michitaka; Sadahiro, Sotaro; Hamada, Chikuma; Maeda, Hiromichi; Mayanagi, Shuhei; Kanda, Mitsuro; Sakamoto, Junichi; Saji, Shigetoyo; Yoshikawa, Takaki

    2017-11-01

    The aim of the present study was to determine whether or not the overall survival (OS) and disease-free survival (DFS) were affected by the tumor location in patients who underwent curative resection for colon cancer in a pooled analysis of three large phase III studies performed in Japan. In total, 4029 patients were included in the present study. Patients were classified as having right-side colon cancer (RC) if the primary tumor was located in the cecum, ascending colon, hepatic flexure or transverse colon, and left-side colon cancer (LCC) if the tumor site was within the splenic flexure, descending colon, sigmoid colon or recto sigmoid junction. The risk factors for the OS and DFS were analyzed. In the present study, 1449 patients were RC, and 2580 were LCC. The OS rates at 3 and 5 years after surgery were 87.6% and 81.6% in the RC group and 91.5% and 84.5% in the LCC group, respectively. Uni- and multivariate analyses showed that RRC increased the risk of death by 19.7% (adjusted hazard ratio = 1.197; 95% confidence interval, 1.020-1.408; P = 0.0272). In contrast, the DFS was similar between the two locations. The present study confirmed that the tumor location was a risk factor for the OS in patients who underwent curative treatment for colon cancer. Tumor location may, therefore, need to be considered a stratification factor in future phase III trials of colon cancer. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  20. Kaplan-Meier Survival Analysis Overestimates the Risk of Revision Arthroplasty: A Meta-analysis.

    Science.gov (United States)

    Lacny, Sarah; Wilson, Todd; Clement, Fiona; Roberts, Derek J; Faris, Peter D; Ghali, William A; Marshall, Deborah A

    2015-11-01

    Although Kaplan-Meier survival analysis is commonly used to estimate the cumulative incidence of revision after joint arthroplasty, it theoretically overestimates the risk of revision in the presence of competing risks (such as death). Because the magnitude of overestimation is not well documented, the potential associated impact on clinical and policy decision-making remains unknown. We performed a meta-analysis to answer the following questions: (1) To what extent does the Kaplan-Meier method overestimate the cumulative incidence of revision after joint replacement compared with alternative competing-risks methods? (2) Is the extent of overestimation influenced by followup time or rate of competing risks? We searched Ovid MEDLINE, EMBASE, BIOSIS Previews, and Web of Science (1946, 1980, 1980, and 1899, respectively, to October 26, 2013) and included article bibliographies for studies comparing estimated cumulative incidence of revision after hip or knee arthroplasty obtained using both Kaplan-Meier and competing-risks methods. We excluded conference abstracts, unpublished studies, or studies using simulated data sets. Two reviewers independently extracted data and evaluated the quality of reporting of the included studies. Among 1160 abstracts identified, six studies were included in our meta-analysis. The principal reason for the steep attrition (1160 to six) was that the initial search was for studies in any clinical area that compared the cumulative incidence estimated using the Kaplan-Meier versus competing-risks methods for any event (not just the cumulative incidence of hip or knee revision); we did this to minimize the likelihood of missing any relevant studies. We calculated risk ratios (RRs) comparing the cumulative incidence estimated using the Kaplan-Meier method with the competing-risks method for each study and used DerSimonian and Laird random effects models to pool these RRs. Heterogeneity was explored using stratified meta-analyses and

  1. Community and District Empowerment for Scale-up (CODES): a complex district-level management intervention to improve child survival in Uganda: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Waiswa, Peter; O'Connell, Thomas; Bagenda, Danstan; Mullachery, Pricila; Mpanga, Flavia; Henriksson, Dorcus Kiwanuka; Katahoire, Anne Ruhweza; Ssegujja, Eric; Mbonye, Anthony K; Peterson, Stefan Swartling

    2016-03-11

    Innovative and sustainable strategies to strengthen districts and other sub-national health systems and management are urgently required to reduce child mortality. Although highly effective evidence-based and affordable child survival interventions are well-known, at the district level, lack of data, motivation, analytic and planning capacity often impedes prioritization and management weaknesses impede implementation. The Community and District Empowerment for Scale-up (CODES) project is a complex management intervention designed to test whether districts when empowered with data and management tools can prioritize and implement evidence-based child survival interventions equitably. The CODES strategy combines management, diagnostic, and evaluation tools to identify and analyze the causes of bottlenecks to implementation, build capacity of district management teams to implement context-specific solutions, and to foster community monitoring and social accountability to increase demand for services. CODES combines UNICEF tools designed to systematize priority setting, allocation of resources and problem solving with Community dialogues based on Citizen Report Cards and U-Reports used to engage and empower communities in monitoring health service provision and to demand for quality services. Implementation and all data collection will be by the districts teams or local Community-based Organizations who will be supported by two local implementing partners. The study will be evaluated as a cluster randomized trial with eight intervention and eight comparison districts over a period of 3 years. Evaluation will focus on differences in uptake of child survival interventions and will follow an intention-to-treat analysis. We will also document and analyze experiences in implementation including changes in management practices. By increasing the District Health Management Teams' capacity to prioritize and implement context-specific solutions, and empowering communities to

  2. Effect of Tailored Dose-Dense Chemotherapy vs Standard 3-Weekly Adjuvant Chemotherapy on Recurrence-Free Survival Among Women With High-Risk Early Breast Cancer: A Randomized Clinical Trial.

    Science.gov (United States)

    Foukakis, Theodoros; von Minckwitz, Gunter; Bengtsson, Nils-Olof; Brandberg, Yvonne; Wallberg, Birgitta; Fornander, Tommy; Mlineritsch, Brigitte; Schmatloch, Sabine; Singer, Christian F; Steger, Günther; Egle, Daniel; Karlsson, Eva; Carlsson, Lena; Loibl, Sibylle; Untch, Michael; Hellström, Mats; Johansson, Hemming; Anderson, Harald; Malmström, Per; Gnant, Michael; Greil, Richard; Möbus, Volker; Bergh, Jonas

    2016-11-08

    Standard dosing of chemotherapy based on body surface area results in marked interpatient variation in pharmacokinetics, toxic effects, and efficacy. Whether tailored dosing can improve outcomes is unknown, as is the role of dose-dense adjuvant chemotherapy. To determine whether tailored dose-dense adjuvant chemotherapy improves the outcomes of early breast cancer compared with a standard 3-weekly chemotherapy schedule. A randomized, open-label, phase 3 trial of women aged 65 years and younger who had surgery for nonmetastatic node-positive or high-risk node-negative breast cancer at 86 sites in Sweden, Germany, and Austria between February 20, 2007, and September 14, 2011. Patients were randomized 1:1 either to 4 cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin and cyclophosphamide every 2 weeks followed by 4 cycles of tailored dose-dense docetaxel every 2 weeks, or to standard-interval chemotherapy with 3 cycles of fluorouracil and epirubicin-cyclophosphamide every 3 weeks followed by 3 cycles of docetaxel every 3 weeks. The primary end point was breast cancer recurrence-free survival (BCRFS). Secondary end points included 5-year event-free survival (EFS), distant disease-free survival (DDFS), overall survival (OS), and rates of grade 3 or 4 toxic effects. Among 2017 randomized patients (1006 in the tailored dose-dense group and 1011 in the control group; median [IQR] age, 51 [45-58] years; 80% with hormone receptor-positive tumors; 97% with node-positive disease), 2000 received study treatment (≥1 cycle of chemotherapy; 1001 in the tailored dose-dense group and 999 in the control group). After a median follow-up of 5.3 years (IQR, 4.5-6.1 years), 269 BCRFS events were reported, 118 in the tailored dose-dense group and 151 in the control group (HR, 0.79; 95% CI, 0.61-1.01; log-rank P = .06; 5-year BCRFS, 88.7% vs 85.0%). The tailored dose-dense group had significantly better EFS than the control group (HR, 0.79; 95% CI, 0

  3. A bivariate optimal replacement policy with cumulative repair cost ...

    Indian Academy of Sciences (India)

    Min-Tsai Lai

    Shock model; cumulative damage model; cumulative repair cost limit; preventive maintenance model. 1. Introduction ... with two types of shocks: one type is failure shock, and the other type is damage ...... Theory, methods and applications.

  4. On interference of cumulative proton production mechanisms

    International Nuclear Information System (INIS)

    Braun, M.A.; Vechernin, V.V.

    1993-01-01

    The dynamical picture of the cumulative proton production in hA-collisions by means of diagram analysis with NN interaction described by a non-relativistic NN potential is considered. The contributions of the various mechanisms (spectator, direct and rescattering) for backward hemisphere proton production within the framework of this common approach is calculated. The emphasis is on the comparison of the relative contributions of these mechanisms for various angles, taking into account the interference of these contributions. Comparison with experimental data is also presented. (author)

  5. Preserved cumulative semantic interference despite amnesia

    Directory of Open Access Journals (Sweden)

    Gary Michael Oppenheim

    2015-05-01

    As predicted by Oppenheim et al’s (2010 implicit incremental learning account, WRP’s BCN RTs demonstrated strong (and significant repetition priming and semantic blocking effects (Figure 1. Similar to typical results from neurally intact undergraduates, WRP took longer to name pictures presented in semantically homogeneous blocks than in heterogeneous blocks, an effect that increased with each cycle. This result challenges accounts that ascribe cumulative semantic interference in this task to explicit memory mechanisms, instead suggesting that the effect has the sort of implicit learning bases that are typically spared in hippocampal amnesia.

  6. Is cumulated pyrethroid exposure associated with prediabetes?

    DEFF Research Database (Denmark)

    Hansen, Martin Rune; Jørs, Erik; Lander, Flemming

    2014-01-01

    was to investigate an association between exposure to pyrethroids and abnormal glucose regulation (prediabetes or diabetes). A cross-sectional study was performed among 116 pesticide sprayers from public vector control programs in Bolivia and 92 nonexposed controls. Pesticide exposure (duration, intensity...... pyrethroids, a significant positive trend was observed between cumulative pesticide exposure (total number of hours sprayed) and adjusted OR of abnormal glucose regulation, with OR 14.7 [0.9-235] in the third exposure quintile. The study found a severely increased prevalence of prediabetes among Bolivian...

  7. Effect of provision of an integrated neonatal survival kit and early cognitive stimulation package by community health workers on developmental outcomes of infants in Kwale County, Kenya: study protocol for a cluster randomized trial.

    Science.gov (United States)

    Pell, Lisa G; Bassani, Diego G; Nyaga, Lucy; Njagi, Isaac; Wanjiku, Catherine; Thiruchselvam, Thulasi; Macharia, William; Minhas, Ripudaman S; Kitsao-Wekulo, Patricia; Lakhani, Amyn; Bhutta, Zulfiqar A; Armstrong, Robert; Morris, Shaun K

    2016-09-08

    Each year, more than 200 million children under the age of 5 years, almost all in low- and middle-income countries (LMICs), fail to achieve their developmental potential. Risk factors for compromised development often coexist and include inadequate cognitive stimulation, poverty, nutritional deficiencies, infection and complications of being born low birthweight and/or premature. Moreover, many of these risk factors are closely associated with newborn morbidity and mortality. As compromised development has significant implications on human capital, inexpensive and scalable interventions are urgently needed to promote neurodevelopment and reduce risk factors for impaired development. This cluster randomized trial aims at evaluating the impact of volunteer community health workers delivering either an integrated neonatal survival kit, an early stimulation package, or a combination of both interventions, to pregnant women during their third trimester of pregnancy, compared to the current standard of care in Kwale County, Kenya. The neonatal survival kit comprises a clean delivery kit (sterile blade, cord clamp, clean plastic sheet, surgical gloves and hand soap), sunflower oil emollient, chlorhexidine, ThermoSpot(TM), Mylar infant sleeve, and a reusable instant heater. Community health workers are also equipped with a portable hand-held electric scale. The early cognitive stimulation package focuses on enhancing caregiver practices by teaching caregivers three key messages that comprise combining a gentle touch with making eye contact and talking to children, responsive feeding and caregiving, and singing. The primary outcome measure is child development at 12 months of age assessed with the Protocol for Child Monitoring (Infant and Toddler version). The main secondary outcome is newborn mortality. This study will provide evidence on effectiveness of delivering an innovative neonatal survival kit and/or early stimulation package to pregnant women in Kwale County

  8. Chapter 19. Cumulative watershed effects and watershed analysis

    Science.gov (United States)

    Leslie M. Reid

    1998-01-01

    Cumulative watershed effects are environmental changes that are affected by more than.one land-use activity and that are influenced by.processes involving the generation or transport.of water. Almost all environmental changes are.cumulative effects, and almost all land-use.activities contribute to cumulative effects

  9. Original and cumulative prospect theory: a discussion of empirical differences

    NARCIS (Netherlands)

    Wakker, P.P.; Fennema, H.

    1997-01-01

    This note discusses differences between prospect theory and cumulative prospect theory. It shows that cumulative prospect theory is not merely a formal correction of some theoretical problems in prospect theory, but it also gives different predictions. Experiments are described that favor cumulative

  10. Adjusting survival time estimates to account for treatment switching in randomized controlled trials--an economic evaluation context: methods, limitations, and recommendations.

    Science.gov (United States)

    Latimer, Nicholas R; Abrams, Keith R; Lambert, Paul C; Crowther, Michael J; Wailoo, Allan J; Morden, James P; Akehurst, Ron L; Campbell, Michael J

    2014-04-01

    Treatment switching commonly occurs in clinical trials of novel interventions in the advanced or metastatic cancer setting. However, methods to adjust for switching have been used inconsistently and potentially inappropriately in health technology assessments (HTAs). We present recommendations on the use of methods to adjust survival estimates in the presence of treatment switching in the context of economic evaluations. We provide background on the treatment switching issue and summarize methods used to adjust for it in HTAs. We discuss the assumptions and limitations associated with adjustment methods and draw on results of a simulation study to make recommendations on their use. We demonstrate that methods used to adjust for treatment switching have important limitations and often produce bias in realistic scenarios. We present an analysis framework that aims to increase the probability that suitable adjustment methods can be identified on a case-by-case basis. We recommend that the characteristics of clinical trials, and the treatment switching mechanism observed within them, should be considered alongside the key assumptions of the adjustment methods. Key assumptions include the "no unmeasured confounders" assumption associated with the inverse probability of censoring weights (IPCW) method and the "common treatment effect" assumption associated with the rank preserving structural failure time model (RPSFTM). The limitations associated with switching adjustment methods such as the RPSFTM and IPCW mean that they are appropriate in different scenarios. In some scenarios, both methods may be prone to bias; "2-stage" methods should be considered, and intention-to-treat analyses may sometimes produce the least bias. The data requirements of adjustment methods also have important implications for clinical trialists.

  11. Cumulative Environmental Management Association : Wood Buffalo Region

    International Nuclear Information System (INIS)

    Friesen, B.

    2001-01-01

    The recently announced oil sands development of the Wood Buffalo Region in Alberta was the focus of this power point presentation. Both mining and in situ development is expected to total $26 billion and 2.6 million barrels per day of bitumen production. This paper described the economic, social and environmental challenges facing the resource development of this region. In addition to the proposed oil sands projects, this region will accommodate the needs of conventional oil and gas production, forestry, building of pipelines and power lines, municipal development, recreation, tourism, mining exploration and open cast mining. The Cumulative Environmental Management Association (CEMA) was inaugurated as a non-profit association in April 2000, and includes 41 members from all sectors. Its major role is to ensure a sustainable ecosystem and to avoid any cumulative impacts on wildlife. Other work underway includes the study of soil and plant species diversity, and the effects of air emissions on human health, wildlife and vegetation. The bioaccumulation of heavy metals and their impacts on surface water and fish is also under consideration to ensure the quality and quantity of surface water and ground water. 3 figs

  12. Immune Biomarkers Predictive for Disease-Free Survival with Adjuvant Sunitinib in High-Risk Locoregional Renal Cell Carcinoma: From Randomized Phase III S-TRAC Study.

    Science.gov (United States)

    George, Daniel J; Martini, Jean-François; Staehler, Michael; Motzer, Robert J; Magheli, Ahmed; Escudier, Bernard; Gerletti, Paola; Li, Sherry; Casey, Michelle; Laguerre, Brigitte; Pandha, Hardev S; Pantuck, Allan J; Patel, Anup; Lechuga, Maria J; Ravaud, Alain

    2018-04-01

    Purpose: Adjuvant sunitinib therapy compared with placebo prolonged disease-free survival (DFS) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov number NCT00375674). A prospectively designed exploratory analysis of tissue biomarkers was conducted to identify predictors of treatment benefit. Experimental Design: Tissue blocks were used for immunohistochemistry (IHC) staining of programmed cell death ligand 1 (PD-L1), CD4, CD8, and CD68. DFS was compared between < versus ≥ median IHC parameter using the Kaplan-Meier method. For biomarkers with predictive potential, receiver operating characteristics curves were generated. Results: Baseline characteristics were similar in patients with ( n = 191) and without ( n = 419) IHC analysis. Among patients with IHC, longer DFS was observed in patients with tumor CD8 + T-cell density ≥ versus < median [median (95% CI), not reached (6.83-not reached) versus 3.47 years (1.73-not reached); hazard ratio (HR) 0.40 (95% CI, 0.20-0.81); P = 0.009] treated with sunitinib ( n = 101), but not with placebo ( n = 90). The sensitivity and specificity for CD8 + T-cell density in predicting DFS were 0.604 and 0.658, respectively. Shorter DFS was observed in placebo-treated patients with PD-L1 + versus PD-L1 - tumors (HR 1.75; P = 0.103). Among all patients with PD-L1 + tumors, DFS was numerically longer with sunitinib versus placebo (HR 0.58; P = 0.175). Conclusions: Greater CD8 + T-cell density in tumor tissue was associated with longer DFS with sunitinib but not placebo, suggesting predictive treatment effect utility. Further independent cohort validation studies are warranted. The prognostic value of PD-L1 expression in primary tumors from patients with high-risk nonmetastatic RCC should also be further explored. Clin Cancer Res; 24(7); 1554-61. ©2018 AACR . ©2018 American Association for Cancer Research.

  13. The use of the multi-cumulant tensor analysis for the algorithmic optimisation of investment portfolios

    Science.gov (United States)

    Domino, Krzysztof

    2017-02-01

    The cumulant analysis plays an important role in non Gaussian distributed data analysis. The shares' prices returns are good example of such data. The purpose of this research is to develop the cumulant based algorithm and use it to determine eigenvectors that represent investment portfolios with low variability. Such algorithm is based on the Alternating Least Square method and involves the simultaneous minimisation 2'nd- 6'th cumulants of the multidimensional random variable (percentage shares' returns of many companies). Then the algorithm was tested during the recent crash on the Warsaw Stock Exchange. To determine incoming crash and provide enter and exit signal for the investment strategy the Hurst exponent was calculated using the local DFA. It was shown that introduced algorithm is on average better that benchmark and other portfolio determination methods, but only within examination window determined by low values of the Hurst exponent. Remark that the algorithm is based on cumulant tensors up to the 6'th order calculated for a multidimensional random variable, what is the novel idea. It can be expected that the algorithm would be useful in the financial data analysis on the world wide scale as well as in the analysis of other types of non Gaussian distributed data.

  14. Long-term survival in the randomized trial of drug treatment in mild to moderate hypertension of the Oslo study 1972-3.

    Science.gov (United States)

    Holme, Ingar; Kjeldsen, Sverre E

    2015-03-01

    In the Oslo cardiovascular study of 1972-3 a 5-year randomized trial in mild to moderate hypertension was performed. Several changes in treatment practices have been recommended since that time. We followed the mortality patterns up to 40 years. Invited to the Oslo study screening were 25,915 middle-aged men and 16,203 (63%) participated. Reexaminations were done to select suitable participants into the trial. Men had blood pressure 150-179/95-109 mm Hg and the active group (n=406) was treated with thiazides, alpha-methyldopa and propranolol versus untreated controls (n=379). Cox regression analysis was used for statistical analyses. There was no trend towards reduction in total mortality by treatment. A nominally significant increase in risk of death at first myocardial infarction was observed in the trial treatment group across the follow-up period, HR=1.51 (1.01-2.25); (P=0.042). The excess risk developed rapidly during the first 15 years, but the gap between the groups diminished to a large extent during the next 15 years, but the curves stayed at a certain distance for the last 10 years. Cerebrovascular death tended to be non-significantly reduced, HR=0.85 (0.52-1.41). Drug treatment of mild hypertensive men initiated in the 1970s did not reduce mortality at first MI or total mortality. However, during the period (late 1980s and whole 1990s), when large changes in hypertension treatment practices occurred into regimes with more use of combination therapies including metabolically neutral drugs at lower doses, beneficial effects on MI mortality could be observed. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  15. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS).

    Science.gov (United States)

    Fukuoka, Masahiro; Wu, Yi-Long; Thongprasert, Sumitra; Sunpaweravong, Patrapim; Leong, Swan-Swan; Sriuranpong, Virote; Chao, Tsu-Yi; Nakagawa, Kazuhiko; Chu, Da-Tong; Saijo, Nagahiro; Duffield, Emma L; Rukazenkov, Yuri; Speake, Georgina; Jiang, Haiyi; Armour, Alison A; To, Ka-Fai; Yang, James Chih-Hsin; Mok, Tony S K

    2011-07-20

    The results of the Iressa Pan-Asia Study (IPASS), which compared gefitinib and carboplatin/paclitaxel in previously untreated never-smokers and light ex-smokers with advanced pulmonary adenocarcinoma were published previously. This report presents overall survival (OS) and efficacy according to epidermal growth factor receptor (EGFR) biomarker status. In all, 1,217 patients were randomly assigned. Biomarkers analyzed were EGFR mutation (amplification mutation refractory system; 437 patients evaluable), EGFR gene copy number (fluorescent in situ hybridization; 406 patients evaluable), and EGFR protein expression (immunohistochemistry; 365 patients evaluable). OS analysis was performed at 78% maturity. A Cox proportional hazards model was used to assess biomarker status by randomly assigned treatment interactions for progression-free survival (PFS) and OS. OS (954 deaths) was similar for gefitinib and carboplatin/paclitaxel with no significant difference between treatments overall (hazard ratio [HR], 0.90; 95% CI, 0.79 to 1.02; P = .109) or in EGFR mutation-positive (HR, 1.00; 95% CI, 0.76 to 1.33; P = .990) or EGFR mutation-negative (HR, 1.18; 95% CI, 0.86 to 1.63; P = .309; treatment by EGFR mutation interaction P = .480) subgroups. A high proportion (64.3%) of EGFR mutation-positive patients randomly assigned to carboplatin/paclitaxel received subsequent EGFR tyrosine kinase inhibitors. PFS was significantly longer with gefitinib for patients whose tumors had both high EGFR gene copy number and EGFR mutation (HR, 0.48; 95% CI, 0.34 to 0.67) but significantly shorter when high EGFR gene copy number was not accompanied by EGFR mutation (HR, 3.85; 95% CI, 2.09 to 7.09). EGFR mutations are the strongest predictive biomarker for PFS and tumor response to first-line gefitinib versus carboplatin/paclitaxel. The predictive value of EGFR gene copy number was driven by coexisting EGFR mutation (post hoc analysis). Treatment-related differences observed for PFS in the EGFR

  16. County-level cumulative environmental quality associated with cancer incidence.

    Science.gov (United States)

    Jagai, Jyotsna S; Messer, Lynne C; Rappazzo, Kristen M; Gray, Christine L; Grabich, Shannon C; Lobdell, Danelle T

    2017-08-01

    Individual environmental exposures are associated with cancer development; however, environmental exposures occur simultaneously. The Environmental Quality Index (EQI) is a county-level measure of cumulative environmental exposures that occur in 5 domains. The EQI was linked to county-level annual age-adjusted cancer incidence rates from the Surveillance, Epidemiology, and End Results (SEER) Program state cancer profiles. All-site cancer and the top 3 site-specific cancers for male and female subjects were considered. Incident rate differences (IRDs; annual rate difference per 100,000 persons) and 95% confidence intervals (CIs) were estimated using fixed-slope, random intercept multilevel linear regression models. Associations were assessed with domain-specific indices and analyses were stratified by rural/urban status. Comparing the highest quintile/poorest environmental quality with the lowest quintile/best environmental quality for overall EQI, all-site county-level cancer incidence rate was positively associated with poor environmental quality overall (IRD, 38.55; 95% CI, 29.57-47.53) and for male (IRD, 32.60; 95% CI, 16.28-48.91) and female (IRD, 30.34; 95% CI, 20.47-40.21) subjects, indicating a potential increase in cancer incidence with decreasing environmental quality. Rural/urban stratified models demonstrated positive associations comparing the highest with the lowest quintiles for all strata, except the thinly populated/rural stratum and in the metropolitan/urbanized stratum. Prostate and breast cancer demonstrated the strongest positive associations with poor environmental quality. We observed strong positive associations between the EQI and all-site cancer incidence rates, and associations differed by rural/urban status and environmental domain. Research focusing on single environmental exposures in cancer development may not address the broader environmental context in which cancers develop, and future research should address cumulative environmental

  17. 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).

    Science.gov (United States)

    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.

  18. Survival Analysis

    CERN Document Server

    Miller, Rupert G

    2011-01-01

    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  19. Evolution model with a cumulative feedback coupling

    Science.gov (United States)

    Trimper, Steffen; Zabrocki, Knud; Schulz, Michael

    2002-05-01

    The paper is concerned with a toy model that generalizes the standard Lotka-Volterra equation for a certain population by introducing a competition between instantaneous and accumulative, history-dependent nonlinear feedback the origin of which could be a contribution from any kind of mismanagement in the past. The results depend on the sign of that additional cumulative loss or gain term of strength λ. In case of a positive coupling the system offers a maximum gain achieved after a finite time but the population will die out in the long time limit. In this case the instantaneous loss term of strength u is irrelevant and the model exhibits an exact solution. In the opposite case λ<0 the time evolution of the system is terminated in a crash after ts provided u=0. This singularity after a finite time can be avoided if u≠0. The approach may well be of relevance for the qualitative understanding of more realistic descriptions.

  20. Psychometric properties of the Cumulated Ambulation Score

    DEFF Research Database (Denmark)

    Ferriero, Giorgio; Kristensen, Morten T; Invernizzi, Marco

    2018-01-01

    INTRODUCTION: In the geriatric population, independent mobility is a key factor in determining readiness for discharge following acute hospitalization. The Cumulated Ambulation Score (CAS) is a potentially valuable score that allows day-to-day measurements of basic mobility. The CAS was developed...... and validated in older patients with hip fracture as an early postoperative predictor of short-term outcome, but it is also used to assess geriatric in-patients with acute medical illness. Despite the fast- accumulating literature on the CAS, to date no systematic review synthesizing its psychometric properties....... Of 49 studies identified, 17 examined the psychometric properties of the CAS. EVIDENCE SYNTHESIS: Most papers dealt with patients after hip fracture surgery, and only 4 studies assessed the CAS psychometric characteristics also in geriatric in-patients with acute medical illness. Two versions of CAS...

  1. A Danish randomized trial comparing breast-preserving therapy with mastectomy in mammary carcinoma

    International Nuclear Information System (INIS)

    Blichert-Toft, M.; Brincker, H.; Andersen, J.A.; Andersen, K.W.; Axelsson, C.K.; Mouridsen, H.T.; Dombernowsky, P.; Overgaard, M.; Gadeberg, C.; Knudsen, G.; Borgeskov, S.; Bertelsen, S.; Knudsen, J.B.; Hansen, J.B.; Poulsen, P.E.; Willumsen, H.; Schousen, P.; Froberg, D.; Oernsholt, J.; Andersen, M.; Olesen, S.; Skovgaard, S.; Oester, M.; Schumacher, H.; Lynderup, E.K.; Holm, C.N.

    1988-01-01

    The present study comprises 847 women operated upon for invasive breast carcinoma at 19 surgical departments and enrolled in protocol DBCG-82TM from January 1983 to November 1987. Among them 662 (78%) were allocated for breast-preserving therapy or mastectomy by randomization, while 185 patients (22%) did not accept randomization. Within the randomized group 6% could not be entered into adjuvant protocols, i.e. subsequent programmes of postoperative therapy and follow-up. This left 619 evaluable patients. In the non-randomized series 26% did not fulfil the demands for entrance into the adjuvant protocols, leaving 136 evaluable patients, 60 of whom had chosen a breast-preserving operation and 76 mastectomy. In the randomized series the patients in the two treatment arms were comparable in age, menopausal status, site of tumour, pathoanatomical diameter of the tumour, number of removed axillary lymph nodes, number of metastatic axillary lymph nodes, and distribution on adjuvant regimens. Ninety per cent of the patients in the randomized group accepted the method offered, whereas 10% declined and wanted the alternate form of operation. The median follow-up period was approximately 1.75 years. The cumulative recurrence rate in the randomized group was 13% and in the non-randomized group 7%. These results are preliminary. Life-table analyses have not so far demonstrated differences in recurrence-free survival either in the randomized or the non-randomized series. (orig.)

  2. Nonimmunogenic hyperthyroidism: Cumulative hypothyroidism incidence after radioiodine and surgical treatment

    International Nuclear Information System (INIS)

    Kinser, J.A.; Roesler, H.; Furrer, T.; Gruetter, D.Z.; Zimmermann, H.

    1989-01-01

    During 1977, 246 hyperthyroid patients were seen in our departments, 140 (57%) with nonimmunogenic hyperthyroidism (NIH)--101 with a toxic adenoma (TA) and 39 with multifocal functional autonomy (MFA). All patients but one could be followed over 9 yr, 101 after 131I treatment (RIT), another 29 after surgery (S). Ten patients were left untreated. Thirty-four treated (24%) patients died, none as a result of thyroid or post-treatment complications. There was no hyperthyroidism later than 9 mo after therapy. Only 1% (RIT) and 24% (S) were hypothyroid 1 yr after treatment. But 19% of all treated NIH patients were hypothyroid after 9 yr or at the time of their death, 12% after RIT and 41% after S. The cumulative hypothyroidism incidences 1.4%/yr for RIT and 2.2%/yr for S, were not significantly different. Out of the five survivers without RIT or S, two TA patients were hypothyroid. The effect of RIT on goiter related loco-regional complications was not worse than after S. We conclude that RIT is the treatment for NIH, leaving surgery for exceptional cases

  3. Palliative radiotherapy in addition to self-expanding metal stent for improving dysphagia and survival in advanced oesophageal cancer (ROCS: Radiotherapy after Oesophageal Cancer Stenting): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Adamson, Douglas; Blazeby, Jane; Nelson, Annmarie; Hurt, Chris; Nixon, Lisette; Fitzgibbon, Jim; Crosby, Tom; Staffurth, John; Evans, Mim; Kelly, Noreen Hopewell; Cohen, David; Griffiths, Gareth; Byrne, Anthony

    2014-10-22

    The single most distressing symptom for patients with advanced esophageal cancer is dysphagia. Amongst the more effective treatments for relief of dysphagia is insertion of a self-expanding metal stent (SEMS). It is possible that the addition of a palliative dose of external beam radiotherapy may prolong the relief of dysphagia and provide additional survival benefit. The ROCS trial will assess the effect of adding palliative radiotherapy after esophageal stent insertion. The study is a randomized multicenter phase III trial, with an internal pilot phase, comparing stent alone versus stent plus palliative radiotherapy in patients with incurable esophageal cancer. Eligible participants are those with advanced esophageal cancer who are in need of stent insertion for primary management of dysphagia. Radiotherapy will be administered as 20 Gray (Gy) in five fractions over one week or 30 Gy in 10 fractions over two weeks, within four weeks of stent insertion. The internal pilot will assess rates and methods of recruitment; pre-agreed criteria will determine progression to the main trial. In total, 496 patients will be randomized in a 1:1 ratio with follow up until death. The primary outcome is time to progression of patient-reported dysphagia. Secondary outcomes include survival, toxicity, health resource utilization, and quality of life. An embedded qualitative study will explore the feasibility of patient recruitment by examining patients' motivations for involvement and their experiences of consent and recruitment, including reasons for not consenting. It will also explore patients' experiences of each trial arm. The ROCS study will be a challenging trial studying palliation in patients with a poor prognosis. The internal pilot design will optimize methods for recruitment and data collection to ensure that the main trial is completed on time. As a pragmatic trial, study strengths include collection of all follow-up data in the usual place of care, and a focus on

  4. Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management

    International Nuclear Information System (INIS)

    Smith, J. Joshua; Chow, Oliver S.; Gollub, Marc J.; Nash, Garrett M.; Temple, Larissa K.; Weiser, Martin R.; Guillem, José G.; Paty, Philip B.; Avila, Karin; Garcia-Aguilar, Julio

    2015-01-01

    Treatment of patients with non-metastatic, locally advanced rectal cancer (LARC) includes pre-operative chemoradiation, total mesorectal excision (TME) and post-operative adjuvant chemotherapy. This trimodality treatment provides local tumor control in most patients; but almost one-third ultimately die from distant metastasis. Most survivors experience significant impairment in quality of life (QoL), due primarily to removal of the rectum. A current challenge lies in identifying patients who could safely undergo rectal preservation without sacrificing survival benefit and QoL. This multi-institutional, phase II study investigates the efficacy of total neoadjuvant therapy (TNT) and selective non-operative management (NOM) in LARC. Patients with MRI-staged Stage II or III rectal cancer amenable to TME will be randomized to receive FOLFOX/CAPEOX: a) before induction neoadjuvant chemotherapy (INCT); or b) after consolidation neoadjuvant chemotherapy (CNCT), with 5-FU or capecitabine-based chemoradiation. Patients in both arms will be re-staged after completing all neoadjuvant therapy. Those with residual tumor at the primary site will undergo TME. Patients with clinical complete response (cCR) will receive non-operative management (NOM). NOM patients will be followed every 3 months for 2 years, and every 6 months thereafter. TME patients will be followed according to NCCN guidelines. All will be followed for at least 5 years from the date of surgery or—in patients treated with NOM—the last day of treatment. The studies published thus far on the safety of NOM in LARC have compared survival between select groups of patients with a cCR after NOM, to patients with a pathologic complete response (pCR) after TME. The current study compares 3-year disease-free survival (DFS) in an entire population of patients with LARC, including those with cCR and those with pCR. We will compare the two arms of the study with respect to organ preservation at 3 years, treatment

  5. Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management.

    Science.gov (United States)

    Smith, J Joshua; Chow, Oliver S; Gollub, Marc J; Nash, Garrett M; Temple, Larissa K; Weiser, Martin R; Guillem, José G; Paty, Philip B; Avila, Karin; Garcia-Aguilar, Julio

    2015-10-23

    Treatment of patients with non-metastatic, locally advanced rectal cancer (LARC) includes pre-operative chemoradiation, total mesorectal excision (TME) and post-operative adjuvant chemotherapy. This trimodality treatment provides local tumor control in most patients; but almost one-third ultimately die from distant metastasis. Most survivors experience significant impairment in quality of life (QoL), due primarily to removal of the rectum. A current challenge lies in identifying patients who could safely undergo rectal preservation without sacrificing survival benefit and QoL. This multi-institutional, phase II study investigates the efficacy of total neoadjuvant therapy (TNT) and selective non-operative management (NOM) in LARC. Patients with MRI-staged Stage II or III rectal cancer amenable to TME will be randomized to receive FOLFOX/CAPEOX: a) before induction neoadjuvant chemotherapy (INCT); or b) after consolidation neoadjuvant chemotherapy (CNCT), with 5-FU or capecitabine-based chemoradiation. Patients in both arms will be re-staged after completing all neoadjuvant therapy. Those with residual tumor at the primary site will undergo TME. Patients with clinical complete response (cCR) will receive non-operative management (NOM). NOM patients will be followed every 3 months for 2 years, and every 6 months thereafter. TME patients will be followed according to NCCN guidelines. All will be followed for at least 5 years from the date of surgery or--in patients treated with NOM--the last day of treatment. The studies published thus far on the safety of NOM in LARC have compared survival between select groups of patients with a cCR after NOM, to patients with a pathologic complete response (pCR) after TME. The current study compares 3-year disease-free survival (DFS) in an entire population of patients with LARC, including those with cCR and those with pCR. We will compare the two arms of the study with respect to organ preservation at 3 years, treatment compliance

  6. Two-year survival of glass ionomer sealants placed as part of ...

    African Journals Online (AJOL)

    , ... Results: The two-year cumulative survival of the sealants was 10.9%, and the survival of the sealants was not significantly affected by the GIC material brand and the toothisolation method used. However, slightly more sealants survived ...

  7. Cumulative radiation dose of multiple trauma patients during their hospitalization

    International Nuclear Information System (INIS)

    Wang Zhikang; Sun Jianzhong; Zhao Zudan

    2012-01-01

    Objective: To study the cumulative radiation dose of multiple trauma patients during their hospitalization and to analyze the dose influence factors. Methods: The DLP for CT and DR were retrospectively collected from the patients during June, 2009 and April, 2011 at a university affiliated hospital. The cumulative radiation doses were calculated by summing typical effective doses of the anatomic regions scanned. Results: The cumulative radiation doses of 113 patients were collected. The maximum,minimum and the mean values of cumulative effective doses were 153.3, 16.48 mSv and (52.3 ± 26.6) mSv. Conclusions: Multiple trauma patients have high cumulative radiation exposure. Therefore, the management of cumulative radiation doses should be enhanced. To establish the individualized radiation exposure archives will be helpful for the clinicians and technicians to make decision whether to image again and how to select the imaging parameters. (authors)

  8. Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group.

    Science.gov (United States)

    Lübbert, Michael; Suciu, Stefan; Hagemeijer, Anne; Rüter, Björn; Platzbecker, Uwe; Giagounidis, Aristoteles; Selleslag, Dominik; Labar, Boris; Germing, Ulrich; Salih, Helmut R; Muus, Petra; Pflüger, Karl-Heinz; Schaefer, Hans-Eckart; Bogatyreva, Lioudmila; Aul, Carlo; de Witte, Theo; Ganser, Arnold; Becker, Heiko; Huls, Gerwin; van der Helm, Lieke; Vellenga, Edo; Baron, Frédéric; Marie, Jean-Pierre; Wijermans, Pierre W

    2016-01-01

    In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lübbert et al., Haematologica 97:393-401, 2012). We now analyzed 206 myelodysplastic syndrome (MDS) patients (88 % of 233 patients randomized in the EORTC/GMDSSG phase III trial 06011, 61 of them with RAEBt, i.e. AML by WHO) with cytogenetics informative for MK status.. Endpoints are the following: complete/partial (CR/PR) and overall response rate (ORR) and progression-free (PFS) and overall survival (OS). Cytogenetic subgroups are the following: 63 cytogenetically normal (CN) patients, 143 with cytogenetic abnormalities, 73 of them MK-negative (MK-), and 70 MK-positive (MK+). These MK+ patients could be divided into 17 with a single autosomal monosomy (MK1) and 53 with at least two monosomies (MK2+). ORR with DAC in CN patients: 36.1 %, in MK- patients: 16.7 %, in MK+ patients: 43.6 % (MK1: 44.4 %, MK2+ 43.3 %). PFS was prolonged by DAC compared to best supportive care (BSC) in the CN (hazard ratio (HR) 0.55, 99 % confidence interval (CI), 0.26; 1.15, p = 0.03) and MK2+ (HR 0.50; 99 % CI, 0.23; 1.06, p = 0.016) but not in the MK-, MK+, and MK1 subgroups. OS was not improved by DAC in any subgroup. In conclusion, we demonstrate for the first time in a randomized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC.

  9. 7 CFR 42.132 - Determining cumulative sum values.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Determining cumulative sum values. 42.132 Section 42... Determining cumulative sum values. (a) The parameters for the on-line cumulative sum sampling plans for AQL's... 3 1 2.5 3 1 2 1 (b) At the beginning of the basic inspection period, the CuSum value is set equal to...

  10. Improving cumulative effects assessment in Alberta: Regional strategic assessment

    International Nuclear Information System (INIS)

    Johnson, Dallas; Lalonde, Kim; McEachern, Menzie; Kenney, John; Mendoza, Gustavo; Buffin, Andrew; Rich, Kate

    2011-01-01

    The Government of Alberta, Canada is developing a regulatory framework to better manage cumulative environmental effects from development in the province. A key component of this effort is regional planning, which will lay the primary foundation for cumulative effects management into the future. Alberta Environment has considered the information needs of regional planning and has concluded that Regional Strategic Assessment may offer significant advantages if integrated into the planning process, including the overall improvement of cumulative environmental effects assessment in the province.

  11. Children neglected: Where cumulative risk theory fails.

    Science.gov (United States)

    O'Hara, Mandy; Legano, Lori; Homel, Peter; Walker-Descartes, Ingrid; Rojas, Mary; Laraque, Danielle

    2015-07-01

    Neglected children, by far the majority of children maltreated, experience an environment most deficient in cognitive stimulation and language exchange. When physical abuse co-occurs with neglect, there is more stimulation through negative parent-child interaction, which may lead to better cognitive outcomes, contrary to Cumulative Risk Theory. The purpose of the current study was to assess whether children only neglected perform worse on cognitive tasks than children neglected and physically abused. Utilizing LONGSCAN archived data, 271 children only neglected and 101 children neglected and physically abused in the first four years of life were compared. The two groups were assessed at age 6 on the WPPSI-R vocabulary and block design subtests, correlates of cognitive intelligence. Regression analyses were performed, controlling for additional predictors of poor cognitive outcome, including socioeconomic variables and caregiver depression. Children only neglected scored significantly worse than children neglected and abused on the WPPSI-R vocabulary subtest (p=0.03). The groups did not differ on the block design subtest (p=0.4). This study shows that for neglected children, additional abuse may not additively accumulate risk when considering intelligence outcomes. Children experiencing only neglect may need to be referred for services that address cognitive development, with emphasis on the linguistic environment, in order to best support the developmental challenges of neglected children. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Standardization of the cumulative absolute velocity

    International Nuclear Information System (INIS)

    O'Hara, T.F.; Jacobson, J.P.

    1991-12-01

    EPRI NP-5930, ''A Criterion for Determining Exceedance of the Operating Basis Earthquake,'' was published in July 1988. As defined in that report, the Operating Basis Earthquake (OBE) is exceeded when both a response spectrum parameter and a second damage parameter, referred to as the Cumulative Absolute Velocity (CAV), are exceeded. In the review process of the above report, it was noted that the calculation of CAV could be confounded by time history records of long duration containing low (nondamaging) acceleration. Therefore, it is necessary to standardize the method of calculating CAV to account for record length. This standardized methodology allows consistent comparisons between future CAV calculations and the adjusted CAV threshold value based upon applying the standardized methodology to the data set presented in EPRI NP-5930. The recommended method to standardize the CAV calculation is to window its calculation on a second-by-second basis for a given time history. If the absolute acceleration exceeds 0.025g at any time during each one second interval, the earthquake records used in EPRI NP-5930 have been reanalyzed and the adjusted threshold of damage for CAV was found to be 0.16g-set

  13. Analysis of Memory Codes and Cumulative Rehearsal in Observational Learning

    Science.gov (United States)

    Bandura, Albert; And Others

    1974-01-01

    The present study examined the influence of memory codes varying in meaningfulness and retrievability and cumulative rehearsal on retention of observationally learned responses over increasing temporal intervals. (Editor)

  14. INTERACTIVE VISUALIZATION OF PROBABILITY AND CUMULATIVE DENSITY FUNCTIONS

    KAUST Repository

    Potter, Kristin; Kirby, Robert Michael; Xiu, Dongbin; Johnson, Chris R.

    2012-01-01

    The probability density function (PDF), and its corresponding cumulative density function (CDF), provide direct statistical insight into the characterization of a random process or field. Typically displayed as a histogram, one can infer probabilities of the occurrence of particular events. When examining a field over some two-dimensional domain in which at each point a PDF of the function values is available, it is challenging to assess the global (stochastic) features present within the field. In this paper, we present a visualization system that allows the user to examine two-dimensional data sets in which PDF (or CDF) information is available at any position within the domain. The tool provides a contour display showing the normed difference between the PDFs and an ansatz PDF selected by the user and, furthermore, allows the user to interactively examine the PDF at any particular position. Canonical examples of the tool are provided to help guide the reader into the mapping of stochastic information to visual cues along with a description of the use of the tool for examining data generated from an uncertainty quantification exercise accomplished within the field of electrophysiology.

