Applying Kaplan-Meier to Item Response Data

ERIC Educational Resources Information Center

McNeish, Daniel

2018-01-01

Some IRT models can be equivalently modeled in alternative frameworks such as logistic regression. Logistic regression can also model time-to-event data, which concerns the probability of an event occurring over time. Using the relation between time-to-event models and logistic regression and the relation between logistic regression and IRT, this…

Genetics Home Reference: Meier-Gorlin syndrome

MedlinePlus

... ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin ... M, Skidmore DL, Samuels ME. Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin syndrome. Nat ...

Acetabular revision with impaction bone grafting and a cemented polyethylene acetabular component: comparison of the Kaplan-Meier analysis to the competing risk analysis in 62 revisions with 25 to 30 years follow-up.

PubMed

Te Stroet, M A J; Keurentjes, J C; Rijnen, W H C; Gardeniers, J W M; Verdonschot, N; Slooff, T J J H; Schreurs, B W

2015-10-01

We present the results of 62 consecutive acetabular revisions using impaction bone grafting and a cemented polyethylene acetabular component in 58 patients (13 men and 45 women) after a mean follow-up of 27 years (25 to 30). All patients were prospectively followed. The mean age at revision was 59.2 years (23 to 82). We performed Kaplan-Meier (KM) analysis and also a Competing Risk (CR) analysis because with long-term follow-up, the presence of a competing event (i.e. death) prevents the occurrence of the endpoint of re-revision. A total of 48 patients (52 hips) had died or had been re-revised at final review in March 2011. None of the deaths were related to the surgery. The mean Harris hip score of the ten surviving hips in ten patients was 76 points (45 to 99). The KM survivorship at 25 years for the endpoint 're-revision for any reason' was 58.0% (95% confidence interval (CI) 38 to 73) and for 're-revision for aseptic loosening' 72.1% (95% CI 51 to 85). With the CR analysis we calculated the KM analysis overestimates the failure rate with respectively 74% and 93% for these endpoints. The current study shows that acetabular impaction bone grafting revisions provide good clinical results at over 25 years. ©2015 The British Editorial Society of Bone & Joint Surgery.

Nonparametric estimation of the multivariate survivor function: the multivariate Kaplan-Meier estimator.

PubMed

Prentice, Ross L; Zhao, Shanshan

2018-01-01

The Dabrowska (Ann Stat 16:1475-1489, 1988) product integral representation of the multivariate survivor function is extended, leading to a nonparametric survivor function estimator for an arbitrary number of failure time variates that has a simple recursive formula for its calculation. Empirical process methods are used to sketch proofs for this estimator's strong consistency and weak convergence properties. Summary measures of pairwise and higher-order dependencies are also defined and nonparametrically estimated. Simulation evaluation is given for the special case of three failure time variates.

Statistical methods for astronomical data with upper limits. I - Univariate distributions

NASA Technical Reports Server (NTRS)

Feigelson, E. D.; Nelson, P. I.

1985-01-01

The statistical treatment of univariate censored data is discussed. A heuristic derivation of the Kaplan-Meier maximum-likelihood estimator from first principles is presented which results in an expression amenable to analytic error analysis. Methods for comparing two or more censored samples are given along with simple computational examples, stressing the fact that most astronomical problems involve upper limits while the standard mathematical methods require lower limits. The application of univariate survival analysis to six data sets in the recent astrophysical literature is described, and various aspects of the use of survival analysis in astronomy, such as the limitations of various two-sample tests and the role of parametric modelling, are discussed.

Edith Kaplan (1924-2009).