  15. Implant and prosthodontic survival rates with implant fixed complete dental prostheses in the edentulous mandible after at least 5 years: a systematic review.

    Science.gov (United States)

    Papaspyridakos, Panos; Mokti, Muizzaddin; Chen, Chun-Jung; Benic, Goran I; Gallucci, German O; Chronopoulos, Vasilios

    2014-10-01

    The treatment of mandibular edentulism with implant fixed complete dental prostheses (IFCDPs) is a routinely used treatment option. The study aims to report the implant and prosthodontic survival rates associated with IFCDPs for the edentulous mandible after an observation period of a minimum 5 years. An electronic MEDLINE/PubMED search was conducted to identify randomized controlled clinical trials and prospective studies with IFCDPs for the edentulous mandible. Clinical studies with at least 5-year follow-up were selected. Pooled data were statistically analyzed and cumulative implant- and prosthesis survival rates were calculated by meta-analysis, regression, and chi-square statistics. Implant-related and prosthesis-related factors were identified and their impact on survival rates was assessed. Seventeen prospective studies, including 501 patients and 2,827 implants, were selected for meta-analysis. The majority of the implants (88.5% of all placed implants) had been placed in the interforaminal area. Cumulative implant survival rates for rough surface ranged from 98.42% (95% confidence interval [CI]: 97.98-98.86) (5 years) to 96.86% (95% CI: 96.00-97.73) (10 years); smooth surface implant survival rates ranged from 98.93% (95% CI: 98.38-99.49) (5 years) to 97.88% (95% CI: 96.78-98.98) (10 years). The prosthodontic survival rates for 1-piece IFCDPs ranged from 98.61% (95% CI: 97.80-99.43) (5 years) to 97.25% (95% CI: 95.66-98.86) (10 years). Treatment with mandibular IFCDPs yields high implant and prosthodontic survival rates (more than 96% after 10 years). Rough surface implants exhibited cumulative survival rates similar to the smooth surface ones (p > .05) in the edentulous mandible. The number of supporting implants and the antero-posterior implant distribution had no influence (p > .05) on the implant survival rate. The prosthetic design and veneering material, the retention type, and the loading protocol (delayed, early, and immediate) had no

  16. Accounting for competing risks in randomized controlled trials: a review and recommendations for improvement.

    Science.gov (United States)

    Austin, Peter C; Fine, Jason P

    2017-04-15

    In studies with survival or time-to-event outcomes, a competing risk is an event whose occurrence precludes the occurrence of the primary event of interest. Specialized statistical methods must be used to analyze survival data in the presence of competing risks. We conducted a review of randomized controlled trials with survival outcomes that were published in high-impact general medical journals. Of 40 studies that we identified, 31 (77.5%) were potentially susceptible to competing risks. However, in the majority of these studies, the potential presence of competing risks was not accounted for in the statistical analyses that were described. Of the 31 studies potentially susceptible to competing risks, 24 (77.4%) reported the results of a Kaplan-Meier survival analysis, while only five (16.1%) reported using cumulative incidence functions to estimate the incidence of the outcome over time in the presence of competing risks. The former approach will tend to result in an overestimate of the incidence of the outcome over time, while the latter approach will result in unbiased estimation of the incidence of the primary outcome over time. We provide recommendations on the analysis and reporting of randomized controlled trials with survival outcomes in the presence of competing risks. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

  17. Cumulative Effect of Depression on Dementia Risk

    Directory of Open Access Journals (Sweden)

    J. Olazarán

    2013-01-01

    Full Text Available Objective. To analyze a potential cumulative effect of life-time depression on dementia and Alzheimer’s disease (AD, with control of vascular factors (VFs. Methods. This study was a subanalysis of the Neurological Disorders in Central Spain (NEDICES study. Past and present depression, VFs, dementia status, and dementia due to AD were documented at study inception. Dementia status was also documented after three years. Four groups were created according to baseline data: never depression (nD, past depression (pD, present depression (prD, and present and past depression (prpD. Logistic regression was used. Results. Data of 1,807 subjects were investigated at baseline (mean age 74.3, 59.3% women, and 1,376 (81.6% subjects were evaluated after three years. The prevalence of dementia at baseline was 6.7%, and dementia incidence was 6.3%. An effect of depression was observed on dementia prevalence (OR [CI 95%] 1.84 [1.01–3.35] for prD and 2.73 [1.08–6.87] for prpD, and on dementia due to AD (OR 1.98 [0.98–3.99] for prD and OR 3.98 [1.48–10.71] for prpD (fully adjusted models, nD as reference. Depression did not influence dementia incidence. Conclusions. Present depression and, particularly, present and past depression are associated with dementia at old age. Multiple mechanisms, including toxic effect of depression on hippocampal neurons, plausibly explain these associations.

  18. Quantitative cumulative biodistribution of antibodies in mice

    Science.gov (United States)

    Yip, Victor; Palma, Enzo; Tesar, Devin B; Mundo, Eduardo E; Bumbaca, Daniela; Torres, Elizabeth K; Reyes, Noe A; Shen, Ben Q; Fielder, Paul J; Prabhu, Saileta; Khawli, Leslie A; Boswell, C Andrew

    2014-01-01

    The neonatal Fc receptor (FcRn) plays an important and well-known role in antibody recycling in endothelial and hematopoietic cells and thus it influences the systemic pharmacokinetics (PK) of immunoglobulin G (IgG). However, considerably less is known about FcRn’s role in the metabolism of IgG within individual tissues after intravenous administration. To elucidate the organ distribution and gain insight into the metabolism of humanized IgG1 antibodies with different binding affinities FcRn, comparative biodistribution studies in normal CD-1 mice were conducted. Here, we generated variants of herpes simplex virus glycoprotein D-specific antibody (humanized anti-gD) with increased and decreased FcRn binding affinity by genetic engineering without affecting antigen specificity. These antibodies were expressed in Chinese hamster ovary cell lines, purified and paired radiolabeled with iodine-125 and indium-111. Equal amounts of I-125-labeled and In-111-labeled antibodies were mixed and intravenously administered into mice at 5 mg/kg. This approach allowed us to measure both the real-time IgG uptake (I-125) and cumulative uptake of IgG and catabolites (In-111) in individual tissues up to 1 week post-injection. The PK and distribution of the wild-type IgG and the variant with enhanced binding for FcRn were largely similar to each other, but vastly different for the rapidly cleared low-FcRn-binding variant. Uptake in individual tissues varied across time, FcRn binding affinity, and radiolabeling method. The liver and spleen emerged as the most concentrated sites of IgG catabolism in the absence of FcRn protection. These data provide an increased understanding of FcRn’s role in antibody PK and catabolism at the tissue level. PMID:24572100

  19. A Framework for Treating Cumulative Trauma with Art Therapy

    Science.gov (United States)

    Naff, Kristina

    2014-01-01

    Cumulative trauma is relatively undocumented in art therapy practice, although there is growing evidence that art therapy provides distinct benefits for resolving various traumas. This qualitative study proposes an art therapy treatment framework for cumulative trauma derived from semi-structured interviews with three art therapists and artistic…

  20. Cumulative effects of forest management activities: how might they occur?

    Science.gov (United States)

    R. M. Rice; R. B. Thomas

    1985-01-01

    Concerns are often voiced about possible environmental damage as the result of the cumulative sedimentation effects of logging and forest road construction. In response to these concerns, National Forests are developing procedures to reduce the possibility that their activities may lead to unacceptable cumulative effects

  1. Cumulative effect in multiple production processes on nuclei

    International Nuclear Information System (INIS)

    Golubyatnikova, E.S.; Shmonin, V.L.; Kalinkin, B.N.

    1989-01-01

    It is shown that the cumulative effect is a natural result of the process of hadron multiple production in nuclear reactions. Interpretation is made of the universality of slopes of inclusive spectra and other characteristics of cumulative hadrons. The character of information from such reactions is discussed, which could be helpful in studying the mechanism of multiparticle production. 27 refs.; 4 figs

  2. Cumulative particle production in the quark recombination model

    International Nuclear Information System (INIS)

    Gavrilov, V.B.; Leksin, G.A.

    1987-01-01

    Production of cumulative particles in hadron-nuclear inteactions at high energies is considered within the framework of recombination quark model. Predictions for inclusive cross sections of production of cumulative particles and different resonances containing quarks in s state are made

  3. Higher order net-proton number cumulants dependence on the centrality definition and other spurious effects

    Science.gov (United States)

    Sombun, S.; Steinheimer, J.; Herold, C.; Limphirat, A.; Yan, Y.; Bleicher, M.

    2018-02-01

    We study the dependence of the normalized moments of the net-proton multiplicity distributions on the definition of centrality in relativistic nuclear collisions at a beam energy of \\sqrt{{s}{NN}}=7.7 {GeV}. Using the ultra relativistic quantum molecular dynamics model as event generator we find that the centrality definition has a large effect on the extracted cumulant ratios. Furthermore we find that the finite efficiency for the determination of the centrality introduces an additional systematic uncertainty. Finally, we quantitatively investigate the effects of event-pile up and other possible spurious effects which may change the measured proton number. We find that pile-up alone is not sufficient to describe the data and show that a random double counting of events, adding significantly to the measured proton number, affects mainly the higher order cumulants in most central collisions.

  4. Towards Greenland Glaciation: cumulative or abrupt transition?

    Science.gov (United States)

    Ramstein, Gilles; Tan, Ning; Ladant, Jean-baptiste; Dumas, Christophe; Contoux, Camille

    2017-04-01

    During the mid-Pliocene warming period (3-3.3 Ma BP), the global annual mean temperatures inferred by data and model studies were 2-3° warmer than pre-industrial values. Accordingly, Greenland ice sheet volume is supposed to reach at the most, only half of that of present-day [Haywood et al. 2010]. Around 2.7-2.6 Ma BP, just ˜ 500 kyr after the warming peak of mid-Pliocene, the Greenland ice sheet has reached its full size [Lunt et al. 2008]. A crucial question concerns the evolution of the Greenland ice sheet from half to full size during the 3 - 2.5 Ma period. Data show a decreasing trend of atmospheric CO2 concentration from 3 Ma to 2.5 Ma [Seki et al.2010; Bartoli et al. 2011; Martinez et al. 2015]. However, a recent study [Contoux et al. 2015] suggests that a lowering of CO2 is not sufficient to initiate a perennial glaciation on Greenland and must be combined with low summer insolation to preserve the ice sheet during insolation maxima. This suggests rather a cumulative process than an abrupt event. In order to diagnose the evolution of the ice sheet build-up, we carry on, for the first time, a transient simulation of climate and ice sheet evolutions from 3 Ma to 2.5 Ma. This strategy enables us to investigate the waxing and waning of the ice sheet during several orbital cycles. We use a tri-dimensional interpolation method designed by Ladant et al. (2014), which allows the evolution of CO2 concentration and of orbital parameters, and the evolution of the Greenland ice sheet size to be taken into account. By interpolating climatic snapshot simulations ran with various possible combinations of CO2, orbits and ice sheet sizes, we can build a continuous climatic forcing that is then used to provide 500 kyrs-long ice sheet simulations. With such a tool, we may offer a physically based answer to different CO2 reconstructions scenarios and analyse which one is the most consistent with Greenland ice sheet buildup.

  5. An Analysis of Cumulative Risks Indicated by Biomonitoring Data of Six Phthalates Using the Maximum Cumulative Ratio

    Science.gov (United States)

    The Maximum Cumulative Ratio (MCR) quantifies the degree to which a single component of a chemical mixture drives the cumulative risk of a receptor.1 This study used the MCR, the Hazard Index (HI) and Hazard Quotient (HQ) to evaluate co-exposures to six phthalates using biomonito...

  6. An analysis of cumulative risks based on biomonitoring data for six phthalates using the Maximum Cumulative Ratio

    Science.gov (United States)

    The Maximum Cumulative Ratio (MCR) quantifies the degree to which a single chemical drives the cumulative risk of an individual exposed to multiple chemicals. Phthalates are a class of chemicals with ubiquitous exposures in the general population that have the potential to cause ...

  7. Surviving Sengstaken.

    Science.gov (United States)

    Jayakumar, S; Odulaja, A; Patel, S; Davenport, M; Ade-Ajayi, N

    2015-07-01

    To report the outcomes of children who underwent Sengstaken-Blakemore tube (SBT) insertion for life-threatening haemetemesis. Single institution retrospective review (1997-2012) of children managed with SBT insertion. Patient demographics, diagnosis and outcomes were noted. Data are expressed as median (range). 19 children [10 male, age 1 (0.4-16) yr] were identified; 18 had gastro-oesophageal varices and 1 aorto-oesophageal fistula. Varices were secondary to: biliary atresia (n=8), portal vein thrombosis (n=5), alpha-1-anti-trypsin deficiency (n=1), cystic fibrosis (n=1), intrahepatic cholestasis (n=1), sclerosing cholangitis (n=1) and nodular hyperplasia with arterio-portal shunt (n=1). Three children deteriorated rapidly and did not survive to have post-SBT endoscopy. The child with an aortooesophageal fistula underwent aortic stent insertion and subsequently oesophageal replacement. Complications included gastric mucosal ulceration (n=3, 16%), pressure necrosis at lips and cheeks (n=6, 31%) and SBT dislodgment (n=1, 6%). Six (31%) children died. The remaining 13 have been followed up for 62 (2-165) months; five required liver transplantation, two underwent a mesocaval shunt procedure and 6 have completed endoscopic variceal obliteration and are under surveillance. SBT can be an effective, albeit temporary, life-saving manoeuvre in children with catastrophic haematemesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.

    Science.gov (United States)

    Topalian, Suzanne L; Sznol, Mario; McDermott, David F; Kluger, Harriet M; Carvajal, Richard D; Sharfman, William H; Brahmer, Julie R; Lawrence, Donald P; Atkins, Michael B; Powderly, John D; Leming, Philip D; Lipson, Evan J; Puzanov, Igor; Smith, David C; Taube, Janis M; Wigginton, Jon M; Kollia, Georgia D; Gupta, Ashok; Pardoll, Drew M; Sosman, Jeffrey A; Hodi, F Stephen

    2014-04-01

    Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued. Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation. Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative. Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.

  9. Cumulative stress and autonomic dysregulation in a community sample.

    Science.gov (United States)

    Lampert, Rachel; Tuit, Keri; Hong, Kwang-Ik; Donovan, Theresa; Lee, Forrester; Sinha, Rajita

    2016-05-01

    Whether cumulative stress, including both chronic stress and adverse life events, is associated with decreased heart rate variability (HRV), a non-invasive measure of autonomic status which predicts poor cardiovascular outcomes, is unknown. Healthy community dwelling volunteers (N = 157, mean age 29 years) participated in the Cumulative Stress/Adversity Interview (CAI), a 140-item event interview measuring cumulative adversity including major life events, life trauma, recent life events and chronic stressors, and underwent 24-h ambulatory ECG monitoring. HRV was analyzed in the frequency domain and standard deviation of NN intervals (SDNN) calculated. Initial simple regression analyses revealed that total cumulative stress score, chronic stressors and cumulative adverse life events (CALE) were all inversely associated with ultra low-frequency (ULF), very low-frequency (VLF) and low-frequency (LF) power and SDNN (all p accounting for additional appreciable variance. For VLF and LF, both total cumulative stress and chronic stress significantly contributed to the variance alone but were not longer significant after adjusting for race and health behaviors. In summary, total cumulative stress, and its components of adverse life events and chronic stress were associated with decreased cardiac autonomic function as measured by HRV. Findings suggest one potential mechanism by which stress may exert adverse effects on mortality in healthy individuals. Primary preventive strategies including stress management may prove beneficial.

  10. On the duration and intensity of cumulative advantage competitions

    Science.gov (United States)

    Jiang, Bo; Sun, Liyuan; Figueiredo, Daniel R.; Ribeiro, Bruno; Towsley, Don

    2015-11-01

    Network growth can be framed as a competition for edges among nodes in the network. As with various other social and physical systems, skill (fitness) and luck (random chance) act as fundamental forces driving competition dynamics. In the context of networks, cumulative advantage (CA)—the rich-get-richer effect—is seen as a driving principle governing the edge accumulation process. However, competitions coupled with CA exhibit non-trivial behavior and little is formally known about duration and intensity of CA competitions. By isolating two nodes in an ideal CA competition, we provide a mathematical understanding of how CA exacerbates the role of luck in detriment of skill. We show, for instance, that when nodes start with few edges, an early stroke of luck can place the less skilled in the lead for an extremely long period of time, a phenomenon we call ‘struggle of the fittest’. We prove that duration of a simple skill and luck competition model exhibit power-law tails when CA is present, regardless of skill difference, which is in sharp contrast to the exponential tails when fitness is distinct but CA is absent. We also prove that competition intensity is always upper bounded by an exponential tail, irrespective of CA and skills. Thus, CA competitions can be extremely long (infinite mean, depending on fitness ratio) but almost never very intense. The theoretical results are corroborated by extensive numerical simulations. Our findings have important implications to competitions not only among nodes in networks but also in contexts that leverage socio-physical models embodying CA competitions.

  11. On the duration and intensity of cumulative advantage competitions

    International Nuclear Information System (INIS)

    Jiang, Bo; Towsley, Don; Sun, Liyuan; Figueiredo, Daniel R; Ribeiro, Bruno

    2015-01-01

    Network growth can be framed as a competition for edges among nodes in the network. As with various other social and physical systems, skill (fitness) and luck (random chance) act as fundamental forces driving competition dynamics. In the context of networks, cumulative advantage (CA)—the rich-get-richer effect—is seen as a driving principle governing the edge accumulation process. However, competitions coupled with CA exhibit non-trivial behavior and little is formally known about duration and intensity of CA competitions. By isolating two nodes in an ideal CA competition, we provide a mathematical understanding of how CA exacerbates the role of luck in detriment of skill. We show, for instance, that when nodes start with few edges, an early stroke of luck can place the less skilled in the lead for an extremely long period of time, a phenomenon we call ‘struggle of the fittest’. We prove that duration of a simple skill and luck competition model exhibit power-law tails when CA is present, regardless of skill difference, which is in sharp contrast to the exponential tails when fitness is distinct but CA is absent. We also prove that competition intensity is always upper bounded by an exponential tail, irrespective of CA and skills. Thus, CA competitions can be extremely long (infinite mean, depending on fitness ratio) but almost never very intense. The theoretical results are corroborated by extensive numerical simulations. Our findings have important implications to competitions not only among nodes in networks but also in contexts that leverage socio-physical models embodying CA competitions. (paper)

  12. Cumulants in perturbation expansions for non-equilibrium field theory

    International Nuclear Information System (INIS)

    Fauser, R.

    1995-11-01

    The formulation of perturbation expansions for a quantum field theory of strongly interacting systems in a general non-equilibrium state is discussed. Non-vanishing initial correlations are included in the formulation of the perturbation expansion in terms of cumulants. The cumulants are shown to be the suitable candidate for summing up the perturbation expansion. Also a linked-cluster theorem for the perturbation series with cumulants is presented. Finally a generating functional of the perturbation series with initial correlations is studied. We apply the methods to a simple model of a fermion-boson system. (orig.)

  13. Estimating a population cumulative incidence under calendar time trends

    DEFF Research Database (Denmark)

    Hansen, Stefan N; Overgaard, Morten; Andersen, Per K

    2017-01-01

    BACKGROUND: The risk of a disease or psychiatric disorder is frequently measured by the age-specific cumulative incidence. Cumulative incidence estimates are often derived in cohort studies with individuals recruited over calendar time and with the end of follow-up governed by a specific date....... It is common practice to apply the Kaplan-Meier or Aalen-Johansen estimator to the total sample and report either the estimated cumulative incidence curve or just a single point on the curve as a description of the disease risk. METHODS: We argue that, whenever the disease or disorder of interest is influenced...

  14. Cumulative occupational shoulder exposures and surgery for subacromial impingement syndrome: a nationwide Danish cohort study.

    Science.gov (United States)

    Dalbøge, Annett; Frost, Poul; Andersen, Johan Hviid; Svendsen, Susanne Wulff

    2014-11-01

    The primary aim was to examine exposure-response relationships between cumulative occupational shoulder exposures and surgery for subacromial impingement syndrome (SIS), and to compare sex-specific exposure-response relationships. The secondary aim was to examine the time window of relevant exposures. We conducted a nationwide register study of all persons born in Denmark (1933-1977), who had at least 5 years of full-time employment. In the follow-up period (2003-2008), we identified first-time events of surgery for SIS. Cumulative exposure estimates for a 10-year exposure time window with a 1-year lag time were obtained by linking occupational codes with a job exposure matrix. The exposure estimates were expressed as, for example, arm-elevation-years in accordance with the pack-year concept of tobacco consumption. We used a multivariable logistic regression technique equivalent to discrete survival analysis. The adjusted OR (ORadj) increased to a maximum of 2.1 for arm-elevation-years, repetition-years and force-years, and to 1.5 for hand-arm-vibration-years. Sex-specific exposure-response relationships were similar for men and women, when assessed using a relative risk scale. The ORadj increased gradually with the number of years contributing to the cumulative exposure estimates. The excess fraction was 24%. Cumulative occupational shoulder exposures carried an increase in risk of surgery for SIS with similar exposure-response curves for men and women. The risk of surgery for SIS increased gradually, when the period of exposure assessment was extended. In the general working population, a substantial fraction of all first-time operations for SIS could be related to occupational exposures. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  15. Cumulative damage fatigue tests on nuclear reactor Zircaloy-2 fuel tubes at room temperature and 3000C

    International Nuclear Information System (INIS)

    Pandarinathan, P.R.; Vasudevan, P.

    1980-01-01

    Cumulative damage fatigue tests were conducted on the Zircaloy-2 fuel tubes at room temperature and 300 0 C on the modified Moore type, four-point-loaded, deflection-controlled, rotating bending fatigue testing machine. The cumulative cycle ratio at fracture for the Zircaloy-2 fuel tubes was found to depend on the sequence of loading, stress history, number of cycles of application of the pre-stress and the test temperature. A Hi-Lo type fatigue loading was found to be very much damaging at room temperature and this feature was not observed in the tests at 300 0 C. Results indicate significant differences in damage interaction and damage propagation under cumulative damage tests at room temperature and at 300 0 C. Block-loading fatigue tests are suggested as the best method to determine the life-time of Zircaloy-2 fuel tubes under random fatigue loading during their service in the reactor. (orig.)

  16. Cumulative Environmental Impacts: Science and Policy to Protect Communities.

    Science.gov (United States)

    Solomon, Gina M; Morello-Frosch, Rachel; Zeise, Lauren; Faust, John B

    2016-01-01

    Many communities are located near multiple sources of pollution, including current and former industrial sites, major roadways, and agricultural operations. Populations in such locations are predominantly low-income, with a large percentage of minorities and non-English speakers. These communities face challenges that can affect the health of their residents, including limited access to health care, a shortage of grocery stores, poor housing quality, and a lack of parks and open spaces. Environmental exposures may interact with social stressors, thereby worsening health outcomes. Age, genetic characteristics, and preexisting health conditions increase the risk of adverse health effects from exposure to pollutants. There are existing approaches for characterizing cumulative exposures, cumulative risks, and cumulative health impacts. Although such approaches have merit, they also have significant constraints. New developments in exposure monitoring, mapping, toxicology, and epidemiology, especially when informed by community participation, have the potential to advance the science on cumulative impacts and to improve decision making.

  17. Pesticide Cumulative Risk Assessment: Framework for Screening Analysis

    Science.gov (United States)

    This document provides guidance on how to screen groups of pesticides for cumulative evaluation using a two-step approach: begin with evaluation of available toxicological information and, if necessary, follow up with a risk-based screening approach.

  18. Online Scheduling in Manufacturing A Cumulative Delay Approach

    CERN Document Server

    Suwa, Haruhiko

    2013-01-01

    Online scheduling is recognized as the crucial decision-making process of production control at a phase of “being in production" according to the released shop floor schedule. Online scheduling can be also considered as one of key enablers to realize prompt capable-to-promise as well as available-to-promise to customers along with reducing production lead times under recent globalized competitive markets. Online Scheduling in Manufacturing introduces new approaches to online scheduling based on a concept of cumulative delay. The cumulative delay is regarded as consolidated information of uncertainties under a dynamic environment in manufacturing and can be collected constantly without much effort at any points in time during a schedule execution. In this approach, the cumulative delay of the schedule has the important role of a criterion for making a decision whether or not a schedule revision is carried out. The cumulative delay approach to trigger schedule revisions has the following capabilities for the ...

  19. Considering Environmental and Occupational Stressors in Cumulative Risk Assessments

    Science.gov (United States)

    While definitions vary across the global scientific community, cumulative risk assessments (CRAs) typically are described as exhibiting a population focus and analyzing the combined risks posed by multiple stressors. CRAs also may consider risk management alternatives as an anal...

  20. Peer tutors as learning and teaching partners: a cumulative ...

    African Journals Online (AJOL)

    ... paper explores the kinds of development in tutors' thinking and action that are possible when training and development is theoretically informed, coherent, and oriented towards improving practice. Keywords: academic development, academic literacies, cumulative learning, higher education, peer tutoring, writing centres.

  1. CTD Information Guide. Preventing Cumulative Trauma Disorders in the Workplace

    National Research Council Canada - National Science Library

    1992-01-01

    The purpose of this report is to provide Army occupational safety and health (OSH) professionals with a primer that explains the basic principles of ergonomic-hazard recognition for common cumulative trauma disorders...

  2. Cumulative radiation exposure in children with cystic fibrosis.

    LENUS (Irish Health Repository)

    O'Reilly, R

    2010-02-01

    This retrospective study calculated the cumulative radiation dose for children with cystic fibrosis (CF) attending a tertiary CF centre. Information on 77 children with a mean age of 9.5 years, a follow up time of 658 person years and 1757 studies including 1485 chest radiographs, 215 abdominal radiographs and 57 computed tomography (CT) scans, of which 51 were thoracic CT scans, were analysed. The average cumulative radiation dose was 6.2 (0.04-25) mSv per CF patient. Cumulative radiation dose increased with increasing age and number of CT scans and was greater in children who presented with meconium ileus. No correlation was identified between cumulative radiation dose and either lung function or patient microbiology cultures. Radiation carries a risk of malignancy and children are particularly susceptible. Every effort must be made to avoid unnecessary radiation exposure in these patients whose life expectancy is increasing.

  3. Random maintenance policies

    CERN Document Server

    Nakagawa, Toshio

    2014-01-01

    Exploring random maintenance models, this book provides an introduction to the implementation of random maintenance, and it is one of the first books to be written on this subject.  It aims to help readers learn new techniques for applying random policies to actual reliability models, and it provides new theoretical analyses of various models including classical replacement, preventive maintenance and inspection policies. These policies are applied to scheduling problems, backup policies of database systems, maintenance policies of cumulative damage models, and reliability of random redundant systems. Reliability theory is a major concern for engineers and managers, and in light of Japan’s recent earthquake, the reliability of large-scale systems has increased in importance. This also highlights the need for a new notion of maintenance and reliability theory, and how this can practically be applied to systems. Providing an essential guide for engineers and managers specializing in reliability maintenance a...

  4. The Mass Media of Entertainment and Human Survival.

    Science.gov (United States)

    Gorney, Roderic; Steele, Gary

    Urgently needed for human survival is a means of influencing large numbers of people to put into rapid action measures which could neutralize such menances as pollution, overpopulation, and violence. Though the cumulative effect of the mass media is not fully established, media entertainment may be the most influential institution in our society.…

  5. Cumulative query method for influenza surveillance using search engine data.

    Science.gov (United States)

    Seo, Dong-Woo; Jo, Min-Woo; Sohn, Chang Hwan; Shin, Soo-Yong; Lee, JaeHo; Yu, Maengsoo; Kim, Won Young; Lim, Kyoung Soo; Lee, Sang-Il

    2014-12-16

    Internet search queries have become an important data source in syndromic surveillance system. However, there is currently no syndromic surveillance system using Internet search query data in South Korea. The objective of this study was to examine correlations between our cumulative query method and national influenza surveillance data. Our study was based on the local search engine, Daum (approximately 25% market share), and influenza-like illness (ILI) data from the Korea Centers for Disease Control and Prevention. A quota sampling survey was conducted with 200 participants to obtain popular queries. We divided the study period into two sets: Set 1 (the 2009/10 epidemiological year for development set 1 and 2010/11 for validation set 1) and Set 2 (2010/11 for development Set 2 and 2011/12 for validation Set 2). Pearson's correlation coefficients were calculated between the Daum data and the ILI data for the development set. We selected the combined queries for which the correlation coefficients were .7 or higher and listed them in descending order. Then, we created a cumulative query method n representing the number of cumulative combined queries in descending order of the correlation coefficient. In validation set 1, 13 cumulative query methods were applied, and 8 had higher correlation coefficients (min=.916, max=.943) than that of the highest single combined query. Further, 11 of 13 cumulative query methods had an r value of ≥.7, but 4 of 13 combined queries had an r value of ≥.7. In validation set 2, 8 of 15 cumulative query methods showed higher correlation coefficients (min=.975, max=.987) than that of the highest single combined query. All 15 cumulative query methods had an r value of ≥.7, but 6 of 15 combined queries had an r value of ≥.7. Cumulative query method showed relatively higher correlation with national influenza surveillance data than combined queries in the development and validation set.

  6. Steps and pips in the history of the cumulative recorder.

    OpenAIRE

    Lattal, Kennon A

    2004-01-01

    From its inception in the 1930s until very recent times, the cumulative recorder was the most widely used measurement instrument in the experimental analysis of behavior. It was an essential instrument in the discovery and analysis of schedules of reinforcement, providing the first real-time analysis of operant response rates and patterns. This review traces the evolution of the cumulative recorder from Skinner's early modified kymographs through various models developed by Skinner and his co...

  7. Mapping Cumulative Impacts of Human Activities on Marine Ecosystems

    OpenAIRE

    , Seaplan

    2018-01-01

    Given the diversity of human uses and natural resources that converge in coastal waters, the potential independent and cumulative impacts of those uses on marine ecosystems are important to consider during ocean planning. This study was designed to support the development and implementation of the 2009 Massachusetts Ocean Management Plan. Its goal was to estimate and visualize the cumulative impacts of human activities on coastal and marine ecosystems in the state and federal waters off of Ma...

  8. Detecting spatial patterns with the cumulant function – Part 1: The theory

    Directory of Open Access Journals (Sweden)

    P. Naveau

    2008-02-01

    Full Text Available In climate studies, detecting spatial patterns that largely deviate from the sample mean still remains a statistical challenge. Although a Principal Component Analysis (PCA, or equivalently a Empirical Orthogonal Functions (EOF decomposition, is often applied for this purpose, it provides meaningful results only if the underlying multivariate distribution is Gaussian. Indeed, PCA is based on optimizing second order moments, and the covariance matrix captures the full dependence structure of multivariate Gaussian vectors. Whenever the application at hand can not satisfy this normality hypothesis (e.g. precipitation data, alternatives and/or improvements to PCA have to be developed and studied. To go beyond this second order statistics constraint, that limits the applicability of the PCA, we take advantage of the cumulant function that can produce higher order moments information. The cumulant function, well-known in the statistical literature, allows us to propose a new, simple and fast procedure to identify spatial patterns for non-Gaussian data. Our algorithm consists in maximizing the cumulant function. Three families of multivariate random vectors, for which explicit computations are obtained, are implemented to illustrate our approach. In addition, we show that our algorithm corresponds to selecting the directions along which projected data display the largest spread over the marginal probability density tails.

  9. Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial.

    Science.gov (United States)

    André, Thierry; Vernerey, Dewi; Mineur, Laurent; Bennouna, Jaafar; Desrame, Jérôme; Faroux, Roger; Fratte, Serge; Hug de Larauze, Marine; Paget-Bailly, Sophie; Chibaudel, Benoist; Bez, Jeremie; Dauba, Jérôme; Louvet, Christophe; Lepere, Céline; Dupuis, Olivier; Becouarn, Yves; Mabro, May; Egreteau, Joëlle; Bouche, Olivier; Deplanque, Gaël; Ychou, Marc; Galais, Marie Pierre; Ghiringhelli, François; Dourthe, Louis Marie; Bachet, Jean-Baptiste; Khalil, Ahmed; Bonnetain, Franck; de Gramont, Aimery; Taieb, Julien

    2018-05-20

    Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared

  10. Survival, Function, and Complications of Oral Implants Placed in Bone Flaps in Jaw Rehabilitation: A Systematic Review.

    Science.gov (United States)

    Zhang, Lei; Ding, Qian; Liu, Cunrui; Sun, Yannan; Xie, Qiufei; Zhou, Yongsheng

    2016-01-01

    This systematic review attempted to determine the survival rate of implants placed in bone flaps in jaw rehabilitation and the functional gains and the most common complications related to these implants. An electronic search was undertaken of PubMed, EMBASE, and CNKI records from 1990 through July 2014. Two independent examiners read the titles and abstracts of the results to identify studies that met the inclusion criteria. Subsequently, the reference lists of the selected publications were hand searched. Descriptive statistics were used to report all data related to the survival rate of implants placed in bone flaps in jaw rehabilitation, the functional gains, and complications. A total of 20 studies were included for systematic review without repetition. The mean follow-up time after implant placement ranged from 1.75 to 9.5 years. Within the limitations of available studies, the survival rate of implants placed in bone flaps in jaw rehabilitation ranged from 82.4% to 100%. Of the 20 included studies, 15 reported a survival rate higher than 90%. The cumulative survival rate was 93.2%, with the longest follow-up time being 12.9 years. The most common complications related to these implants were peri-implant bone resorption or peri-implant inflammation, and peri-implant soft tissue proliferation. The main factors associated with the survival rate of implants in bone flaps were reported as time of implant placement and radiotherapy. Despite some persistent soft tissue problems and implant loss, most patients reached a satisfactory functional and esthetic outcome, as evaluated by clinical examination and subjectively by the patients at interview. Implant-supported dental prosthetic rehabilitation in reconstructed jaws improved the quality of life in terms of speech, nutrition, oral competence, and facial appearance. Placement of implants in bone flaps in jaw rehabilitation was demonstrated to be a reliable technique with a high survival rate. Multicentered

  11. Process monitoring in intensive care with the use of cumulative expected minus observed mortality and risk-adjusted P charts.

    Science.gov (United States)

    Cockings, Jerome G L; Cook, David A; Iqbal, Rehana K

    2006-02-01

    A health care system is a complex adaptive system. The effect of a single intervention, incorporated into a complex clinical environment, may be different from that expected. A national database such as the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme in the UK represents a centralised monitoring, surveillance and reporting system for retrospective quality and comparative audit. This can be supplemented with real-time process monitoring at a local level for continuous process improvement, allowing early detection of the impact of both unplanned and deliberately imposed changes in the clinical environment. Demographic and UK Acute Physiology and Chronic Health Evaluation II (APACHE II) data were prospectively collected on all patients admitted to a UK regional hospital between 1 January 2003 and 30 June 2004 in accordance with the ICNARC Case Mix Programme. We present a cumulative expected minus observed (E-O) plot and the risk-adjusted p chart as methods of continuous process monitoring. We describe the construction and interpretation of these charts and show how they can be used to detect planned or unplanned organisational process changes affecting mortality outcomes. Five hundred and eighty-nine adult patients were included. The overall death rate was 0.78 of predicted. Calibration showed excess survival in ranges above 30% risk of death. The E-O plot confirmed a survival above that predicted. Small transient variations were seen in the slope that could represent random effects, or real but transient changes in the quality of care. The risk-adjusted p chart showed several observations below the 2 SD control limits of the expected mortality rate. These plots provide rapid analysis of risk-adjusted performance suitable for local application and interpretation. The E-O chart provided rapid easily visible feedback of changes in risk-adjusted mortality, while the risk-adjusted p chart allowed statistical evaluation. Local analysis of

  12. Survival of Root-filled Teeth in the Swedish Adult Population

    DEFF Research Database (Denmark)

    Fransson, Helena; Dawson, Victoria S; Frisk, Fredrik

    2016-01-01

    INTRODUCTION: The aim was to assess survival in the Swedish population of teeth treated by nonsurgical root canal treatment during 2009. METHODS: Data from the Swedish Social Insurance Agency were analyzed by Kaplan-Meier analysis to assess cumulative tooth survival during a period of 5-6 years o...

  13. Maintenance hemodialysis patients have high cumulative radiation exposure.

    LENUS (Irish Health Repository)

    Kinsella, Sinead M

    2010-10-01

    Hemodialysis is associated with an increased risk of neoplasms which may result, at least in part, from exposure to ionizing radiation associated with frequent radiographic procedures. In order to estimate the average radiation exposure of those on hemodialysis, we conducted a retrospective study of 100 patients in a university-based dialysis unit followed for a median of 3.4 years. The number and type of radiological procedures were obtained from a central radiology database, and the cumulative effective radiation dose was calculated using standardized, procedure-specific radiation levels. The median annual radiation dose was 6.9 millisieverts (mSv) per patient-year. However, 14 patients had an annual cumulative effective radiation dose over 20 mSv, the upper averaged annual limit for occupational exposure. The median total cumulative effective radiation dose per patient over the study period was 21.7 mSv, in which 13 patients had a total cumulative effective radiation dose over 75 mSv, a value reported to be associated with a 7% increased risk of cancer-related mortality. Two-thirds of the total cumulative effective radiation dose was due to CT scanning. The average radiation exposure was significantly associated with the cause of end-stage renal disease, history of ischemic heart disease, transplant waitlist status, number of in-patient hospital days over follow-up, and death during the study period. These results highlight the substantial exposure to ionizing radiation in hemodialysis patients.

  14. Probability and Cumulative Density Function Methods for the Stochastic Advection-Reaction Equation

    Energy Technology Data Exchange (ETDEWEB)

    Barajas-Solano, David A.; Tartakovsky, Alexandre M.

    2018-01-01

    We present a cumulative density function (CDF) method for the probabilistic analysis of $d$-dimensional advection-dominated reactive transport in heterogeneous media. We employ a probabilistic approach in which epistemic uncertainty on the spatial heterogeneity of Darcy-scale transport coefficients is modeled in terms of random fields with given correlation structures. Our proposed CDF method employs a modified Large-Eddy-Diffusivity (LED) approach to close and localize the nonlocal equations governing the one-point PDF and CDF of the concentration field, resulting in a $(d + 1)$ dimensional PDE. Compared to the classsical LED localization, the proposed modified LED localization explicitly accounts for the mean-field advective dynamics over the phase space of the PDF and CDF. To illustrate the accuracy of the proposed closure, we apply our CDF method to one-dimensional single-species reactive transport with uncertain, heterogeneous advection velocities and reaction rates modeled as random fields.

  15. Comparison of the Valuations of Alternatives Based on Cumulative Prospect Theory and Almost Stochastic Dominance

    Directory of Open Access Journals (Sweden)

    Ewa Michalska

    2012-01-01

    Full Text Available There are commonly accepted and objective decision rules, which are consistent with rationality, for example stochastic dominance rules. But, as can be seen in many research studies in behavioral economics, decision makers do not always act rationally. Rules based on cumulative prospect theory or almost stochastic dominance are relatively new tools which model real choices. Both approaches take into account some behavioral factors. The aim of this paper is to check the consistency of orders of the valuations of random alternatives based on these behavioral rules. The order of the alternatives is generated by a preference relation over the decision set. In this paper, we show that the methodology for creating rankings based on total orders can be used for the preference relations considered, because they enable comparison of all the elements in a set of random alternatives. For almost second degree stochastic dominance, this is possible due to its particular properties, which stochastic dominance does not possess. (original abstract

  16. Gradual and Cumulative Improvements to the Classical Differential Evolution Scheme through Experiments

    Directory of Open Access Journals (Sweden)

    Anescu George

    2016-12-01

    Full Text Available The paper presents the experimental results of some tests conducted with the purpose to gradually and cumulatively improve the classical DE scheme in both efficiency and success rate. The modifications consisted in the randomization of the scaling factor (a simple jitter scheme, a more efficient Random Greedy Selection scheme, an adaptive scheme for the crossover probability and a resetting mechanism for the agents. After each modification step, experiments have been conducted on a set of 11 scalable, multimodal, continuous optimization functions in order to analyze the improvements and decide the new improvement direction. Finally, only the initial classical scheme and the constructed Fast Self-Adaptive DE (FSA-DE variant were compared with the purpose of testing their performance degradation with the increase of the search space dimension. The experimental results demonstrated the superiority of the proposed FSA-DE variant.

  17. Cumulative Trauma Among Mayas Living in Southeast Florida.

    Science.gov (United States)

    Millender, Eugenia I; Lowe, John

    2017-06-01

    Mayas, having experienced genocide, exile, and severe poverty, are at high risk for the consequences of cumulative trauma that continually resurfaces through current fear of an uncertain future. Little is known about the mental health and alcohol use status of this population. This correlational study explored t/he relationship of cumulative trauma as it relates to social determinants of health (years in the United States, education, health insurance status, marital status, and employment), psychological health (depression symptoms), and health behaviors (alcohol use) of 102 Guatemalan Mayas living in Southeast Florida. The results of this study indicated that, as specific social determinants of health and cumulative trauma increased, depression symptoms (particularly among women) and the risk for harmful alcohol use (particularly among men) increased. Identifying risk factors at an early stage before serious disease or problems are manifest provides room for early screening leading to early identification, early treatment, and better outcomes.

  18. Session: What do we know about cumulative or population impacts

    Energy Technology Data Exchange (ETDEWEB)

    Kerlinger, Paul; Manville, Al; Kendall, Bill

    2004-09-01

    This session at the Wind Energy and Birds/Bats workshop consisted of a panel discussion followed by a discussion/question and answer period. The panelists were Paul Kerlinger, Curry and Kerlinger, LLC, Al Manville, U.S. Fish and Wildlife Service, and Bill Kendall, US Geological Service. The panel addressed the potential cumulative impacts of wind turbines on bird and bat populations over time. Panel members gave brief presentations that touched on what is currently known, what laws apply, and the usefulness of population modeling. Topics addressed included which sources of modeling should be included in cumulative impacts, comparison of impacts from different modes of energy generation, as well as what research is still needed regarding cumulative impacts of wind energy development on bird and bat populations.

  19. Estimating a population cumulative incidence under calendar time trends

    DEFF Research Database (Denmark)

    Hansen, Stefan N; Overgaard, Morten; Andersen, Per K

    2017-01-01

    BACKGROUND: The risk of a disease or psychiatric disorder is frequently measured by the age-specific cumulative incidence. Cumulative incidence estimates are often derived in cohort studies with individuals recruited over calendar time and with the end of follow-up governed by a specific date...... by calendar time trends, the total sample Kaplan-Meier and Aalen-Johansen estimators do not provide useful estimates of the general risk in the target population. We present some alternatives to this type of analysis. RESULTS: We show how a proportional hazards model may be used to extrapolate disease risk...... estimates if proportionality is a reasonable assumption. If not reasonable, we instead advocate that a more useful description of the disease risk lies in the age-specific cumulative incidence curves across strata given by time of entry or perhaps just the end of follow-up estimates across all strata...

  20. Evolutionary neural network modeling for software cumulative failure time prediction

    International Nuclear Information System (INIS)

    Tian Liang; Noore, Afzel

    2005-01-01

    An evolutionary neural network modeling approach for software cumulative failure time prediction based on multiple-delayed-input single-output architecture is proposed. Genetic algorithm is used to globally optimize the number of the delayed input neurons and the number of neurons in the hidden layer of the neural network architecture. Modification of Levenberg-Marquardt algorithm with Bayesian regularization is used to improve the ability to predict software cumulative failure time. The performance of our proposed approach has been compared using real-time control and flight dynamic application data sets. Numerical results show that both the goodness-of-fit and the next-step-predictability of our proposed approach have greater accuracy in predicting software cumulative failure time compared to existing approaches

  1. Baltic Sea biodiversity status vs. cumulative human pressures

    DEFF Research Database (Denmark)

    Andersen, Jesper H.; Halpern, Benjamin S.; Korpinen, Samuli

    2015-01-01

    Abstract Many studies have tried to explain spatial and temporal variations in biodiversity status of marine areas from a single-issue perspective, such as fishing pressure or coastal pollution, yet most continental seas experience a wide range of human pressures. Cumulative impact assessments have...... been developed to capture the consequences of multiple stressors for biodiversity, but the ability of these assessments to accurately predict biodiversity status has never been tested or ground-truthed. This relationship has similarly been assumed for the Baltic Sea, especially in areas with impaired...... status, but has also never been documented. Here we provide a first tentative indication that cumulative human impacts relate to ecosystem condition, i.e. biodiversity status, in the Baltic Sea. Thus, cumulative impact assessments offer a promising tool for informed marine spatial planning, designation...

  2. A Randomized Trial (Irish Clinical Oncology Research Group 97-01) Comparing Short Versus Protracted Neoadjuvant Hormonal Therapy Before Radiotherapy for Localized Prostate Cancer.

    LENUS (Irish Health Repository)

    Armstrong, John G

    2010-08-24

    PURPOSE: To examine the long-term outcomes of a randomized trial comparing short (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer. METHODS AND MATERIALS: Between 1997 and 2001, 276 patients were enrolled and the data from 261 were analyzed. The stratification risk factors were prostate-specific antigen level >20 ng\\/mL, Gleason score >\\/=7, and Stage T3 or more. The intermediate-risk stratum had one factor and the high-risk stratum had two or more. Staging was done from the bone scan and computed tomography findings. The primary endpoint was biochemical failure-free survival. RESULTS: The median follow-up was 102 months. The overall survival, biochemical failure-free survival. and prostate cancer-specific survival did not differ significantly between the two treatment arms, overall or at 5 years. The cumulative probability of overall survival at 5 years was 90% (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63% (range, 58-67%) in Arm 2. CONCLUSION: No statistically significant difference was found in biochemical failure-free survival between 4 months and 8 months of neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.

  3. Cumulative carbon as a policy framework for achieving climate stabilization

    Science.gov (United States)

    Matthews, H. Damon; Solomon, Susan; Pierrehumbert, Raymond

    2012-01-01

    The primary objective of the United Nations Framework Convention on Climate Change is to stabilize greenhouse gas concentrations at a level that will avoid dangerous climate impacts. However, greenhouse gas concentration stabilization is an awkward framework within which to assess dangerous climate change on account of the significant lag between a given concentration level and the eventual equilibrium temperature change. By contrast, recent research has shown that global temperature change can be well described by a given cumulative carbon emissions budget. Here, we propose that cumulative carbon emissions represent an alternative framework that is applicable both as a tool for climate mitigation as well as for the assessment of potential climate impacts. We show first that both atmospheric CO2 concentration at a given year and the associated temperature change are generally associated with a unique cumulative carbon emissions budget that is largely independent of the emissions scenario. The rate of global temperature change can therefore be related to first order to the rate of increase of cumulative carbon emissions. However, transient warming over the next century will also be strongly affected by emissions of shorter lived forcing agents such as aerosols and methane. Non-CO2 emissions therefore contribute to uncertainty in the cumulative carbon budget associated with near-term temperature targets, and may suggest the need for a mitigation approach that considers separately short- and long-lived gas emissions. By contrast, long-term temperature change remains primarily associated with total cumulative carbon emissions owing to the much longer atmospheric residence time of CO2 relative to other major climate forcing agents. PMID:22869803

  4. The role of factorial cumulants in reactor neutron noise theory

    International Nuclear Information System (INIS)

    Colombino, A.; Pacilio, N.; Sena, G.

    1979-01-01

    The physical meaning and the combinatorial implications of the factorial cumulant of a state variable such as the number of neutrons or the number of neutron counts are specified. Features of the presentation are: (1) the fission process is treated in its entirety without the customary binary emission restriction, (b) the introduction of the factorial cumulants helps in reducing the complexity of the mathematical problems, (c) all the solutions can be obtained analytically. Only the ergodic hypothesis for the neutron population evolution is dealt with. (author)

  5. Super-Resolution Algorithm in Cumulative Virtual Blanking

    Science.gov (United States)

    Montillet, J. P.; Meng, X.; Roberts, G. W.; Woolfson, M. S.

    2008-11-01

    The proliferation of mobile devices and the emergence of wireless location-based services have generated consumer demand for precise location. In this paper, the MUSIC super-resolution algorithm is applied to time delay estimation for positioning purposes in cellular networks. The goal is to position a Mobile Station with UMTS technology. The problem of Base-Stations herability is solved using Cumulative Virtual Blanking. A simple simulator is presented using DS-SS signal. The results show that MUSIC algorithm improves the time delay estimation in both the cases whether or not Cumulative Virtual Blanking was carried out.

  6. High cumulative incidence of urinary tract transitional cell carcinoma after kidney transplantation in Taiwan.

    Science.gov (United States)

    Wu, Ming-Ju; Lian, Jong-Da; Yang, Chi-Rei; Cheng, Chi-Hung; Chen, Cheng-Hsu; Lee, Wen-Chin; Shu, Kuo-Hsiung; Tang, Ming-Jer

    2004-06-01

    Cancer is a well-documented complication after kidney transplantation. Increased incidence of bladder cancer had been reported in long-term hemodialysis patients in Taiwan. Herein, the authors report a very high cumulative incidence of transitional cell carcinoma (TCC) of the urinary tract after kidney transplantation in Taiwan. The authors retrospectively reviewed the clinical data, medical records, and outcome of 730 kidney transplant (KT) recipients. The cumulative incidence of TCC was computed. The Cox regression method was used to analysis the role of potential risk factors. After a mean follow-up duration of 72.2 +/- 54.4 months, 69 cancers were diagnosed in 63 (8.6%) KT recipients. Of them, 30 cases (4.1%) were TCC. The cumulative incidence for TCC was 3.0% after 3 years of graft survival, increasing to 7.2% at 6 years and 17.5% at 10 years. Compared with the general population in Taiwan, the standardized mortality ratio was 398.4 (male, 192.6; female, 875.6). Painless gross hematuria was the cardinal initial symptom in 22 (73.3%) of the 30 KT recipients with TCC. Another 4 (13.3%) KT recipients with TCC presented with chronic urinary tract infection (UTI). Bilateral nephroureterectomy with removal of bladder cuffs was performed in 18 (60%) patients. Synchronous TCC in bilateral upper urinary tracts was confirmed in 11 (36.7%) of KT recipients with TCC. The age at the time of KT, female sex, compound analgesics usage, Chinese herb usage, and underground water intake had statistical significance as risk factors (P Taiwan, with an incidence of 4.1%. This study indicates that hematuria and chronic UTI are the initial presentation of TCC in KT recipients. Carefully urologic screening is indicated for patients with high risk for TCC, including those with older age, compound analgesics usage, Chinese herbs usage, and underground water intake as well as women.

  7. Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Morris, W. James, E-mail: jmorris@bccancer.bc.ca [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Tyldesley, Scott [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Rodda, Sree [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); Halperin, Ross [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Centre for the Southern Interior, Vancouver, British Columbia (Canada); Pai, Howard [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Island Centre, Vancouver, British Columbia (Canada); McKenzie, Michael; Duncan, Graeme [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Morton, Gerard [Department of Radiation Oncology, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Hamm, Jeremy [Department of Population Oncology, BC Cancer Agency, Vancouver, British Columbia (Canada); Murray, Nevin [BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Department of Medicine, University of British Columbia, Vancouver, British Columbia (Canada)

    2017-06-01

    Purpose: To report the primary endpoint of biochemical progression-free survival (b-PFS) and secondary survival endpoints from ASCENDE-RT, a randomized trial comparing 2 methods of dose escalation for intermediate- and high-risk prostate cancer. Methods and Materials: ASCENDE-RT enrolled 398 men, with a median age of 68 years; 69% (n=276) had high-risk disease. After stratification by risk group, the subjects were randomized to a standard arm with 12 months of androgen deprivation therapy, pelvic irradiation to 46 Gy, followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. Of the 398 trial subjects, 200 were assigned to DE-EBRT boost and 198 to LDR-PB boost. The median follow-up was 6.5 years. Results: In an intent-to-treat analysis, men randomized to DE-EBRT were twice as likely to experience biochemical failure (multivariable analysis [MVA] hazard ratio [HR] 2.04; P=.004). The 5-, 7-, and 9-year Kaplan-Meier b-PFS estimates were 89%, 86%, and 83% for the LDR-PB boost versus 84%, 75%, and 62% for the DE-EBRT boost (log-rank P<.001). The LDR-PB boost benefited both intermediate- and high-risk patients. Because the b-PFS curves for the treatment arms diverge sharply after 4 years, the relative advantage of the LDR-PB should increase with longer follow-up. On MVA, the only variables correlated with reduced overall survival were age (MVA HR 1.06/y; P=.004) and biochemical failure (MVA HR 6.30; P<.001). Although biochemical failure was associated with increased mortality and randomization to DE-EBRT doubled the rate of biochemical failure, no significant overall survival difference was observed between the treatment arms (MVA HR 1.13; P=.62). Conclusions: Compared with 78 Gy EBRT, men randomized to the LDR-PB boost were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years.

  8. Impact of T and N substage on survival and disease relapse in adjuvant rectal cancer: a pooled analysis

    International Nuclear Information System (INIS)

    Gunderson, Leonard L.; Sargent, Daniel J.; Tepper, Joel E.; O'Connell, Michael J.; Allmer, Cristine; Smalley, Steven R.; Martenson, James A.; Haller, Daniel G.; Mayer, Robert J.; Rich, Tyvin A.; Ajani, Jaffer A.; Macdonald, John S.; Goldberg, Richard M.

    2002-01-01

    Purpose: To determine the rates of survival and disease control by TNM and MAC stage in three randomized North American rectal adjuvant studies. Materials and Methods: Data were merged from 2551 eligible patients on NCCTG 79-47-51 (n=200), NCCTG 86-47-51 (n=656), and INT 114 (n=1695). All patients received postoperative radiation, and 96% were randomized to receive concomitant and maintenance chemotherapy. Five-year follow-up was available in 94% of patients and 7-yr follow-up in 84%. Kaplan-Meier curves were used to estimate the distribution of overall survival (OS) and disease-free survival (DFS), and p values were derived using the log-rank test. Time to local and distant relapse was estimated using cumulative incidence methodology. Analyses were adjusted for treatment effect using Cox proportional hazards models. Results: OS and DFS were dependent on both TN stage and NT stage (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more LN+), T stage influenced 5-yr OS (T1-2, 69%; T3, 48%; T4, 38%). Three risk groups of patients were defined: (1) intermediate: T3N0, T1-2N1; (2) moderately high: T4N0, T1-2N2, T3N1; and (3) high: T3N2, T4N1, T4N2. For Group 1, 5-yr OS was 74% and 81%, and 5-yr DFS was 66% and 74%. For Group 2, 5-yr OS ranged from 61% to 69%, and for Group 3, OS ranged from 33% to 48%. Cumulative incidence rates of local relapse and distant metastases revealed similar differences by TN and NT stage, as seen in the survival analyses. Conclusion: Patients with a single high-risk factor of either extension beyond the rectal wall (T3N0) or nodal involvement (T1-2N1) have improved OS, DFS, and disease control when compared to those with both high risk factors. Different treatment strategies may be indicated for intermediate- (T3N0, T1-2N1) vs. moderately high or high-risk patients in view of differential survival and rates of relapse. For future trial design, it may be preferable to perform separate studies, or a planned

  9. Cumulative effects of wind turbines. Volume 3: Report on results of consultations on cumulative effects of wind turbines on birds

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    This report gives details of the consultations held in developing the consensus approach taken in assessing the cumulative effects of wind turbines. Contributions on bird issues, and views of stakeholders, the Countryside Council for Wales, electric utilities, Scottish Natural Heritage, and the National Wind Power Association are reported. The scoping of key species groups, where cumulative effects might be expected, consideration of other developments, the significance of any adverse effects, mitigation, regional capacity assessments, and predictive models are discussed. Topics considered at two stakeholder workshops are outlined in the appendices.

  10. Cumulative impacts: current research and current opinions at PSW

    Science.gov (United States)

    R. M. Rice

    1987-01-01

    Consideration of cumulative watershed effects (CWEs) has both political and physical aspects. Regardless of the practical usefulness of present methods of dealing with CWEs, the legal requirement to address them remains. Management of federal land is regulated by the National Environmental Policy Act (NEPA) and the Federal Water Pollution Control Act of 1972. The...

  11. Cumulative Risks of Foster Care Placement for Danish Children

    DEFF Research Database (Denmark)

    Fallesen, Peter; Emanuel, Natalia; Wildeman, Christopher

    2014-01-01

    children. Our results also show some variations by parental ethnicity and sex, but these differences are small. Indeed, they appear quite muted relative to racial/ethnic differences in these risks in the United States. Last, though cumulative risks are similar between Danish and American children...

  12. Disintegration of a profiled shock wave at the cumulation point

    International Nuclear Information System (INIS)

    Kaliski, S.

    1978-01-01

    The disintegration at the cumulation point is analyzed of a shock wave generated with the aid of a profiled pressure. The quantitative relations are analyzed for the disintegration waves for typical compression parameters in systems of thermonuclear microfusion. The quantitative conclusions are drawn for the application of simplifying approximate calculations in problems of microfusion. (author)

  13. Cumulative Prospect Theory, Option Returns, and the Variance Premium

    NARCIS (Netherlands)

    Baele, Lieven; Driessen, Joost; Ebert, Sebastian; Londono Yarce, J.M.; Spalt, Oliver

    The variance premium and the pricing of out-of-the-money (OTM) equity index options are major challenges to standard asset pricing models. We develop a tractable equilibrium model with Cumulative Prospect Theory (CPT) preferences that can overcome both challenges. The key insight is that the

  14. Steps and Pips in the History of the Cumulative Recorder

    Science.gov (United States)

    Lattal, Kennon A.

    2004-01-01

    From its inception in the 1930s until very recent times, the cumulative recorder was the most widely used measurement instrument in the experimental analysis of behavior. It was an essential instrument in the discovery and analysis of schedules of reinforcement, providing the first real-time analysis of operant response rates and patterns. This…

  15. The effects of cumulative practice on mathematics problem solving.

    Science.gov (United States)

    Mayfield, Kristin H; Chase, Philip N

    2002-01-01

    This study compared three different methods of teaching five basic algebra rules to college students. All methods used the same procedures to teach the rules and included four 50-question review sessions interspersed among the training of the individual rules. The differences among methods involved the kinds of practice provided during the four review sessions. Participants who received cumulative practice answered 50 questions covering a mix of the rules learned prior to each review session. Participants who received a simple review answered 50 questions on one previously trained rule. Participants who received extra practice answered 50 extra questions on the rule they had just learned. Tests administered after each review included new questions for applying each rule (application items) and problems that required novel combinations of the rules (problem-solving items). On the final test, the cumulative group outscored the other groups on application and problem-solving items. In addition, the cumulative group solved the problem-solving items significantly faster than the other groups. These results suggest that cumulative practice of component skills is an effective method of training problem solving.

  16. Anti-irritants II: Efficacy against cumulative irritation

    DEFF Research Database (Denmark)

    Andersen, Flemming; Hedegaard, Kathryn; Petersen, Thomas Kongstad

    2006-01-01

    window of opportunity in which to demonstrate efficacy. Therefore, the effect of AI was studied in a cumulative irritation model by inducing irritant dermatitis with 10 min daily exposures for 5+4 days (no irritation on weekend) to 1% sodium lauryl sulfate on the right and 20% nonanoic acid on the left...

  17. Cumulative Beam Breakup with Time-Dependent Parameters

    CERN Document Server

    Delayen, J R

    2004-01-01

    A general analytical formalism developed recently for cumulative beam breakup (BBU) in linear accelerators with arbitrary beam current profile and misalignments [1] is extended to include time-dependent parameters such as energy chirp or rf focusing in order to reduce BBU-induced instabilities and emittance growth. Analytical results are presented and applied to practical accelerator configurations.

  18. On the mechanism of hadron cumulative production on nucleus

    International Nuclear Information System (INIS)

    Efremov, A.V.

    1976-01-01

    A mechanism of cumulative production of hadrons on nucleus is proposed which is similar to that of high perpendicular hadron production. The cross section obtained describes the main qualitative features of such prosesses, e.g., initial energy dependence atomic number behaviour, dependence on the rest mass of the produced particle and its production angle

  19. How to manage the cumulative flood safety of catchment dams ...

    African Journals Online (AJOL)

    Dam safety is a significant issue being taken seriously worldwide. However, in Australia, although much attention is being devoted to the medium- to large-scale dams, minimal attention is being paid to the serious potential problems associated with smaller dams, particularly the potential cumulative safety threats they pose ...

  20. Cumulative Beam Breakup due to Resistive-Wall Wake

    International Nuclear Information System (INIS)

    Wang, J.-M.

    2004-01-01

    The cumulative beam breakup problem excited by the resistive-wall wake is formulated. An approximate analytic method of finding the asymptotic behavior for the transverse bunch displacement is developed and solved. Comparison between the asymptotic analytical expression and the direct numerical solution is presented. Good agreement is found. The criterion of using the asymptotic analytical expression is discussed

  1. Analysis of sensory ratings data with cumulative link models

    DEFF Research Database (Denmark)

    Christensen, Rune Haubo Bojesen; Brockhoff, Per B.

    2013-01-01

    Examples of categorical rating scales include discrete preference, liking and hedonic rating scales. Data obtained on these scales are often analyzed with normal linear regression methods or with omnibus Pearson chi2 tests. In this paper we propose to use cumulative link models that allow for reg...

  2. Tests of Cumulative Prospect Theory with graphical displays of probability

    Directory of Open Access Journals (Sweden)

    Michael H. Birnbaum

    2008-10-01

    Full Text Available Recent research reported evidence that contradicts cumulative prospect theory and the priority heuristic. The same body of research also violates two editing principles of original prospect theory: cancellation (the principle that people delete any attribute that is the same in both alternatives before deciding between them and combination (the principle that people combine branches leading to the same consequence by adding their probabilities. This study was designed to replicate previous results and to test whether the violations of cumulative prospect theory might be eliminated or reduced by using formats for presentation of risky gambles in which cancellation and combination could be facilitated visually. Contrary to the idea that decision behavior contradicting cumulative prospect theory and the priority heuristic would be altered by use of these formats, however, data with two new graphical formats as well as fresh replication data continued to show the patterns of evidence that violate cumulative prospect theory, the priority heuristic, and the editing principles of combination and cancellation. Systematic violations of restricted branch independence also contradicted predictions of ``stripped'' prospect theory (subjectively weighted additive utility without the editing rules.

  3. Implications of applying cumulative risk assessment to the workplace.

    Science.gov (United States)

    Fox, Mary A; Spicer, Kristen; Chosewood, L Casey; Susi, Pam; Johns, Douglas O; Dotson, G Scott

    2018-06-01

    Multiple changes are influencing work, workplaces and workers in the US including shifts in the main types of work and the rise of the 'gig' economy. Work and workplace changes have coincided with a decline in unions and associated advocacy for improved safety and health conditions. Risk assessment has been the primary method to inform occupational and environmental health policy and management for many types of hazards. Although often focused on one hazard at a time, risk assessment frameworks and methods have advanced toward cumulative risk assessment recognizing that exposure to a single chemical or non-chemical stressor rarely occurs in isolation. We explore how applying cumulative risk approaches may change the roles of workers and employers as they pursue improved health and safety and elucidate some of the challenges and opportunities that might arise. Application of cumulative risk assessment should result in better understanding of complex exposures and health risks with the potential to inform more effective controls and improved safety and health risk management overall. Roles and responsibilities of both employers and workers are anticipated to change with potential for a greater burden of responsibility on workers to address risk factors both inside and outside the workplace that affect health at work. A range of policies, guidance and training have helped develop cumulative risk assessment for the environmental health field and similar approaches are available to foster the practice in occupational safety and health. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Hierarchical Bayesian parameter estimation for cumulative prospect theory

    NARCIS (Netherlands)

    Nilsson, H.; Rieskamp, J.; Wagenmakers, E.-J.

    2011-01-01

    Cumulative prospect theory (CPT Tversky & Kahneman, 1992) has provided one of the most influential accounts of how people make decisions under risk. CPT is a formal model with parameters that quantify psychological processes such as loss aversion, subjective values of gains and losses, and

  5. An Axiomatization of Cumulative Prospect Theory for Decision under Risk

    NARCIS (Netherlands)

    Wakker, P.P.; Chateauneuf, A.

    1999-01-01

    Cumulative prospect theory was introduced by Tversky and Kahneman so as to combine the empirical realism of their original prospect theory with the theoretical advantages of Quiggin's rank-dependent utility. Preference axiomatizations were provided in several papers. All those axiomatizations,

  6. Cumulative assessment: does it improve students’ knowledge acquisition and retention?

    NARCIS (Netherlands)

    Cecilio Fernandes, Dario; Nagtegaal, Manouk; Noordzij, Gera; Tio, Rene

    2017-01-01

    Introduction Assessment for learning means changing students’ behaviour regarding their learning. Cumulative assessment has been shown to increase students’ self-study time and spread their study time throughout a course. However, there was no difference regarding students’ knowledge at the end of

  7. CASAS: Cancer Survival Analysis Suite, a web based application.

    Science.gov (United States)

    Rupji, Manali; Zhang, Xinyan; Kowalski, Jeanne

    2017-01-01

    We present CASAS, a shiny R based tool for interactive survival analysis and visualization of results. The tool provides a web-based one stop shop to perform the following types of survival analysis:  quantile, landmark and competing risks, in addition to standard survival analysis.  The interface makes it easy to perform such survival analyses and obtain results using the interactive Kaplan-Meier and cumulative incidence plots.  Univariate analysis can be performed on one or several user specified variable(s) simultaneously, the results of which are displayed in a single table that includes log rank p-values and hazard ratios along with their significance. For several quantile survival analyses from multiple cancer types, a single summary grid is constructed. The CASAS package has been implemented in R and is available via http://shinygispa.winship.emory.edu/CASAS/. The developmental repository is available at https://github.com/manalirupji/CASAS/.

  8. The challenges and opportunities in cumulative effects assessment

    Energy Technology Data Exchange (ETDEWEB)

    Foley, Melissa M., E-mail: mfoley@usgs.gov [U.S. Geological Survey, Pacific Coastal and Marine Science Center, 400 Natural Bridges, Dr., Santa Cruz, CA 95060 (United States); Center for Ocean Solutions, Stanford University, 99 Pacific St., Monterey, CA 93940 (United States); Mease, Lindley A., E-mail: lamease@stanford.edu [Center for Ocean Solutions, Stanford University, 473 Via Ortega, Stanford, CA 94305 (United States); Martone, Rebecca G., E-mail: rmartone@stanford.edu [Center for Ocean Solutions, Stanford University, 99 Pacific St., Monterey, CA 93940 (United States); Prahler, Erin E. [Center for Ocean Solutions, Stanford University, 473 Via Ortega, Stanford, CA 94305 (United States); Morrison, Tiffany H., E-mail: tiffany.morrison@jcu.edu.au [ARC Centre of Excellence for Coral Reef Studies, James Cook University, Townsville, QLD, 4811 (Australia); Murray, Cathryn Clarke, E-mail: cmurray@pices.int [WWF-Canada, 409 Granville Street, Suite 1588, Vancouver, BC V6C 1T2 (Canada); Wojcik, Deborah, E-mail: deb.wojcik@duke.edu [Nicholas School for the Environment, Duke University, 9 Circuit Dr., Durham, NC 27708 (United States)

    2017-01-15

    The cumulative effects of increasing human use of the ocean and coastal zone have contributed to a rapid decline in ocean and coastal resources. As a result, scientists are investigating how multiple, overlapping stressors accumulate in the environment and impact ecosystems. These investigations are the foundation for the development of new tools that account for and predict cumulative effects in order to more adequately prevent or mitigate negative effects. Despite scientific advances, legal requirements, and management guidance, those who conduct assessments—including resource managers, agency staff, and consultants—continue to struggle to thoroughly evaluate cumulative effects, particularly as part of the environmental assessment process. Even though 45 years have passed since the United States National Environmental Policy Act was enacted, which set a precedent for environmental assessment around the world, defining impacts, baseline, scale, and significance are still major challenges associated with assessing cumulative effects. In addition, we know little about how practitioners tackle these challenges or how assessment aligns with current scientific recommendations. To shed more light on these challenges and gaps, we undertook a comparative study on how cumulative effects assessment (CEA) is conducted by practitioners operating under some of the most well-developed environmental laws around the globe: California, USA; British Columbia, Canada; Queensland, Australia; and New Zealand. We found that practitioners used a broad and varied definition of impact for CEA, which led to differences in how baseline, scale, and significance were determined. We also found that practice and science are not closely aligned and, as such, we highlight opportunities for managers, policy makers, practitioners, and scientists to improve environmental assessment.

  9. The challenges and opportunities in cumulative effects assessment

    International Nuclear Information System (INIS)

    Foley, Melissa M.; Mease, Lindley A.; Martone, Rebecca G.; Prahler, Erin E.; Morrison, Tiffany H.; Murray, Cathryn Clarke; Wojcik, Deborah

    2017-01-01

    The cumulative effects of increasing human use of the ocean and coastal zone have contributed to a rapid decline in ocean and coastal resources. As a result, scientists are investigating how multiple, overlapping stressors accumulate in the environment and impact ecosystems. These investigations are the foundation for the development of new tools that account for and predict cumulative effects in order to more adequately prevent or mitigate negative effects. Despite scientific advances, legal requirements, and management guidance, those who conduct assessments—including resource managers, agency staff, and consultants—continue to struggle to thoroughly evaluate cumulative effects, particularly as part of the environmental assessment process. Even though 45 years have passed since the United States National Environmental Policy Act was enacted, which set a precedent for environmental assessment around the world, defining impacts, baseline, scale, and significance are still major challenges associated with assessing cumulative effects. In addition, we know little about how practitioners tackle these challenges or how assessment aligns with current scientific recommendations. To shed more light on these challenges and gaps, we undertook a comparative study on how cumulative effects assessment (CEA) is conducted by practitioners operating under some of the most well-developed environmental laws around the globe: California, USA; British Columbia, Canada; Queensland, Australia; and New Zealand. We found that practitioners used a broad and varied definition of impact for CEA, which led to differences in how baseline, scale, and significance were determined. We also found that practice and science are not closely aligned and, as such, we highlight opportunities for managers, policy makers, practitioners, and scientists to improve environmental assessment.

  10. The challenges and opportunities in cumulative effects assessment

    Science.gov (United States)

    Foley, Melissa M.; Mease, Lindley A; Martone, Rebecca G; Prahler, Erin E; Morrison, Tiffany H; Clarke Murray, Cathryn; Wojcik, Deborah

    2016-01-01

    The cumulative effects of increasing human use of the ocean and coastal zone have contributed to a rapid decline in ocean and coastal resources. As a result, scientists are investigating how multiple, overlapping stressors accumulate in the environment and impact ecosystems. These investigations are the foundation for the development of new tools that account for and predict cumulative effects in order to more adequately prevent or mitigate negative effects. Despite scientific advances, legal requirements, and management guidance, those who conduct assessments—including resource managers, agency staff, and consultants—continue to struggle to thoroughly evaluate cumulative effects, particularly as part of the environmental assessment process. Even though 45 years have passed since the United States National Environmental Policy Act was enacted, which set a precedent for environmental assessment around the world, defining impacts, baseline, scale, and significance are still major challenges associated with assessing cumulative effects. In addition, we know little about how practitioners tackle these challenges or how assessment aligns with current scientific recommendations. To shed more light on these challenges and gaps, we undertook a comparative study on how cumulative effects assessment (CEA) is conducted by practitioners operating under some of the most well-developed environmental laws around the globe: California, USA; British Columbia, Canada; Queensland, Australia; and New Zealand. We found that practitioners used a broad and varied definition of impact for CEA, which led to differences in how baseline, scale, and significance were determined. We also found that practice and science are not closely aligned and, as such, we highlight opportunities for managers, policy makers, practitioners, and scientists to improve environmental assessment.

  11. Early Educational Intervention, Early Cumulative Risk, and the Early Home Environment as Predictors of Young Adult Outcomes within a High-Risk Sample

    Science.gov (United States)

    Pungello, Elizabeth P.; Kainz, Kirsten; Burchinal, Margaret; Wasik, Barbara H.; Sparling, Joseph J.; Ramey, Craig T.; Campbell, Frances A.

    2010-01-01

    The extent to which early educational intervention, early cumulative risk, and the early home environment were associated with young adult outcomes was investigated in a sample of 139 young adults (age 21) from high-risk families enrolled in randomized trials of early intervention. Positive effects of treatment were found for education attainment,…

  12. Decompounding random sums: A nonparametric approach

    DEFF Research Database (Denmark)

    Hansen, Martin Bøgsted; Pitts, Susan M.

    Observations from sums of random variables with a random number of summands, known as random, compound or stopped sums arise within many areas of engineering and science. Quite often it is desirable to infer properties of the distribution of the terms in the random sum. In the present paper we...... review a number of applications and consider the nonlinear inverse problem of inferring the cumulative distribution function of the components in the random sum. We review the existing literature on non-parametric approaches to the problem. The models amenable to the analysis are generalized considerably...

  13. Cognitive-Behavioral Family Treatment for Suicide Attempt Prevention: A Randomized Controlled Trial.

    Science.gov (United States)

    Asarnow, Joan Rosenbaum; Hughes, Jennifer L; Babeva, Kalina N; Sugar, Catherine A

    2017-06-01

    Suicide is a leading cause of death. New data indicate alarming increases in suicide death rates, yet no treatments with replicated efficacy or effectiveness exist for youths with self-harm presentations, a high-risk group for both fatal and nonfatal suicide attempts. We addressed this gap by evaluating Safe Alternatives for Teens and Youths (SAFETY), a cognitive-behavioral, dialectical behavior therapy-informed family treatment designed to promote safety. Randomized controlled trial for adolescents (12-18 years of age) with recent (past 3 months) suicide attempts or other self-harm. Youth were randomized either to SAFETY or to treatment as usual enhanced by parent education and support accessing community treatment (E-TAU). Outcomes were evaluated at baseline, 3 months, or end of treatment period, and were followed up through 6 to 12 months. The primary outcome was youth-reported incident suicide attempts through the 3-month follow-up. Survival analyses indicated a significantly higher probability of survival without a suicide attempt by the 3-month follow-up point among SAFETY youths (cumulative estimated probability of survival without suicide attempt = 1.00, standard error = 0), compared to E-TAU youths (cumulative estimated probability of survival without suicide attempt = 0.67, standard error = 0.14; z = 2.45, p = .02, number needed to treat = 3) and for the overall survival curves (Wilcoxon χ 2 1  = 5.81, p = .02). Sensitivity analyses using parent report when youth report was unavailable and conservative assumptions regarding missing data yielded similar results for 3-month outcomes. Results support the efficacy of SAFETY for preventing suicide attempts in adolescents presenting with recent self-harm. This is the second randomized trial to demonstrate that treatment including cognitive-behavioral and family components can provide some protection from suicide attempt risk in these high-risk youths. Clinical trial registration information

  14. Solution Methods for Structures with Random Properties Subject to Random Excitation

    DEFF Research Database (Denmark)

    Köylüoglu, H. U.; Nielsen, Søren R. K.; Cakmak, A. S.

    This paper deals with the lower order statistical moments of the response of structures with random stiffness and random damping properties subject to random excitation. The arising stochastic differential equations (SDE) with random coefficients are solved by two methods, a second order...... the SDE with random coefficients with deterministic initial conditions to an equivalent nonlinear SDE with deterministic coefficient and random initial conditions. In both methods, the statistical moment equations are used. Hierarchy of statistical moments in the markovian approach is closed...... by the cumulant neglect closure method applied at the fourth order level....

  15. Measurement of four-particle cumulants and symmetric cumulants with subevent methods in small collision systems with the ATLAS detector

    CERN Document Server

    Derendarz, Dominik; The ATLAS collaboration

    2018-01-01

    Measurements of symmetric cumulants SC(n,m)=⟨v2nv2m⟩−⟨v2n⟩⟨v2m⟩ for (n,m)=(2,3) and (2,4) and asymmetric cumulant AC(n) are presented in pp, p+Pb and peripheral Pb+Pb collisions at various collision energies, aiming to probe the long-range collective nature of multi-particle production in small systems. Results are obtained using the standard cumulant method, as well as the two-subevent and three-subevent cumulant methods. Results from the standard method are found to be strongly biased by non-flow correlations as indicated by strong sensitivity to the chosen event class definition. A systematic reduction of non-flow effects is observed when using the two-subevent method and the results become independent of event class definition when the three-subevent method is used. The measured SC(n,m) shows an anti-correlation between v2 and v3, and a positive correlation between v2 and v4. The magnitude of SC(n,m) is constant with Nch in pp collisions, but increases with Nch in p+Pb and Pb+Pb collisions. ...

  16. Survival and weak chaos.

    Science.gov (United States)

    Nee, Sean

    2018-05-01

    Survival analysis in biology and reliability theory in engineering concern the dynamical functioning of bio/electro/mechanical units. Here we incorporate effects of chaotic dynamics into the classical theory. Dynamical systems theory now distinguishes strong and weak chaos. Strong chaos generates Type II survivorship curves entirely as a result of the internal operation of the system, without any age-independent, external, random forces of mortality. Weak chaos exhibits (a) intermittency and (b) Type III survivorship, defined as a decreasing per capita mortality rate: engineering explicitly defines this pattern of decreasing hazard as 'infant mortality'. Weak chaos generates two phenomena from the normal functioning of the same system. First, infant mortality- sensu engineering-without any external explanatory factors, such as manufacturing defects, which is followed by increased average longevity of survivors. Second, sudden failure of units during their normal period of operation, before the onset of age-dependent mortality arising from senescence. The relevance of these phenomena encompasses, for example: no-fault-found failure of electronic devices; high rates of human early spontaneous miscarriage/abortion; runaway pacemakers; sudden cardiac death in young adults; bipolar disorder; and epilepsy.

  17. Usefulness of the preoperative administration of tegafur suppositories as alternative adjuvant chemotherapy for patients with resectable stage II or III colorectal cancer: a KODK4 multicenter randomized control trial.

    Science.gov (United States)

    Okabayashi, Koji; Hasegawa, Hirotoshi; Watanabe, Masahiko; Ohishi, Takashi; Hisa, Akio; Kitagawa, Yuko

    2012-01-01

    The aim of this study was to evaluate the feasibility and conferred protection against recurrence of preoperatively administered tegafur suppositories following the intravenous and oral administration of fluoropyrimidine in a multicenter randomized control trial. Patients with clinical T3/4 colorectal cancer were randomly assigned to receive the preoperative administration of tegafur suppositories (group A) or no preoperative treatment (group B). The primary end points were disease-free survival (DFS) and overall survival (OS). The mean follow-up periods were 80.9 ± 31.0 months in group A and 64.5 ± 28.8 months in group B. The 5-year DFS rates were 89.3% in group A and 70.3% in group B (p = 0.045), whereas the 5-year OS rates were 91.4% in group A and 73.2% in group B (p = 0.051). Furthermore, a significant difference in the cumulative distant metastatic rate was observed (group A, 7.4% vs. group B, 23.4%; p = 0.03). However, no significant difference in the cumulative local recurrence rate was seen (group A, 4.6% vs. group B, 8.2%; p = 0.68). Despite a relatively small sample size, preoperative tegafur suppositories might protect recurrences and improve survival rates, mainly by preventing distant metastasis. These findings suggest the utility of tegafur suppositories as an alternative neoadjuvant treatment in modern chemotherapy for colorectal cancer. Copyright © 2012 S. Karger AG, Basel.

  18. Survival pathways under stress

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Survival pathways under stress. Bacteria survive by changing gene expression. pattern. Three important pathways will be discussed: Stringent response. Quorum sensing. Proteins performing function to control oxidative damage.

  19. Non-randomized study on the effects of preoperative radiotherapy and daily administration of low-dose cisplatin against those of radiotherapy alone for oral cancer. Effects on local control, control of metastases, and overall survival

    International Nuclear Information System (INIS)

    Kurita, Hiroshi; Ohtsuka, Akiko; Kobayashi, Hiroichi; Kurashina, Kenji; Shikama, Naoto; Oguchi, Masahiko

    2000-01-01

    Cisplatin is a known radiation modifier. Our previous study suggested that daily administration of low-dose cisplatin enhanced the efficacy of radiotherapy against primary oral squamous carcinoma. In this paper, we follow the patients who participated in the previous study and survey the benefit of combination low-dose cisplatin in improving local control, prevention of metastases, and overall survival. This study included patients with surgically resectable advanced oral tumors. Ten patients underwent preoperative radiotherapy of 30-40 Gy/15-20 days with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten other patients received external radiotherapy alone. All patients then underwent a planned radical tumor resection. No significant difference was see in loco-regional control rates (primary: 86 vs. 88%, neck: 83 vs. 78% at 48 months) or incidence of metastasis (70 vs. 64%) between the two groups. Nor was there a significant difference in the overall survival rate (60 vs. 66%). The results of this study suggest that the concomitant use of daily administration of low-dose cisplatin with preoperative radiation brings no statistically significant benefit in improving local control and survival rate in patients with advanced resectable oral cancer. (author)

  20. Cumulants of heat transfer across nonlinear quantum systems

    Science.gov (United States)

    Li, Huanan; Agarwalla, Bijay Kumar; Li, Baowen; Wang, Jian-Sheng

    2013-12-01

    We consider thermal conduction across a general nonlinear phononic junction. Based on two-time observation protocol and the nonequilibrium Green's function method, heat transfer in steady-state regimes is studied, and practical formulas for the calculation of the cumulant generating function are obtained. As an application, the general formalism is used to study anharmonic effects on fluctuation of steady-state heat transfer across a single-site junction with a quartic nonlinear on-site pinning potential. An explicit nonlinear modification to the cumulant generating function exact up to the first order is given, in which the Gallavotti-Cohen fluctuation symmetry is found still valid. Numerically a self-consistent procedure is introduced, which works well for strong nonlinearity.

  1. A cumulant functional for static and dynamic correlation

    International Nuclear Information System (INIS)

    Hollett, Joshua W.; Hosseini, Hessam; Menzies, Cameron

    2016-01-01

    A functional for the cumulant energy is introduced. The functional is composed of a pair-correction and static and dynamic correlation energy components. The pair-correction and static correlation energies are functionals of the natural orbitals and the occupancy transferred between near-degenerate orbital pairs, rather than the orbital occupancies themselves. The dynamic correlation energy is a functional of the statically correlated on-top two-electron density. The on-top density functional used in this study is the well-known Colle-Salvetti functional. Using the cc-pVTZ basis set, the functional effectively models the bond dissociation of H 2 , LiH, and N 2 with equilibrium bond lengths and dissociation energies comparable to those provided by multireference second-order perturbation theory. The performance of the cumulant functional is less impressive for HF and F 2 , mainly due to an underestimation of the dynamic correlation energy by the Colle-Salvetti functional.

  2. Fragmentation of tensor polarized deuterons into cumulative pions

    International Nuclear Information System (INIS)

    Afanas'ev, S.; Arkhipov, V.; Bondarev, V.

    1998-01-01

    The tensor analyzing power T 20 of the reaction d polarized + A → π - (0 0 ) + X has been measured in the fragmentation of 9 GeV tensor polarized deuterons into pions with momenta from 3.5 to 5.3 GeV/c on hydrogen, beryllium and carbon targets. This kinematic range corresponds to the region of cumulative hadron production with the cumulative variable x c from 1.08 to 1.76. The values of T 20 have been found to be small and consistent with positive values. This contradicts the predictions based on a direct mechanism assuming NN collision between a high momentum nucleon in the deuteron and a target nucleon (NN → NNπ)

  3. Experience of cumulative effects assessment in the UK

    Directory of Open Access Journals (Sweden)

    Piper Jake

    2004-01-01

    Full Text Available Cumulative effects assessment (CEA is a development of environmental impact assessment which attempts to take into account the wider picture of what impacts may affect the environment as a result of either multiple or linear projects, or development plans. CEA is seen as a further valuable tool in promoting sustainable development. The broader canvas upon which the assessment is made leads to a suite of issues such as complexity in methods and assessment of significance, the desirability of co-operation between developers and other parties, new ways of addressing mitigation and monitoring. After outlining the legislative position and the process of CEA, this paper looks at three cases studies in the UK where cumulative assessment has been carried out - the cases concern wind farms, major infrastructure and off-shore developments.

  4. Ecosystem assessment methods for cumulative effects at the regional scale

    International Nuclear Information System (INIS)

    Hunsaker, C.T.

    1989-01-01

    Environmental issues such as nonpoint-source pollution, acid rain, reduced biodiversity, land use change, and climate change have widespread ecological impacts and require an integrated assessment approach. Since 1978, the implementing regulations for the National Environmental Policy Act (NEPA) have required assessment of potential cumulative environmental impacts. Current environmental issues have encouraged ecologists to improve their understanding of ecosystem process and function at several spatial scales. However, management activities usually occur at the local scale, and there is little consideration of the potential impacts to the environmental quality of a region. This paper proposes that regional ecological risk assessment provides a useful approach for assisting scientists in accomplishing the task of assessing cumulative impacts. Critical issues such as spatial heterogeneity, boundary definition, and data aggregation are discussed. Examples from an assessment of acidic deposition effects on fish in Adirondack lakes illustrate the importance of integrated data bases, associated modeling efforts, and boundary definition at the regional scale

  5. Polarization in high Psub(trans) and cumulative hadron production

    International Nuclear Information System (INIS)

    Efremov, A.V.

    1978-01-01

    The final hadron polarization in the high Psub(trans) processes is analyzed in the parton hard scattering picture. Scaling assumption allows a correct qualitative description to be given for the Psub(trans)-behaviour of polarization or escape angle behaviour in cumulative production. The energy scaling and weak dependence on the beam and target type is predicted. A method is proposed for measuring the polarization of hadron jets

  6. Seasonal climate change patterns due to cumulative CO2 emissions

    Science.gov (United States)

    Partanen, Antti-Ilari; Leduc, Martin; Damon Matthews, H.

    2017-07-01

    Cumulative CO2 emissions are near linearly related to both global and regional changes in annual-mean surface temperature. These relationships are known as the transient climate response to cumulative CO2 emissions (TCRE) and the regional TCRE (RTCRE), and have been shown to remain approximately constant over a wide range of cumulative emissions. Here, we assessed how well this relationship holds for seasonal patterns of temperature change, as well as for annual-mean and seasonal precipitation patterns. We analyzed an idealized scenario with CO2 concentration growing at an annual rate of 1% using data from 12 Earth system models from the Coupled Model Intercomparison Project Phase 5 (CMIP5). Seasonal RTCRE values for temperature varied considerably, with the highest seasonal variation evident in the Arctic, where RTCRE was about 5.5 °C per Tt C for boreal winter and about 2.0 °C per Tt C for boreal summer. Also the precipitation response in the Arctic during boreal winter was stronger than during other seasons. We found that emission-normalized seasonal patterns of temperature change were relatively robust with respect to time, though they were sub-linear with respect to emissions particularly near the Arctic. Moreover, RTCRE patterns for precipitation could not be quantified robustly due to the large internal variability of precipitation. Our results suggest that cumulative CO2 emissions are a useful metric to predict regional and seasonal changes in precipitation and temperature. This extension of the TCRE framework to seasonal and regional climate change is helpful for communicating the link between emissions and climate change to policy-makers and the general public, and is well-suited for impact studies that could make use of estimated regional-scale climate changes that are consistent with the carbon budgets associated with global temperature targets.

  7. Firm heterogeneity, Rules of Origin and Rules of Cumulation

    OpenAIRE

    Bombarda , Pamela; Gamberoni , Elisa

    2013-01-01

    We analyse the impact of relaxing rules of origin (ROOs) in a simple setting with heterogeneous firms that buy intermediate inputs from domestic and foreign sources. In particular, we consider the impact of switching from bilateral to diagonal cumulation when using preferences (instead of paying the MFN tariff) involving the respect of rules of origin. We find that relaxing the restrictiveness of the ROOs leads the least productive exporters to stop exporting. The empirical part confirms thes...