PubMed

Delis, Dean C

2010-01-01

This article honors the life accomplishments of Edith Kaplan. She is widely regarded as the mother of clinical neuropsychology; she passed away on September 3, 2009, at the age of 85. Her modifications to the original Wechsler Adult Intelligence Scale (WAIS) and Wechsler Memory Scale led to the development of a new school of clinical neuropsychology known as "the process approach," of which Kaplan is unequivocally regarded as the pioneer and chief architect. She is best known for her work in test development, and she is the lead or senior author on numerous assessment instruments designed for both children and adults that are used nationally and internationally. At the time of her death, Kaplan was working as a professor of psychology at Suffolk University, an adjunct professor of neurology and psychiatry at Boston University School of Medicine, and an affiliate professor of psychology at Clark University. And, of great importance to the field, she continued to be vigorously involved in her most beloved activity of all, teaching students about neuropsychology. 2009 APA, all rights reserved.

Statistical methods for astronomical data with upper limits. II - Correlation and regression

NASA Technical Reports Server (NTRS)

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

1986-01-01

Statistical methods for calculating correlations and regressions in bivariate censored data where the dependent variable can have upper or lower limits are presented. Cox's regression and the generalization of Kendall's rank correlation coefficient provide significant levels of correlations, and the EM algorithm, under the assumption of normally distributed errors, and its nonparametric analog using the Kaplan-Meier estimator, give estimates for the slope of a regression line. Monte Carlo simulations demonstrate that survival analysis is reliable in determining correlations between luminosities at different bands. Survival analysis is applied to CO emission in infrared galaxies, X-ray emission in radio galaxies, H-alpha emission in cooling cluster cores, and radio emission in Seyfert galaxies.

[Survival analysis with competing risks: estimating failure probability].

PubMed

Llorca, Javier; Delgado-Rodríguez, Miguel

2004-01-01

To show the impact of competing risks of death on survival analysis. We provide an example of survival time without chronic rejection after heart transplantation, where death before rejection acts as a competing risk. Using a computer simulation, we compare the Kaplan-Meier estimator and the multiple decrement model. The Kaplan-Meier method overestimated the probability of rejection. Next, we illustrate the use of the multiple decrement model to analyze secondary end points (in our example: death after rejection). Finally, we discuss Kaplan-Meier assumptions and why they fail in the presence of competing risks. Survival analysis should be adjusted for competing risks of death to avoid overestimation of the risk of rejection produced with the Kaplan-Meier method.

Kaplan SpellRead. What Works Clearinghouse Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2007

2007-01-01

"Kaplan SpellRead" (formerly known as "SpellRead Phonological Auditory Training"[R]) is a literacy program for struggling readers in grades 2 or above, including special education students, English language learners, and students more than two years below grade level in reading. "Kaplan SpellRead" integrates the…

Unsteady load on an oscillating Kaplan turbine runner

NASA Astrophysics Data System (ADS)

Puolakka, O.; Keto-Tokoi, J.; Matusiak, J.

2013-02-01

A Kaplan turbine runner oscillating in turbine waterways is subjected to a varying hydrodynamic load. Numerical simulation of the related unsteady flow is time-consuming and research is very limited. In this study, a simplified method based on unsteady airfoil theory is presented for evaluation of the unsteady load for vibration analyses of the turbine shaft line. The runner is assumed to oscillate as a rigid body in spin and axial heave, and the reaction force is resolved into added masses and dampings. The method is applied on three Kaplan runners at nominal operating conditions. Estimates for added masses and dampings are considered to be of a magnitude significant for shaft line vibration. Moderate variation in the added masses and minor variation in the added dampings is found in the frequency range of interest. Reference results for added masses are derived by solving the boundary value problem for small motions of inviscid fluid using the finite element method. Good correspondence is found in the added mass estimates of the two methods. The unsteady airfoil method is considered accurate enough for design purposes. Experimental results are needed for validation of unsteady load analyses.