  8. Cumulant approach to dynamical correlation functions at finite temperatures

    International Nuclear Information System (INIS)

    Tran Minhtien.

    1993-11-01

    A new theoretical approach, based on the introduction of cumulants, to calculate thermodynamic averages and dynamical correlation functions at finite temperatures is developed. The method is formulated in Liouville instead of Hilbert space and can be applied to operators which do not require to satisfy fermion or boson commutation relations. The application of the partitioning and projection methods for the dynamical correlation functions is discussed. The present method can be applied to weakly as well as to strongly correlated systems. (author). 9 refs

  9. Severe occupational hand eczema, job stress and cumulative sickness absence.

    Science.gov (United States)

    Böhm, D; Stock Gissendanner, S; Finkeldey, F; John, S M; Werfel, T; Diepgen, T L; Breuer, K

    2014-10-01

    Stress is known to activate or exacerbate dermatoses, but the relationships between chronic stress, job-related stress and sickness absence among occupational hand eczema (OHE) patients are inadequately understood. To see whether chronic stress or burnout symptoms were associated with cumulative sickness absence in patients with OHE and to determine which factors predicted sickness absence in a model including measures of job-related and chronic stress. We investigated correlations of these factors in employed adult inpatients with a history of sickness absence due to OHE in a retrospective cross-sectional explorative study, which assessed chronic stress (Trier Inventory for the Assessment of Chronic Stress), burnout (Shirom Melamed Burnout Measure), clinical symptom severity (Osnabrück Hand Eczema Severity Index), perceived symptom severity, demographic characteristics and cumulative days of sickness absence. The study group consisted of 122 patients. OHE symptoms were not more severe among patients experiencing greater stress and burnout. Women reported higher levels of chronic stress on some measures. Cumulative days of sickness absence correlated with individual dimensions of job-related stress and, in multiple regression analysis, with an overall measure of chronic stress. Chronic stress is an additional factor predicting cumulative sickness absence among severely affected OHE patients. Other relevant factors for this study sample included the 'cognitive weariness' subscale of the Shirom Melamed Burnout Measure and the physical component summary score of the SF-36, a measure of health-related life quality. Prevention and rehabilitation should take job stress into consideration in multidisciplinary treatment strategies for severely affected OHE patients. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Finite-volume cumulant expansion in QCD-colorless plasma

    Energy Technology Data Exchange (ETDEWEB)

    Ladrem, M. [Taibah University, Physics Department, Faculty of Science, Al-Madinah, Al-Munawwarah (Saudi Arabia); Physics Department, Algiers (Algeria); ENS-Vieux Kouba (Bachir El-Ibrahimi), Laboratoire de Physique et de Mathematiques Appliquees (LPMA), Algiers (Algeria); Ahmed, M.A.A. [Taibah University, Physics Department, Faculty of Science, Al-Madinah, Al-Munawwarah (Saudi Arabia); ENS-Vieux Kouba (Bachir El-Ibrahimi), Laboratoire de Physique et de Mathematiques Appliquees (LPMA), Algiers (Algeria); Taiz University in Turba, Physics Department, Taiz (Yemen); Alfull, Z.Z. [Taibah University, Physics Department, Faculty of Science, Al-Madinah, Al-Munawwarah (Saudi Arabia); Cherif, S. [ENS-Vieux Kouba (Bachir El-Ibrahimi), Laboratoire de Physique et de Mathematiques Appliquees (LPMA), Algiers (Algeria); Ghardaia University, Sciences and Technologies Department, Ghardaia (Algeria)

    2015-09-15

    Due to the finite-size effects, the localization of the phase transition in finite systems and the determination of its order, become an extremely difficult task, even in the simplest known cases. In order to identify and locate the finite-volume transition point T{sub 0}(V) of the QCD deconfinement phase transition to a colorless QGP, we have developed a new approach using the finite-size cumulant expansion of the order parameter and the L{sub mn}-method. The first six cumulants C{sub 1,2,3,4,5,6} with the corresponding under-normalized ratios (skewness Σ, kurtosis κ, pentosis Π{sub ±}, and hexosis H{sub 1,2,3}) and three unnormalized combinations of them, (O = σ{sup 2}κΣ{sup -1},U = σ{sup -2}Σ{sup -1},N = σ{sup 2}κ) are calculated and studied as functions of (T, V). A new approach, unifying in a clear and consistent way the definitions of cumulant ratios, is proposed.Anumerical FSS analysis of the obtained results has allowed us to locate accurately the finite-volume transition point. The extracted transition temperature value T{sub 0}(V) agrees with that expected T{sub 0}{sup N}(V) from the order parameter and the thermal susceptibility χ{sub T} (T, V), according to the standard procedure of localization to within about 2%. In addition to this, a very good correlation factor is obtained proving the validity of our cumulants method. The agreement of our results with those obtained by means of other models is remarkable. (orig.)

  11. Science and Societal Partnerships to Address Cumulative Impacts

    OpenAIRE

    Lundquist, Carolyn J.; Fisher, Karen T.; Le Heron, Richard; Lewis, Nick I.; Ellis, Joanne I.; Hewitt, Judi E.; Greenaway, Alison J.; Cartner, Katie J.; Burgess-Jones, Tracey C.; Schiel, David R.; Thrush, Simon F.

    2016-01-01

    Funding and priorities for ocean research are not separate from the underlying sociological, economic, and political landscapes that determine values attributed to ecological systems. Here we present a variation on science prioritization exercises, focussing on inter-disciplinary research questions with the objective of shifting broad scale management practices to better address cumulative impacts and multiple users. Marine scientists in New Zealand from a broad range of scientific and social...

  12. Cumulative prospect theory and mean variance analysis. A rigorous comparison

    OpenAIRE

    Hens, Thorsten; Mayer, Janos

    2012-01-01

    We compare asset allocations derived for cumulative prospect theory(CPT) based on two different methods: Maximizing CPT along the mean–variance efficient frontier and maximizing it without that restriction. We find that with normally distributed returns the difference is negligible. However, using standard asset allocation data of pension funds the difference is considerable. Moreover, with derivatives like call options the restriction to the mean-variance efficient frontier results in a siza...

  13. Signal anomaly detection using modified CUSUM [cumulative sum] method

    International Nuclear Information System (INIS)

    Morgenstern, V.; Upadhyaya, B.R.; Benedetti, M.

    1988-01-01

    An important aspect of detection of anomalies in signals is the identification of changes in signal behavior caused by noise, jumps, changes in band-width, sudden pulses and signal bias. A methodology is developed to identify, isolate and characterize these anomalies using a modification of the cumulative sum (CUSUM) approach. The new algorithm performs anomaly detection at three levels and is implemented on a general purpose computer. 7 refs., 4 figs

  14. Problems of describing the cumulative effect in relativistic nuclear physics

    International Nuclear Information System (INIS)

    Baldin, A.M.

    1979-01-01

    The problem of describing the cumulative effect i.e., the particle production on nuclei in the range kinematically forbidden for one-nucleon collisions, is studied. Discrimination of events containing cumulative particles fixes configurations in the wave function of a nucleus, when several nucleons are closely spaced and their quark-parton components are collectivized. For the cumulative processes under consideration large distances between quarks are very important. The fundamental facts and theoretical interpretation of the quantum field theory and of the condensed media theory in the relativistic nuclear physics are presented in brief. The collisions of the relativistic nuclei with low momentum transfers is considered in a fast moving coordinate system. The basic parameter determining this type of collisions is the energy of nucleon binding in nuclei. It has been shown that the short-range correlation model provides a good presentation of many characteristics of the multiple particle production and it may be regarded as an approximate universal property of hadron interactions

  15. Dynamic prediction of cumulative incidence functions by direct binomial regression.

    Science.gov (United States)

    Grand, Mia K; de Witte, Theo J M; Putter, Hein

    2018-03-25

    In recent years there have been a series of advances in the field of dynamic prediction. Among those is the development of methods for dynamic prediction of the cumulative incidence function in a competing risk setting. These models enable the predictions to be updated as time progresses and more information becomes available, for example when a patient comes back for a follow-up visit after completing a year of treatment, the risk of death, and adverse events may have changed since treatment initiation. One approach to model the cumulative incidence function in competing risks is by direct binomial regression, where right censoring of the event times is handled by inverse probability of censoring weights. We extend the approach by combining it with landmarking to enable dynamic prediction of the cumulative incidence function. The proposed models are very flexible, as they allow the covariates to have complex time-varying effects, and we illustrate how to investigate possible time-varying structures using Wald tests. The models are fitted using generalized estimating equations. The method is applied to bone marrow transplant data and the performance is investigated in a simulation study. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Cumulative Risk Assessment Toolbox: Methods and Approaches for the Practitioner

    Directory of Open Access Journals (Sweden)

    Margaret M. MacDonell

    2013-01-01

    Full Text Available The historical approach to assessing health risks of environmental chemicals has been to evaluate them one at a time. In fact, we are exposed every day to a wide variety of chemicals and are increasingly aware of potential health implications. Although considerable progress has been made in the science underlying risk assessments for real-world exposures, implementation has lagged because many practitioners are unaware of methods and tools available to support these analyses. To address this issue, the US Environmental Protection Agency developed a toolbox of cumulative risk resources for contaminated sites, as part of a resource document that was published in 2007. This paper highlights information for nearly 80 resources from the toolbox and provides selected updates, with practical notes for cumulative risk applications. Resources are organized according to the main elements of the assessment process: (1 planning, scoping, and problem formulation; (2 environmental fate and transport; (3 exposure analysis extending to human factors; (4 toxicity analysis; and (5 risk and uncertainty characterization, including presentation of results. In addition to providing online access, plans for the toolbox include addressing nonchemical stressors and applications beyond contaminated sites and further strengthening resource accessibility to support evolving analyses for cumulative risk and sustainable communities.

  17. Energy Current Cumulants in One-Dimensional Systems in Equilibrium

    Science.gov (United States)

    Dhar, Abhishek; Saito, Keiji; Roy, Anjan

    2018-06-01

    A recent theory based on fluctuating hydrodynamics predicts that one-dimensional interacting systems with particle, momentum, and energy conservation exhibit anomalous transport that falls into two main universality classes. The classification is based on behavior of equilibrium dynamical correlations of the conserved quantities. One class is characterized by sound modes with Kardar-Parisi-Zhang scaling, while the second class has diffusive sound modes. The heat mode follows Lévy statistics, with different exponents for the two classes. Here we consider heat current fluctuations in two specific systems, which are expected to be in the above two universality classes, namely, a hard particle gas with Hamiltonian dynamics and a harmonic chain with momentum conserving stochastic dynamics. Numerical simulations show completely different system-size dependence of current cumulants in these two systems. We explain this numerical observation using a phenomenological model of Lévy walkers with inputs from fluctuating hydrodynamics. This consistently explains the system-size dependence of heat current fluctuations. For the latter system, we derive the cumulant-generating function from a more microscopic theory, which also gives the same system-size dependence of cumulants.

  18. Preference, resistance to change, and the cumulative decision model.

    Science.gov (United States)

    Grace, Randolph C

    2018-01-01

    According to behavioral momentum theory (Nevin & Grace, 2000a), preference in concurrent chains and resistance to change in multiple schedules are independent measures of a common construct representing reinforcement history. Here I review the original studies on preference and resistance to change in which reinforcement variables were manipulated parametrically, conducted by Nevin, Grace and colleagues between 1997 and 2002, as well as more recent research. The cumulative decision model proposed by Grace and colleagues for concurrent chains is shown to provide a good account of both preference and resistance to change, and is able to predict the increased sensitivity to reinforcer rate and magnitude observed with constant-duration components. Residuals from fits of the cumulative decision model to preference and resistance to change data were positively correlated, supporting the prediction of behavioral momentum theory. Although some questions remain, the learning process assumed by the cumulative decision model, in which outcomes are compared against a criterion that represents the average outcome value in the current context, may provide a plausible model for the acquisition of differential resistance to change. © 2018 Society for the Experimental Analysis of Behavior.

  19. Stakeholder attitudes towards cumulative and aggregate exposure assessment of pesticides.

    Science.gov (United States)

    Verbeke, Wim; Van Loo, Ellen J; Vanhonacker, Filiep; Delcour, Ilse; Spanoghe, Pieter; van Klaveren, Jacob D

    2015-05-01

    This study evaluates the attitudes and perspectives of different stakeholder groups (agricultural producers, pesticide manufacturers, trading companies, retailers, regulators, food safety authorities, scientists and NGOs) towards the concepts of cumulative and aggregate exposure assessment of pesticides by means of qualitative in-depth interviews (n = 15) and a quantitative stakeholder survey (n = 65). The stakeholders involved generally agreed that the use of chemical pesticides is needed, primarily for meeting the need of feeding the growing world population, while clearly acknowledging the problematic nature of human exposure to pesticide residues. Current monitoring was generally perceived to be adequate, but the timeliness and consistency of monitoring practices across countries were questioned. The concept of cumulative exposure assessment was better understood by stakeholders than the concept of aggregate exposure assessment. Identified pitfalls were data availability, data limitations, sources and ways of dealing with uncertainties, as well as information and training needs. Regulators and food safety authorities were perceived as the stakeholder groups for whom cumulative and aggregate pesticide exposure assessment methods and tools would be most useful and acceptable. Insights obtained from this exploratory study have been integrated in the development of targeted and stakeholder-tailored dissemination and training programmes that were implemented within the EU-FP7 project ACROPOLIS. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. A randomized trial of diet and physical activity in women treated for stage II—IV ovarian cancer: Rationale and design of the Lifestyle Intervention for Ovarian Cancer Enhanced Survival (LIVES): An NRG Oncology/Gynecologic Oncology Group (GOG-225) Study☆,☆☆

    Science.gov (United States)

    Thomson, Cynthia A.; Crane, Tracy E.; Miller, Austin; Garcia, David O.; Basen-Engquist, Karen; Alberts, David S.

    2016-01-01

    Ovarian cancer is the most common cause of gynecological cancer death in United States women. Efforts to improve progression free survival (PFS) and quality of life (QoL) after treatment for ovarian cancer are necessary. Observational studies suggest that lifestyle behaviors, including diet and physical activity, are associated with lower mortality in this population. The Lifestyle Intervention for Ovarian Cancer Enhanced Survival (LIVES) NRG 0225 study is a randomized, controlled trial designed to test the hypothesis that a 24 month lifestyle intervention will significantly increase PFS after oncological therapy for stage II-IV ovarian cancer. Women are randomized 1:1 to a high vegetable and fiber, low-fat diet with daily physical activity goals or an attention control group. Secondary outcomes to be evaluated include QoL and gastrointestinal health. Moreover an a priori lifestyle adherence score will be used to evaluate relationships between adoption of the diet and activity goals and PFS. Blood specimens are collected at baseline, 6, 12 and 24 months for analysis of dietary adherence (carotenoids) in addition to mechanistic biomarkers (lipids, insulin, telomere length). Women are enrolled at NRG clinic sites nationally and the telephone based lifestyle intervention is delivered from The University of Arizona call center by trained health coaches. A study specific multi-modal telephone, email, and SMS behavior change software platform is utilized for information delivery, coaching and data capture. When completed, LIVES will be the largest behavior-based lifestyle intervention trial conducted among ovarian cancer survivors. PMID:27394382

  1. Combination of transcatheter arterial chemoembolization and interrupted dosing sorafenib improves patient survival in early–intermediate stage hepatocellular carcinoma

    Science.gov (United States)

    Lee, Teng-Yu; Lin, Chen-Chun; Chen, Chiung-Yu; Wang, Tsang-En; Lo, Gin-Ho; Chang, Chi-Sen; Chao, Yee

    2017-01-01

    Abstract Background/Objective: The survival benefit of treatment for unresectable hepatocellular carcinoma (HCC) with transcatheter arterial chemoembolization (TACE) combined with sorafenib remains uncertain. We compared the survival of patients treated with TACE and sorafenib with that of patients treated with TACE alone. Methods: This was a post hoc analysis of the Study in Asia of the Combination of TACE with Sorafenib in Patients with HCC (START) trial. All patients who received TACE and interrupted dosing of sorafenib for early or intermediate-stage HCC in Taiwan from 2009 to 2010 were recruited into the TACE and sorafenib group. They were randomly matched 1:1 by age, sex, Child–Pugh score, tumor size, tumor number, and tumor stage with patients from Taichung Veterans General Hospital in Taiwan who received TACE alone and who fulfilled the selection criteria of the START trial during the same time period (control group). Patient survival [cumulative incidence and hazard ratio (HR)] of the 2 groups were analyzed and compared. Results: The baseline characteristics of the 36 patients in each group were similar. Tumor response rates were significantly better in the TACE and sorafenib group (P < .04). Overall survival of the TACE and sorafenib group was also significantly better than that of the control (TACE alone) group over the 2 years [78%, 95% confidence interval (95% CI) 64–91 vs 49, 95% CI 32–66; P = .012]. In the multivariate regression analysis, TACE and sorafenib was found to be independently associated with a decreased risk of mortality (HR 0.33, 95% CI 0.12–0.89; P = .015). Multivariate stratified analyses verified this association in each patient subgroup (all HR < 1.0). Conclusion: With a high patient tolerance to an interrupted sorafenib dosing schedule, the combination of TACE with sorafenib was associated with improved overall survival in early–intermediate stage HCC when compared with treatment with TACE alone. PMID

  2. Probability, conditional probability and complementary cumulative distribution functions in performance assessment for radioactive waste disposal

    International Nuclear Information System (INIS)

    Helton, J.C.

    1996-03-01

    A formal description of the structure of several recent performance assessments (PAs) for the Waste Isolation Pilot Plant (WIPP) is given in terms of the following three components: a probability space (S st , S st , p st ) for stochastic uncertainty, a probability space (S su , S su , p su ) for subjective uncertainty and a function (i.e., a random variable) defined on the product space associated with (S st , S st , p st ) and (S su , S su , p su ). The explicit recognition of the existence of these three components allows a careful description of the use of probability, conditional probability and complementary cumulative distribution functions within the WIPP PA. This usage is illustrated in the context of the U.S. Environmental Protection Agency's standard for the geologic disposal of radioactive waste (40 CFR 191, Subpart B). The paradigm described in this presentation can also be used to impose a logically consistent structure on PAs for other complex systems

  3. Probability, conditional probability and complementary cumulative distribution functions in performance assessment for radioactive waste disposal

    International Nuclear Information System (INIS)

    Helton, J.C.

    1996-01-01

    A formal description of the structure of several recent performance assessments (PAs) for the Waste Isolation Pilot Plant (WIPP) is given in terms of the following three components: a probability space (S st , L st , P st ) for stochastic uncertainty, a probability space (S su , L su , P su ) for subjective uncertainty and a function (i.e., a random variable) defined on the product space associated with (S st , L st , P st ) and (S su , L su , P su ). The explicit recognition of the existence of these three components allows a careful description of the use of probability, conditional probability and complementary cumulative distribution functions within the WIPP PA. This usage is illustrated in the context of the US Environmental Protection Agency's standard for the geologic disposal of radioactive waste (40 CFR 191, Subpart B). The paradigm described in this presentation can also be used to impose a logically consistent structure on PAs for other complex systems

  4. Nonuniform Sparse Data Clustering Cascade Algorithm Based on Dynamic Cumulative Entropy

    Directory of Open Access Journals (Sweden)

    Ning Li

    2016-01-01

    Full Text Available A small amount of prior knowledge and randomly chosen initial cluster centers have a direct impact on the accuracy of the performance of iterative clustering algorithm. In this paper we propose a new algorithm to compute initial cluster centers for k-means clustering and the best number of the clusters with little prior knowledge and optimize clustering result. It constructs the Euclidean distance control factor based on aggregation density sparse degree to select the initial cluster center of nonuniform sparse data and obtains initial data clusters by multidimensional diffusion density distribution. Multiobjective clustering approach based on dynamic cumulative entropy is adopted to optimize the initial data clusters and the best number of the clusters. The experimental results show that the newly proposed algorithm has good performance to obtain the initial cluster centers for the k-means algorithm and it effectively improves the clustering accuracy of nonuniform sparse data by about 5%.

  5. Randomization tests

    CERN Document Server

    Edgington, Eugene

    2007-01-01

    Statistical Tests That Do Not Require Random Sampling Randomization Tests Numerical Examples Randomization Tests and Nonrandom Samples The Prevalence of Nonrandom Samples in Experiments The Irrelevance of Random Samples for the Typical Experiment Generalizing from Nonrandom Samples Intelligibility Respect for the Validity of Randomization Tests Versatility Practicality Precursors of Randomization Tests Other Applications of Permutation Tests Questions and Exercises Notes References Randomized Experiments Unique Benefits of Experiments Experimentation without Mani

  6. Network survivability performance

    Science.gov (United States)

    1993-11-01

    This technical report has been developed to address the survivability of telecommunications networks including services. It responds to the need for a common understanding of, and assessment techniques for network survivability, availability, integrity, and reliability. It provides a basis for designing and operating telecommunications networks to user expectations for network survivability and a foundation for continuing industry activities in the subject area. This report focuses on the survivability of both public and private networks and covers a wide range of users. Two frameworks are established for quantifying and categorizing service outages, and for classifying network survivability techniques and measures. The performance of the network survivability techniques is considered; however, recommended objectives are not established for network survivability performance.

  7. Evolution of costly explicit memory and cumulative culture.

    Science.gov (United States)

    Nakamaru, Mayuko

    2016-06-21

    Humans can acquire new information and modify it (cumulative culture) based on their learning and memory abilities, especially explicit memory, through the processes of encoding, consolidation, storage, and retrieval. Explicit memory is categorized into semantic and episodic memories. Animals have semantic memory, while episodic memory is unique to humans and essential for innovation and the evolution of culture. As both episodic and semantic memory are needed for innovation, the evolution of explicit memory influences the evolution of culture. However, previous theoretical studies have shown that environmental fluctuations influence the evolution of imitation (social learning) and innovation (individual learning) and assume that memory is not an evolutionary trait. If individuals can store and retrieve acquired information properly, they can modify it and innovate new information. Therefore, being able to store and retrieve information is essential from the perspective of cultural evolution. However, if both storage and retrieval were too costly, forgetting and relearning would have an advantage over storing and retrieving acquired information. In this study, using mathematical analysis and individual-based simulations, we investigate whether cumulative culture can promote the coevolution of costly memory and social and individual learning, assuming that cumulative culture improves the fitness of each individual. The conclusions are: (1) without cumulative culture, a social learning cost is essential for the evolution of storage-retrieval. Costly storage-retrieval can evolve with individual learning but costly social learning does not evolve. When low-cost social learning evolves, the repetition of forgetting and learning is favored more than the evolution of costly storage-retrieval, even though a cultural trait improves the fitness. (2) When cumulative culture exists and improves fitness, storage-retrieval can evolve with social and/or individual learning, which

  8. El Carreto o Cumulá - Aspidosperma Dugandii Standl El Carreto o Cumulá - Aspidosperma Dugandii Standl

    Directory of Open Access Journals (Sweden)

    Dugand Armando

    1944-03-01

    Full Text Available Nombres vulgares: Carreto (Atlántico, Bolívar, Magdalena; Cumulá, Cumulá (Cundinamarca, ToIima. Según el Dr. Emilio Robledo (Lecciones de Bot. ed. 3, 2: 544. 1939 el nombre Carreto también es empleado en Puerto Berrío (Antioquia. El mismo autor (loc. cit. da el nombre Comulá para una especie indeterminada de Viburnum en Mariquita (Tolima y J. M. Duque, refiriendose a la misma planta y localidad (en Bot. Gen. Colomb. 340, 356. 1943 atribuye este nombre vulgar al Aspidosperma ellipticum Rusby.  Sin embargo, las muestras de madera de Cumulá o Comulá que yo he examinado, procedentes de la región de Mariquita -una de las cuales me fue recientemente enviada por el distinguido ictiólogo Sr. Cecil Miles- pertenecen sin duda alguna al A. Dugandii StandI. Por otra parte, Santiago Cortés (FI. Colomb. 206. 1898; ed, 2: 239. 1912 cita el Cumulá "de Anapoima y otros lugares del (rio Magdalena" diciendo que pertenece a las Leguminosas, pero la brevísima descripción que este autor hace de la madera "naranjada y notable por densidad, dureza y resistencia a la humedad", me induce a creer que se trata del mismo Cumula coleccionado recientemente en Tocaima, ya que esta población esta situada a pocos kilómetros de Anapoima. Nombres vulgares: Carreto (Atlántico, Bolívar, Magdalena; Cumulá, Cumulá (Cundinamarca, ToIima. Según el Dr. Emilio Robledo (Lecciones de Bot. ed. 3, 2: 544. 1939 el nombre Carreto también es empleado en Puerto Berrío (Antioquia. El mismo autor (loc. cit. da el nombre Comulá para una especie indeterminada de Viburnum en Mariquita (Tolima y J. M. Duque, refiriendose a la misma planta y localidad (en Bot. Gen. Colomb. 340, 356. 1943 atribuye este nombre vulgar al Aspidosperma ellipticum Rusby.  Sin embargo, las muestras de madera de Cumulá o Comulá que yo he examinado, procedentes de la región de Mariquita -una de las cuales me fue recientemente enviada por el distinguido ictiólogo Sr. Cecil Miles- pertenecen sin

  9. Biostatistics series module 9: Survival analysis

    Directory of Open Access Journals (Sweden)

    Avijit Hazra

    2017-01-01

    Full Text Available Survival analysis is concerned with “time to event“ data. Conventionally, it dealt with cancer death as the event in question, but it can handle any event occurring over a time frame, and this need not be always adverse in nature. When the outcome of a study is the time to an event, it is often not possible to wait until the event in question has happened to all the subjects, for example, until all are dead. In addition, subjects may leave the study prematurely. Such situations lead to what is called censored observations as complete information is not available for these subjects. The data set is thus an assemblage of times to the event in question and times after which no more information on the individual is available. Survival analysis methods are the only techniques capable of handling censored observations without treating them as missing data. They also make no assumption regarding normal distribution of time to event data. Descriptive methods for exploring survival times in a sample include life table and Kaplan–Meier techniques as well as various kinds of distribution fitting as advanced modeling techniques. The Kaplan–Meier cumulative survival probability over time plot has become the signature plot for biomedical survival analysis. Several techniques are available for comparing the survival experience in two or more groups – the log-rank test is popularly used. This test can also be used to produce an odds ratio as an estimate of risk of the event in the test group; this is called hazard ratio (HR. Limitations of the traditional log-rank test have led to various modifications and enhancements. Finally, survival analysis offers different regression models for estimating the impact of multiple predictors on survival. Cox's proportional hazard model is the most general of the regression methods that allows the hazard function to be modeled on a set of explanatory variables without making restrictive assumptions concerning the

  10. Optimal Policies for Random and Periodic Garbage Collections with Tenuring Threshold

    Science.gov (United States)

    Zhao, Xufeng; Nakamura, Syouji; Nakagawa, Toshio

    It is an important problem to determine the tenuring threshold to meet the pause time goal for a generational garbage collector. From such viewpoint, this paper proposes two stochastic models based on the working schemes of a generational garbage collector: One is random collection which occurs at a nonhomogeneous Poisson process and the other is periodic collection which occurs at periodic times. Since the cost suffered for minor collection increases, as the amount of surviving objects accumulates, tenuring minor collection should be made at some tenuring threshold. Using the techniques of cumulative processes and reliability theory, expected cost rates with tenuring threshold are obtained, and optimal policies which minimize them are discussed analytically and computed numerically.

  11. Clinical significance of cumulative biological effective dose and overall treatment time in the treatment of carcinoma cervix

    Directory of Open Access Journals (Sweden)

    Mandal Abhijit

    2007-01-01

    Full Text Available The purpose of this retrospective study is to report the radiotherapy treatment response of, and complications in, patients with cervical cancer on the basis of cumulative biologic effective dose (BED and overall treatment time (OTT. Sixty-four (stage II - 35/64; stage III - 29/64 patients of cervical cancer were treated with combination of external beam radiotherapy (EBRT and low dose rate intracavitary brachytherapy (ICBT. The cumulative BED was calculated at Point A (BED 10 ; and bladder, rectal reference points (BED 2.5 using the linear-quadratic BED equations. The local control (LC rate and 5-year disease-free survival (DFS rate in patients of stage II were comparable for BED 10 < 84.5 and BED 10 > 84.5 but were much higher for BED 10 > 84.5 than BED 10 < 84.5 ( P < 0.01 in stage III patients. In the stage II patients, The LC rate and 5-year DFS rate were comparable for OTT < 50 days and for OTT> 50 days but were much higher in stage III patients with OTT < 50 than OTT> 50 days ( P < 0.001. It was also observed that patients who received BED 2.5 < 105 had lesser rectal ( P < 0.001 and bladder complications than BED 2.5 > 105. Higher rectal complication-free survival (CFS R rate, bladder complication-free survival (CFS B rate and all-type late complication-free survival rate were observed in patients who received BED 2.5 < 105 than BED 2.5 > 105. A balanced, optimal and justified radiotherapy treatment schedule to deliver higher BED 10 (>84.5 and lower BED 2.5 (< 105 in lesser OTT (< 50 days is essential in carcinoma cervix to expect a better treatment outcome in all respects.

  12. Survival Analysis of Patients with End Stage Renal Disease

    Science.gov (United States)

    Urrutia, J. D.; Gayo, W. S.; Bautista, L. A.; Baccay, E. B.

    2015-06-01

    This paper provides a survival analysis of End Stage Renal Disease (ESRD) under Kaplan-Meier Estimates and Weibull Distribution. The data were obtained from the records of V. L. MakabaliMemorial Hospital with respect to time t (patient's age), covariates such as developed secondary disease (Pulmonary Congestion and Cardiovascular Disease), gender, and the event of interest: the death of ESRD patients. Survival and hazard rates were estimated using NCSS for Weibull Distribution and SPSS for Kaplan-Meier Estimates. These lead to the same conclusion that hazard rate increases and survival rate decreases of ESRD patient diagnosed with Pulmonary Congestion, Cardiovascular Disease and both diseases with respect to time. It also shows that female patients have a greater risk of death compared to males. The probability risk was given the equation R = 1 — e-H(t) where e-H(t) is the survival function, H(t) the cumulative hazard function which was created using Cox-Regression.

  13. Mean exit time and survival probability within the CTRW formalism

    Science.gov (United States)

    Montero, M.; Masoliver, J.

    2007-05-01

    An intense research on financial market microstructure is presently in progress. Continuous time random walks (CTRWs) are general models capable to capture the small-scale properties that high frequency data series show. The use of CTRW models in the analysis of financial problems is quite recent and their potentials have not been fully developed. Here we present two (closely related) applications of great interest in risk control. In the first place, we will review the problem of modelling the behaviour of the mean exit time (MET) of a process out of a given region of fixed size. The surveyed stochastic processes are the cumulative returns of asset prices. The link between the value of the MET and the timescale of the market fluctuations of a certain degree is crystal clear. In this sense, MET value may help, for instance, in deciding the optimal time horizon for the investment. The MET is, however, one among the statistics of a distribution of bigger interest: the survival probability (SP), the likelihood that after some lapse of time a process remains inside the given region without having crossed its boundaries. The final part of the manuscript is devoted to the study of this quantity. Note that the use of SPs may outperform the standard “Value at Risk" (VaR) method for two reasons: we can consider other market dynamics than the limited Wiener process and, even in this case, a risk level derived from the SP will ensure (within the desired quintile) that the quoted value of the portfolio will not leave the safety zone. We present some preliminary theoretical and applied results concerning this topic.

  14. Developing a cumulative anatomic scoring system for military perineal and pelvic blast injuries.

    Science.gov (United States)

    Mossadegh, Somayyeh; Midwinter, M; Parker, P

    2013-03-01

    Improvised explosive device (IED) yields in Afghanistan have increased resulting in more proximal injuries. The injury severity score (ISS) is an anatomic aggregate score of the three most severely injured anatomical areas but does not accurately predict severity in IED related pelvi-perineal trauma patients. A scoring system based on abbreviated injury score (AIS) was developed to reflect the severity of these injuries in order to better understand risk factors, develop a tool for future audit and improve performance. Using standard AIS descriptors, injury scales were constructed for the pelvis (1, minor to 6, maximal). The perineum was divided into anterior and posterior zones as relevant to injury patterns and blast direction with each soft tissue structure being allocated a score from its own severity scale. A cumulative score, from 1 to 36 for soft tissue, or a maximum of 42 if a pelvic fracture was involved, was created for all structures injured in the anterior and posterior zones. Using this new scoring system, 77% of patients survived with a pelvi-perineal trauma score (PPTS) below 5. There was a significant increase in mortality, number of pelvic fractures and amputations with increase in score when comparing the first group (score 1-5) to the second group (score 6-10). For scores between 6 and 16 survival was 42% and 22% for scores between 17 and 21. In our cohort of 62 survivors, 1 patient with an IED related pelvi-perineal injury had a 'theoretically un-survivable' maximal ISS of 75 and survived, whereas there were no survivors with a PPTS greater than 22 but this group had no-one with an ISS of 75 suggesting ISS is not an accurate reflection of the true severity of pelvi-perineal blast injury. This scoring system is the initial part of a more complex logistic regression model that will contribute towards a unique trauma scoring system to aid surgical teams in predicting fluid requirements and operative timelines. In austere environments, it may also

  15. Multinationals and plant survival

    DEFF Research Database (Denmark)

    Bandick, Roger

    2010-01-01

    The aim of this paper is twofold: first, to investigate how different ownership structures affect plant survival, and second, to analyze how the presence of foreign multinational enterprises (MNEs) affects domestic plants’ survival. Using a unique and detailed data set on the Swedish manufacturing...... sector, I am able to separate plants into those owned by foreign MNEs, domestic MNEs, exporting non-MNEs, and purely domestic firms. In line with previous findings, the result, when conditioned on other factors affecting survival, shows that foreign MNE plants have lower survival rates than non......-MNE plants. However, separating the non-MNEs into exporters and non-exporters, the result shows that foreign MNE plants have higher survival rates than non-exporting non-MNEs, while the survival rates of foreign MNE plants and exporting non-MNE plants do not seem to differ. Moreover, the simple non...

  16. Cumulative effects of road de-icing salt on amphibian behavior.

    Science.gov (United States)

    Denoël, Mathieu; Bichot, Marion; Ficetola, Gentile Francesco; Delcourt, Johann; Ylieff, Marc; Kestemont, Patrick; Poncin, Pascal

    2010-08-15

    Despite growing evidence of the detrimental effect of chemical substances on organisms, limited research has focused on changes in behavioral patterns, in part due to the difficulties to obtain detailed quantitative data. Recent developments in efficient computer-based video analyses have allowed testing pesticide effects on model species such as the zebrafish. However, these new techniques have not yet been applied to amphibians and directly to conservation issues, i.e., to assess toxicological risks on threatened species. We used video-tracking analyses to test a quantitative effect of an environmental contaminant on the locomotion of amphibian tadpoles (Rana temporaria) by taking into account cumulative effects. Because recent research has demonstrated effects of de-icing salts on survival and community structure, we used sodium chloride in our experimental design (25 replicates, 4 concentrations, 4 times) to test for an effect at the scale of behavior at environmentally relevant concentrations. Analysis of 372 1-h video-tracks (5 samples/s) showed a complex action of salts on behavioral patterns with a dose and cumulative response over time. Although no effects were found on mortality or growth, the highest salt concentrations reduced the speed and movement of tadpoles in comparison with control treatments. The reduced locomotor performance could have detrimental consequences in terms of tadpoles' responses to competition and predation and may be an indicator of the low concentration effect of the contaminant. On one hand, this study demonstrates the usefulness of examining behavior to address conservation issues and understand the complex action of environmental factors and, more particularly, pollutants on organisms. On the other hand, our results highlight the need of new computerized techniques to quantitatively analyze these patterns. (c) 2010 Elsevier B.V. All rights reserved.

  17. The cumulative impact of annual coral bleaching can turn some coral species winners into losers.

    Science.gov (United States)

    Grottoli, Andréa G; Warner, Mark E; Levas, Stephen J; Aschaffenburg, Matthew D; Schoepf, Verena; McGinley, Michael; Baumann, Justin; Matsui, Yohei

    2014-12-01

    Mass coral bleaching events caused by elevated seawater temperatures result in extensive coral loss throughout the tropics, and are projected to increase in frequency and severity. If bleaching becomes an annual event later in this century, more than 90% of coral reefs worldwide may be at risk of long-term degradation. While corals can recover from single isolated bleaching and can acclimate to recurring bleaching events that are separated by multiple years, it is currently unknown if and how they will survive and possibly acclimatize to annual coral bleaching. Here, we demonstrate for the first time that annual coral bleaching can dramatically alter thermal tolerance in Caribbean corals. We found that high coral energy reserves and changes in the dominant algal endosymbiont type (Symbiodinium spp.) facilitated rapid acclimation in Porites divaricata, whereas low energy reserves and a lack of algal phenotypic plasticity significantly increased susceptibility in Porites astreoides to bleaching the following year. Phenotypic plasticity in the dominant endosymbiont type of Orbicella faveolata did not prevent repeat bleaching, but may have facilitated rapid recovery. Thus, coral holobiont response to an isolated single bleaching event is not an accurate predictor of its response to bleaching the following year. Rather, the cumulative impact of annual coral bleaching can turn some coral species 'winners' into 'losers', and can also facilitate acclimation and turn some coral species 'losers' into 'winners'. Overall, these findings indicate that cumulative impact of annual coral bleaching could result in some species becoming increasingly susceptible to bleaching and face a long-term decline, while phenotypically plastic coral species will acclimatize and persist. Thus, annual coral bleaching and recovery could contribute to the selective loss of coral diversity as well as the overall decline of coral reefs in the Caribbean. © 2014 John Wiley & Sons Ltd.

  18. An inflammation-based cumulative prognostic score system in patients with diffuse large B cell lymphoma in rituximab era.

    Science.gov (United States)

    Sun, Feifei; Zhu, Jia; Lu, Suying; Zhen, Zijun; Wang, Juan; Huang, Junting; Ding, Zonghui; Zeng, Musheng; Sun, Xiaofei

    2018-01-02

    Systemic inflammatory parameters are associated with poor outcomes in malignant patients. Several inflammation-based cumulative prognostic score systems were established for various solid tumors. However, there is few inflammation based cumulative prognostic score system for patients with diffuse large B cell lymphoma (DLBCL). We retrospectively reviewed 564 adult DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy between Nov 1 2006 and Dec 30 2013 and assessed the prognostic significance of six systemic inflammatory parameters evaluated in previous studies by univariate and multivariate analysis:C-reactive protein(CRP), albumin levels, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio(NLR), the platelet-lymphocyte ratio(PLR)and fibrinogen levels. Multivariate analysis identified CRP, albumin levels and the LMR are three independent prognostic parameters for overall survival (OS). Based on these three factors, we constructed a novel inflammation-based cumulative prognostic score (ICPS) system. Four risk groups were formed: group ICPS = 0, ICPS = 1, ICPS = 2 and ICPS = 3. Advanced multivariate analysis indicated that the ICPS model is a prognostic score system independent of International Prognostic Index (IPI) for both progression-free survival (PFS) (p systemic inflammatory status was associated with clinical outcomes of patients with DLBCL in rituximab era. The ICPS model was shown to classify risk groups more accurately than any single inflammatory prognostic parameters. These findings may be useful for identifying candidates for further inflammation-related mechanism research or novel anti-inflammation target therapies.

  19. Mismatch or cumulative stress : Toward an integrated hypothesis of programming effects

    NARCIS (Netherlands)

    Nederhof, Esther; Schmidt, Mathias V.

    2012-01-01

    This paper integrates the cumulative stress hypothesis with the mismatch hypothesis, taking into account individual differences in sensitivity to programming. According to the cumulative stress hypothesis, individuals are more likely to suffer from disease as adversity accumulates. According to the

  20. Body mass index and breast cancer survival

    DEFF Research Database (Denmark)

    Guo, Qi; Burgess, Stephen; Turman, Constance

    2017-01-01

    Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival...... from breast cancer. Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between...... the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER...

  1. Science and societal partnerships to address cumulative impacts

    Directory of Open Access Journals (Sweden)

    Carolyn J Lundquist

    2016-02-01

    Full Text Available Funding and priorities for ocean research are not separate from the underlying sociological, economic, and political landscapes that determine values attributed to ecological systems. Here we present a variation on science prioritisation exercises, focussing on inter-disciplinary research questions with the objective of shifting broad scale management practices to better address cumulative impacts and multiple users. Marine scientists in New Zealand from a broad range of scientific and social-scientific backgrounds ranked 48 statements of research priorities. At a follow up workshop, participants discussed five over-arching themes based on survey results. These themes were used to develop mechanisms to increase the relevance and efficiency of scientific research while acknowledging socio-economic and political drivers of research agendas in New Zealand’s ocean ecosystems. Overarching messages included the need to: 1 determine the conditions under which ‘surprises’ (sudden and substantive undesirable changes are likely to occur and the socio-ecological implications of such changes; 2 develop methodologies to reveal the complex and cumulative effects of change in marine systems, and their implications for resource use, stewardship, and restoration; 3 assess potential solutions to management issues that balance long-term and short-term benefits and encompass societal engagement in decision-making; 4 establish effective and appropriately resourced institutional networks to foster collaborative, solution-focused marine science; and 5 establish cross-disciplinary dialogues to translate diverse scientific and social-scientific knowledge into innovative regulatory, social and economic practice. In the face of multiple uses and cumulative stressors, ocean management frameworks must be adapted to build a collaborative framework across science, governance and society that can help stakeholders navigate uncertainties and socio-ecological surprises.

  2. Cumulative risk hypothesis: Predicting and preventing child maltreatment recidivism.

    Science.gov (United States)

    Solomon, David; Åsberg, Kia; Peer, Samuel; Prince, Gwendolyn

    2016-08-01

    Although Child Protective Services (CPS) and other child welfare agencies aim to prevent further maltreatment in cases of child abuse and neglect, recidivism is common. Having a better understanding of recidivism predictors could aid in preventing additional instances of maltreatment. A previous study identified two CPS interventions that predicted recidivism: psychotherapy for the parent, which was related to a reduced risk of recidivism, and temporary removal of the child from the parent's custody, which was related to an increased recidivism risk. However, counter to expectations, this previous study did not identify any other specific risk factors related to maltreatment recidivism. For the current study, it was hypothesized that (a) cumulative risk (i.e., the total number of risk factors) would significantly predict maltreatment recidivism above and beyond intervention variables in a sample of CPS case files and that (b) therapy for the parent would be related to a reduced likelihood of recidivism. Because it was believed that the relation between temporary removal of a child from the parent's custody and maltreatment recidivism is explained by cumulative risk, the study also hypothesized that that the relation between temporary removal of the child from the parent's custody and recidivism would be mediated by cumulative risk. After performing a hierarchical logistic regression analysis, the first two hypotheses were supported, and an additional predictor, psychotherapy for the child, also was related to reduced chances of recidivism. However, Hypothesis 3 was not supported, as risk did not significantly mediate the relation between temporary removal and recidivism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Cumulative or delayed nephrotoxicity after cisplatin (DDP) treatment.

    Science.gov (United States)

    Pinnarò, P; Ruggeri, E M; Carlini, P; Giovannelli, M; Cognetti, F

    1986-04-30

    The present retrospective study reports data regarding renal toxicity in 115 patients (63 males, 52 females; median age, 56 years) who received cumulative doses of cisplatin (DDP) greater than or equal to 200 mg/m2. DDP was administered alone or in combination at a dose of 50-70 mg/m2 in 91 patients, and at a dose of 100 mg/m2 in 22 patients. Two patients after progression of ovarian carcinoma treated with conventional doses of DDP received 4 and 2 courses, respectively, of high-dose DDP (40 mg/m2 for 5 days) in hypertonic saline. The median number of DDP courses was 6 (range 2-14), and the median cumulative dose was 350 mg/m2 (range, 200-1200). Serum creatinine and urea nitrogen were determined before initiating the treatment and again 13-16 days after each administration. The incidence of azotemia (creatinina levels that exceeded 1.5 mg/dl) was similar before (7.8%) and after (6.1%) DDP doses of 200 mg/m2. Azotemia appears to be related to the association of DDP with other potentially nephrotoxic antineoplastic drugs (methotrexate) more than to the dose per course of DDP. Of 59 patients followed for 2 months or more after discontinuing the DDP treatment, 3 (5.1%) presented creatinine values higher than 1.5 mg/dl. The data deny that the incidence of nephrotoxicity is higher in patients receiving higher cumulative doses of DDP and confirm that increases in serum creatinine levels may occur some time after discontinuation of the drug.

  4. The proportional odds cumulative incidence model for competing risks

    DEFF Research Database (Denmark)

    Eriksson, Frank; Li, Jianing; Scheike, Thomas

    2015-01-01

    We suggest an estimator for the proportional odds cumulative incidence model for competing risks data. The key advantage of this model is that the regression parameters have the simple and useful odds ratio interpretation. The model has been considered by many authors, but it is rarely used...... in practice due to the lack of reliable estimation procedures. We suggest such procedures and show that their performance improve considerably on existing methods. We also suggest a goodness-of-fit test for the proportional odds assumption. We derive the large sample properties and provide estimators...

  5. Cumulative exposure to phthalates from phthalate-containing drug products

    DEFF Research Database (Denmark)

    Ennis, Zandra Nymand; Broe, Anne; Pottegård, Anton

    2018-01-01

    European regulatory limit of exposure ranging between 380-1710 mg/year throughout the study period. Lithium-products constituted the majority of dibutyl phthalate exposure. Diethyl phthalate exposure, mainly caused by erythromycin, theophylline and diclofenac products, did not exceed the EMA regulatory...... to quantify annual cumulated phthalate exposure from drug products among users of phthalate-containing oral medications in Denmark throughout the period of 2004-2016. METHODS: We conducted a Danish nationwide cohort study using The Danish National Prescription Registry and an internal database held...

  6. Exact probability distribution function for the volatility of cumulative production

    Science.gov (United States)

    Zadourian, Rubina; Klümper, Andreas

    2018-04-01

    In this paper we study the volatility and its probability distribution function for the cumulative production based on the experience curve hypothesis. This work presents a generalization of the study of volatility in Lafond et al. (2017), which addressed the effects of normally distributed noise in the production process. Due to its wide applicability in industrial and technological activities we present here the mathematical foundation for an arbitrary distribution function of the process, which we expect will pave the future research on forecasting of the production process.

  7. Numerical simulation of explosive magnetic cumulative generator EMG-720

    Energy Technology Data Exchange (ETDEWEB)

    Deryugin, Yu N; Zelenskij, D K; Kazakova, I F; Kargin, V I; Mironychev, P V; Pikar, A S; Popkov, N F; Ryaslov, E A; Ryzhatskova, E G [All-Russian Research Inst. of Experimental Physics, Sarov (Russian Federation)

    1997-12-31

    The paper discusses the methods and results of numerical simulations used in the development of a helical-coaxial explosive magnetic cumulative generator (EMG) with the stator up to 720 mm in diameter. In the process of designing, separate units were numerically modeled, as was the generator operation with a constant inductive-ohmic load. The 2-D processes of the armature acceleration by the explosion products were modeled as well as those of the formation of the sliding high-current contact between the armature and stator`s insulated turns. The problem of the armature integrity in the region of the detonation waves collision was numerically analyzed. 8 figs., 2 refs.

  8. Cumulative exergy losses associated with the production of lead metal

    Energy Technology Data Exchange (ETDEWEB)

    Szargut, J [Technical Univ. of Silesia, Gliwice (PL). Inst. of Thermal-Engineering; Morris, D R [New Brunswick Univ., Fredericton, NB (Canada). Dept. of Chemical Engineering

    1990-08-01

    Cumulative exergy losses result from the irreversibility of the links of a technological network leading from raw materials and fuels extracted from nature to the product under consideration. The sum of these losses can be apportioned into partial exergy losses (associated with particular links of the technological network) or into constituent exergy losses (associated with constituent subprocesses of the network). The methods of calculation of the partial and constituent exergy losses are presented, taking into account the useful byproducts substituting the major products of other processes. Analyses of partial and constituent exergy losses are made for the technological network of lead metal production. (author).

  9. Expansion formulae for characteristics of cumulative cost in finite horizon production models

    NARCIS (Netherlands)

    Ayhan, H.; Schlegel, S.

    2001-01-01

    We consider the expected value and the tail probability of cumulative shortage and holding cost (i.e. the probability that cumulative cost is more than a certain value) in finite horizon production models. An exact expression is provided for the expected value of the cumulative cost for general

  10. Survival of Patients With Cervical Cancer in Rural India

    OpenAIRE

    Vinoda Thulaseedharan, Jissa; Malila, Nea; Swaminathan, Rajaraman; Esmy Pulikottil, Okuru; Hakama, Matti; Muwonge, Richard; Sankaranarayanan, Rengaswamy

    2015-01-01

    Background: Patients’ survival after diagnosis of cervical cancer is indirectly influenced by socio-economic factors. We evaluated this survival and its socio-economic determinants in a rural population in south India. Methods: We assessed 165 women diagnosed with cervical cancer from the routine care control arm of a randomized screening trial conducted in rural south India. Kaplan-Meier curves were plotted to illustrate the observed survival of cancer patients. The effect of socio-econom...

  11. Cumulative hierarchies and computability over universes of sets

    Directory of Open Access Journals (Sweden)

    Domenico Cantone

    2008-05-01

    Full Text Available Various metamathematical investigations, beginning with Fraenkel’s historical proof of the independence of the axiom of choice, called for suitable definitions of hierarchical universes of sets. This led to the discovery of such important cumulative structures as the one singled out by von Neumann (generally taken as the universe of all sets and Godel’s universe of the so-called constructibles. Variants of those are exploited occasionally in studies concerning the foundations of analysis (according to Abraham Robinson’s approach, or concerning non-well-founded sets. We hence offer a systematic presentation of these many structures, partly motivated by their relevance and pervasiveness in mathematics. As we report, numerous properties of hierarchy-related notions such as rank, have been verified with the assistance of the ÆtnaNova proof-checker.Through SETL and Maple implementations of procedures which effectively handle the Ackermann’s hereditarily finite sets, we illustrate a particularly significant case among those in which the entities which form a universe of sets can be algorithmically constructed and manipulated; hereby, the fruitful bearing on pure mathematics of cumulative set hierarchies ramifies into the realms of theoretical computer science and algorithmics.

  12. Cumulative Effects Assessment: Linking Social, Ecological, and Governance Dimensions

    Directory of Open Access Journals (Sweden)

    Marian Weber

    2012-06-01

    Full Text Available Setting social, economic, and ecological objectives is ultimately a process of social choice informed by science. In this special feature we provide a multidisciplinary framework for the use of cumulative effects assessment in land use planning. Forest ecosystems are facing considerable challenges driven by population growth and increasing demands for resources. In a suite of case studies that span the boreal forest of Western Canada to the interior Atlantic forest of Paraguay we show how transparent and defensible methods for scenario analysis can be applied in data-limited regions and how social dimensions of land use change can be incorporated in these methods, particularly in aboriginal communities that have lived in these ecosystems for generations. The case studies explore how scenario analysis can be used to evaluate various land use options and highlight specific challenges with identifying social and ecological responses, determining thresholds and targets for land use, and integrating local and traditional knowledge in land use planning. Given that land use planning is ultimately a value-laden and often politically charged process we also provide some perspective on various collective and expert-based processes for identifying cumulative impacts and thresholds. The need for good science to inform and be informed by culturally appropriate democratic processes calls for well-planned and multifaceted approaches both to achieve an informed understanding of both residents and governments of the interactive and additive changes caused by development, and to design action agendas to influence such change at the ecological and social level.

  13. Maternal distress and parenting in the context of cumulative disadvantage.

    Science.gov (United States)

    Arditti, Joyce; Burton, Linda; Neeves-Botelho, Sara

    2010-06-01

    This article presents an emergent conceptual model of the features and links between cumulative disadvantage, maternal distress, and parenting practices in low-income families in which parental incarceration has occurred. The model emerged from the integration of extant conceptual and empirical research with grounded theory analysis of longitudinal ethnographic data from Welfare, Children, and Families: A Three-City Study. Fourteen exemplar family cases were used in the analysis. Results indicated that mothers in these families experienced life in the context of cumulative disadvantage, reporting a cascade of difficulties characterized by neighborhood worries, provider concerns, bureaucratic difficulties, violent intimate relationships, and the inability to meet children's needs. Mothers, however, also had an intense desire to protect their children, and to make up for past mistakes. Although, in response to high levels of maternal distress and disadvantage, most mothers exhibited harsh discipline of their children, some mothers transformed their distress by advocating for their children under difficult circumstances. Women's use of harsh discipline and advocacy was not necessarily an "either/or" phenomenon as half of the mothers included in our analysis exhibited both harsh discipline and care/advocacy behaviors. Maternal distress characterized by substance use, while connected to harsh disciplinary behavior, did not preclude mothers engaging in positive parenting behaviors.

  14. Cumulative phase delay imaging for contrast-enhanced ultrasound tomography

    International Nuclear Information System (INIS)

    Demi, Libertario; Van Sloun, Ruud J G; Wijkstra, Hessel; Mischi, Massimo

    2015-01-01

    Standard dynamic-contrast enhanced ultrasound (DCE-US) imaging detects and estimates ultrasound-contrast-agent (UCA) concentration based on the amplitude of the nonlinear (harmonic) components generated during ultrasound (US) propagation through UCAs. However, harmonic components generation is not specific to UCAs, as it also occurs for US propagating through tissue. Moreover, nonlinear artifacts affect standard DCE-US imaging, causing contrast to tissue ratio reduction, and resulting in possible misclassification of tissue and misinterpretation of UCA concentration. Furthermore, no contrast-specific modality exists for DCE-US tomography; in particular speed-of-sound changes due to UCAs are well within those caused by different tissue types. Recently, a new marker for UCAs has been introduced. A cumulative phase delay (CPD) between the second harmonic and fundamental component is in fact observable for US propagating through UCAs, and is absent in tissue. In this paper, tomographic US images based on CPD are for the first time presented and compared to speed-of-sound US tomography. Results show the applicability of this marker for contrast specific US imaging, with cumulative phase delay imaging (CPDI) showing superior capabilities in detecting and localizing UCA, as compared to speed-of-sound US tomography. Cavities (filled with UCA) which were down to 1 mm in diameter were clearly detectable. Moreover, CPDI is free of the above mentioned nonlinear artifacts. These results open important possibilities to DCE-US tomography, with potential applications to breast imaging for cancer localization. (fast track communication)

  15. Cumulant expansions for measuring water exchange using diffusion MRI

    Science.gov (United States)

    Ning, Lipeng; Nilsson, Markus; Lasič, Samo; Westin, Carl-Fredrik; Rathi, Yogesh

    2018-02-01

    The rate of water exchange across cell membranes is a parameter of biological interest and can be measured by diffusion magnetic resonance imaging (dMRI). In this work, we investigate a stochastic model for the diffusion-and-exchange of water molecules. This model provides a general solution for the temporal evolution of dMRI signal using any type of gradient waveform, thereby generalizing the signal expressions for the Kärger model. Moreover, we also derive a general nth order cumulant expansion of the dMRI signal accounting for water exchange, which has not been explored in earlier studies. Based on this analytical expression, we compute the cumulant expansion for dMRI signals for the special case of single diffusion encoding (SDE) and double diffusion encoding (DDE) sequences. Our results provide a theoretical guideline on optimizing experimental parameters for SDE and DDE sequences, respectively. Moreover, we show that DDE signals are more sensitive to water exchange at short-time scale but provide less attenuation at long-time scale than SDE signals. Our theoretical analysis is also validated using Monte Carlo simulations on synthetic structures.

  16. A Cumulant-based Analysis of Nonlinear Magnetospheric Dynamics

    International Nuclear Information System (INIS)

    Johnson, Jay R.; Wing, Simon

    2004-01-01

    Understanding magnetospheric dynamics and predicting future behavior of the magnetosphere is of great practical interest because it could potentially help to avert catastrophic loss of power and communications. In order to build good predictive models it is necessary to understand the most critical nonlinear dependencies among observed plasma and electromagnetic field variables in the coupled solar wind/magnetosphere system. In this work, we apply a cumulant-based information dynamical measure to characterize the nonlinear dynamics underlying the time evolution of the Dst and Kp geomagnetic indices, given solar wind magnetic field and plasma input. We examine the underlying dynamics of the system, the temporal statistical dependencies, the degree of nonlinearity, and the rate of information loss. We find a significant solar cycle dependence in the underlying dynamics of the system with greater nonlinearity for solar minimum. The cumulant-based approach also has the advantage that it is reliable even in the case of small data sets and therefore it is possible to avoid the assumption of stationarity, which allows for a measure of predictability even when the underlying system dynamics may change character. Evaluations of several leading Kp prediction models indicate that their performances are sub-optimal during active times. We discuss possible improvements of these models based on this nonparametric approach

  17. Strategy for an assessment of cumulative ecological impacts

    International Nuclear Information System (INIS)

    Boucher, P.; Collins, J.; Nelsen, J.

    1995-01-01

    The US Department of Energy (DOE) has developed a strategy to conduct an assessment of the cumulative ecological impact of operations at the 300-square-mile Savannah River Site. This facility has over 400 identified waste units and contains several large watersheds. In addition to individual waste units, residual contamination must be evaluated in terms of its contribution to ecological risks at zonal and site-wide levels. DOE must be able to generate sufficient information to facilitate cleanup in the immediate future within the context of a site-wide ecological risk assessment that may not be completed for many years. The strategy superimposes a more global perspective on ecological assessments of individual waste units and provides strategic underpinnings for conducting individual screening-level and baseline risk assessments at the operable unit and zonal or watershed levels. It identifies ecological endpoints and risk assessment tools appropriate for each level of the risk assessment. In addition, it provides a clear mechanism for identifying clean sites through screening-level risk assessments and for elevating sites with residual contamination to the next level of assessment. Whereas screening-level and operable unit-level risk assessments relate directly to cleanup, zonal and site-wide assessments verity or confirm the overall effectiveness of remediation. The latter assessments must show, for example, whether multiple small areas with residual pesticide contamination that have minimal individual impact would pose a cumulative risk from bioaccumulation because they are within the habitat range of an ecological receptor

  18. ASURV: Astronomical SURVival Statistics

    Science.gov (United States)

    Feigelson, E. D.; Nelson, P. I.; Isobe, T.; LaValley, M.

    2014-06-01

    ASURV (Astronomical SURVival Statistics) provides astronomy survival analysis for right- and left-censored data including the maximum-likelihood Kaplan-Meier estimator and several univariate two-sample tests, bivariate correlation measures, and linear regressions. ASURV is written in FORTRAN 77, and is stand-alone and does not call any specialized libraries.

  19. Steroid treatment of acute graft-versus-host disease grade I: a randomized trial.

    Science.gov (United States)

    Bacigalupo, Andrea; Milone, Giuseppe; Cupri, Alessandra; Severino, Antonio; Fagioli, Franca; Berger, Massimo; Santarone, Stella; Chiusolo, Patrizia; Sica, Simona; Mammoliti, Sonia; Sorasio, Roberto; Massi, Daniela; Van Lint, Maria Teresa; Raiola, Anna Maria; Gualandi, Francesca; Selleri, Carmine; Sormani, Maria Pia; Signori, Alessio; Risitano, Antonio; Bonifazi, Francesca

    2017-12-01

    Patients with acute graft- versus -host disease (GvHD) grade I were randomized to an observation arm (n=85) or to a treatment arm (n=86) consisting of 6-methylprednisolone 1 mg/kg/day, after stratification for age and donor type. The primary end point was development of grade II-IV GvHD. The cumulative incidence of grade II-IV GvHD was 50% in the observation arm and 33% in the treatment arm ( P =0.005). However, grade III-IV GvHD was comparable (13% vs 10%, respectively; P =0.6), and this was true for sibling and alternative donor transplants. Moderate/severe chronic GvHD was also comparable (17% vs 9%). In multivariate analysis, an early interval between transplant and randomization (survival was 51% versus 41% ( P =0.3) in the observation and treatment arms, respectively. In multivariate analysis, advanced disease phase, older age and an early onset of GvHD were significant negative predictors of survival, independent of the randomization arm. In conclusion, steroid treatment of acute grade I GvHD prevents progression to grade II but not to grade III-IV GvHD, and there is no effect on non-relapse mortality and survival. Patients treated with steroids are at a higher risk of developing infections and have more adverse events. ( Trial registered as EUDTRACT 2008-000413-29 ). Copyright© 2017 Ferrata Storti Foundation.

  20. Older cancer patients in cancer clinical trials are underrepresented. Systematic literature review of almost 5000 meta- and pooled analyses of phase III randomized trials of survival from breast, prostate and lung cancer.

    Science.gov (United States)

    Dunn, Cita; Wilson, Andrew; Sitas, Freddy

    2017-12-01

    Older people represent increasing proportions of the population with cancer. To understand the representivity of cancer treatments in older people, we performed a systematic literature review using PRISMA guidelines of the age distribution of clinical trial participants for three leading cancer types, namely breast, prostate, and lung. We used PubMed to identify articles detailing meta or pooled-analyses of phase III, randomised controlled trials (RCTs) of survival for breast, prostate and lung cancer, published ≤5 years from 2016. We compared the age distribution of participants to that of these cancers for "More developed regions". 4993 potential papers were identified, but only three papers on breast cancer, three on lung cancer, and none on prostate cancer presented the age distribution of their participants. Except for one paper of breast cancer, participants ≥70 years in all other papers were underrepresented. We recommend the age distribution of patients be clearly reported in all clinical trials, as per guidelines. Clinical trials ought to be more representative of the populations most affected by the disease for which treatments are being tested. This should lead to better knowledge of effectiveness of treatments and better translation of trial results to optimal care of older cancer patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. The effect of the calcium antagonist, isradipine, on working capacity, pulmonary function, morbidity and survival rate in patients with severe chronic obstructive pulmonary disease (COPD): a randomized, double-blind, placebo-controlled study

    DEFF Research Database (Denmark)

    Galløe, Anders Michael; Graudal, Niels Albert; Petersen, J.R.

    1991-01-01

    Beneficial effects of calcium antagonists on the pulmonary haemodynamics of patients with chronic obstructive pulmonary disease (COPD) have been observed in several studies. Such effects include a decrease in pulmonary vascular resistance, an increase in cardiac output, and an increase in oxygen...... delivery. The clinical implications of these effects are uncertain. The randomized, double-blind, placebo-controlled, long-term study described here is the first to investigate the clinical effects of a calcium antagonist on patients with COPD. The aim was to test the hypothesis that the calcium antagonist......, isradipine, could increase working capacity and lung function, and decrease morbidity and mortality. Fifty-two patients with COPD were investigated. During a 22-month observation period no statistically significant differences between the isradipine group and the placebo group were found with regard...

  2. Universal global imprints of genome growth and evolution--equivalent length and cumulative mutation density.

    Directory of Open Access Journals (Sweden)

    Hong-Da Chen

    Full Text Available BACKGROUND: Segmental duplication is widely held to be an important mode of genome growth and evolution. Yet how this would affect the global structure of genomes has been little discussed. METHODS/PRINCIPAL FINDINGS: Here, we show that equivalent length, or L(e, a quantity determined by the variance of fluctuating part of the distribution of the k-mer frequencies in a genome, characterizes the latter's global structure. We computed the L(es of 865 complete chromosomes and found that they have nearly universal but (k-dependent values. The differences among the L(e of a chromosome and those of its coding and non-coding parts were found to be slight. CONCLUSIONS: We verified that these non-trivial results are natural consequences of a genome growth model characterized by random segmental duplication and random point mutation, but not of any model whose dominant growth mechanism is not segmental duplication. Our study also indicates that genomes have a nearly universal cumulative "point" mutation density of about 0.73 mutations per site that is compatible with the relatively low mutation rates of (1-5 x 10(-3/site/Mya previously determined by sequence comparison for the human and E. coli genomes.

  3. Statistical analysis of random duration times

    International Nuclear Information System (INIS)

    Engelhardt, M.E.

    1996-04-01

    This report presents basic statistical methods for analyzing data obtained by observing random time durations. It gives nonparametric estimates of the cumulative distribution function, reliability function and cumulative hazard function. These results can be applied with either complete or censored data. Several models which are commonly used with time data are discussed, and methods for model checking and goodness-of-fit tests are discussed. Maximum likelihood estimates and confidence limits are given for the various models considered. Some results for situations where repeated durations such as repairable systems are also discussed

  4. Quantification of tillage, plant cover, and cumulative rainfall effects on soil surface microrelief by statistical, geostatistical and fractal indices

    Science.gov (United States)

    Paz-Ferreiro, J.; Bertol, I.; Vidal Vázquez, E.

    2008-07-01

    Changes in soil surface microrelief with cumulative rainfall under different tillage systems and crop cover conditions were investigated in southern Brazil. Surface cover was none (fallow) or the crop succession maize followed by oats. Tillage treatments were: 1) conventional tillage on bare soil (BS), 2) conventional tillage (CT), 3) minimum tillage (MT) and 4) no tillage (NT) under maize and oats. Measurements were taken with a manual relief meter on small rectangular grids of 0.234 and 0.156 m2, throughout growing season of maize and oats, respectively. Each data set consisted of 200 point height readings, the size of the smallest cells being 3×5 cm during maize and 2×5 cm during oats growth periods. Random Roughness (RR), Limiting Difference (LD), Limiting Slope (LS) and two fractal parameters, fractal dimension (D) and crossover length (l) were estimated from the measured microtopographic data sets. Indices describing the vertical component of soil roughness such as RR, LD and l generally decreased with cumulative rain in the BS treatment, left fallow, and in the CT and MT treatments under maize and oats canopy. However, these indices were not substantially affected by cumulative rain in the NT treatment, whose surface was protected with previous crop residues. Roughness decay from initial values was larger in the BS treatment than in CT and MT treatments. Moreover, roughness decay generally tended to be faster under maize than under oats. The RR and LD indices decreased quadratically, while the l index decreased exponentially in the tilled, BS, CT and MT treatments. Crossover length was sensitive to differences in soil roughness conditions allowing a description of microrelief decay due to rainfall in the tilled treatments, although better correlations between cumulative rainfall and the most commonly used indices RR and LD were obtained. At the studied scale, parameters l and D have been found to be useful in interpreting the configuration properties of

  5. Long-term cumulative depressive symptom burden and risk of cognitive decline and dementia among very old women.

    Science.gov (United States)

    Zeki Al Hazzouri, Adina; Vittinghoff, Eric; Byers, Amy; Covinsky, Ken; Blazer, Dan; Diem, Susan; Ensrud, Kristine E; Yaffe, Kristine

    2014-05-01

    Depressive symptoms and cognitive outcomes are strongly interrelated. Despite that rates of depressive symptoms fluctuate during late life, little is known about the impact of long-term cumulative depressive symptom burden on cognitive decline and dementia in older adults. This study examines the association of nearly 20 years of cumulative depressive symptoms with cognitive outcomes in a cohort of older women. We assessed depressive symptoms in 7,240 women using the Geriatric Depression scale (GDS) at serial visits. We used a Poisson model with random slopes to estimate GDS trajectories for each participant from baseline to death or end of follow-up, and then characterized depressive symptom burden by quartile of the area under the curve. We assessed cognitive outcomes using repeated measures of the Mini-Mental State Examination (MMSE) and Trails B score over 20 years, Year-20 neuropsychological test battery, and adjudicated dementia and mild cognitive impairment (MCI). Adjusting for potential confounders, compared with women in the lowest quartile of cumulative depressive symptoms burden, women in the highest quartile had 21% more MMSE errors over time (95% CI = 17%, 26%), 20% worse Trails B score over time (95% CI = 17%, 23%), worse scores on most of the Year-20 cognitive tests, and a twofold greater likelihood of developing dementia or MCI (95% CI = 1.48, 3.11). Long-term cumulative depressive symptom burden was associated with cognitive decline and risk of dementia or MCI. Older adults with a history of depression should be closely monitored for recurrent episodes or unresolved depressive symptoms as well as any cognitive deficits.

  6. Comparison of Boer, Kiko, and Spanish meat goat does for stayability and cumulative reproductive output in the humid subtropical southeastern United States

    Directory of Open Access Journals (Sweden)

    Pellerin Ashley N

    2012-08-01

    Full Text Available Abstract Background Longevity is the amount of time breeding females stay active in a herd by avoiding death or culling because of illness or reproductive failure. This is a trait of economic relevance in commercial small ruminant breeding herds as it affects lifetime reproductive output. The purpose of this study was to determine if breed of meat goat influences breeding doe survival rates and cumulative reproductive performance under semi-intensive management. Results Boer (n = 132, Kiko (n = 92 and Spanish (n = 79 does were evaluated for longevity trends and cumulative kid production. The herd was managed on humid subtropical pasture. Does had the chance to complete 2 to 6 production years. Survival curves were analyzed for 2 culling methods. The actual culling practice removed does after two failures to wean a kid. An alternative culling protocol removed doe records after the first failure to wean a kid. Kid production traits analyzed across herd life were the total number of kids weaned and cumulative kid weight weaned to the 2-, 3-, and 5-year stayability endpoints. Most (82% doe exits were illness-related under the actual culling method. Reproductive failure represented 51% of doe exits under the alternative culling protocol. Boer does had greater survival declines (P P P  Conclusion Boer does had low stayability and cumulative kid production rates compared with Kiko and Spanish does. Poor health was the primary driver of does exiting the herd. Kiko and Spanish does did not differ for longevity and lifetime performance indicators.

  7. Random walk on random walks

    NARCIS (Netherlands)

    Hilário, M.; Hollander, den W.Th.F.; Sidoravicius, V.; Soares dos Santos, R.; Teixeira, A.

    2014-01-01

    In this paper we study a random walk in a one-dimensional dynamic random environment consisting of a collection of independent particles performing simple symmetric random walks in a Poisson equilibrium with density ¿¿(0,8). At each step the random walk performs a nearest-neighbour jump, moving to

  8. Cumulative effects in Swedish EIA practice - difficulties and obstacles

    International Nuclear Information System (INIS)

    Waernbaeck, Antoienette; Hilding-Rydevik, Tuija

    2009-01-01

    The importance of considering cumulative effects (CE) in the context of environmental assessment is manifested in the EU regulations. The demands on the contents of Environmental Impact Assessment (EIA) and Strategic Environmental Assessment (SEA) documents explicitly ask for CE to be described. In Swedish environmental assessment documents CE are rarely described or included. The aim of this paper is to look into the reasons behind this fact in the Swedish context. The paper describes and analyse how actors implementing the EIA and SEA legislation in Sweden perceive the current situation in relation to the legislative demands and the inclusion of cumulative effects. Through semi-structured interviews the following questions have been explored: Is the phenomenon of CE discussed and included in the EIA/SEA process? What do the actors include in and what is their knowledge of the term and concept of CE? Which difficulties and obstacles do these actors experience and what possibilities for inclusion of CE do they see in the EIA/SEA process? A large number of obstacles and hindrances emerged from the interviews conducted. It can be concluded from the analysis that the will to act does seem to exist. A lack of knowledge in respect of how to include cumulative effects and a lack of clear regulations concerning how this should be done seem to be perceived as the main obstacles. The knowledge of the term and the phenomenon is furthermore quite narrow and not all encompassing. They experience that there is a lack of procedures in place. They also seem to lack knowledge of methods in relation to how to actually work, in practice, with CE and how to include CE in the EIA/SEA process. It can be stated that the existence of this poor picture in relation to practice concerning CE in the context of impact assessment mirrors the existing and so far rather vague demands in respect of the inclusion and assessment of CE in Swedish EIA and SEA legislation, regulations, guidelines and

  9. Technical Note: SCUDA: A software platform for cumulative dose assessment

    Energy Technology Data Exchange (ETDEWEB)

    Park, Seyoun; McNutt, Todd; Quon, Harry; Wong, John; Lee, Junghoon, E-mail: rshekhar@childrensnational.org, E-mail: junghoon@jhu.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland 21231 (United States); Plishker, William [IGI Technologies, Inc., College Park, Maryland 20742 (United States); Shekhar, Raj, E-mail: rshekhar@childrensnational.org, E-mail: junghoon@jhu.edu [IGI Technologies, Inc., College Park, Maryland 20742 and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Health System, Washington, DC 20010 (United States)

    2016-10-15

    Purpose: Accurate tracking of anatomical changes and computation of actually delivered dose to the patient are critical for successful adaptive radiation therapy (ART). Additionally, efficient data management and fast processing are practically important for the adoption in clinic as ART involves a large amount of image and treatment data. The purpose of this study was to develop an accurate and efficient Software platform for CUmulative Dose Assessment (SCUDA) that can be seamlessly integrated into the clinical workflow. Methods: SCUDA consists of deformable image registration (DIR), segmentation, dose computation modules, and a graphical user interface. It is connected to our image PACS and radiotherapy informatics databases from which it automatically queries/retrieves patient images, radiotherapy plan, beam data, and daily treatment information, thus providing an efficient and unified workflow. For accurate registration of the planning CT and daily CBCTs, the authors iteratively correct CBCT intensities by matching local intensity histograms during the DIR process. Contours of the target tumor and critical structures are then propagated from the planning CT to daily CBCTs using the computed deformations. The actual delivered daily dose is computed using the registered CT and patient setup information by a superposition/convolution algorithm, and accumulated using the computed deformation fields. Both DIR and dose computation modules are accelerated by a graphics processing unit. Results: The cumulative dose computation process has been validated on 30 head and neck (HN) cancer cases, showing 3.5 ± 5.0 Gy (mean±STD) absolute mean dose differences between the planned and the actually delivered doses in the parotid glands. On average, DIR, dose computation, and segmentation take 20 s/fraction and 17 min for a 35-fraction treatment including additional computation for dose accumulation. Conclusions: The authors developed a unified software platform that provides

  10. Aspirin plus dipyridamole has the highest surface under the cumulative ranking curves (SUCRA) values in terms of mortality, intracranial hemorrhage, and adverse event rate among 7 drug therapies in the treatment of cerebral infarction.

    Science.gov (United States)

    Zhang, Jian-Jun; Liu, Xin

    2018-03-01

    The standardization for the clinical use of drug therapy for cerebral infarction (CI) has not yet determined in some aspects. In this paper, we discussed the efficacies of different drug therapies (aspirin, aspirin plus dipyridamole, aspirin plus clopidogrel, aspirin plus warfarin, cilostazol, warfarin, and ticlopidine) for CI. We searched databases of PubMed and Cochrane Library from the inception to April, 2017, randomized controlled trials (RCTs) met the inclusion and exclusion criteria were enrolled in this study. The network meta-analysis integrated evidences of direct and indirect comparisons to assess odd ratios (OR) and surface under the cumulative ranking curves (SUCRA) value. Thirteen eligible RCTs including 7 drug therapies were included into this network meta-analysis. The network meta-analysis results showed that CI patients who received aspirin plus dipyridamole presented lower mortality when compared with those received aspirin plus clopidogrel (OR = 0.46, 95% CI = 0.18-0.99), indicating aspirin plus dipyridamole therapy had better efficacy for CI. As for intracranial hemorrhage (ICH), stroke recurrence, and adverse event (AE) rate, there were no significant differences of efficacy among 7 drug therapies. Besides, SUCRA values demonstrated that in the 7 drug therapies, aspirin plus dipyridamole therapy was more effective than others (mortality: 80.67%; ICH: 76.6%; AE rate: 90.2%). Our findings revealed that aspirin plus dipyridamole therapy might be the optimum one for patients with CI, which could help to improve the survival of CI patients.

  11. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial.

    Science.gov (United States)

    Breugom, A J; van Gijn, W; Muller, E W; Berglund, Å; van den Broek, C B M; Fokstuen, T; Gelderblom, H; Kapiteijn, E; Leer, J W H; Marijnen, C A M; Martijn, H; Meershoek-Klein Kranenbarg, E; Nagtegaal, I D; Påhlman, L; Punt, C J A; Putter, H; Roodvoets, A G H; Rutten, H J T; Steup, W H; Glimelius, B; van de Velde, C J H

    2015-04-01

    The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME). The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete

  12. Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer

    DEFF Research Database (Denmark)

    Møller, Pål; Seppälä, Toni; Bernstein, Inge

    2017-01-01

    age 40 to age 70 years were 73% for pathogenic MLH1 (path_MLH1), 76% for path_MSH2 carriers and 52% for path_MSH6 carriers, and for colorectal cancer (CRC) the cumulative incidences were 46%, 48% and 23%, respectively. Crude survival after any subsequent cancer was 82% (95% CI 76% to 87%) and 10-year...

  13. Statistical Analysis of Competing Risks: Overall Survival in a Group of Chronic Myeloid Leukemia Patients

    Czech Academy of Sciences Publication Activity Database

    Fürstová, Jana; Valenta, Zdeněk

    2011-01-01

    Roč. 7, č. 1 (2011), s. 2-10 ISSN 1801-5603 Institutional research plan: CEZ:AV0Z10300504 Keywords : competing risks * chronic myeloid leukemia (CML) * overall survival * cause-specific hazard * cumulative incidence function Subject RIV: IN - Informatics, Computer Science http://www.ejbi.eu/images/2011-1/Furstova_en.pdf

  14. EFFICACY AND SAFETY OF INHALED NITRIC OXIDE USE IN PATIENTS WITH PULMONARY HYPERTENSION AND CHRONIC HEART FAILURE III-IV FUNCTIONAL CLASS, SURVIVED LEFT VENTRICULAR MYOCARDIAL INFARCTION: RESULTS OF NON-RANDOMIZED COMAPARIVE STUDY

    Directory of Open Access Journals (Sweden)

    P. N. Pavlenko

    2011-01-01

    Full Text Available Aim – assessment of the influence of inhaled nitric oxide (NO on the course of pulmonary hypertension (PH in patients with chronic heartfailure (CHF III–IV functional class (FC, myocardial infarction (MI.Materials and methods. Results of comparative non-randomized study that included 45 patients (26 men and 19 women aged 51 to 98 years with PH III–IV functional class, left ventricular myocardial infarction. In the study, patients underwent physical examination and Doppler echocardiography, and assessed FC LH (carried out with six-minute walking test, to determine the degree of dyspnea by Borg.Results. Symptoms of CHF and PH regressed in both groups of patients against the background of the therapy. Conclusion. It is established that the use of inhaled NO is a safe therapy and helps to reduce mean pulmonary arterial pressure (PAPmean in patients with PH and CHF III–IV FC, myocardial infarction. The method of inhaled NO is simple and easy to use.

  15. EFFICACY AND SAFETY OF INHALED NITRIC OXIDE USE IN PATIENTS WITH PULMONARY HYPERTENSION AND CHRONIC HEART FAILURE III-IV FUNCTIONAL CLASS, SURVIVED LEFT VENTRICULAR MYOCARDIAL INFARCTION: RESULTS OF NON-RANDOMIZED COMAPARIVE STUDY

    Directory of Open Access Journals (Sweden)

    P. N. Pavlenko

    2014-07-01

    Full Text Available Aim – assessment of the influence of inhaled nitric oxide (NO on the course of pulmonary hypertension (PH in patients with chronic heartfailure (CHF III–IV functional class (FC, myocardial infarction (MI.Materials and methods. Results of comparative non-randomized study that included 45 patients (26 men and 19 women aged 51 to 98 years with PH III–IV functional class, left ventricular myocardial infarction. In the study, patients underwent physical examination and Doppler echocardiography, and assessed FC LH (carried out with six-minute walking test, to determine the degree of dyspnea by Borg.Results. Symptoms of CHF and PH regressed in both groups of patients against the background of the therapy. Conclusion. It is established that the use of inhaled NO is a safe therapy and helps to reduce mean pulmonary arterial pressure (PAPmean in patients with PH and CHF III–IV FC, myocardial infarction. The method of inhaled NO is simple and easy to use.

  16. NatHER: protocol for systematic evaluation of trends in survival among patients with HER2-positive advanced breast cancer.

    Science.gov (United States)

    Korner, Eli J; Morris, Anne; Allen, Isabel Elaine; Hurvitz, Sara; Beattie, Mary S; Kalesan, Bindu

    2015-10-01

    Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) is an aggressive form of breast cancer and is historically associated with poor outcomes compared with HER2-negative MBC. Since 1998, four drugs have been globally approved for the targeted treatment of HER2-positive MBC. Additional advances in patient care-such as improved breast cancer screening, HER2 testing, and supportive care-have also occurred. The objective of this systematic review and meta-analysis is to determine whether there has been a cumulative change in survival over time in patients with HER2-positive advanced breast cancer based on results from interventional clinical trials (ICTs) and observational studies and to compare outcomes across these types of studies. A systematic search of Medline, EMBASE, and the Cochrane Central Register of Controlled Trials will be performed. Two investigators will independently assess each abstract for inclusion. English language reports of ICTs and observational studies that include patients with HER2-positive advanced breast cancer from 1987 onwards will be considered. The primary outcome of interest is overall survival; secondary outcomes include progression-free survival and safety. Data on clinical outcomes, as well as on study design, study population, treatment/intervention, methodological quality, and outcomes, will be extracted using a structured codebook developed by the authors for this study. Standard and cumulative random effects meta-analysis will be performed to derive pooled risk estimates, both overall and by study design, controlling for covariates such as aggregate demographic and clinical characteristics of patients, treatment/intervention, and study characteristics. Heterogeneity of studies will be evaluated using the I(2) statistic. Differences in risk estimates by quality characteristics will be performed using meta-regression. This study will evaluate current and evolving trends in survival associated with

  17. Cumulative trauma and symptom complexity in children: a path analysis.

    Science.gov (United States)

    Hodges, Monica; Godbout, Natacha; Briere, John; Lanktree, Cheryl; Gilbert, Alicia; Kletzka, Nicole Taylor

    2013-11-01

    Multiple trauma exposures during childhood are associated with a range of psychological symptoms later in life. In this study, we examined whether the total number of different types of trauma experienced by children (cumulative trauma) is associated with the complexity of their subsequent symptomatology, where complexity is defined as the number of different symptom clusters simultaneously elevated into the clinical range. Children's symptoms in six different trauma-related areas (e.g., depression, anger, posttraumatic stress) were reported both by child clients and their caretakers in a clinical sample of 318 children. Path analysis revealed that accumulated exposure to multiple different trauma types predicts symptom complexity as reported by both children and their caretakers. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Near-Field Source Localization Using a Special Cumulant Matrix

    Science.gov (United States)

    Cui, Han; Wei, Gang

    A new near-field source localization algorithm based on a uniform linear array was proposed. The proposed algorithm estimates each parameter separately but does not need pairing parameters. It can be divided into two important steps. The first step is bearing-related electric angle estimation based on the ESPRIT algorithm by constructing a special cumulant matrix. The second step is the other electric angle estimation based on the 1-D MUSIC spectrum. It offers much lower computational complexity than the traditional near-field 2-D MUSIC algorithm and has better performance than the high-order ESPRIT algorithm. Simulation results demonstrate that the performance of the proposed algorithm is close to the Cramer-Rao Bound (CRB).

  19. Cumulative growth of minor hysteresis loops in the Kolmogorov model

    International Nuclear Information System (INIS)

    Meilikhov, E. Z.; Farzetdinova, R. M.

    2013-01-01

    The phenomenon of nonrepeatability of successive remagnetization cycles in Co/M (M = Pt, Pd, Au) multilayer film structures is explained in the framework of the Kolmogorov crystallization model. It is shown that this model of phase transitions can be adapted so as to adequately describe the process of magnetic relaxation in the indicated systems with “memory.” For this purpose, it is necessary to introduce some additional elements into the model, in particular, (i) to take into account the fact that every cycle starts from a state “inherited” from the preceding cycle and (ii) to assume that the rate of growth of a new magnetic phase depends on the cycle number. This modified model provides a quite satisfactory qualitative and quantitative description of all features of successive magnetic relaxation cycles in the system under consideration, including the surprising phenomenon of cumulative growth of minor hysteresis loops.

  20. Cumulative protons in 12C fragmentation at intermediate energy

    International Nuclear Information System (INIS)

    Abramov, B.M.; Alekseev, P.N.; Borodin, Y.A.; Bulychjov, S.A.; Dukhovskoi, I.A.; Khanov, A.I.; Krutenkova, A.P.; Kulikov, V.V.; Martemianov, M.A.; Matsuk, M.A.; Turdakina, E.N.

    2014-01-01

    In the FRAGM experiment at heavy ion accelerator complex TWAC-ITEP, the proton yields at an angle 3.5 degrees have been measured in fragmentation of carbon ions at T 0 equals 0.3, 0.6, 0.95 and 2.0 GeV/nucleon on beryllium target. The data are presented as invariant proton yields on cumulative variable x in the range 0.9 < x < 2.4. Proton spectra cover six orders of invariant cross section magnitude. They have been analyzed in the framework of quark cluster fragmentation model. Fragmentation functions of quark- gluon string model are used. The probabilities of the existence of multi-quark clusters in carbon nuclei are estimated to be 8 - 12% for six-quark clusters and 0.2 - 0.6% for nine- quark clusters. (authors)

  1. Ratcheting up the ratchet: on the evolution of cumulative culture.

    Science.gov (United States)

    Tennie, Claudio; Call, Josep; Tomasello, Michael

    2009-08-27

    Some researchers have claimed that chimpanzee and human culture rest on homologous cognitive and learning mechanisms. While clearly there are some homologous mechanisms, we argue here that there are some different mechanisms at work as well. Chimpanzee cultural traditions represent behavioural biases of different populations, all within the species' existing cognitive repertoire (what we call the 'zone of latent solutions') that are generated by founder effects, individual learning and mostly product-oriented (rather than process-oriented) copying. Human culture, in contrast, has the distinctive characteristic that it accumulates modifications over time (what we call the 'ratchet effect'). This difference results from the facts that (i) human social learning is more oriented towards process than product and (ii) unique forms of human cooperation lead to active teaching, social motivations for conformity and normative sanctions against non-conformity. Together, these unique processes of social learning and cooperation lead to humans' unique form of cumulative cultural evolution.

  2. EXPERIMENTAL VALIDATION OF CUMULATIVE SURFACE LOCATION ERROR FOR TURNING PROCESSES

    Directory of Open Access Journals (Sweden)

    Adam K. Kiss

    2016-02-01

    Full Text Available The aim of this study is to create a mechanical model which is suitable to investigate the surface quality in turning processes, based on the Cumulative Surface Location Error (CSLE, which describes the series of the consecutive Surface Location Errors (SLE in roughing operations. In the established model, the investigated CSLE depends on the currently and the previously resulted SLE by means of the variation of the width of cut. The phenomenon of the system can be described as an implicit discrete map. The stationary Surface Location Error and its bifurcations were analysed and flip-type bifurcation was observed for CSLE. Experimental verification of the theoretical results was carried out.