The Delis-Kaplan Executive Function System: A Review

ERIC Educational Resources Information Center

Swanson, Jewel

2005-01-01

The Delis-Kaplan Executive Function System (D-KEFS; Delis, Kaplan, & Kramer, 2001a) is a set of standardized tests for comprehensively assessing higher-level cognitive functions, referred to as "executive functions," in both children and adults (aged 8 to 89). Executive functions draw on the individual's more fundamental or primary cognitive…

Interview with Danny Kaplan

ERIC Educational Resources Information Center

Rossman, Allan; Kaplan, Danny

2017-01-01

Danny Kaplan is DeWitt Wallace Professor of Mathematics and Computer Science at Macalester College. He received Macalester's Excellence in teaching Award in 2006 and the CAUSE/USCOTS Lifetime Achievement Award in 2017. This interview took place via email on March 4-June 17, 2017. Topics covered in the interview include: (1) the current state of…

Analysis of censored data.

PubMed

Lucijanic, Marko; Petrovecki, Mladen

2012-01-01

Analyzing events over time is often complicated by incomplete, or censored, observations. Special non-parametric statistical methods were developed to overcome difficulties in summarizing and comparing censored data. Life-table (actuarial) method and Kaplan-Meier method are described with an explanation of survival curves. For the didactic purpose authors prepared a workbook based on most widely used Kaplan-Meier method. It should help the reader understand how Kaplan-Meier method is conceptualized and how it can be used to obtain statistics and survival curves needed to completely describe a sample of patients. Log-rank test and hazard ratio are also discussed.

Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) in pediatric and young adult patients: Results from a prospective study using limited-margin radiotherapy.

PubMed

Tinkle, Christopher L; Fernandez-Pineda, Israel; Sykes, April; Lu, Zhaohua; Hua, Chia-Ho; Neel, Michael D; Bahrami, Armita; Shulkin, Barry L; Kaste, Sue C; Pappo, Alberto; Spunt, Sheri L; Krasin, Matthew J

2017-11-15

Indications for and delivery of adjuvant therapies for pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) have been derived largely from adult studies; therefore, significant concern remains regarding radiation exposure to normal tissue. The authors report long-term treatment outcomes and toxicities for pediatric and young adult patients with high-grade NRSTS who were treated on a prospective trial using limited-margin radiotherapy. Sixty-two patients (ages 3-22 years) with predominantly high-grade NRSTS requiring radiation were treated on a phase 2 institutional study of conformal external-beam radiotherapy and/or brachytherapy using a 1.5-cm to 2-cm anatomically constrained margin. The estimated cumulative incidence of local failure, Gray's method estimated cumulative incidence of local failure, Kaplan-Meier method estimated survival, competing-risk regression model determined predictors of disease outcome, and toxicity was reported according to CTCAE v2.0. At a median follow-up of 5.1 years (range, 0.2-10.9 years), 9 patients had experienced local failure. The 5-year overall cumulative incidence of local failure was 14.8% (95% confidence interval [CI], 7.2%-25%), and all but 1 local failure occurred outside the highest-dose irradiation volume. The 5-year Kaplan-Meier estimates for event-free and overall survival were 49.3% (95% CI, 36.3%-61.1%) and 67.9% (95% CI, 54.2%-78.3%), respectively. Multivariable analysis indicated that younger age was the only independent predictor of local recurrence (P = .004). The 5-year cumulative incidence of grade 3 or 4 late toxicity was 15% (95% CI, 7.2%-25.3%). The delivery of limited-margin radiotherapy using conformal external-beam radiotherapy or brachytherapy provides a high rate of local tumor control without an increase in marginal failures and with acceptable treatment-related morbidity. Cancer 2017;123:4419-29. © 2017 American Cancer Society. © 2017 American Cancer Society.

Assessing the effect of quantitative and qualitative predictors on gastric cancer individuals survival using hierarchical artificial neural network models.