  3. Ratcheting up the ratchet: on the evolution of cumulative culture

    Science.gov (United States)

    Tennie, Claudio; Call, Josep; Tomasello, Michael

    2009-01-01

    Some researchers have claimed that chimpanzee and human culture rest on homologous cognitive and learning mechanisms. While clearly there are some homologous mechanisms, we argue here that there are some different mechanisms at work as well. Chimpanzee cultural traditions represent behavioural biases of different populations, all within the species’ existing cognitive repertoire (what we call the ‘zone of latent solutions’) that are generated by founder effects, individual learning and mostly product-oriented (rather than process-oriented) copying. Human culture, in contrast, has the distinctive characteristic that it accumulates modifications over time (what we call the ‘ratchet effect’). This difference results from the facts that (i) human social learning is more oriented towards process than product and (ii) unique forms of human cooperation lead to active teaching, social motivations for conformity and normative sanctions against non-conformity. Together, these unique processes of social learning and cooperation lead to humans’ unique form of cumulative cultural evolution. PMID:19620111

  4. Cumulative neutrino background from quasar-driven outflows

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiawei; Loeb, Abraham, E-mail: xiawei.wang@cfa.harvard.edu, E-mail: aloeb@cfa.harvard.edu [Department of Astronomy, Harvard University, 60 Garden Street, Cambridge, MA 02138 (United States)

    2016-12-01

    Quasar-driven outflows naturally account for the missing component of the extragalactic γ-ray background through neutral pion production in interactions between protons accelerated by the forward outflow shock and interstellar protons. We study the simultaneous neutrino emission by the same protons. We adopt outflow parameters that best fit the extragalactic γ-ray background data and derive a cumulative neutrino background of ∼ 10{sup −7} GeV cm{sup −2} s{sup −1} sr{sup −1} at neutrino energies E {sub ν} ∼> 10 TeV, which naturally explains the most recent IceCube data without tuning any free parameters. The link between the γ-ray and neutrino emission from quasar outflows can be used to constrain the high-energy physics of strong shocks at cosmological distances.

  5. Using Fuzzy Probability Weights in Cumulative Prospect Theory

    Directory of Open Access Journals (Sweden)

    Užga-Rebrovs Oļegs

    2016-12-01

    Full Text Available During the past years, a rapid growth has been seen in the descriptive approaches to decision choice. As opposed to normative expected utility theory, these approaches are based on the subjective perception of probabilities by the individuals, which takes place in real situations of risky choice. The modelling of this kind of perceptions is made on the basis of probability weighting functions. In cumulative prospect theory, which is the focus of this paper, decision prospect outcome weights are calculated using the obtained probability weights. If the value functions are constructed in the sets of positive and negative outcomes, then, based on the outcome value evaluations and outcome decision weights, generalised evaluations of prospect value are calculated, which are the basis for choosing an optimal prospect.

  6. Modelling the evolution and diversity of cumulative culture

    Science.gov (United States)

    Enquist, Magnus; Ghirlanda, Stefano; Eriksson, Kimmo

    2011-01-01

    Previous work on mathematical models of cultural evolution has mainly focused on the diffusion of simple cultural elements. However, a characteristic feature of human cultural evolution is the seemingly limitless appearance of new and increasingly complex cultural elements. Here, we develop a general modelling framework to study such cumulative processes, in which we assume that the appearance and disappearance of cultural elements are stochastic events that depend on the current state of culture. Five scenarios are explored: evolution of independent cultural elements, stepwise modification of elements, differentiation or combination of elements and systems of cultural elements. As one application of our framework, we study the evolution of cultural diversity (in time as well as between groups). PMID:21199845

  7. Optimal execution with price impact under Cumulative Prospect Theory

    Science.gov (United States)

    Zhao, Jingdong; Zhu, Hongliang; Li, Xindan

    2018-01-01

    Optimal execution of a stock (or portfolio) has been widely studied in academia and in practice over the past decade, and minimizing transaction costs is a critical point. However, few researchers consider the psychological factors for the traders. What are traders truly concerned with - buying low in the paper accounts or buying lower compared to others? We consider the optimal trading strategies in terms of the price impact and Cumulative Prospect Theory and identify some specific properties. Our analyses indicate that a large proportion of the execution volume is distributed at both ends of the transaction time. But the trader's optimal strategies may not be implemented at the same transaction size and speed in different market environments.

  8. Practical management of cumulative anthropogenic impacts with working marine examples

    DEFF Research Database (Denmark)

    Kyhn, Line Anker; Wright, Andrew J.

    2014-01-01

    for petroleum. Human disturbances, including the noise almost ubiquitously associated with human activity, are likely to increase the incidence, magnitude, and duration of adverse effects on marine life, including stress responses. Stress responses have the potential to induce fitness consequences...... on impact can be facilitated through implementation of regular application cycles for project authorization or improved programmatic and aggregated impact assessments that simultaneously consider multiple projects. Cross-company collaborations and a better incorporation of uncertainty into decision making...... could also help limit, if not reduce, cumulative impacts of multiple human activities. These simple management steps may also form the basis of a rudimentary form of marine spatial planning and could be used in support of future ecosystem-based management efforts....

  9. Practical management of cumulative anthropogenic impacts with working marine examples.

    Science.gov (United States)

    Wright, Andrew J; Kyhn, Line A

    2015-04-01

    Human pressure on the environment is expanding and intensifying, especially in coastal and offshore areas. Major contributors to this are the current push for offshore renewable energy sources, which are thought of as environmentally friendly sources of power, as well as the continued demand for petroleum. Human disturbances, including the noise almost ubiquitously associated with human activity, are likely to increase the incidence, magnitude, and duration of adverse effects on marine life, including stress responses. Stress responses have the potential to induce fitness consequences for individuals, which add to more obvious directed takes (e.g., hunting or fishing) to increase the overall population-level impact. To meet the requirements of marine spatial planning and ecosystem-based management, many efforts are ongoing to quantify the cumulative impacts of all human actions on marine species or populations. Meanwhile, regulators face the challenge of managing these accumulating and interacting impacts with limited scientific guidance. We believe there is scientific support for capping the level of impact for (at a minimum) populations in decline or with unknown statuses. This cap on impact can be facilitated through implementation of regular application cycles for project authorization or improved programmatic and aggregated impact assessments that simultaneously consider multiple projects. Cross-company collaborations and a better incorporation of uncertainty into decision making could also help limit, if not reduce, cumulative impacts of multiple human activities. These simple management steps may also form the basis of a rudimentary form of marine spatial planning and could be used in support of future ecosystem-based management efforts. © 2014 Society for Conservation Biology.

  10. Economic and policy implications of the cumulative carbon budget

    Science.gov (United States)

    Allen, M. R.; Otto, F. E. L.; Otto, A.; Hepburn, C.

    2014-12-01

    The importance of cumulative carbon emissions in determining long-term risks of climate change presents considerable challenges to policy makers. The traditional notion of "total CO2-equivalent emissions", which forms the backbone of agreements such as the Kyoto Protocol and the European Emissions Trading System, is fundamentally flawed. Measures to reduce short-lived climate pollutants benefit the current generation, while measures to reduce long-lived climate pollutants benefit future generations, so there is no sense in which they can ever be considered equivalent. Debates over the correct metric used to compute CO2-equivalence are thus entirely moot: both long-lived and short-lived emissions will need to be addressed if all generations are to be protected from dangerous climate change. As far as long-lived climate pollutants are concerned, the latest IPCC report highlights the overwhelming importance of carbon capture and storage in determining the cost of meeting the goal of limiting anthropogenic warming to two degrees. We will show that this importance arises directly from the cumulative carbon budget and the role of CCS as the technology of last resort before economic activity needs to be restricted to meet ambitious climate targets. It highlights the need to increase the rate of CCS deployment by orders of magnitude if the option of avoiding two degrees is to be retained. The difficulty of achieving this speed of deployment through conventional incentives and carbon-pricing mechanisms suggests a need for a much more direct mandatory approach. Despite their theoretical economic inefficiency, the success of recent regulatory measures in achieving greenhouse gas emissions reductions in jurisdictions such as the United States suggests an extension of the regulatory approach could be a more effective and politically acceptable means of achieving adequately rapid CCS deployment than conventional carbon taxes or cap-and-trade systems.

  11. Instrumental variables estimation of exposure effects on a time-to-event endpoint using structural cumulative survival models

    DEFF Research Database (Denmark)

    Martinussen, Torben; Vansteelandt, Stijn; Tchetgen Tchetgen, Eric J.

    2017-01-01

    The use of instrumental variables for estimating the effect of an exposure on an outcome is popular in econometrics, and increasingly so in epidemiology. This increasing popularity may be attributed to the natural occurrence of instrumental variables in observational studies that incorporate elem...

  12. Standard model group: Survival of the fittest

    Science.gov (United States)

    Nielsen, H. B.; Brene, N.

    1983-09-01

    The essential content of this paper is related to random dynamics. We speculate that the world seen through a sub-Planck-scale microscope has a lattice structure and that the dynamics on this lattice is almost completely random, except for the requirement that the random (plaquette) action is invariant under some "world (gauge) group". We see that the randomness may lead to spontaneous symmetry breakdown in the vacuum (spontaneous collapse) without explicit appeal to any scalar field associated with the usual Higgs mechanism. We further argue that the subgroup which survives as the end product of a possible chain of collapses is likely to have certain properties; the most important is that it has a topologically connected center. The standard group, i.e. the group of the gauge theory which combines the Salam-Weinberg model with QCD, has this property.

  13. Standard model group: survival of the fittest

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, H.B. (Niels Bohr Inst., Copenhagen (Denmark); Nordisk Inst. for Teoretisk Atomfysik, Copenhagen (Denmark)); Brene, N. (Niels Bohr Inst., Copenhagen (Denmark))

    1983-09-19

    The essential content of this paper is related to random dynamics. We speculate that the world seen through a sub-Planck-scale microscope has a lattice structure and that the dynamics on this lattice is almost completely random, except for the requirement that the random (plaquette) action is invariant under some ''world (gauge) group''. We see that the randomness may lead to spontaneous symmetry breakdown in the vacuum (spontaneous collapse) without explicit appeal to any scalar field associated with the usual Higgs mechanism. We further argue that the subgroup which survives as the end product of a possible chain of collapse is likely to have certain properties; the most important is that it has a topologically connected center. The standard group, i.e. the group of the gauge theory which combines the Salam-Weinberg model with QCD, has this property.

  14. Standard model group: survival of the fittest

    International Nuclear Information System (INIS)

    Nielsen, H.B.; Brene, N.

    1983-01-01

    Th essential content of this paper is related to random dynamics. We speculate that the world seen through a sub-Planck-scale microscope has a lattice structure and that the dynamics on this lattice is almost completely random, except for the requirement that the random (plaquette) action is invariant under some ''world (gauge) group''. We see that the randomness may lead to spontaneous symmetry breakdown in the vacuum (spontaneous collapse) without explicit appeal to any scalar field associated with the usual Higgs mechanism. We further argue that the subgroup which survives as the end product of a possible chain of collapse is likely to have certain properties; the most important is that it has a topologically connected center. The standard group, i.e. the group of the gauge theory which combines the Salam-Weinberg model with QCD, has this property. (orig.)

  15. Standard model group survival of the fittest

    International Nuclear Information System (INIS)

    Nielsen, H.B.; Brene, N.

    1983-02-01

    The essential content of this note is related to random dynamics. The authors speculate that the world seen through a sub Planck scale microscope has a lattice structure and that the dynamics on this lattice is almost completely random, except for the requirement that the random (plaquette) action is invariant under some ''world (gauge) group''. It is seen that the randomness may lead to spontaneous symmetry breakdown in the vacuum (spontaneous collapse) without explicit appeal to any scalar field associated with the usual Higgs mechanism. It is further argued that the subgroup which survives as the end product of a possible chain of collapses is likely to have certain properties; the most important is that it has a topologically connected center. The standard group, i.e. the group of the gauge theory which combines the Salam-Weinberg model with QCD, has this property. (Auth.)

  16. The Brain in Congenital Heart Disease across the Lifespan: The Cumulative Burden of Injury

    Science.gov (United States)

    Marelli, Ariane; Miller, Steven P.; Marino, Bradley Scott; Jefferson, Angela L.; Newburger, Jane W.

    2017-01-01

    The number of patients surviving with congenital heart disease (CHD) has soared over the last three decades. Adults constitute the fastest growing segment of the CHD population, now outnumbering children. Research to date on the heart-brain intersection in this population has largely been focused on neurodevelopmental outcomes in childhood and adolescence. Mutations in genes that are highly expressed in heart and brain may cause cerebral dysgenesis. Together with altered cerebral perfusion in utero, these factors are associated with abnormalities of brain structure and brain immaturity in a significant portion of neonates with critical CHD even before they undergo cardiac surgery. In infancy and childhood, the brain may be affected by risk factors related to heart disease itself or to its interventional treatments. As children with CHD become adults, they increasingly develop heart failure, atrial fibrillation, hypertension, diabetes and coronary disease. These acquired cardiovascular comorbidities can be expected to have effects similar to those in the general population on cerebral blood flow, brain volumes, and dementia. In both children and adults, cardiovascular disease may have adverse effects on achievement, executive function, memory, language, social interactions, and quality of life. In summary, against the backdrop of shifting demographics, risk factors for brain injury in the CHD population are cumulative and synergistic. As neurodevelopmental sequelae in children with CHD evolve to cognitive decline or dementia during adulthood, a growing population of CHD can be expected to require support services. We highlight evidence gaps and future research directions. PMID:27185022

  17. Setting the stage for chronic health problems: cumulative childhood adversity among homeless adults with mental illness in Vancouver, British Columbia.

    Science.gov (United States)

    Patterson, Michelle L; Moniruzzaman, Akm; Somers, Julian M

    2014-04-12

    It is well documented that childhood abuse, neglect and household dysfunction are disproportionately present in the backgrounds of homeless adults, and that these experiences adversely impact child development and a wide range of adult outcomes. However, few studies have examined the cumulative impact of adverse childhood experiences on homeless adults with mental illness. This study examines adverse events in childhood as predictors of duration of homelessness, psychiatric and substance use disorders, and physical health in a sample of homeless adults with mental illness. This study was conducted using baseline data from a randomized controlled trial in Vancouver, British Columbia for participants who completed the Adverse Childhood Experiences (ACE) scale at 18 months follow-up (n=364). Primary outcomes included current mental disorders; substance use including type, frequency and severity; physical health; duration of homelessness; and vocational functioning. In multivariable regression models, ACE total score independently predicted a range of mental health, physical health, and substance use problems, and marginally predicted duration of homelessness. Adverse childhood experiences are overrepresented among homeless adults with complex comorbidities and chronic homelessness. Our findings are consistent with a growing body of literature indicating that childhood traumas are potent risk factors for a number of adult health and psychiatric problems, particularly substance use problems. Results are discussed in the context of cumulative adversity and self-trauma theory. This trial has been registered with the International Standard Randomized Control Trial Number Register and assigned ISRCTN42520374.

  18. Network ties and survival

    DEFF Research Database (Denmark)

    Acheampong, George; Narteh, Bedman; Rand, John

    2017-01-01

    Poultry farming has been touted as one of the major ways by which poverty can be reduced in low-income economies like Ghana. Yet, anecdotally there is a high failure rate among these poultry farms. This current study seeks to understand the relationship between network ties and survival chances...... of small commercial poultry farms (SCPFs). We utilize data from a 2-year network survey of SCPFs in rural Ghana. The survival of these poultry farms are modelled using a lagged probit model of farms that persisted from 2014 into 2015. We find that network ties are important to the survival chances...... but this probability reduces as the number of industry ties increases but moderation with dynamic capability of the firm reverses this trend. Our findings show that not all network ties aid survival and therefore small commercial poultry farmers need to be circumspect in the network ties they cultivate and develop....

  19. Survival of falling robots

    Science.gov (United States)

    Cameron, Jonathan M.; Arkin, Ronald C.

    1992-01-01

    As mobile robots are used in more uncertain and dangerous environments, it will become important to design them so that they can survive falls. In this paper, we examine a number of mechanisms and strategies that animals use to withstand these potentially catastrophic events and extend them to the design of robots. A brief survey of several aspects of how common cats survive falls provides an understanding of the issues involved in preventing traumatic injury during a falling event. After outlining situations in which robots might fall, a number of factors affecting their survival are described. From this background, several robot design guidelines are derived. These include recommendations for the physical structure of the robot as well as requirements for the robot control architecture. A control architecture is proposed based on reactive control techniques and action-oriented perception that is geared to support this form of survival behavior.

  20. Survivability and Hope

    Science.gov (United States)

    ... Current Issue Past Issues Special Section Survivability and Hope Past Issues / Spring 2007 Table of Contents For ... cure or long-term survivorship." This message of hope is a hallmark of the latest advances in ...

  1. Survival of falling robots

    Science.gov (United States)

    Cameron, Jonathan M.; Arkin, Ronald C.

    1992-02-01

    As mobile robots are used in more uncertain and dangerous environments, it will become important to design them so that they can survive falls. In this paper, we examine a number of mechanisms and strategies that animals use to withstand these potentially catastrophic events and extend them to the design of robots. A brief survey of several aspects of how common cats survive falls provides an understanding of the issues involved in preventing traumatic injury during a falling event. After outlining situations in which robots might fall, a number of factors affecting their survival are described. From this background, several robot design guidelines are derived. These include recommendations for the physical structure of the robot as well as requirements for the robot control architecture. A control architecture is proposed based on reactive control techniques and action-oriented perception that is geared to support this form of survival behavior.

  2. Survival and maturation rates of the African rodent Mastomys natalensis

    DEFF Research Database (Denmark)

    Sluydts, Vincent; Crespin, Laurent; Davis, Stephen

    2008-01-01

    the model fit. On the other hand we showed that maturation rates were correlated negatively with density the previous month and positively to cumulative rainfall over the past three months. Survival estimates of both adults and subadults varied seasonally, with higher estimates during the increase phase......Survival and maturation rates of female Mastomys natalensis were analysed based on a ten-year onthly capture-recapture data set. We investigated whether direct and delayed density dependent and independent (rainfall) variables accounted for the considerable variation in demographic traits....... It was estimated that seasonal and annual covariates accounted for respectively 29 and 26% of the total variation in maturation rates and respectively 17 and 11% of the variation in survival rates. Explaining the between-year differences in maturation rates with annual past rainfall or density did not improve...

  3. Random magnetism

    International Nuclear Information System (INIS)

    Tahir-Kheli, R.A.

    1975-01-01

    A few simple problems relating to random magnetic systems are presented. Translational symmetry, only on the macroscopic scale, is assumed for these systems. A random set of parameters, on the microscopic scale, for the various regions of these systems is also assumed. A probability distribution for randomness is obeyed. Knowledge of the form of these probability distributions, is assumed in all cases [pt

  4. Role of Aspirin in Breast Cancer Survival.

    Science.gov (United States)

    Chen, Wendy Y; Holmes, Michelle D

    2017-07-01

    Chemotherapy and hormonal therapy have significantly decreased breast cancer mortality, although with considerable side effects and financial costs. In the USA, over three million women are living after a breast cancer diagnosis and are eager for new treatments that are low in toxicity and cost. Multiple observational studies have reported improved breast cancer survival with regular aspirin use. Furthermore, pooled data from five large randomized trials of aspirin for cardiovascular disease showed that subjects on aspirin had decreased risk of cancer mortality and decreased risk of metastatic cancer. Although the potential mechanism for aspirin preventing breast cancer is not known, possible pathways may involve platelets, inflammation, cyclooxygenase (COX) 2, hormones, or PI3 kinase. This review article summarizes the current epidemiologic and clinical trial evidence as well as possible underlying mechanisms that justify current phase III randomized trials of aspirin to improve breast cancer survival.

  5. Analysis of LDPE-ZnO-clay nanocomposites using novel cumulative rheological parameters

    Science.gov (United States)

    Kracalik, Milan

    2017-05-01

    Polymer nanocomposites exhibit complex rheological behaviour due to physical and also possibly chemical interactions between individual phases. Up to now, rheology of dispersive polymer systems has been usually described by evaluation of viscosity curve (shear thinning phenomenon), storage modulus curve (formation of secondary plateau) or plotting information about dumping behaviour (e.g. Van Gurp-Palmen-plot, comparison of loss factor tan δ). On the contrary to evaluation of damping behaviour, values of cot δ were calculated and called as "storage factor", analogically to loss factor. Then values of storage factor were integrated over specific frequency range and called as "cumulative storage factor". In this contribution, LDPE-ZnO-clay nanocomposites with different dispersion grades (physical networks) have been prepared and characterized by both conventional as well as novel analysis approach. Next to cumulative storage factor, further cumulative rheological parameters like cumulative complex viscosity, cumulative complex modulus or cumulative storage modulus have been introduced.

  6. Randomized random walk on a random walk

    International Nuclear Information System (INIS)

    Lee, P.A.

    1983-06-01

    This paper discusses generalizations of the model introduced by Kehr and Kunter of the random walk of a particle on a one-dimensional chain which in turn has been constructed by a random walk procedure. The superimposed random walk is randomised in time according to the occurrences of a stochastic point process. The probability of finding the particle in a particular position at a certain instant is obtained explicitly in the transform domain. It is found that the asymptotic behaviour for large time of the mean-square displacement of the particle depends critically on the assumed structure of the basic random walk, giving a diffusion-like term for an asymmetric walk or a square root law if the walk is symmetric. Many results are obtained in closed form for the Poisson process case, and these agree with those given previously by Kehr and Kunter. (author)

  7. Cumulative Author Index for Soviet Laser Bibliographies Nos. 67-93, September 1983-February 1989

    Science.gov (United States)

    1990-02-01

    C) 0 00 I: Cumulative Author Index for Soviet Laser Bibliographies September 1983 - February 1989 A Defense S&T Intelligence Special Purpose Document...90 CUMULATIVE AUTHOR INDEX FOR SOVIET LASER BIBLIOGRAPHIES Nos. 67-93 SEPTEMBER 1983 - FEBRUARY 1989 Date of Report March 31, 19 Vice Director for...RECIPIENT’S CATALOG NUMBER DST-2700Z-001-90 4. TITLE (and Subtitle) S. TYPE OF REPORT & PERIOD COVERED CUMULATIVE AUTHOR INDEX FOR SOVIET LASER

  8. Fatigue Reliability under Random Loads

    DEFF Research Database (Denmark)

    Talreja, R.

    1979-01-01

    We consider the problem of estimating the probability of survival (non-failure) and the probability of safe operation (strength greater than a limiting value) of structures subjected to random loads. These probabilities are formulated in terms of the probability distributions of the loads...... propagation stage. The consequences of this behaviour on the fatigue reliability are discussed....

  9. High selection pressure promotes increase in cumulative adaptive culture.

    Directory of Open Access Journals (Sweden)

    Carolin Vegvari

    Full Text Available The evolution of cumulative adaptive culture has received widespread interest in recent years, especially the factors promoting its occurrence. Current evolutionary models suggest that an increase in population size may lead to an increase in cultural complexity via a higher rate of cultural transmission and innovation. However, relatively little attention has been paid to the role of natural selection in the evolution of cultural complexity. Here we use an agent-based simulation model to demonstrate that high selection pressure in the form of resource pressure promotes the accumulation of adaptive culture in spite of small population sizes and high innovation costs. We argue that the interaction of demography and selection is important, and that neither can be considered in isolation. We predict that an increase in cultural complexity is most likely to occur under conditions of population pressure relative to resource availability. Our model may help to explain why culture change can occur without major environmental change. We suggest that understanding the interaction between shifting selective pressures and demography is essential for explaining the evolution of cultural complexity.

  10. Cumulative sum quality control for calibrated breast density measurements

    International Nuclear Information System (INIS)

    Heine, John J.; Cao Ke; Beam, Craig

    2009-01-01

    Purpose: Breast density is a significant breast cancer risk factor. Although various methods are used to estimate breast density, there is no standard measurement for this important factor. The authors are developing a breast density standardization method for use in full field digital mammography (FFDM). The approach calibrates for interpatient acquisition technique differences. The calibration produces a normalized breast density pixel value scale. The method relies on first generating a baseline (BL) calibration dataset, which required extensive phantom imaging. Standardizing prospective mammograms with calibration data generated in the past could introduce unanticipated error in the standardized output if the calibration dataset is no longer valid. Methods: Sample points from the BL calibration dataset were imaged approximately biweekly over an extended timeframe. These serial samples were used to evaluate the BL dataset reproducibility and quantify the serial calibration accuracy. The cumulative sum (Cusum) quality control method was used to evaluate the serial sampling. Results: There is considerable drift in the serial sample points from the BL calibration dataset that is x-ray beam dependent. Systematic deviation from the BL dataset caused significant calibration errors. This system drift was not captured with routine system quality control measures. Cusum analysis indicated that the drift is a sign of system wear and eventual x-ray tube failure. Conclusions: The BL calibration dataset must be monitored and periodically updated, when necessary, to account for sustained system variations to maintain the calibration accuracy.

  11. Cumulative sum quality control for calibrated breast density measurements

    Energy Technology Data Exchange (ETDEWEB)

    Heine, John J.; Cao Ke; Beam, Craig [Cancer Prevention and Control Division, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, Florida 33612 (United States); Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, 1603 W. Taylor St., Chicago, Illinois 60612 (United States)

    2009-12-15

    Purpose: Breast density is a significant breast cancer risk factor. Although various methods are used to estimate breast density, there is no standard measurement for this important factor. The authors are developing a breast density standardization method for use in full field digital mammography (FFDM). The approach calibrates for interpatient acquisition technique differences. The calibration produces a normalized breast density pixel value scale. The method relies on first generating a baseline (BL) calibration dataset, which required extensive phantom imaging. Standardizing prospective mammograms with calibration data generated in the past could introduce unanticipated error in the standardized output if the calibration dataset is no longer valid. Methods: Sample points from the BL calibration dataset were imaged approximately biweekly over an extended timeframe. These serial samples were used to evaluate the BL dataset reproducibility and quantify the serial calibration accuracy. The cumulative sum (Cusum) quality control method was used to evaluate the serial sampling. Results: There is considerable drift in the serial sample points from the BL calibration dataset that is x-ray beam dependent. Systematic deviation from the BL dataset caused significant calibration errors. This system drift was not captured with routine system quality control measures. Cusum analysis indicated that the drift is a sign of system wear and eventual x-ray tube failure. Conclusions: The BL calibration dataset must be monitored and periodically updated, when necessary, to account for sustained system variations to maintain the calibration accuracy.

  12. Cumulative biological impacts of The Geysers geothermal development

    Energy Technology Data Exchange (ETDEWEB)

    Brownell, J.A.

    1981-10-01

    The cumulative nature of current and potential future biological impacts from full geothermal development in the steam-dominated portion of The Geysers-Calistoga KGRA are identified by the California Energy Commission staff. Vegetation, wildlife, and aquatic resources information have been reviewed and evaluated. Impacts and their significance are discussed and staff recommendations presented. Development of 3000 MW of electrical energy will result in direct vegetation losses of 2790 acres, based on an estimate of 11.5% loss per lease-hold of 0.93 acres/MW. If unmitigated, losses will be greater. Indirect vegetation losses and damage occur from steam emissions which contain elements (particularly boron) toxic to vegetation. Other potential impacts include chronic low-level boron exposure, acid rain, local climate modification, and mechanical damage. A potential exists for significant reduction and changes in wildlife from direct habitat loss and development influences. Highly erosive soils create the potential for significant reduction of aquatic resources, particularly game fish. Toxic spills have caused some temporary losses of aquatic species. Staff recommends monitoring and implementation of mitigation measures at all geothermal development stages.

  13. Estimation of Cumulative Absolute Velocity using Empirical Green's Function Method

    International Nuclear Information System (INIS)

    Park, Dong Hee; Yun, Kwan Hee; Chang, Chun Joong; Park, Se Moon

    2009-01-01

    In recognition of the needs to develop a new criterion for determining when the OBE (Operating Basis Earthquake) has been exceeded at nuclear power plants, Cumulative Absolute Velocity (CAV) was introduced by EPRI. The concept of CAV is the area accumulation with the values more than 0.025g occurred during every one second. The equation of the CAV is as follows. CAV = ∫ 0 max |a(t)|dt (1) t max = duration of record, a(t) = acceleration (>0.025g) Currently, the OBE exceedance criteria in Korea is Peak Ground Acceleration (PGA, PGA>0.1g). When Odesan earthquake (M L =4.8, January 20th, 2007) and Gyeongju earthquake (M L =3.4, June 2nd, 1999) were occurred, we have had already experiences of PGA greater than 0.1g that did not even cause any damage to the poorly-designed structures nearby. This moderate earthquake has motivated Korea to begin the use of the CAV for OBE exceedance criteria for NPPs. Because the present OBE level has proved itself to be a poor indicator for small-to-moderate earthquakes, for which the low OBE level can cause an inappropriate shut down the plant. A more serious possibility is that this scenario will become a reality at a very high level. Empirical Green's Function method was a simulation technique which can estimate the CAV value and it is hereby introduced

  14. Cumulative causation, market transition, and emigration from China.

    Science.gov (United States)

    Liang, Zai; Chunyu, Miao David; Zhuang, Guotu; Ye, Wenzhen

    2008-11-01

    This article reports findings from a recent survey of international migration from China's Fujian Province to the United States. Using the ethnosurvey approach developed in the Mexican Migration Project, the authors conducted surveys in migrant-sending communities in China as well as in destination communities in New York City. Hypotheses are derived from the international migration literature and the market transition debate. The results are generally consistent with hypotheses derived from cumulative causation of migration; however, geographical location creates some differences in migration patterns to the United States. In China as in Mexico, the existence of migration networks increases the propensity of migration for others in the community. In contrast to the Mexican case, among Chinese immigrants, having a previously migrated household member increases the propensity of other household members to migrate only after the debt for previous migration is paid off. In step with market transition theory, the authors also find that political power influences the migration experience from the coastal Fujian Province.

  15. Correlated stopping, proton clusters and higher order proton cumulants

    Energy Technology Data Exchange (ETDEWEB)

    Bzdak, Adam [AGH University of Science and Technology, Faculty of Physics and Applied Computer Science, Krakow (Poland); Koch, Volker [Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Skokov, Vladimir [RIKEN/BNL, Brookhaven National Laboratory, Upton, NY (United States)

    2017-05-15

    We investigate possible effects of correlations between stopped nucleons on higher order proton cumulants at low energy heavy-ion collisions. We find that fluctuations of the number of wounded nucleons N{sub part} lead to rather nontrivial dependence of the correlations on the centrality; however, this effect is too small to explain the large and positive four-proton correlations found in the preliminary data collected by the STAR collaboration at √(s) = 7.7 GeV. We further demonstrate that, by taking into account additional proton clustering, we are able to qualitatively reproduce the preliminary experimental data. We speculate that this clustering may originate either from collective/multi-collision stopping which is expected to be effective at lower energies or from a possible first-order phase transition, or from (attractive) final state interactions. To test these ideas we propose to measure a mixed multi-particle correlation between stopped protons and a produced particle (e.g. pion, antiproton). (orig.)

  16. Decision making generalized by a cumulative probability weighting function

    Science.gov (United States)

    dos Santos, Lindomar Soares; Destefano, Natália; Martinez, Alexandre Souto

    2018-01-01

    Typical examples of intertemporal decision making involve situations in which individuals must choose between a smaller reward, but more immediate, and a larger one, delivered later. Analogously, probabilistic decision making involves choices between options whose consequences differ in relation to their probability of receiving. In Economics, the expected utility theory (EUT) and the discounted utility theory (DUT) are traditionally accepted normative models for describing, respectively, probabilistic and intertemporal decision making. A large number of experiments confirmed that the linearity assumed by the EUT does not explain some observed behaviors, as nonlinear preference, risk-seeking and loss aversion. That observation led to the development of new theoretical models, called non-expected utility theories (NEUT), which include a nonlinear transformation of the probability scale. An essential feature of the so-called preference function of these theories is that the probabilities are transformed by decision weights by means of a (cumulative) probability weighting function, w(p) . We obtain in this article a generalized function for the probabilistic discount process. This function has as particular cases mathematical forms already consecrated in the literature, including discount models that consider effects of psychophysical perception. We also propose a new generalized function for the functional form of w. The limiting cases of this function encompass some parametric forms already proposed in the literature. Far beyond a mere generalization, our function allows the interpretation of probabilistic decision making theories based on the assumption that individuals behave similarly in the face of probabilities and delays and is supported by phenomenological models.

  17. New tests of cumulative prospect theory and the priority heuristic

    Directory of Open Access Journals (Sweden)

    Michael H. Birnbaum

    2008-04-01

    Full Text Available Previous tests of cumulative prospect theory (CPT and of the priority heuristic (PH found evidence contradicting these two models of risky decision making. However, those tests were criticized because they had characteristics that might ``trigger'' use of other heuristics. This paper presents new tests that avoid those characteristics. Expected values of the gambles are nearly equal in each choice. In addition, if a person followed expected value (EV, expected utility (EU, CPT, or PH in these tests, she would shift her preferences in the same direction as shifts in EV or EU. In contrast, the transfer of attention exchange model (TAX and a similarity model predict that people will reverse preferences in the opposite direction. Results contradict the PH, even when PH is modified to include a preliminary similarity evaluation using the PH parameters. New tests of probability-consequence interaction were also conducted. Strong interactions were observed, contrary to PH. These results add to the growing bodies of evidence showing that neither CPT nor PH is an accurate description of risky decision making.

  18. Model-checking techniques based on cumulative residuals.

    Science.gov (United States)

    Lin, D Y; Wei, L J; Ying, Z

    2002-03-01

    Residuals have long been used for graphical and numerical examinations of the adequacy of regression models. Conventional residual analysis based on the plots of raw residuals or their smoothed curves is highly subjective, whereas most numerical goodness-of-fit tests provide little information about the nature of model misspecification. In this paper, we develop objective and informative model-checking techniques by taking the cumulative sums of residuals over certain coordinates (e.g., covariates or fitted values) or by considering some related aggregates of residuals, such as moving sums and moving averages. For a variety of statistical models and data structures, including generalized linear models with independent or dependent observations, the distributions of these stochastic processes tinder the assumed model can be approximated by the distributions of certain zero-mean Gaussian processes whose realizations can be easily generated by computer simulation. Each observed process can then be compared, both graphically and numerically, with a number of realizations from the Gaussian process. Such comparisons enable one to assess objectively whether a trend seen in a residual plot reflects model misspecification or natural variation. The proposed techniques are particularly useful in checking the functional form of a covariate and the link function. Illustrations with several medical studies are provided.

  19. Cumulative damage fraction design approach for LMFBR metallic fuel elements

    International Nuclear Information System (INIS)

    Johnson, D.L.; Einziger, R.E.; Huchman, G.D.

    1979-01-01

    The cumulative damage fraction (CDF) analytical technique is currently being used to analyze the performance of metallic fuel elements for proliferation-resistant LMFBRs. In this technique, the fraction of the total time to rupture of the cladding is calculated as a function of the thermal, stress, and neutronic history. Cladding breach or rupture is implied by CDF = 1. Cladding wastage, caused by interactions with both the fuel and sodium coolant, is assumed to uniformly thin the cladding wall. The irradiation experience of the EBR-II Mark-II driver fuel with solution-annealed Type 316 stainless steel cladding provides an excellent data base for testing the applicability of the CDF technique to metallic fuel. The advanced metal fuels being considered for use in LMFBRs are U-15-Pu-10Zr, Th-20Pu and Th-2OU (compositions are given in weight percent). The two cladding alloys being considered are Type 316 stainless steel and a titanium-stabilized Type 316 stainless steel. Both are in the cold-worked condition. The CDF technique was applied to these fuels and claddings under the assumed steady-state operating conditions

  20. Cumulative exposure to carbon monoxide during the day

    Energy Technology Data Exchange (ETDEWEB)

    Joumard, R. (INRETS, 69 - Bron (FR))

    The carbon monoxide, CO, has the advantage of being very easily and accurately measured under various conditions. In addition, it allows the translation of CO concentrations into their biological effects. The cumulative CO exposure should be considered according to current environment conditions during a given period of life, e.g. the day. In addition, the translation of concentrations and exposure times of CO fixed on blood haemoglobine (carboxyhaemoglobine) depends on physiological factors such as age, size, sex, or physical activity. This paper gives some examples of CO exposure translated into curves of carboxyhaemoglobine: case of 92 persons whose schedule was studied in details, of customs officers whose exposure was measured during one week, or other theoretical cases. In all the cases studied, smoking is by far the first factor of pollution by carbon monoxide. If not considering this case, the CO contents observed are preoccupying for sensitive subjects (in particular children) only in very rare cases. Furthermore, this approach allows the assessment of maximal allowable concentrations during specific exposures (work, e.g. in a tunnel) by integrating them into normal life conditions and population current exposure.

  1. Cumulative incidence of youth obesity is associated with low cardiorespiratory fitness levels and with maternal overweight

    Directory of Open Access Journals (Sweden)

    Anelise Reis Gaya

    2015-12-01

    Full Text Available Abstract This longitudinal study evaluated the association between the incidence of youth overweight/obesity (Ow/Ob and low levels of cardiorespiratory fitness (CRF over 4 years and youths' and their parents' demographic and nutritional characteristics. The randomized sample comprised 398 youth, aged 7-17 years at baseline, from a city in southern Brazil. Subjects were classified as being Ow/Ob according to international body mass index (BMI parameters. Parental weight and height were determined by direct questioning. Youth CRF was measured by a 9-minute walk-and-run test. The cumulative incidences of Ow/Ob and of low CRF levels were 25.1% and 20.5%, respectively. Relative to other youth, youth who were classified as "unhealthy" at baseline (with respect to CRF and by the fourth year were more likely to be classified as Ow/Ob (relative risks: 1.12 and 1.10, respectively. Youth whose mothers were categorized as Ow/Ob were at higher risk of being classified as Ow/Ob than youth whose mothers had normal BMIs (relative risks: 1.19 at baseline and 1.20 in the fourth year. The incidence of Ow/Ob among the former youth was associated with low CRF levels and with maternal Ob.

  2. Probability, conditional probability and complementary cumulative distribution functions in performance assessment for radioactive waste disposal

    Energy Technology Data Exchange (ETDEWEB)

    Helton, J.C. [Arizona State Univ., Tempe, AZ (United States)

    1996-03-01

    A formal description of the structure of several recent performance assessments (PAs) for the Waste Isolation Pilot Plant (WIPP) is given in terms of the following three components: a probability space (S{sub st}, S{sub st}, p{sub st}) for stochastic uncertainty, a probability space (S{sub su}, S{sub su}, p{sub su}) for subjective uncertainty and a function (i.e., a random variable) defined on the product space associated with (S{sub st}, S{sub st}, p{sub st}) and (S{sub su}, S{sub su}, p{sub su}). The explicit recognition of the existence of these three components allows a careful description of the use of probability, conditional probability and complementary cumulative distribution functions within the WIPP PA. This usage is illustrated in the context of the U.S. Environmental Protection Agency`s standard for the geologic disposal of radioactive waste (40 CFR 191, Subpart B). The paradigm described in this presentation can also be used to impose a logically consistent structure on PAs for other complex systems.

  3. Surviving After Suicide

    Science.gov (United States)

    ... fewer tools for communicating their feelings. Surviving After Suicide Fact Sheet 3 Children are especially vulnerable to feelings of guilt and ... to take care of them. Secrecy about the suicide in the hopes of protecting children may cause further complications. Explain the situation and ...

  4. Survivability via Control Objectives

    Energy Technology Data Exchange (ETDEWEB)

    CAMPBELL,PHILIP L.

    2000-08-11

    Control objectives open an additional front in the survivability battle. A given set of control objectives is valuable if it represents good practices, it is complete (it covers all the necessary areas), and it is auditable. CobiT and BS 7799 are two examples of control objective sets.

  5. Education for Survival.

    Science.gov (United States)

    Allen, James E., Jr.

    In this address, James E. Allen, Jr., Assistant Secretary for Education and U.S. Commissioner of Education, discusses the relationship of education to the problem of ecological destruction. He states that the solutions to the problems of air, water, and soil pollution may be found in redirected education. This "education for survival" can serve to…

  6. Artists’ Survival Rate

    DEFF Research Database (Denmark)

    Bille, Trine; Jensen, Søren

    2017-01-01

    The literature of cultural economics generally finds that an artistic education has no significant impact on artists’ income and careers in the arts. In our research, we have readdressed this question by looking at the artists’ survival in the arts occupations. The results show that an artistic...... education has a significant impact on artists’ careers in the arts and we find important industry differences....

  7. The treatment of soft-tissue sarcomas of the extremities - prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy

    International Nuclear Information System (INIS)

    Rosenberg, S.A.; Tepper, J.; Glatstein, E.

    1982-01-01

    Between May 1975 and April 1981, 43 adult patients with high-grade soft tissue sarcomas of the extremities were prospectively randomized to receive either amputation at or above the joint proximal to the tumor, including all involved muscle groups, or to receive a limb-sparing resection plus adjuvant radiation therapy. The limb-sparing resection group received wide local excision followed by 5000 rads to the entire anatomic area at risk for local spread and 6000 to 7000 rads to the tumor bed. Both randomization groups received postoperative chemotherapy with doxorubicin (maximum cumulative dose 550 mg/m 2 ), cyclophosphamide, and high-dose methotrexate. Twenty-seven patients randomized to receive limb-sparing resection and radiotherapy, and 16 received amputation (randomization was 2:1). There were four local recurrences in the limb-sparing group and none in the amputation group (p 1 = 0.06 generalized Wilcoxon test). However, there were no differences in disease-free survival rates (83% and 88% at five years; p 2 = 0.99) between the limb-sparing group and the amputation treatment groups. Multivariate analysis indicated that the only correlate of local recurrence was the final margin of resection. Patients with positive margins of resection had a higher likelihood of local recurrence compared with those with negative margins (p 1 1 = 0.00008) and overall survival (95% vs. 74%; p 1 = 0.04)

  8. Toward computational cumulative biology by combining models of biological datasets.

    Science.gov (United States)

    Faisal, Ali; Peltonen, Jaakko; Georgii, Elisabeth; Rung, Johan; Kaski, Samuel

    2014-01-01

    A main challenge of data-driven sciences is how to make maximal use of the progressively expanding databases of experimental datasets in order to keep research cumulative. We introduce the idea of a modeling-based dataset retrieval engine designed for relating a researcher's experimental dataset to earlier work in the field. The search is (i) data-driven to enable new findings, going beyond the state of the art of keyword searches in annotations, (ii) modeling-driven, to include both biological knowledge and insights learned from data, and (iii) scalable, as it is accomplished without building one unified grand model of all data. Assuming each dataset has been modeled beforehand, by the researchers or automatically by database managers, we apply a rapidly computable and optimizable combination model to decompose a new dataset into contributions from earlier relevant models. By using the data-driven decomposition, we identify a network of interrelated datasets from a large annotated human gene expression atlas. While tissue type and disease were major driving forces for determining relevant datasets, the found relationships were richer, and the model-based search was more accurate than the keyword search; moreover, it recovered biologically meaningful relationships that are not straightforwardly visible from annotations-for instance, between cells in different developmental stages such as thymocytes and T-cells. Data-driven links and citations matched to a large extent; the data-driven links even uncovered corrections to the publication data, as two of the most linked datasets were not highly cited and turned out to have wrong publication entries in the database.

  9. Cumulative childhood stress and autoimmune diseases in adults.

    Science.gov (United States)

    Dube, Shanta R; Fairweather, DeLisa; Pearson, William S; Felitti, Vincent J; Anda, Robert F; Croft, Janet B

    2009-02-01

    To examine whether childhood traumatic stress increased the risk of developing autoimmune diseases as an adult. Retrospective cohort study of 15,357 adult health maintenance organization members enrolled in the Adverse Childhood Experiences (ACEs) Study from 1995 to 1997 in San Diego, California, and eligible for follow-up through 2005. ACEs included childhood physical, emotional, or sexual abuse; witnessing domestic violence; growing up with household substance abuse, mental illness, parental divorce, and/or an incarcerated household member. The total number of ACEs (ACE Score range = 0-8) was used as a measure of cumulative childhood stress. The outcome was hospitalizations for any of 21 selected autoimmune diseases and 4 immunopathology groupings: T- helper 1 (Th1) (e.g., idiopathic myocarditis); T-helper 2 (Th2) (e.g., myasthenia gravis); Th2 rheumatic (e.g., rheumatoid arthritis); and mixed Th1/Th2 (e.g., autoimmune hemolytic anemia). Sixty-four percent reported at least one ACE. The event rate (per 10,000 person-years) for a first hospitalization with any autoimmune disease was 31.4 in women and 34.4 in men. First hospitalizations for any autoimmune disease increased with increasing number of ACEs (p or=2 ACEs were at a 70% increased risk for hospitalizations with Th1, 80% increased risk for Th2, and 100% increased risk for rheumatic diseases (p Childhood traumatic stress increased the likelihood of hospitalization with a diagnosed autoimmune disease decades into adulthood. These findings are consistent with recent biological studies on the impact of early life stress on subsequent inflammatory responses.