PubMed

Amiri, Zohreh; Mohammad, Kazem; Mahmoudi, Mahmood; Parsaeian, Mahbubeh; Zeraati, Hojjat

2013-01-01

There are numerous unanswered questions in the application of artificial neural network models for analysis of survival data. In most studies, independent variables have been studied as qualitative dichotomous variables, and results of using discrete and continuous quantitative, ordinal, or multinomial categorical predictive variables in these models are not well understood in comparison to conventional models. This study was designed and conducted to examine the application of these models in order to determine the survival of gastric cancer patients, in comparison to the Cox proportional hazards model. We studied the postoperative survival of 330 gastric cancer patients who suffered surgery at a surgical unit of the Iran Cancer Institute over a five-year period. Covariates of age, gender, history of substance abuse, cancer site, type of pathology, presence of metastasis, stage, and number of complementary treatments were entered in the models, and survival probabilities were calculated at 6, 12, 18, 24, 36, 48, and 60 months using the Cox proportional hazards and neural network models. We estimated coefficients of the Cox model and the weights in the neural network (with 3, 5, and 7 nodes in the hidden layer) in the training group, and used them to derive predictions in the study group. Predictions with these two methods were compared with those of the Kaplan-Meier product limit estimator as the gold standard. Comparisons were performed with the Friedman and Kruskal-Wallis tests. Survival probabilities at different times were determined using the Cox proportional hazards and a neural network with three nodes in the hidden layer; the ratios of standard errors with these two methods to the Kaplan-Meier method were 1.1593 and 1.0071, respectively, revealed a significant difference between Cox and Kaplan-Meier (P < 0.05) and no significant difference between Cox and the neural network, and the neural network and the standard (Kaplan-Meier), as well as better accuracy

Understanding Art Testing: Past Influences, Norman C. Meier's Contributions, Present Concerns, and Future Possibilities.

ERIC Educational Resources Information Center

Clark, Gilbert; And Others

This collection of 10 papers focuses on art testing and Norman C. Meier's role in this area of study. The titles written by Gilbert Clark are: (1) "Early Inquiry, Research, and Testing of Children's Art Abilities"; (2) "Norman C. Meier: A Critique of His Tests and Research"; and (3) "Recent Inquiry and Testing of…

Analysis of the Kaplan turbine draft tube effect

NASA Astrophysics Data System (ADS)

Motycak, L.; Skotak, A.; Obrovsky, J.

2010-08-01

The aim of this paper is to present information about possible problems and errors which can appear during numerical analyses of low head Kaplan turbines with a view to the runner - draft tube interaction. The setting of numerical model, grid size, used boundary conditions are the interface definition between runner and draft tube are discussed. There are available data from physical model tests which gives a great opportunity to compare CFD and experiment results and on the basis of this comparison to determine the approach to the CFD flow modeling. The main purpose for the Kaplan turbine model measurement was to gather the information about real flow field. The model tests were carried out in new hydraulic laboratory of CKD Blansko Engineering. The model tests were focused on the detailed velocity measurements downstream of the runner by differential pressure probe and on the velocity measurement downstream of the draft tube elbow by Particle Image Velocimetry method (PIV). The data from CFD simulation were compared to the velocity measurement results. In the paper also the design of the original draft tube modification due to flow improvement is discussed in the case of the Kaplan turbine uprating project. The results of the draft tube modification were confirmed by model tests in the hydraulic laboratory as well.

Edith Kaplan and the Boston Process Approach.

PubMed

Libon, David J; Swenson, Rodney; Ashendorf, Lee; Bauer, Russell M; Bowers, Dawn

2013-01-01

The history including some of the intellectual origins of the Boston Process Approach and some misconceptions about the Boston Process Approach are reviewed. The influence of Gestalt psychology and Edith Kaplan's principal collaborators regarding the development of the Boston Process Approach is discussed.

["That flesh, pink and perishable": analysis of disease-free survival analysis in breast cancer in Gipuzkoa (Spain) in the presence of competing risks].