  10. Integrating environmental monitoring with cumulative effects management and decision making.

    Science.gov (United States)

    Cronmiller, Joshua G; Noble, Bram F

    2018-05-01

    Cumulative effects (CE) monitoring is foundational to emerging regional and watershed CE management frameworks, yet monitoring is often poorly integrated with CE management and decision-making processes. The challenges are largely institutional and organizational, more so than scientific or technical. Calls for improved integration of monitoring with CE management and decision making are not new, but there has been limited research on how best to integrate environmental monitoring programs to ensure credible CE science and to deliver results that respond to the more immediate questions and needs of regulatory decision makers. This paper examines options for the integration of environmental monitoring with CE frameworks. Based on semistructured interviews with practitioners, regulators, and other experts in the Lower Athabasca, Alberta, Canada, 3 approaches to monitoring system design are presented. First, a distributed monitoring system, reflecting the current approach in the Lower Athabasca, where monitoring is delegated to different external programs and organizations; second, a 1-window system in which monitoring is undertaken by a single, in-house agency for the purpose of informing management and regulatory decision making; third, an independent system driven primarily by CE science and understanding causal relationships, with knowledge adopted for decision support where relevant to specific management questions. The strengths and limitations of each approach are presented. A hybrid approach may be optimal-an independent, nongovernment, 1-window model for CE science, monitoring, and information delivery-capitalizing on the strengths of distributed, 1-window, and independent monitoring systems while mitigating their weaknesses. If governments are committed to solving CE problems, they must invest in the long-term science needed to do so; at the same time, if science-based monitoring programs are to be sustainable over the long term, they must be responsive to

  11. Cumulative Effects of Barriers on the Movements of Forest Birds

    Directory of Open Access Journals (Sweden)

    Marc Bélisle

    2002-01-01

    Full Text Available Although there is a consensus of opinion that habitat fragmentation has deleterious effects on animal populations, primarily by inhibiting dispersal among remaining patches, there have been few explicit demonstrations of the ways by which degraded habitats actually constrain individual movement. Two impediments are primarily responsible for this paucity: it is difficult to separate the effects of habitat fragmentation (configuration from habitat loss (composition, and conventional measures of fragmented habitats are assumed to be, but probably are not, isotropic. We addressed these limitations by standardizing differences in forest cover in a clearly anisotropic configuration of habitat fragmentation by conducting a homing experiment with three species of forest birds in the Bow Valley of Banff National Park, Canada. Birds were translocated (1.2-3.5  km either parallel or perpendicular to four/five parallel barriers that are assumed to impede the cross-valley travel of forest-dependent animals. Taken together, individuals exhibited longer return times when they were translocated across these barriers, but differences among species suggest a more complex interpretation. A long-distance migrant (Yellow-rumped Warbler, Dendroica coronata behaved as predicted, but a short-distance migrant (Golden-crowned Kinglet, Regulus satrapa was indifferent to barrier configuration. A resident (Red-breasted Nuthatch, Sitta canadensis exhibited longer return times when it was translocated parallel to the barriers. Our results suggest that an anisotropic arrangement of small, open areas in fragmented landscapes can have a cumulative barrier effect on the movement of forest animals, but that both modelers and managers will have to acknowledge potentially counterintuitive differences among species to predict the effect that these may have on individual movement and, ultimately, dispersal.

  12. Measuring a fair and ambitious climate agreement using cumulative emissions

    International Nuclear Information System (INIS)

    Peters, Glen P; Andrew, Robbie M; Solomon, Susan; Friedlingstein, Pierre

    2015-01-01

    Policy makers have called for a ‘fair and ambitious’ global climate agreement. Scientific constraints, such as the allowable carbon emissions to avoid exceeding a 2 °C global warming limit with 66% probability, can help define ambitious approaches to climate targets. However, fairly sharing the mitigation challenge to meet a global target involves human values rather than just scientific facts. We develop a framework based on cumulative emissions of carbon dioxide to compare the consistency of countries’ current emission pledges to the ambition of keeping global temperatures below 2 °C, and, further, compare two alternative methods of sharing the remaining emission allowance. We focus on the recent pledges and other official statements of the EU, USA, and China. The EU and US pledges are close to a 2 °C level of ambition only if the remaining emission allowance is distributed based on current emission shares, which is unlikely to be viewed as ‘fair and ambitious’ by others who presently emit less. China’s stated emissions target also differs from measures of global fairness, owing to emissions that continue to grow into the 2020s. We find that, combined, the EU, US, and Chinese pledges leave little room for other countries to emit CO 2 if a 2 °C limit is the objective, essentially requiring all other countries to move towards per capita emissions 7 to 14 times lower than the EU, USA, or China by 2030. We argue that a fair and ambitious agreement for a 2 °C limit that would be globally inclusive and effective in the long term will require stronger mitigation than the goals currently proposed. Given such necessary and unprecedented mitigation and the current lack of availability of some key technologies, we suggest a new diplomatic effort directed at ensuring that the necessary technologies become available in the near future. (letter)

  13. Downstream cumulative effects of land use on freshwater communities

    Science.gov (United States)

    Kuglerová, L.; Kielstra, B. W.; Moore, D.; Richardson, J. S.

    2015-12-01

    Many streams and rivers are subject to disturbance from intense land use such as urbanization and agriculture, and this is especially obvious for small headwaters. Streams are spatially organized into networks where headwaters represent the tributaries and provide water, nutrients, and organic material to the main stems. Therefore perturbations within the headwaters might be cumulatively carried on downstream. Although we know that the disturbance of headwaters in urban and agricultural landscapes poses threats to downstream river reaches, the magnitude and severity of these changes for ecological communities is less known. We studied stream networks along a gradient of disturbance connected to land use intensity, from urbanized watersheds to watersheds placed in agricultural settings in the Greater Toronto Area. Further, we compared the patterns and processes found in the modified watershed to a control watershed, situated in a forested, less impacted landscape. Preliminary results suggest that hydrological modifications (flash floods), habitat loss (drainage and sewer systems), and water quality issues of small streams in urbanized and agricultural watersheds represent major disturbances and threats for aquatic and riparian biota on local as well as larger spatial scales. For example, communities of riparian plants are dominated by species typical of the land use on adjacent uplands as well as the dominant land use on the upstream contributing area, instead of riparian obligates commonly found in forested watersheds. Further, riparian communities in disturbed environments are dominated by invasive species. The changes in riparian communities are vital for various functions of riparian vegetation. Bank erosion control is suppressed, leading to severe channel transformations and sediment loadings in urbanized watersheds. Food sources for instream biota and thermal regimes are also changed, which further triggers alterations of in-stream biological communities

  14. Psychotherapy with children in refugee families who have survived torture

    DEFF Research Database (Denmark)

    Grünbaum, Liselotte

    1997-01-01

    and recurring exposure to shocking violence. The traumatic experiences of the child in the country of origin take place in the broader context of chronic danger and persecution, often to be followed in the country of exile both by recurrent family strain and social estrangement. In the transference......Children of refugee families who have survived torture often have emotional, psychosomatic and behavioural problems as well as problems with learning. In order to understand the difficulties of these children, we have to recognize the complicated interaction of cumulative traumatic strain...

  15. Levy flights and random searches

    Energy Technology Data Exchange (ETDEWEB)

    Raposo, E P [Laboratorio de Fisica Teorica e Computacional, Departamento de Fisica, Universidade Federal de Pernambuco, Recife-PE, 50670-901 (Brazil); Buldyrev, S V [Department of Physics, Yeshiva University, New York, 10033 (United States); Da Luz, M G E [Departamento de Fisica, Universidade Federal do Parana, Curitiba-PR, 81531-990 (Brazil); Viswanathan, G M [Instituto de Fisica, Universidade Federal de Alagoas, Maceio-AL, 57072-970 (Brazil); Stanley, H E [Center for Polymer Studies and Department of Physics, Boston University, Boston, MA 02215 (United States)

    2009-10-30

    In this work we discuss some recent contributions to the random search problem. Our analysis includes superdiffusive Levy processes and correlated random walks in several regimes of target site density, mobility and revisitability. We present results in the context of mean-field-like and closed-form average calculations, as well as numerical simulations. We then consider random searches performed in regular lattices and lattices with defects, and we discuss a necessary criterion for distinguishing true superdiffusion from correlated random walk processes. We invoke energy considerations in relation to critical survival states on the edge of extinction, and we analyze the emergence of Levy behavior in deterministic search walks. Finally, we comment on the random search problem in the context of biological foraging.

  16. Split Course Hyperfractionated Accelerated Radio-Chemotherapy (SCHARC) for patients with advanced head and neck cancer: Influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis

    International Nuclear Information System (INIS)

    Stadler, Peter; Putnik, Kurt; Kreimeyer, Thore; Sprague, Lisa D; Koelbl, Oliver; Schäfer, Christof

    2006-01-01

    The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol 'SCHARC' and the overall survival of our patients. From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III) were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %), one third with tongue and floor of mouth tumors (29 %) and one fifth (19 %) suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1–5: 20 mg/m 2 /d DDP + 750–1000 mg/m 2 /d 5FU (cont. infusion). This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69–70.5 Gy). All patients assigned to this scheme were included in the survival evaluation. Forty patients (63 %) received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d) and the median follow up was 1.9 years (678 d), respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 %) had acute grade 2–3 mucositis, and 33 patients (58 %) suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient < 1.0 g/nl) and the mean hemoglobin value decreased from 13.2 to 10.5 g/dl. Univariate analysis of survival showed a better outcome for patients with a hemoglobin nadir >10.5 g/dl and for patients who completed the protocol. The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led

  17. Split course hyperfractionated accelerated radio-chemotherapy (SCHARC) for patients with advanced head and neck cancer: influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis.

    Science.gov (United States)

    Stadler, Peter; Putnik, Kurt; Kreimeyer, Thore; Sprague, Lisa D; Koelbl, Oliver; Schäfer, Christof

    2006-12-07

    The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol "SCHARC" and the overall survival of our patients. From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III) were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %), one third with tongue and floor of mouth tumors (29 %) and one fifth (19 %) suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1-5: 20 mg/m2/d DDP + 750-1000 mg/m2/d 5FU (cont. infusion). This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69-70.5 Gy). All patients assigned to this scheme were included in the survival evaluation. Forty patients (63 %) received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d) and the median follow up was 1.9 years (678 d), respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 %) had acute grade 2-3 mucositis, and 33 patients (58 %) suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient hemoglobin value decreased from 13.2 to 10.5 g/dl. Univariate analysis of survival showed a better outcome for patients with a hemoglobin nadir >10.5 g/dl and for patients who completed the protocol. The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led to long-term disease control and survival in

  18. The cumulative verification image analysis tool for offline evaluation of portal images

    International Nuclear Information System (INIS)

    Wong, John; Yan Di; Michalski, Jeff; Graham, Mary; Halverson, Karen; Harms, William; Purdy, James

    1995-01-01

    Purpose: Daily portal images acquired using electronic portal imaging devices contain important information about the setup variation of the individual patient. The data can be used to evaluate the treatment and to derive correction for the individual patient. The large volume of images also require software tools for efficient analysis. This article describes the approach of cumulative verification image analysis (CVIA) specifically designed as an offline tool to extract quantitative information from daily portal images. Methods and Materials: The user interface, image and graphics display, and algorithms of the CVIA tool have been implemented in ANSCI C using the X Window graphics standards. The tool consists of three major components: (a) definition of treatment geometry and anatomical information; (b) registration of portal images with a reference image to determine setup variation; and (c) quantitative analysis of all setup variation measurements. The CVIA tool is not automated. User interaction is required and preferred. Successful alignment of anatomies on portal images at present remains mostly dependent on clinical judgment. Predefined templates of block shapes and anatomies are used for image registration to enhance efficiency, taking advantage of the fact that much of the tool's operation is repeated in the analysis of daily portal images. Results: The CVIA tool is portable and has been implemented on workstations with different operating systems. Analysis of 20 sequential daily portal images can be completed in less than 1 h. The temporal information is used to characterize setup variation in terms of its systematic, random and time-dependent components. The cumulative information is used to derive block overlap isofrequency distributions (BOIDs), which quantify the effective coverage of the prescribed treatment area throughout the course of treatment. Finally, a set of software utilities is available to facilitate feedback of the information for

  19. The Fibrin-Derived Peptide Bβ15-42 (FX06) Ameliorates Vascular Leakage and Improves Survival and Neurocognitive Recovery: Implications From Two Animal Models of Cardiopulmonary Resuscitation.

    Science.gov (United States)

    Bergt, Stefan; Gruenewald, Matthias; Beltschany, Claudia; Grub, Andrea; Neumann, Tobias; Albrecht, Martin; Vollmar, Brigitte; Zacharowski, Kai; Roesner, Jan P; Meybohm, Patrick

    2016-10-01

    The fibrin-derived peptide Bβ15-42 (FX06) has been proven to attenuate ischemia/reperfusion injury. We tested the hypothesis that Bβ15-42 improves survival rate and neurocognitive recovery after cardiopulmonary resuscitation. Pig and mouse model of cardiopulmonary resuscitation. Two university hospitals. Pigs and mice. Pigs (n = 16) were subjected to 8-minute cardiac arrest. Successful resuscitated pigs (n = 12) were randomized either to 3 mg/kg Bβ15-42 followed by a continuous infusion of 1 mg/kg/hr for 5 hours (pFX06; n = 6) or the control group (pCONTROL; n = 6). Cardiac damage, function, and hemodynamics were recorded up to 8 hours. Mice (n = 52) were subjected to 4-minute cardiac arrest followed by cardiopulmonary resuscitation, and randomized either to two boli of 2.4 mg/kg Bβ15-42 (mFX06; n = 26) or the control group (mCONTROL; n = 26). Fourteen-day survival rate, neurocognitive function, and endothelial integrity (additional experiment with n = 26 mice) were evaluated. Bβ15-42 reduced cumulative fluid intake (3,500 [2,600-4,200] vs 6,800 [5,700-7,400] mL; p = 0.004) within 8 hours in pigs. In mice, Bβ15-42 improved 14-day survival rate (mFX06 vs mCONTROL; 11/26 vs 6/26; p Water-Maze test (15/26 vs 9/26 mice with competence to perform test; p < 0.05). Bβ15-42-treated mice showed a significant higher length of intact pulmonary endothelium and reduced pulmonary leukocyte infiltration. This study confirms the new concept of an important role of fibrin derivatives in global ischemia/reperfusion injury, which can be attenuated by the fibrin-derived peptide Bβ15-42.

  20. Random Fields

    Science.gov (United States)

    Vanmarcke, Erik

    1983-03-01

    Random variation over space and time is one of the few attributes that might safely be predicted as characterizing almost any given complex system. Random fields or "distributed disorder systems" confront astronomers, physicists, geologists, meteorologists, biologists, and other natural scientists. They appear in the artifacts developed by electrical, mechanical, civil, and other engineers. They even underlie the processes of social and economic change. The purpose of this book is to bring together existing and new methodologies of random field theory and indicate how they can be applied to these diverse areas where a "deterministic treatment is inefficient and conventional statistics insufficient." Many new results and methods are included. After outlining the extent and characteristics of the random field approach, the book reviews the classical theory of multidimensional random processes and introduces basic probability concepts and methods in the random field context. It next gives a concise amount of the second-order analysis of homogeneous random fields, in both the space-time domain and the wave number-frequency domain. This is followed by a chapter on spectral moments and related measures of disorder and on level excursions and extremes of Gaussian and related random fields. After developing a new framework of analysis based on local averages of one-, two-, and n-dimensional processes, the book concludes with a chapter discussing ramifications in the important areas of estimation, prediction, and control. The mathematical prerequisite has been held to basic college-level calculus.

  1. Origin of path independence between cumulative CO2 emissions and global warming

    Science.gov (United States)

    Seshadri, Ashwin K.

    2017-11-01

    Observations and GCMs exhibit approximate proportionality between cumulative carbon dioxide (CO2) emissions and global warming. Here we identify sufficient conditions for the relationship between cumulative CO2 emissions and global warming to be independent of the path of CO2 emissions; referred to as "path independence". Our starting point is a closed form expression for global warming in a two-box energy balance model (EBM), which depends explicitly on cumulative emissions, airborne fraction and time. Path independence requires that this function can be approximated as depending on cumulative emissions alone. We show that path independence arises from weak constraints, occurring if the timescale for changes in cumulative emissions (equal to ratio between cumulative emissions and emissions rate) is small compared to the timescale for changes in airborne fraction (which depends on CO2 uptake), and also small relative to a derived climate model parameter called the damping-timescale, which is related to the rate at which deep-ocean warming affects global warming. Effects of uncertainties in the climate model and carbon cycle are examined. Large deep-ocean heat capacity in the Earth system is not necessary for path independence, which appears resilient to climate modeling uncertainties. However long time-constants in the Earth system carbon cycle are essential, ensuring that airborne fraction changes slowly with timescale much longer than the timescale for changes in cumulative emissions. Therefore path independence between cumulative emissions and warming cannot arise for short-lived greenhouse gases.

  2. Cumulative effects of planned industrial development and climate change on marine ecosystems

    Directory of Open Access Journals (Sweden)

    Cathryn Clarke Murray

    2015-07-01

    Full Text Available With increasing human population, large scale climate changes, and the interaction of multiple stressors, understanding cumulative effects on marine ecosystems is increasingly important. Two major drivers of change in coastal and marine ecosystems are industrial developments with acute impacts on local ecosystems, and global climate change stressors with widespread impacts. We conducted a cumulative effects mapping analysis of the marine waters of British Columbia, Canada, under different scenarios: climate change and planned developments. At the coast-wide scale, climate change drove the largest change in cumulative effects with both widespread impacts and high vulnerability scores. Where the impacts of planned developments occur, planned industrial and pipeline activities had high cumulative effects, but the footprint of these effects was comparatively localized. Nearshore habitats were at greatest risk from planned industrial and pipeline activities; in particular, the impacts of planned pipelines on rocky intertidal habitats were predicted to cause the highest change in cumulative effects. This method of incorporating planned industrial development in cumulative effects mapping allows explicit comparison of different scenarios with the potential to be used in environmental impact assessments at various scales. Its use allows resource managers to consider cumulative effect hotspots when making decisions regarding industrial developments and avoid unacceptable cumulative effects. Management needs to consider both global and local stressors in managing marine ecosystems for the protection of biodiversity and the provisioning of ecosystem services.

  3. Cumulative effective dose associated with radiography and CT of adolescents with spinal injuries.

    Science.gov (United States)

    Lemburg, Stefan P; Peters, Soeren A; Roggenland, Daniela; Nicolas, Volkmar; Heyer, Christoph M

    2010-12-01

    The purpose of this study was to analyze the quantity and distribution of cumulative effective doses in diagnostic imaging of adolescents with spinal injuries. At a level 1 trauma center from July 2003 through June 2009, imaging procedures during initial evaluation and hospitalization and after discharge of all patients 10-20 years old with spinal fractures were retrospectively analyzed. The cumulative effective doses for all imaging studies were calculated, and the doses to patients with spinal injuries who had multiple traumatic injuries were compared with the doses to patients with spinal injuries but without multiple injuries. The significance level was set at 5%. Imaging studies of 72 patients (32 with multiple injuries; average age, 17.5 years) entailed a median cumulative effective dose of 18.89 mSv. Patients with multiple injuries had a significantly higher total cumulative effective dose (29.70 versus 10.86 mSv, p cumulative effective dose to multiple injury patients during the initial evaluation (18.39 versus 2.83 mSv, p cumulative effective dose. Adolescents with spinal injuries receive a cumulative effective dose equal to that of adult trauma patients and nearly three times that of pediatric trauma patients. Areas of focus in lowering cumulative effective dose should be appropriate initial estimation of trauma severity and careful selection of CT scan parameters.

  4. Turning stumbling blocks into stepping stones in the analysis of cumulative impacts

    Science.gov (United States)

    Leslie M. Reid

    2004-01-01

    Federal and state legislation, such as the National Environmental Policy Act and the California Environmental Quality Act, require that responsible agency staff consider the cumulative impacts of proposed activities before permits are issued for certain kinds of public or private projects. The Council on Environmental Quality (CEQ 1997) defined a cumulative impact as...

  5. 14 CFR Section 18 - Objective Classification-Cumulative Effect of Changes in Accounting Principles

    Science.gov (United States)

    2010-01-01

    ... of Changes in Accounting Principles Section 18 Section 18 Aeronautics and Space OFFICE OF THE... Objective Classification—Cumulative Effect of Changes in Accounting Principles 98Cumulative Effect of Changes in Accounting Principles. Record here the difference between the amount of retained earnings at...

  6. The Scarring Effects of Bankruptcy: Cumulative Disadvantage across Credit and Labor Markets

    Science.gov (United States)

    Maroto, Michelle

    2012-01-01

    As the recent economic crisis has demonstrated, inequality often spans credit and labor markets, supporting a system of cumulative disadvantage. Using data from the National Longitudinal Survey of Youth, this research draws on stigma, cumulative disadvantage and status characteristics theories to examine whether credit and labor markets intersect…

  7. Mapping cumulative environmental risks: examples from the EU NoMiracle project

    NARCIS (Netherlands)

    Pistocchi, A.; Groenwold, J.; Lahr, J.; Loos, M.; Mujica, M.; Ragas, A.M.J.; Rallo, R.; Sala, S.; Schlink, U.; Strebel, K.; Vighi, M.; Vizcaino, P.

    2011-01-01

    We present examples of cumulative chemical risk mapping methods developed within the NoMiracle project. The different examples illustrate the application of the concentration addition (CA) approach to pesticides at different scale, the integration in space of cumulative risks to individual organisms

  8. 78 FR 25440 - Request for Information and Citations on Methods for Cumulative Risk Assessment

    Science.gov (United States)

    2013-05-01

    ... Citations on Methods for Cumulative Risk Assessment AGENCY: Office of the Science Advisor, Environmental... influence exposures, dose-response or risk/hazard posed by environmental contaminant exposures, and methods... who wish to receive further information about submitting information on methods for cumulative risk...

  9. Radiologic imaging in cystic fibrosis: cumulative effective dose and changing trends over 2 decades.

    LENUS (Irish Health Repository)

    O'Connell, Oisin J

    2012-06-01

    With the increasing life expectancy for patients with cystic fibrosis (CF), and a known predisposition to certain cancers, cumulative radiation exposure from radiologic imaging is of increasing significance. This study explores the estimated cumulative effective radiation dose over a 17-year period from radiologic procedures and changing trends of imaging modalities over this period.

  10. 30 CFR 250.921 - How do I analyze my platform for cumulative fatigue?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false How do I analyze my platform for cumulative fatigue? 250.921 Section 250.921 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR... fatigue? (a) If you are required to analyze cumulative fatigue on your platform because of the results of...

  11. A Review of Non-Chemical Stressors and Their Importance in Cumulative Risk Assessment

    Science.gov (United States)

    Cumulative exposure/risk assessments need to include non-chemical stressors as well as human activities and chemical data. Multiple stressor research can offer information on the interactions between chemical and non-chemical stressors needed for cumulative risk assessment resea...

  12. Ten-Year Cumulative Author Index Volume 2001, 36(1) through 2010, 45(4)

    Science.gov (United States)

    Zucker, Stanley H.; Hassert, Silva

    2011-01-01

    This cumulative author index was developed as a service for the readership of Education and Training in Autism and Developmental Disabilities. It was prepared as a resource for scholars wishing to access the 391 articles published in volumes 36-45 of this journal. It also serves as a timely supplement to the 25-year (1966-1990) cumulative author…

  13. TREND: a program using cumulative sum methods to detect long-term trends in data

    International Nuclear Information System (INIS)

    Cranston, R.J.; Dunbar, R.M.; Jarvis, R.G.

    1976-01-01

    TREND is a computer program, in FORTRAN, to investigate data for long-term trends that are masked by short-term statistical fluctuations. To do this, it calculates and plots the cumulative sum of deviations from a chosen mean. As a further aid to diagnosis, the procedure can be repeated with a summation of the cumulative sum itself. (author)

  14. Error Analysis on the Estimation of Cumulative Infiltration in Soil Using Green and AMPT Model

    Directory of Open Access Journals (Sweden)

    Muhamad Askari

    2006-08-01

    Full Text Available Green and Ampt infiltration model is still useful for the infiltration process because of a clear physical basis of the model and of the existence of the model parameter values for a wide range of soil. The objective of thise study was to analyze error on the esimation of cumulative infiltration in sooil using Green and Ampt model and to design laboratory experiment in measuring cumulative infiltration. Parameter of the model was determined based on soil physical properties from laboratory experiment. Newton –Raphson method was esed to estimate wetting front during calculation using visual Basic for Application (VBA in MS Word. The result showed that  contributed the highest error in estimation of cumulative infiltration and was followed by K, H0, H1, and t respectively. It also showed that the calculated cumulative infiltration is always lower than both measured cumulative infiltration and volumetric soil water content.

  15. Managing regional cumulative effects of oil sands development in Alberta, Canada

    International Nuclear Information System (INIS)

    Spaling, H.; Zwier, J.

    2000-01-01

    This paper demonstrates an approach to regional cumulative effects management using the case of oil sands development in Alberta, Canada. The 17 existing, approved, or planned projects, all concentrated in a relatively small region, pose significant challenges for conducting and reviewing cumulative effects assessment (CEA) on a project-by-project basis. In response, stakeholders have initiated a regional cumulative effects management system that is among the first such initiatives anywhere. Advantages of this system include (1) more efficient gathering and sharing of information, including a common regional database, (2) setting acceptable regional environmental thresholds for all projects, (3) collaborative assessment of similar cumulative effects from related projects, (4) co-ordinated regulatory review and approval process for overlapping CEAs, and (5) institutional empowerment from a Regional Sustainable Development Strategy administered by a public authority. This case provides a model for integrating project-based CEA with regional management of cumulative effects. (author)

  16. Cumulative second-harmonic generation of Lamb waves propagating in a two-layered solid plate

    International Nuclear Information System (INIS)

    Xiang Yanxun; Deng Mingxi

    2008-01-01

    The physical process of cumulative second-harmonic generation of Lamb waves propagating in a two-layered solid plate is presented by using the second-order perturbation and the technique of nonlinear reflection of acoustic waves at an interface. In general, the cumulative second-harmonic generation of a dispersive guided wave propagation does not occur. However, the present paper shows that the second-harmonic of Lamb wave propagation arising from the nonlinear interaction of the partial bulk acoustic waves and the restriction of the three boundaries of the solid plates does have a cumulative growth effect if some conditions are satisfied. Through boundary condition and initial condition of excitation, the analytical expression of cumulative second-harmonic of Lamb waves propagation is determined. Numerical results show the cumulative effect of Lamb waves on second-harmonic field patterns. (classical areas of phenomenology)

  17. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial.

    Science.gov (United States)

    van Laar, Jacob M; Farge, Dominique; Sont, Jacob K; Naraghi, Kamran; Marjanovic, Zora; Larghero, Jérôme; Schuerwegh, Annemie J; Marijt, Erik W A; Vonk, Madelon C; Schattenberg, Anton V; Matucci-Cerinic, Marco; Voskuyl, Alexandre E; van de Loosdrecht, Arjan A; Daikeler, Thomas; Kötter, Ina; Schmalzing, Marc; Martin, Thierry; Lioure, Bruno; Weiner, Stefan M; Kreuter, Alexander; Deligny, Christophe; Durand, Jean-Marc; Emery, Paul; Machold, Klaus P; Sarrot-Reynauld, Francoise; Warnatz, Klaus; Adoue, Daniel F P; Constans, Joël; Tony, Hans-Peter; Del Papa, Nicoletta; Fassas, Athanasios; Himsel, Andrea; Launay, David; Lo Monaco, Andrea; Philippe, Pierre; Quéré, Isabelle; Rich, Éric; Westhovens, Rene; Griffiths, Bridget; Saccardi, Riccardo; van den Hoogen, Frank H; Fibbe, Willem E; Socié, Gérard; Gratwohl, Alois; Tyndall, Alan

    2014-06-25

    High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. HSCT vs intravenous pulse cyclophosphamide. The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year

  18. Radiobilogical cell survival models

    International Nuclear Information System (INIS)

    Zackrisson, B.

    1992-01-01

    A central issue in clinical radiobiological research is the prediction of responses to different radiation qualities. The choice of cell survival and dose-response model greatly influences the results. In this context the relationship between theory and model is emphasized. Generally, the interpretations of experimental data depend on the model. Cell survival models are systematized with respect to their relations to radiobiological theories of cell kill. The growing knowlegde of biological, physical, and chemical mechanisms is reflected in the formulation of new models. The present overview shows that recent modelling has been more oriented towards the stochastic fluctuations connected to radiation energy deposition. This implies that the traditional cell surivival models ought to be complemented by models of stochastic energy deposition processes and repair processes at the intracellular level. (orig.)

  19. Effects of oral hygiene, residual caries and cervical Marginal-gaps on the survival of proximal atraumatic restorative treatment approach restorations

    Directory of Open Access Journals (Sweden)

    Arthur M Kemoli

    2011-01-01

    Full Text Available Background: Although Atraumatic restorative treatment (ART approach has been in existence for a while, the reasons for the poor performance of multisurface ART restorations are not very clear. Aim: The aim of this study is to investigate the effects of oral hygiene, residual caries and cervical marginal-gaps on survival of proximal ART restorations. Settings: Two rural divisions in Kenya were selected for the study. Design: A randomized clinical trial. Material and Methods: The 804 children in the study had their baseline- and 2-year dental plaque levels documented. Each child received one proximal restoration in a primary molar using ART approach, together with trained and pre-tested operators/assistants, three glass ionomer cements (GIC-brands and two tooth-isolation methods. The restorations were clinically evaluated soon after placement and after 2 years. Post-restorative bite-wing radiographs taken soon after restoration were also evaluated. Statistical analysis: Statistical Package for Social Sciences (SPSS version 14 computer programme was used and results tested using Pearson′s correlation, Cox Proportional Hazards regression analysis and Multiple Logistic regression models tests. Results: At baseline and after 2 years, the mean cumulative survival and plaque index changed from 94.4% to 30.8% and 2.34 (Standard Deviation, or SD of 0.46 to 1.92 (SD 2.1 respectively, with higher plaque indices associated with higher restoration failures. Of the 507 radiographs evaluated, 48 (9.5%, 63 (12.4% and 9 (1.8% restorations had residual caries (RC, cervical marginal-gaps (CMG and both RC/CMG respectively. Survival of the restorations with RC/CMG was significantly lower (p = 0.003 compared to those with RC or without RC. Conclusion: Low survival of proximal restorations in the study was associated with the presence of cervical marginal-gaps.

  20. Carbonaceous Survivability on Impact

    Science.gov (United States)

    Bunch, T. E.; Becker, Luann; Morrison, David (Technical Monitor)

    1994-01-01

    In order to gain knowledge about the potential contributions of comets and cosmic dust to the origin of life on Earth, we need to explore the survivability of their potential organic compounds on impact and the formation of secondary products that may have arisen from the chaotic events sustained by the carriers as they fell to Earth. We have performed a series of hypervelocity impact experiments using carbon-bearing impactors (diamond, graphite, kerogens, PAH crystals, and Murchison and Nogoya meteorites) into Al plate targets at velocities - 6 km/s. Estimated peak shock pressures probably did not exceed 120 GPa and peak shock temperatures were probably less than 4000 K for times of nano- to microsecs. Nominal crater dia. are less than one mm. The most significant results of these experiments are the preservation of the higher mass PAHs (e. g., pyrene relative to napthalene) and the formation of additional alkylated PAHs. We have also examined the residues of polystyrene projectiles impacted by a microparticle accelerator into targets at velocities up to 15 km/s. This talk will discuss the results of these experiments and their implications with respect to the survival of carbonaceous deliverables to early Earth. The prospects of survivability of organic molecules on "intact" capture of cosmic dust in space via soft: and hard cosmic dust collectors will also be discussed.

  1. Changing Pattern in Malignant Mesothelioma Survival

    Directory of Open Access Journals (Sweden)

    Jennifer Faig

    2015-02-01

    Full Text Available Survival for mesothelioma has been shown to be poor, with marginal improvement over time. Recent advances in the understanding of pathophysiology and treatment of mesothelioma may impact therapy to improve survival that may not be evident from available clinical trials that are often small and not randomized. Therapies may affect survival differently based on mesothelioma location (pleural vs peritoneal. Data are conflicting regarding the effect of asbestos exposure on mesothelioma location. OBJECTIVES: We examined survival in a large cohort of mesothelioma subjects analyzed by tumor location and presence and mode of asbestos exposure. METHODS: Data were analyzed from cases (n = 380 diagnosed with mesothelioma from 1992 to 2012. Cases were either drawn from treatment referrals, independent medical evaluation for medical legal purposes, or volunteers who were diagnosed with mesothelioma. Subjects completed an occupational medical questionnaire, personal interview with the examining physician, and physician review of the medical record. RESULTS: This study reports better survival for mesothelioma than historical reports. Survival for peritoneal mesothelioma was longer than that for pleural mesothelioma (hazard ratio = 0.36, 95% confidence interval = 0.24-0.54, P < .001 after adjusting for gender and age at diagnosis. Non-occupational cases were more likely to be 1 diagnosed with peritoneal mesothelioma, 2 female, 3 exposed, and 4 diagnosed at a younger age and to have a 5 shorter latency compared to occupational cases (P < .001. CONCLUSION: Peritoneal mesothelioma was more likely associated with non-occupational exposure, thus emphasizing the importance of exposure history in enhancing early diagnosis and treatment impact.

  2. Survival analysis models and applications

    CERN Document Server

    Liu, Xian

    2012-01-01

    Survival analysis concerns sequential occurrences of events governed by probabilistic laws.  Recent decades have witnessed many applications of survival analysis in various disciplines. This book introduces both classic survival models and theories along with newly developed techniques. Readers will learn how to perform analysis of survival data by following numerous empirical illustrations in SAS. Survival Analysis: Models and Applications: Presents basic techniques before leading onto some of the most advanced topics in survival analysis.Assumes only a minimal knowledge of SAS whilst enablin

  3. Use of cumulative mortality data in patients with acute myocardial infarction for early detection of variation in clinical practice: observational study.

    Science.gov (United States)

    Lawrance, R A; Dorsch, M F; Sapsford, R J; Mackintosh, A F; Greenwood, D C; Jackson, B M; Morrell, C; Robinson, M B; Hall, A S

    2001-08-11

    Use of cumulative mortality adjusted for case mix in patients with acute myocardial infarction for early detection of variation in clinical practice. Observational study. 20 hospitals across the former Yorkshire region. All 2153 consecutive patients with confirmed acute myocardial infarction identified during three months. Variable life-adjusted displays showing cumulative differences between observed and expected mortality of patients; expected mortality calculated from risk model based on admission characteristics of age, heart rate, and systolic blood pressure. The performance of two individual hospitals over three months was examined as an example. One, the smallest district hospital in the region, had a series of 30 consecutive patients but had five more deaths than predicted. The variable life-adjusted display showed minimal variation from that predicted for the first 15 patients followed by a run of unexpectedly high mortality. The second example was the main tertiary referral centre for the region, which admitted 188 consecutive patients. The display showed a period of apparently poor performance followed by substantial improvement, where the plot rose steadily from a cumulative net lives saved of -4 to 7. These variations in patient outcome are unlikely to have been revealed during conventional audit practice. Variable life-adjusted display has been integrated into surgical care as a graphical display of risk-adjusted survival for individual surgeons or centres. In combination with a simple risk model, it may have a role in monitoring performance and outcome in patients with acute myocardial infarction.

  4. Chinese Herbal Medicine Treatment Improves the Overall Survival Rate of Individuals with Hypertension among Type 2 Diabetes Patients and Modulates In Vitro Smooth Muscle Cell Contractility

    Science.gov (United States)

    Yeh, Yi-Chun; Cheng, Chi-Fung; Shiao, Yi-Tzone; Wang, Chang-Bi; Chien, Wen-Kuei; Chen, Jin-Hua; Liu, Xiang; Tsang, Hsinyi; Lin, Ting-Hsu; Liao, Chiu-Chu; Huang, Shao-Mei; Li, Ju-Pi; Lin, Cheng-Wen; Pang, Hao-Yu; Lin, Jaung-Geng; Lan, Yu-Ching; Liu, Yu-Huei; Chen, Shih-Yin; Tsai, Fuu-Jen; Liang, Wen-Miin

    2015-01-01

    Type 2 diabetes (T2D) is a chronic, multifactorial, and metabolic disorder accounting for 90% diabetes cases worldwide. Among them, almost half of T2D have hypertension, which is responsible for cardiovascular disease, morbidity, and mortality in these patients. The Chinese herbal medicine (CHM) prescription patterns of hypertension individuals among T2D patients have yet to be characterized. This study, therefore, aimed to determine their prescription patterns and evaluate the CHM effect. A cohort of one million randomly sampled cases from the National Health Insurance Research Database (NHIRD) was used to investigate the overall survival rate of CHM users, and prescription patterns. After matching CHM and non-CHM users for age, gender and date of diagnosis of hypertension, 980 subjects for each group were selected. The CHM users were characterized with slightly longer duration time from diabetes to hypertension, and more cases for hyperlipidaemia. The cumulative survival probabilities were higher in CHM users than in non-CHM users. Among these top 12 herbs, Liu-Wei-Di-Huang-Wan, Jia-Wei-Xiao-Yao-San, Dan-Shen, and Ge-Gen were the most common herbs and inhibited in vitro smooth muscle cell contractility. Our study also provides a CHM comprehensive list that may be useful in future investigation of the safety and efficacy for individuals with hypertension among type 2 diabetes patients. PMID:26699542

  5. Survival of postfledging Forster's terns in relation to mercury exposure in San Francisco Bay

    Science.gov (United States)

    Ackerman, Joshua T.; Eagles-Smith, Collin A.; Takekawa, John Y.; Iverson, S.A.

    2008-01-01

    We examined factors influencing mercury concentrations in 90 fledgling Forster's terns (Sterna forsteri) and evaluated whether mercury influenced postfledging survival in San Francisco Bay, California. Mercury concentrations (??SE) in chicks 21-29 days old (just before fledging) were 0.33 ?? 0.01 ??g g-1 ww for blood and 6.44 ?? 0.28 ??g g -1 fw for breast feathers. Colony site had an overriding influence on fledgling contamination, however hatching date and age also affected blood, but not feather, mercury concentrations. Blood mercury concentrations decreased by 28% during the 50-day hatching period and increased with chick age by 30% during the last week prior to fledging. Using radio-telemetry, we calculated that cumulative survival during the 35-day postfledging time period was 0.81 ?? 0.09 (SE). Postfledging survival rates increased with size-adjusted mass, and cumulative survival probability was 61% lower for terns with the lowest, compared to the highest, observed masses. Conversely, survival was not influenced by blood mercury concentration, time since fledging, sex, or hatch date. Mercury concentrations in breast feathers of fledglings found dead at nesting colonies also were no different than those in live chicks. Our results indicate that colony site, hatching date, and age influenced mercury concentrations in fledgling Forster's terns, but that mercury did not influence postfledging survival. ?? 2008 Springer Science+Business Media, LLC.

  6. Assessing environmental impacts on stream water quality: the use of cumulative flux and cumulative flux difference approaches to deforestation of the Hafren Forest, mid-Wales

    Directory of Open Access Journals (Sweden)

    C. Neal

    2002-01-01

    Full Text Available A method for examining the impacts of disturbance on stream water quality based on paired catchment “controlâ€? and “responseâ€? water quality time series is described in relation to diagrams of cumulative flux and cumulative flux difference. The paper describes the equations used and illustrates the patterns expected for idealised flux changes followed by an application to stream water quality data for a spruce forested catchment, the Hore, subjected to clear fell. The water quality determinands examined are sodium, chloride, nitrate, calcium and acid neutralisation capacity. The anticipated effects of felling are shown in relation to reduction in mist capture and nitrate release with felling as well as to the influence of weathering and cation exchange mechanisms, but in a much clearer way than observed previously using other approaches. Keywords: Plynlimon, stream, Hore, acid neutralisation capacity, calcium, chloride, nitrate, sodium, cumulative flux, flux

  7. Elaboration of a concept for the cumulative environmental exposure assessment of biocides

    Energy Technology Data Exchange (ETDEWEB)

    Gross, Rita; Bunke, Dirk; Moch, Katja [Oeko-Institut e.V. - Institut fuer Angewandte Oekologie e.V., Freiburg im Breisgau (Germany); Gartiser, Stefan [Hydrotox GmbH, Freiburg im Breisgau (Germany)

    2011-12-15

    Article 10(1) of the EU Biocidal Products Directive 98/8/EC (BPD) requires that for the inclusion of an active substance in Annex I, Annex IA or IB, cumulation effects from the use of biocidal products containing the same active substance shall be taken into account, where relevant. The study proves the feasibility of a technical realisation of Article 10(1) of the BPD and elaborates a first concept for the cumulative environmental exposure assessment of biocides. Existing requirements concerning cumulative assessments in other regulatory frameworks have been evaluated and their applicability for biocides has been examined. Technical terms and definitions used in this context were documented with the aim to harmonise terminology with other frameworks and to set up a precise definition within the BPD. Furthermore, application conditions of biocidal products have been analysed to find out for which cumulative exposure assessments may be relevant. Different parameters were identified which might serve as indicators for the relevance of cumulative exposure assessments. These indicators were then integrated in a flow chart by means of which the relevance of cumulative exposure assessments can be checked. Finally, proposals for the technical performance of cumulative exposure assessments within the Review Programme have been elaborated with the aim to bring the results of the project into the upcoming development and harmonization processes on EU level. (orig.)

  8. CUMULATE ROCKS ASSOCIATED WITH CARBONATE ASSIMILATION, HORTAVÆR COMPLEX, NORTH-CENTRAL NORWAY

    Science.gov (United States)

    Barnes, C. G.; Prestvik, T.; Li, Y.

    2009-12-01

    The Hortavær igneous complex intruded high-grade metamorphic rocks of the Caledonian Helgeland Nappe Complex at ca. 466 Ma. The complex is an unusual mafic-silicic layered intrusion (MASLI) because the principal felsic rock type is syenite and because the syenite formed in situ rather than by deep-seated partial melting of crustal rocks. Magma differentiation in the complex was by assimilation, primarily of calc-silicate rocks and melts with contributions from marble and semi-pelites, plus fractional crystallization. The effect of assimilation of calcite-rich rocks was to enhance stability of fassaitic clinopyroxene at the expense of olivine, which resulted in alkali-rich residual melts and lowering of silica activity. This combination of MASLI-style emplacement and carbonate assimilation produced three types of cumulate rocks: (1) Syenitic cumulates formed by liquid-crystal separation. As sheets of mafic magma were loaded on crystal-rich syenitic magma, residual liquid was expelled, penetrating the overlying mafic sheets in flame structures, and leaving a cumulate syenite. (2) Reaction cumulates. Carbonate assimilation, illustrated by a simple assimilation reaction: olivine + calcite + melt = clinopyroxene + CO2 resulted in cpx-rich cumulates such as clinopyroxenite, gabbro, and mela-monzodiorite, many of which contain igneous calcite. (3) Magmatic skarns. Calc-silicate host rocks underwent partial melting during assimilation, yielding a Ca-rich melt as the principal assimilated material and permitting extensive reaction with surrounding magma to form Kspar + cpx + garnet-rich ‘cumulate’ rocks. Cumulate types (2) and (3) do not reflect traditional views of cumulate rocks but instead result from a series of melt-present discontinuous (peritectic) reactions and partial melting of calc-silicate xenoliths. In the Hortavær complex, such cumulates are evident because of the distinctive peritectic cumulate assemblages. It is unclear whether assimilation of

  9. Applied survival analysis using R

    CERN Document Server

    Moore, Dirk F

    2016-01-01

    Applied Survival Analysis Using R covers the main principles of survival analysis, gives examples of how it is applied, and teaches how to put those principles to use to analyze data using R as a vehicle. Survival data, where the primary outcome is time to a specific event, arise in many areas of biomedical research, including clinical trials, epidemiological studies, and studies of animals. Many survival methods are extensions of techniques used in linear regression and categorical data, while other aspects of this field are unique to survival data. This text employs numerous actual examples to illustrate survival curve estimation, comparison of survivals of different groups, proper accounting for censoring and truncation, model variable selection, and residual analysis. Because explaining survival analysis requires more advanced mathematics than many other statistical topics, this book is organized with basic concepts and most frequently used procedures covered in earlier chapters, with more advanced topics...

  10. Anemia: friend or foe? Low hemoglobin is associated with decreased survival, loco-regional control and late complications: a secondary analysis of RTOG 85-27

    International Nuclear Information System (INIS)

    Lee, W. Robert; Berkey, B.; Marcial, V.; Fu, K.K.; Cooper, J. S.; Vikram, B.; Coia, L.R.; Rotman, M.; Ortiz, H.

    1997-01-01

    Purpose: Classical teaching holds that hypoxia reduces the lethal effects of ionizing radiation. Many reports have correlated low hemoglobin (Hgb) levels with reduced loco-regional control (LRC) following radiotherapy (RT) suggesting that anemia may be associated with tumor hypoxia. If hypoxia protects tumors from the lethal effects of ionizing radiation then it might protect normal tissues in a similar fashion. The purpose of the present study was to examine the effect of Hgb level on the LRC, survival and late complications in patients with advanced head and neck cancer treated with conventional radiotherapy with or without a hypoxic cell sensitizer. Methods: From March 1988 to September 1991, 521 patients with Stage III or IV squamous cell carcinoma of the head and neck were entered onto a randomized trial examining the addition of etanidazole (SR 2508) to conventional RT (66 Gy in 33 fractions to 74 Gy in 37 fractions, 5 days a week). Hgb levels were stratified as high (≥ 14.5 grams-percent for men, ≥ 13.0 grams-percent for women) or low (<14.5 for men, <13.0 for women). Loco-regional failure rates were calculated using the cumulative incidence approach. Overall survival was estimated according to the Kaplan-Meier method. Late RT toxicity was scored according to the RTOG morbidity scale. Differences in rates of LRC, survival and late complications were tested by the Cox proportional hazard model. The median follow-up of surviving patients was 57 months with a range of 1-7.5 years. Results: Of 504 eligible patients, 451 had Hgb measured prior to the second week of RT. One hundred and sixty-two patients (35.9%) were classified as having a high Hgb (HH) and 289 (64.1%) patients were classified as having a low Hgb (LH). Patients in the LH group had significantly lower survival and a trend towards lower LRC and late RT complications (see Table). Conclusion: Low Hgb levels are associated with a statistically significant reduction in survival and a trend towards

  11. Split Course Hyperfractionated Accelerated Radio-Chemotherapy (SCHARC for patients with advanced head and neck cancer: Influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Sprague Lisa D

    2006-12-01

    Full Text Available Abstract Background The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol "SCHARC" and the overall survival of our patients. Methods From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %, one third with tongue and floor of mouth tumors (29 % and one fifth (19 % suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1–5: 20 mg/m2/d DDP + 750–1000 mg/m2/d 5FU (cont. infusion. This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69–70.5 Gy. All patients assigned to this scheme were included in the survival evaluation. Results Forty patients (63 % received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d and the median follow up was 1.9 years (678 d, respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 % had acute grade 2–3 mucositis, and 33 patients (58 % suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient 10.5 g/dl and for patients who completed the protocol. Conclusion The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led to long-term disease control and survival in about 50 % of the patients with significant but acceptable toxicity. Most patients

  12. The Implementation of Cumulative Learning Theory in Calculating Triangular Prism and Tube Volumes

    Science.gov (United States)

    Muklis, M.; Abidin, C.; Pamungkas, M. D.; Masriyah

    2018-01-01

    This study aims at describing the application of cumulative learning theory in calculating the volume of a triangular prism and a tube as well as revealing the students’ responses toward the learning. The research method used was descriptive qualitative with elementary school students as the subjects of the research. Data obtained through observation, field notes, questionnaire, tests, and interviews. The results from the application of cumulative learning theory obtained positive students’ responses in following the learning and students’ learning outcomes was dominantly above the average. This showed that cumulative learning could be used as a reference to be implemented in learning, so as to improve the students’ achievement.

  13. Structure functions and particle production in the cumulative region: two different exponentials

    International Nuclear Information System (INIS)

    Braun, M.; Vechernin, V.

    1997-01-01

    In the framework of the recently proposed (QCD-based parton model for the cumulative phenomena in the interactions with nuclei two mechanisms for particle production, direct and spectator ones, are analyzed. It is shown that due to final-state interactions the leading terms of the direct mechanism contribution are cancelled and the spectator mechanism is the dominant one. It leads to a smaller slope of the cumulative particle production rates compared to the slope of the nuclear structure function in the cumulative region x ≥ 1, in agreement with the recent experimental data

  14. Nuclear War Survival Skills

    Energy Technology Data Exchange (ETDEWEB)

    Kearny, C.H.

    2002-06-24

    The purpose of this book is to provide Americans with information and instructions that will significantly increase their chances of surviving a possible nuclear attack. It brings together field-tested instructions that, if followed by a large fraction of Americans during a crisis that preceded an attack, could save millions of lives. The author is convinced that the vulnerability of our country to nuclear threat or attack must be reduced and that the wide dissemination of the information contained in this book would help achieve that objective of our overall defense strategy.

  15. Survival after blood transfusion

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Ahlgren, Martin; Rostgaard, Klaus

    2008-01-01

    of transfusion recipients in Denmark and Sweden followed for up to 20 years after their first blood transfusion. Main outcome measure was all-cause mortality. RESULTS: A total of 1,118,261 transfusion recipients were identified, of whom 62.0 percent were aged 65 years or older at the time of their first...... the SMR remained significantly 1.3-fold increased. CONCLUSION: The survival and relative mortality patterns among blood transfusion recipients were characterized with unprecedented detail and precision. Our results are relevant to assessments of the consequences of possible transfusion-transmitted disease...... as well as for cost-benefit estimation of new blood safety interventions....

  16. Survival curves for irradiated cells

    International Nuclear Information System (INIS)

    Gibson, D.K.

    1975-01-01

    The subject of the lecture is the probability of survival of biological cells which have been subjected to ionising radiation. The basic mathematical theories of cell survival as a function of radiation dose are developed. A brief comparison with observed survival curves is made. (author)

  17. Survival and Toxicity in Patients With Disseminated Germ CellCancer Aged 40 Years and Older

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Bandak, Mikkel; Thomsen, Maria F

    2014-01-01

    , etoposide and cisplatin (BEP). A control-group of 135 patients aged 18-35 years was randomly selected matched on year of BEP treatment. Cumulated doses of BEP as well as bone marrow toxicity, renal- and lung functions were recorded before, during and after termination of treatment. All patients were...... followed until death or October 1, 2011. RESULTS: The cumulated doses of BEP were comparable between the two groups, however, more patients aged ≥40 years were reduced in bleomycin doses based on a decrease in carbon monoxide diffusion capacity corrected for haemoglobin (P = 0.03). No differences between...

  18. Nuclear war survival skills

    International Nuclear Information System (INIS)

    Kearney, C.H.

    1979-09-01

    This book includes chapters on psychological preparations, warning and communications, and evacuation. It describes the building of expedient shelters, their ventilation and cooling, the purification and storage of adequate water, the processing and cooking of whole grains and legumes, fallout meters, protection against fires and carbon monoxide, and expedient furnishings for shelters. Other chapters cover sanitation and preventive medicine, medical advice for nuclear survivors lacking the help of doctors, improvised footwear and clothing, and advice on minimum preparations that can be made at low cost and should be made before a crisis arises. One appendix of the handbook gives detailed, field-tested instructions for building six types of earth-covered expedient fallout shelters, with criteria to guide the choice of which shelter to build. Others contain instructions for making an efficient shelter-ventilating pump and a homemade fallout meter that is accurate and dependable with inexpensive materials found in most households. This report is primarily a compilation and summary of civil defense measures and inventions developed at ORNL over the past 14 years and field-tested in six states, from Florida to Utah. It is the first comprehensive handbook of survival information for use by untrained citizens who want to improve their chances of surviving a possible nuclear attack. Sections may be easily excerpted and reproduced for mass distribution through news media

  19. Deriving Genomic Breeding Values for Residual Feed Intake from Covariance Functions of Random Regression Models

    DEFF Research Database (Denmark)

    Strathe, Anders B; Mark, Thomas; Nielsen, Bjarne

    2014-01-01

    Random regression models were used to estimate covariance functions between cumulated feed intake (CFI) and body weight (BW) in 8424 Danish Duroc pigs. Random regressions on second order Legendre polynomials of age were used to describe genetic and permanent environmental curves in BW and CFI...

  20. Prehospital cardiac arrest survival and neurologic recovery.

    Science.gov (United States)

    Hillis, M; Sinclair, D; Butler, G; Cain, E

    1993-01-01

    Many studies of prehospital defibrillation have been conducted but the effects of airway intervention are unknown and neurologic follow-up has been incomplete. A non-randomized cohort prospective study was conducted to determine the effectiveness of defibrillation in prehospital cardiac arrest. Two ambulance companies in the study area developed a defibrillation protocol and they formed the experimental group. A subgroup of these patients received airway management with an esophageal obturator airway (EOA) or endotracheal intubation (ETT). The control group was composed of patients who suffered a prehospital cardiac arrest and did not receive prehospital defibrillation. All survivors were assessed for residual deficits using the Sickness Impact Profile (SIP) and the Dementia Rating Scale (DRS). A total of 221 patients were studied over a 32-month period. Both the experimental group (N = 161) and the control group (N = 60) were comparable with respect to age, sex distribution, and ambulance response time. Survival to hospital discharge was 2/60 (3.3%) in the control group and 12/161 (6.3%) in the experimental group. This difference is not statistically significant. Survival in the experimental group by airway management technique was basic airway support (3/76 3.9%), EOA (3/67 4.5%), and ETT (6/48 12.5%). The improved effect on survival by ETT management was statistically significant. Survivors had minor differences in memory, work, and recreation as compared to ischemic heart disease patients as measured by the SIP and DRS. No effect of defibrillation was found on survival to hospital discharge. However, endotracheal intubation improved survival in defibrillated patients. Survivors had a good functional outcome.

  1. Excess mortality in treated and untreated hyperthyroidism is related to cumulative periods of low serum TSH

    DEFF Research Database (Denmark)

    Lillevang-Johansen, Mads; Abrahamsen, Bo; Jørgensen, Henrik Løvendahl

    2017-01-01

    Introduction and Aim: Cumulative time-dependent excess mortality in hyperthyroid patients has been suggested. However, the effect of anti-thyroid treatment on mortality, especially in subclinical hyperthyroidism remains unclarified. We investigated the association between hyperthyroidism and mort...

  2. 76 FR 69726 - Pyrethrins/Pyrethroid Cumulative Risk Assessment; Notice of Availability

    Science.gov (United States)

    2011-11-09

    ... exposure to multiple chemicals that have a common mechanism of toxicity when making regulatory decisions... stakeholders including environmental, human health, farm worker, and agricultural advocates; the chemical... Cumulative Risk Assessment; Notice of Availability AGENCY: Environmental Protection Agency (EPA). ACTION...

  3. Evaluating Cumulative Ecosystem Response to Restoration Projects in the Columbia River Estuary, Annual Report 2007

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Gary E.; Diefenderfer, Heida L.; Borde, Amy B.; Dawley, Earl M.; Ebberts, Blaine D.; Putman, Douglas A.; Roegner, G. C.; Russell, Micah; Skalski, John R.; Thom, Ronald M.; Vavrinec, John

    2008-10-01

    The goal of this multi-year study (2004-2010) is to develop a methodology to evaluate the cumulative effects of multiple habitat restoration projects intended to benefit ecosystems supporting juvenile salmonids in the lower Columbia River and estuary. Literature review in 2004 revealed no existing methods for such an evaluation and suggested that cumulative effects could be additive or synergistic. Field research in 2005, 2006, and 2007 involved intensive, comparative studies paired by habitat type (tidal swamp vs. marsh), trajectory (restoration vs. reference site), and restoration action (tide gate vs. culvert vs. dike breach). The field work established two kinds of monitoring indicators for eventual cumulative effects analysis: core and higher-order indicators. Management implications of limitations and applications of site-specific effectiveness monitoring and cumulative effects analysis were identified.

  4. Some Additional Remarks on the Cumulant Expansion for Linear Stochastic Differential Equations

    NARCIS (Netherlands)

    Roerdink, J.B.T.M.

    1984-01-01

    We summarize our previous results on cumulant expansions for linear stochastic differential equations with correlated multipliclative and additive noise. The application of the general formulas to equations with statistically independent multiplicative and additive noise is reconsidered in detail,

  5. An Integrated Cumulative Transformation and Feature Fusion Approach for Bearing Degradation Prognostics

    Directory of Open Access Journals (Sweden)

    Lixiang Duan

    2018-01-01

    Full Text Available Aimed at degradation prognostics of a rolling bearing, this paper proposed a novel cumulative transformation algorithm for data processing and a feature fusion technique for bearing degradation assessment. First, a cumulative transformation is presented to map the original features extracted from a vibration signal to their respective cumulative forms. The technique not only makes the extracted features show a monotonic trend but also reduces the fluctuation; such properties are more propitious to reflect the bearing degradation trend. Then, a new degradation index system is constructed, which fuses multidimensional cumulative features by kernel principal component analysis (KPCA. Finally, an extreme learning machine model based on phase space reconstruction is proposed to predict the degradation trend. The model performance is experimentally validated with a whole-life experiment of a rolling bearing. The results prove that the proposed method reflects the bearing degradation process clearly and achieves a good balance between model accuracy and complexity.

  6. Application of Higher-Order Cumulant in Fault Diagnosis of Rolling Bearing

    International Nuclear Information System (INIS)

    Shen, Yongjun; Yang, Shaopu; Wang, Junfeng

    2013-01-01

    In this paper a new method of pattern recognition based on higher-order cumulant and envelope analysis is presented. The core of this new method is to construct analytical signals from the given signals and obtain the envelope signals firstly, then compute and compare the higher-order cumulants of the envelope signals. The higher-order cumulants could be used as a characteristic quantity to distinguish these given signals. As an example, this method is applied in fault diagnosis for 197726 rolling bearing of freight locomotive. The comparisons of the second-order, third-order and fourth-order cumulants of the envelope signals from different vibration signals of rolling bearing show this new method could discriminate the normal and two fault signals distinctly

  7. Do Holocaust survivors show increased vulnerability or resilience to post-Holocaust cumulative adversity?

    Science.gov (United States)

    Shrira, Amit; Palgi, Yuval; Ben-Ezra, Menachem; Shmotkin, Dov

    2010-06-01

    Prior trauma can hinder coping with additional adversity or inoculate against the effect of recurrent adversity. The present study further addressed this issue by examining whether a subsample of Holocaust survivors and comparison groups, drawn from the Israeli component of the Survey of Health, Ageing, and Retirement in Europe, were differentially affected by post-Holocaust cumulative adversity. Post-Holocaust cumulative adversity had a stronger effect on the lifetime depression of Holocaust survivors than on that of comparisons. However, comparisons were more negatively affected by post-Holocaust cumulative adversity when examining markers of physical and cognitive functioning. Our findings suggest that previous trauma can both sensitize and immunize, as Holocaust survivors show general resilience intertwined with specific vulnerability when confronted with additional cumulative adversity.

  8. Twenty-years of lung transplantation in Taiwan: Effects of cumulative institutional experience on early outcomes

    Directory of Open Access Journals (Sweden)

    Shun-Mao Yang

    2017-11-01

    Conclusion: Although the results were undesirable in the first decade of the transplant program, the cumulative institutional experience led to significantly improved outcomes in the second decade of the transplant program.

  9. Cost Cumulant-Based Control for a Class of Linear Quadratic Tracking Problems

    National Research Council Canada - National Science Library

    Pham, Khanh D

    2007-01-01

    .... For instance, the present paper extends the application of cost-cumulant controller design to control of a wide class of linear-quadratic tracking systems where output measurements of a tracker...

  10. Does the acute pulmonary response to ozone depend on the cumulative exposure?

    International Nuclear Information System (INIS)

    Anon.

    2008-01-01

    In experimental conditions, repeated ozone exposure induces adaptive phenomena that attenuate lung function and inflammatory responses. But this study did not find that lifetime cumulative exposure had a protective effect; indeed, it found the contrary. (author)

  11. Causal inference in survival analysis using pseudo-observations.

    Science.gov (United States)

    Andersen, Per K; Syriopoulou, Elisavet; Parner, Erik T

    2017-07-30

    Causal inference for non-censored response variables, such as binary or quantitative outcomes, is often based on either (1) direct standardization ('G-formula') or (2) inverse probability of treatment assignment weights ('propensity score'). To do causal inference in survival analysis, one needs to address right-censoring, and often, special techniques are required for that purpose. We will show how censoring can be dealt with 'once and for all' by means of so-called pseudo-observations when doing causal inference in survival analysis. The pseudo-observations can be used as a replacement of the outcomes without censoring when applying 'standard' causal inference methods, such as (1) or (2) earlier. We study this idea for estimating the average causal effect of a binary treatment on the survival probability, the restricted mean lifetime, and the cumulative incidence in a competing risks situation. The methods will be illustrated in a small simulation study and via a study of patients with acute myeloid leukemia who received either myeloablative or non-myeloablative conditioning before allogeneic hematopoetic cell transplantation. We will estimate the average causal effect of the conditioning regime on outcomes such as the 3-year overall survival probability and the 3-year risk of chronic graft-versus-host disease. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Random magnetism

    International Nuclear Information System (INIS)

    Tsallis, C.

    1980-03-01

    The 'ingredients' which control a phase transition in well defined system as well as in random ones (e.g. random magnetic systems) are listed and discussed within a somehow unifying perspective. Among these 'ingredients' we find the couplings and elements responsible for the cooperative phenomenon, the topological connectivity as well as possible topological incompatibilities, the influence of new degrees of freedom, the order parameter dimensionality, the ground state degeneracy and finally the 'quanticity' of the system. The general trends, though illustrated in magnetic systems, essentially hold for all phase transitions, and give a basis for connection of this area with Field theory, Theory of dynamical systems, etc. (Author) [pt

  13. Random magnetism

    International Nuclear Information System (INIS)

    Tsallis, C.

    1981-01-01

    The 'ingredients' which control a phase transition in well defined systems as well as in random ones (e.q. random magnetic systems) are listed and discussed within a somehow unifying perspective. Among these 'ingredients' the couplings and elements responsible for the cooperative phenomenon, the topological connectivity as well as possible topological incompatibilities, the influence of new degrees of freedom, the order parameter dimensionality, the ground state degeneracy and finally the 'quanticity' of the system are found. The general trends, though illustrated in magnetic systems, essentially hold for all phase transitions, and give a basis for connection of this area with Field theory, Theory of dynamical systems, etc. (Author) [pt

  14. Summary report of a workshop on establishing cumulative effects thresholds : a suggested approach for establishing cumulative effects thresholds in a Yukon context

    International Nuclear Information System (INIS)

    2003-01-01

    Increasingly, thresholds are being used as a land and cumulative effects assessment and management tool. To assist in the management of wildlife species such as woodland caribou, the Department of Indian and Northern Affairs (DIAND) Environment Directorate, Yukon sponsored a workshop to develop and use cumulative thresholds in the Yukon. The approximately 30 participants reviewed recent initiatives in the Yukon and other jurisdictions. The workshop is expected to help formulate a strategic vision for implementing cumulative effects thresholds in the Yukon. The key to success resides in building relationships with Umbrella Final Agreement (UFA) Boards, the Development Assessment Process (DAP), and the Yukon Environmental and Socio-Economic Assessment Act (YESAA). Broad support is required within an integrated resource management framework. The workshop featured discussions on current science and theory of cumulative effects thresholds. Potential data and implementation issues were also discussed. It was concluded that thresholds are useful and scientifically defensible. The threshold research results obtained in Alberta, British Columbia and the Northwest Territories are applicable to the Yukon. One of the best tools for establishing and tracking thresholds is habitat effectiveness. Effects must be monitored and tracked. Biologists must share their information with decision makers. Interagency coordination and assistance should be facilitated through the establishment of working groups. Regional land use plans should include thresholds. 7 refs.

  15. The Role of Cumulative Trauma, Betrayal, and Appraisals in Understanding Trauma Symptomatology

    OpenAIRE

    Martin, Christina Gamache; Cromer, Lisa DeMarni; DePrince, Anne P.; Freyd, Jennifer J.

    2011-01-01

    Poor psychological outcomes are common among trauma survivors, yet not all survivors experience adverse sequelae. The current study examined links between cumulative trauma exposure as a function of the level of betrayal (measured by the relational closeness of the survivor and the perpetrator), trauma appraisals, gender, and trauma symptoms. Participants were 273 college students who reported experiencing at least one traumatic event on a trauma checklist. Three cumulative indices were const...

  16. Extending the relationship between global warming and cumulative carbon emissions to multi-millennial timescales

    International Nuclear Information System (INIS)

    Frölicher, Thomas L; Paynter, David J

    2015-01-01

    The transient climate response to cumulative carbon emissions (TCRE) is a highly policy-relevant quantity in climate science. The TCRE suggests that peak warming is linearly proportional to cumulative carbon emissions and nearly independent of the emissions scenario. Here, we use simulations of the Earth System Model (ESM) from the Geophysical Fluid Dynamics Laboratory (GFDL) to show that global mean surface temperature may increase by 0.5 °C after carbon emissions are stopped at 2 °C global warming, implying an increase in the coefficient relating global warming to cumulative carbon emissions on multi-centennial timescales. The simulations also suggest a 20% lower quota on cumulative carbon emissions allowed to achieve a policy-driven limit on global warming. ESM estimates from the Coupled Model Intercomparison Project Phase 5 (CMIP5–ESMs) qualitatively agree on this result, whereas Earth System Models of Intermediate Complexity (EMICs) simulations, used in the IPCC 5th assessment report to assess the robustness of TCRE on multi-centennial timescales, suggest a post-emissions decrease in temperature. The reason for this discrepancy lies in the smaller simulated realized warming fraction in CMIP5–ESMs, including GFDL ESM2M, than in EMICs when carbon emissions increase. The temperature response to cumulative carbon emissions can be characterized by three different phases and the linear TCRE framework is only valid during the first phase when carbon emissions increase. For longer timescales, when emissions tape off, two new metrics are introduced that better characterize the time-dependent temperature response to cumulative carbon emissions: the equilibrium climate response to cumulative carbon emissions and the multi-millennial climate response to cumulative carbon emissions. (letter)

  17. Cumulative keyboard strokes: a possible risk factor for carpal tunnel syndrome

    Directory of Open Access Journals (Sweden)

    Eleftheriou Andreas

    2012-08-01

    Full Text Available Abstract Background Contradictory reports have been published regarding the association of Carpal Tunnel Syndrome (CTS and the use of computer keyboard. Previous studies did not take into account the cumulative exposure to keyboard strokes among computer workers. The aim of the present study was to investigate the association between cumulative keyboard use (keyboard strokes and CTS. Methods Employees (461 from a Governmental data entry & processing unit agreed to participate (response rate: 84.1 % in a cross-sectional study. Α questionnaire was distributed to the participants to obtain information on socio-demographics and risk factors for CTS. The participants were examined for signs and symptoms related to CTS and were asked if they had previous history or surgery for CTS. The cumulative amount of the keyboard strokes per worker per year was calculated by the use of payroll’s registry. Two case definitions for CTS were used. The first included subjects with personal history/surgery for CTS while the second included subjects that belonged to the first case definition plus those participants were identified through clinical examination. Results Multivariate analysis used for both case definitions, indicated that those employees with high cumulative exposure to keyboard strokes were at increased risk of CTS (case definition A: OR = 2.23;95 % CI = 1.09-4.52 and case definition B: OR = 2.41; 95%CI = 1.36-4.25. A dose response pattern between cumulative exposure to keyboard strokes and CTS has been revealed (p  Conclusions The present study indicated a possible association between cumulative exposure to keyboard strokes and development of CTS. Cumulative exposure to key-board strokes would be taken into account as an exposure indicator regarding exposure assessment of computer workers. Further research is needed in order to test the results of the current study and assess causality between cumulative keyboard strokes and

  18. Cumulative Human Impacts on Coral Reefs: Assessing Risk and Management Implications for Brazilian Coral Reefs

    OpenAIRE

    Rafael A. Magris; Alana Grech; Robert L. Pressey

    2018-01-01

    Effective management of coral reefs requires strategies tailored to cope with cumulative disturbances from human activities. In Brazil, where coral reefs are a priority for conservation, intensifying threats from local and global stressors are of paramount concern to management agencies. Using a cumulative impact assessment approach, our goal was to inform management actions for coral reefs in Brazil by assessing their exposure to multiple stressors (fishing, land-based activities, coastal de...

  19. A remark on the sign change of the four-particle azimuthal cumulant in small systems

    Science.gov (United States)

    Bzdak, Adam; Ma, Guo-Liang

    2018-06-01

    The azimuthal cumulants, c2 { 2 } and c2 { 4 }, originating from the global conservation of transverse momentum in the presence of hydro-like elliptic flow are calculated. We observe the sign change of c2 { 4 } for small number of produced particles. This is in a qualitative agreement with the recent ATLAS measurement of multi-particle azimuthal correlations with the subevent cumulant method.

  20. Cumulative Mass and NIOSH Variable Lifting Index Method for Risk Assessment: Possible Relations.

    Science.gov (United States)

    Stucchi, Giulia; Battevi, Natale; Pandolfi, Monica; Galinotti, Luca; Iodice, Simona; Favero, Chiara

    2018-02-01

    Objective The aim of this study was to explore whether the Variable Lifting Index (VLI) can be corrected for cumulative mass and thus test its efficacy in predicting the risk of low-back pain (LBP). Background A validation study of the VLI method was published in this journal reporting promising results. Although several studies highlighted a positive correlation between cumulative load and LBP, cumulative mass has never been considered in any of the studies investigating the relationship between manual material handling and LBP. Method Both VLI and cumulative mass were calculated for 2,374 exposed subjects using a systematic approach. Due to high variability of cumulative mass values, a stratification within VLI categories was employed. Dummy variables (1-4) were assigned to each class and used as a multiplier factor for the VLI, resulting in a new index (VLI_CMM). Data on LBP were collected by occupational physicians at the study sites. Logistic regression was used to estimate the risk of acute LBP within levels of risk exposure when compared with a control group formed by 1,028 unexposed subjects. Results Data showed greatly variable values of cumulative mass across all VLI classes. The potential effect of cumulative mass on damage emerged as not significant ( p value = .6526). Conclusion When comparing VLI_CMM with raw VLI, the former failed to prove itself as a better predictor of LBP risk. Application To recognize cumulative mass as a modifier, especially for lumbar degenerative spine diseases, authors of future studies should investigate potential association between the VLI and other damage variables.

  1. Spatial and temporal changes in cumulative human impacts on the world's ocean

    OpenAIRE

    Halpern, Benjamin S.; Frazier, Melanie; Potapenko, John; Casey, Kenneth S.; Koenig, Kellee; Longo, Catherine; Lowndes, Julia Stewart; Rockwood, R. Cotton; Selig, Elizabeth R.; Selkoe, Kimberly A.; Walbridge, Shaun

    2015-01-01

    Human pressures on the ocean are thought to be increasing globally, yet we know little about their patterns of cumulative change, which pressures are most responsible for change, and which places are experiencing the greatest increases. Managers and policymakers require such information to make strategic decisions and monitor progress towards management objectives. Here we calculate and map recent change over 5 years in cumulative impacts to marine ecosystems globally from fishing, climate ch...

  2. Acute and Cumulative Effects of Unmodified 50-nm Nano-ZnO on Mice.

    Science.gov (United States)

    Kong, Tao; Zhang, Shu-Hui; Zhang, Ji-Liang; Hao, Xue-Qin; Yang, Fan; Zhang, Cai; Yang, Zi-Jun; Zhang, Meng-Yu; Wang, Jie

    2018-01-02

    Nanometer zinc oxide (nano-ZnO) is widely used in diverse industrial and agricultural fields. Due to the extensive contact humans have with these particles, it is crucial to understand the potential effects that nano-ZnO have on human health. Currently, information related to the toxicity and mechanisms of nano-ZnO is limited. The aim of the present study was to investigate acute and cumulative toxic effects of 50-nm unmodified ZnO in mice. This investigation will seek to establish median lethal dose (LD50), a cumulative coefficient, and target organs. The acute and cumulative toxicity was investigated by Karber's method and via a dose-increasing method, respectively. During the experiment, clinical signs, mortality, body weights, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. The LD50 was 5177-mg/kg·bw; the 95% confidence limits for the LD50 were 5116-5238-mg/kg·bw. It could be concluded that the liver, kidney, lung, and gastrointestinal tract were target organs for the 50-nm nano-ZnO acute oral treatment. The cumulative coefficient (K) was 1.9 which indicated that the cumulative toxicity was apparent. The results also indicated that the liver, kidney, lung, and pancrea were target organs for 50-nm nano-ZnO cumulative oral exposure and might be target organs for subchronic and chronic toxicity of oral administered 50-nm ZnO.

  3. Correlation Between Monthly Cumulative Auroral Electrojet Indices, DST Index and Interplanetary Electric Field During Magnetic Storms

    Directory of Open Access Journals (Sweden)

    Yoon-Kyung Park

    2005-12-01

    Full Text Available Magnetospheric substorms occur frequently during magnetic storms, suggesting that the two phenomena are closely associated. We can investigate the relation between magnetospheric substorms and magnetic storms by examining the correlation between AE and Dst indices. For this purpose, we calculated the monthly cumulative AU, |AL| and |Dst| indices. The correlation coefficient between the monthly cumulative |AL| and |Dst| index is found to be 0.60, while that between monthly cumulative AU and |Dst| index is 0.28. This result indicates that substorms seem to contribute to the development of magnetic storms. On the other hand, it has been reported that the interplanetary electric field associated with southward IMF intensifies the magnetospheric convection, which injects charged particles into the inner magnetosphere, thus developing the ring current. To evaluate the contribution of the interplanetary electric field to the development of the storm time ring current belt, we compared the monthly cumulative interplanetary electric field and the monthly cumulative Dst index. The correlation coefficient between the two cumulative indices is 0.83 for southward IMF and 0.39 for northward IMF. It indicates that magnetospheric convection induced by southward IMF is also important in developing magnetic storms. Therefore, both magnetospheric substorm and enhanced magnetospheric convection seem to contribute to the buildup of magnetic storm.

  4. Cumulative Human Impacts on Coral Reefs: Assessing Risk and Management Implications for Brazilian Coral Reefs

    Directory of Open Access Journals (Sweden)

    Rafael A. Magris

    2018-04-01

    Full Text Available Effective management of coral reefs requires strategies tailored to cope with cumulative disturbances from human activities. In Brazil, where coral reefs are a priority for conservation, intensifying threats from local and global stressors are of paramount concern to management agencies. Using a cumulative impact assessment approach, our goal was to inform management actions for coral reefs in Brazil by assessing their exposure to multiple stressors (fishing, land-based activities, coastal development, mining, aquaculture, shipping, and global warming. We calculated an index of the risk to cumulative impacts: (i assuming uniform sensitivity of coral reefs to stressors; and (ii using impact weights to reflect varying tolerance levels of coral reefs to each stressor. We also predicted the index in both the presence and absence of global warming. We found that 16% and 37% of coral reefs had high to very high risk of cumulative impacts, without and with information on sensitivity respectively, and 42% of reefs had low risk to cumulative impacts from both local and global stressors. Our outputs are the first comprehensive spatial dataset of cumulative impact on coral reefs in Brazil, and show that areas requiring attention mostly corresponded to those closer to population centres. We demonstrate how the relationships between risks from local and global stressors can be used to derive strategic management actions.

  5. Gender and survival in patients with heart failure

    DEFF Research Database (Denmark)

    Martínez-Sellés, Manuel; Doughty, Robert N; Poppe, Katrina

    2012-01-01

    The aim of this study was to investigate the relationship between gender and survival of patients with heart failure, using data from both randomized trials and observational studies, and the relative contribution of age, left ventricular systolic function, aetiology, and diabetes to differences...

  6. Estimating the joint survival probabilities of married individuals

    NARCIS (Netherlands)

    Sanders, Lisanne; Melenberg, Bertrand

    We estimate the joint survival probability of spouses using a large random sample drawn from a Dutch census. As benchmarks we use two bivariate Weibull models. We consider more flexible models, using a semi-nonparametric approach, by extending the independent Weibull distribution using squared

  7. Improving protein mass and cumulative body weight gain of local chicken fed ration fortified with a combination of Lactobacillus sp. and dahlia inulin

    Science.gov (United States)

    Wahyuni, H. I.; Suthama, N.; Mangisah, I.; Krismiyanto, L.

    2018-01-01

    The research aimed to evaluate meat calcium and protein content of local chicken fed diet fortified with a combination of Lactobacillus sp and Dahlia Inulin. One hundred and twenty birds of 4 months old local chicken with average body weight of 1001 g were assigned in a completely randomized design with 4 treatments and 5 replications. The treatments were the farmer formulated ration (FF) and the improved ration (IR), fortified with 1.2% inulin and 1.2 ml Lactobacillus sp. (FFIL and IRIL). Parameters were calcium retention, protein coefficient digestibility, meat calcium and protein mass, and cumulative body weight gain. The results showed that all parameters were significantly affected by dietary treatments. The improved ration resulted in higher calcium retention and protein coefficient digestibility than the farmer formulated ration when fed by both with and without fortification of dahlia inulin and Lactobacillus sp. Meat protein mass of chicken fed by both FR and IR fortified with dahlia inulin and Lactobacillus sp. showed higher value than chicken fed by unfortified FR and IR. Cumulative body weight gain of chicken fed by both FR and IR fortified with dahlia inulin and Lactobacillus sp. also showed higher value than chicken fed by without fortification. In conclusion, both FR and IR fortified with dahlia inulin and Lactobacillus sp. improved meat protein mass and cumulative body weight gain, especially the farmer formulated ration was pronouncedly improved by fortification of Lactobacillus sp. and dahlia inulin.

  8. Surviving Sepsis Campaign

    DEFF Research Database (Denmark)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed

    2017-01-01

    OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings...... (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups......, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low...

  9. Surviving Sepsis Campaign

    DEFF Research Database (Denmark)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed

    2017-01-01

    OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings...... (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups......, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low...

  10. Surviving relatives after suicide

    DEFF Research Database (Denmark)

    Nørrelykke, Helle; Cohrt, Pernille

    and that suicide has become a subject of research, prevention and treatment. Auxiliary Strategies In the 1990s there have been established the Centre for Suicide Research and the Centre for Prevention of Suicide in Denmark and there has been drafted a national policy document which focuses on the need......We would like to focus on the surviving relatives after suicides, because it is generally accepted that it is especially difficult to recover after the loss from suicide and because we know as a fact that one suicide affects five persons on average. Every year approximately 700 people commit...... suicide in Denmark. This means that at least 400 people undergo the trauma it is when one of their near relatives commits suicide. We also know that the loss from suicide involves a lot of conflicting feelings - like anger, shame, guilt and loss and that the lack of therapy/treatment of these difficult...

  11. Predicting the cumulative effect of multiple disturbances on seagrass connectivity.

    Science.gov (United States)

    Grech, Alana; Hanert, Emmanuel; McKenzie, Len; Rasheed, Michael; Thomas, Christopher; Tol, Samantha; Wang, Mingzhu; Waycott, Michelle; Wolter, Jolan; Coles, Rob

    2018-03-15

    The rate of exchange, or connectivity, among populations effects their ability to recover after disturbance events. However, there is limited information on the extent to which populations are connected or how multiple disturbances affect connectivity, especially in coastal and marine ecosystems. We used network analysis and the outputs of a biophysical model to measure potential functional connectivity and predict the impact of multiple disturbances on seagrasses in the central Great Barrier Reef World Heritage Area (GBRWHA), Australia. The seagrass networks were densely connected, indicating that seagrasses are resilient to the random loss of meadows. Our analysis identified discrete meadows that are important sources of seagrass propagules and that serve as stepping stones connecting various different parts of the network. Several of these meadows were close to urban areas or ports and likely to be at risk from coastal development. Deep water meadows were highly connected to coastal meadows and may function as a refuge, but only for non-foundation species. We evaluated changes to the structure and functioning of the seagrass networks when one or more discrete meadows were removed due to multiple disturbance events. The scale of disturbance required to disconnect the seagrass networks into two or more components was on average >245 km, about half the length of the metapopulation. The densely connected seagrass meadows of the central GBRWHA are not limited by the supply of propagules; therefore, management should focus on improving environmental conditions that support natural seagrass recruitment and recovery processes. Our study provides a new framework for assessing the impact of global change on the connectivity and persistence of coastal and marine ecosystems. Without this knowledge, management actions, including coastal restoration, may prove unnecessary and be unsuccessful. © 2018 John Wiley & Sons Ltd.

  12. Random Decrement

    DEFF Research Database (Denmark)

    Asmussen, J.C.; Ibrahim, S.R.; Brincker, Rune

    Abstraet Thispaper demansirates how to use the Random Decrement (RD) technique for identification o flinear structures subjected to ambient excitation. The theory behind the technique will be presented and guidelines how to choose the different variables will be given. This is done by introducing...

  13. Random Decrement

    DEFF Research Database (Denmark)

    Asmussen, J. C.; Ibrahim, S. R.; Brincker, Rune

    This paper demonstrates how to use the Random Decrement (RD) technique for identification of linear structures subjected to ambient excitation. The theory behind the technique will be presented and guidelines how to choose the different variables will be given. This is done by introducing a new...

  14. Random Decrement

    DEFF Research Database (Denmark)

    Asmussen, J. C.; Ibrahim, R.; Brincker, Rune

    1998-01-01

    This paper demonstrates how to use the Random Decrement (RD) technique for identification of linear structures subjected to ambient excitation. The theory behind the technique will be presented and guidelines how to choose the different variables will be given. This is done by introducing a new...

  15. Random dynamics

    International Nuclear Information System (INIS)

    Bennett, D.L.; Brene, N.; Nielsen, H.B.

    1986-06-01

    The goal of random dynamics is the derivation of the laws of Nature as we know them (standard model) from inessential assumptions. The inessential assumptions made here are expressed as sets of general models at extremely high energies: gauge glass and spacetime foam. Both sets of models lead tentatively to the standard model. (orig.)

  16. Random dynamics

    International Nuclear Information System (INIS)

    Bennett, D.L.

    1987-01-01

    The goal of random dynamics is the derivation of the laws of Nature as we know them (standard model) from inessential assumptions. The inessential assumptions made here are expressed as sets of general models at extremely high energies: Gauge glass and spacetime foam. Both sets of models lead tentatively to the standard model. (orig.)

  17. Random Dynamics

    Science.gov (United States)

    Bennett, D. L.; Brene, N.; Nielsen, H. B.

    1987-01-01

    The goal of random dynamics is the derivation of the laws of Nature as we know them (standard model) from inessential assumptions. The inessential assumptions made here are expressed as sets of general models at extremely high energies: gauge glass and spacetime foam. Both sets of models lead tentatively to the standard model.

  18. Myositis-associated usual interstitial pneumonia has a better survival than idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Aggarwal, Rohit; McBurney, Christine; Schneider, Frank; Yousem, Samuel A; Gibson, Kevin F; Lindell, Kathleen; Fuhrman, Carl R; Oddis, Chester V

    2017-03-01

    To compare the survival outcomes between myositis-associated usual interstitial pneumonia (MA-UIP) and idiopathic pulmonary fibrosis (IPF-UIP). Adult MA-UIP and IPF-UIP patients were identified using CTD and IPF registries. The MA-UIP cohort included myositis or anti-synthetase syndrome patients with interstitial lung disease while manifesting UIP on high-resolution CT chest and/or a lung biopsy revealing UIP histology. IPF subjects met American Thoracic Society criteria and similarly had UIP histopathology. Kaplan-Meier survival curves compared cumulative and pulmonary event-free survival (event = transplant or death) between (i) all MA-UIP and IPF-UIP subjects, (ii) MA-UIP with biopsy proven UIP (n = 25) vs IPF-UIP subjects matched for age, gender and baseline forced vital capacity (±10%). Cox proportional hazards ratios compared the survival controlling for co-variates. Eighty-one IPF-UIP and 43 MA-UIP subjects were identified. The median cumulative and event-free survival time in IPF vs MA-UIP was 5.25/1.8 years vs 16.2/10.8 years, respectively. Cumulative and event-free survival was significantly worse in IPF-UIP vs MA-UIP [hazards ratio of IPF-UIP was 2.9 (95% CI: 1.5, 5.6) and 5.0 (95% CI: 2.8, 8.7) (P < 0.001), respectively]. IPF-UIP event-free survival (but not cumulative) remained significantly worse than MA-UIP with a hazards ratio of 6.4 (95% CI: 3.0, 13.8) after controlling for age at interstitial lung disease diagnosis, gender, ethnicity and baseline forced vital capacity%. Respiratory failure was the most common cause of death in both groups. A sub-analysis of 25 biopsy-proven MA-UIP subjects showed similar results. MA-UIP patients demonstrated a significant survival advantage over a matched IPF cohort, suggesting that despite similar histological and radiographic findings at presentation, the prognosis of MA-UIP is superior to that of IPF-UIP. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology

  19. Adaptive sampling based on the cumulative distribution function of order statistics to delineate heavy-metal contaminated soils using kriging

    International Nuclear Information System (INIS)

    Juang, K.-W.; Lee, D.-Y.; Teng, Y.-L.

    2005-01-01

    Correctly classifying 'contaminated' areas in soils, based on the threshold for a contaminated site, is important for determining effective clean-up actions. Pollutant mapping by means of kriging is increasingly being used for the delineation of contaminated soils. However, those areas where the kriged pollutant concentrations are close to the threshold have a high possibility for being misclassified. In order to reduce the misclassification due to the over- or under-estimation from kriging, an adaptive sampling using the cumulative distribution function of order statistics (CDFOS) was developed to draw additional samples for delineating contaminated soils, while kriging. A heavy-metal contaminated site in Hsinchu, Taiwan was used to illustrate this approach. The results showed that compared with random sampling, adaptive sampling using CDFOS reduced the kriging estimation errors and misclassification rates, and thus would appear to be a better choice than random sampling, as additional sampling is required for delineating the 'contaminated' areas. - A sampling approach was derived for drawing additional samples while kriging

  20. Partitioning of excess mortality in population-based cancer patient survival studies using flexible parametric survival models

    Directory of Open Access Journals (Sweden)

    Eloranta Sandra

    2012-06-01

    Full Text Available Abstract Background Relative survival is commonly used for studying survival of cancer patients as it captures both the direct and indirect contribution of a cancer diagnosis on mortality by comparing the observed survival of the patients to the expected survival in a comparable cancer-free population. However, existing methods do not allow estimation of the impact of isolated conditions (e.g., excess cardiovascular mortality on the total excess mortality. For this purpose we extend flexible parametric survival models for relative survival, which use restricted cubic splines for the baseline cumulative excess hazard and for any time-dependent effects. Methods In the extended model we partition the excess mortality associated with a diagnosis of cancer through estimating a separate baseline excess hazard function for the outcomes under investigation. This is done by incorporating mutually exclusive background mortality rates, stratified by the underlying causes of death reported in the Swedish population, and by introducing cause of death as a time-dependent effect in the extended model. This approach thereby enables modeling of temporal trends in e.g., excess cardiovascular mortality and remaining cancer excess mortality simultaneously. Furthermore, we illustrate how the results from the proposed model can be used to derive crude probabilities of death due to the component parts, i.e., probabilities estimated in the presence of competing causes of death. Results The method is illustrated with examples where the total excess mortality experienced by patients diagnosed with breast cancer is partitioned into excess cardiovascular mortality and remaining cancer excess mortality. Conclusions The proposed method can be used to simultaneously study disease patterns and temporal trends for various causes of cancer-consequent deaths. Such information should be of interest for patients and clinicians as one way of improving prognosis after cancer is