PubMed

Martínez-Camblor, Pablo; Larrañaga, Nerea; Sarasqueta, Cristina; Mitxelena, María José; Basterretxea, Mikel

2009-01-01

To analyze time of disease-free survival and relative survival in women diagnosed with breast cancer in the province of Gipuzkoa within the context of competing risks by assessing differences between the direct use of the Kaplan-Meier estimator and the multiple decrement method on the one hand, and relative survival on the other. All registered breast cancer cases in Gipuzkoa in 1995 and 1996 with stages other than stage IV were included. An 8-year follow-up for recurrence and a 10-year follow-up for survival were performed. Time of disease-free survival was studied by the multiple decrement model. Observed survival and survival corrected by the expected mortality in the population (relative survival) were also studied. Estimation of the probability of recurrence at 8 years with the multiple decrement method was 8.8% lower than that obtained with the Kaplan-Meier method. The difference between the observed and relative survival rates at 10 years was 10.8%. Both results show how, in this case, the Kaplan-Meier estimator overestimates both the probability of recurrence and that of mortality from the disease. Two issues are often overlooked when performing survival analyses: firstly, because of the lack of independence between survival time and censoring time, the results obtained by the Kaplan-Meier estimator are uninterpretable; secondly, it is an incontrovertible fact that one way or another, everyone causes failures. In this approach, survival analyses must take into account the probability of failure in the general population of reference. The results obtained in this study show that superficial use of the Kaplan Meier estimator overestimates both the probability of recurrence and that of mortality caused by the disease.

Some Supplementary Methods for the Analysis of the Delis-Kaplan Executive Function System

ERIC Educational Resources Information Center

Crawford, John R.; Garthwaite, Paul H.; Sutherland, David; Borland, Nicola

2011-01-01

Supplementary methods for the analysis of the Delis-Kaplan Executive Function System (Delis, Kaplan, & Kramer, 2001) are made available, including (a) quantifying the number of abnormally low achievement scores exhibited by an individual and accompanying this with an estimate of the percentage of the normative population expected to exhibit at…

Multi-objective shape optimization of runner blade for Kaplan turbine

NASA Astrophysics Data System (ADS)

Semenova, A.; Chirkov, D.; Lyutov, A.; Chemy, S.; Skorospelov, V.; Pylev, I.

2014-03-01

Automatic runner shape optimization based on extensive CFD analysis proved to be a useful design tool in hydraulic turbomachinery. Previously the authors developed an efficient method for Francis runner optimization. It was successfully applied to the design of several runners with different specific speeds. In present work this method is extended to the task of a Kaplan runner optimization. Despite of relatively simpler blade shape, Kaplan turbines have several features, complicating the optimization problem. First, Kaplan turbines normally operate in a wide range of discharges, thus CFD analysis of each variant of the runner should be carried out for several operation points. Next, due to a high specific speed, draft tube losses have a great impact on the overall turbine efficiency, and thus should be accurately evaluated. Then, the flow in blade tip and hub clearances significantly affects the velocity profile behind the runner and draft tube behavior. All these features are accounted in the present optimization technique. Parameterization of runner blade surface using 24 geometrical parameters is described in details. For each variant of runner geometry steady state three-dimensional turbulent flow computations are carried out in the domain, including wicket gate, runner, draft tube, blade tip and hub clearances. The objectives are maximization of efficiency in best efficiency and high discharge operation points, with simultaneous minimization of cavitation area on the suction side of the blade. Multiobjective genetic algorithm is used for the solution of optimization problem, requiring the analysis of several thousands of runner variants. The method is applied to optimization of runner shape for several Kaplan turbines with different heads.

Mathematical, numerical and experimental analysis of the swirling flow at a Kaplan runner outlet

NASA Astrophysics Data System (ADS)

Muntean, S.; Ciocan, T.; Susan-Resiga, R. F.; Cervantes, M.; Nilsson, H.

2012-11-01

The paper presents a novel mathematical model for a-priori computation of the swirling flow at Kaplan runners outlet. The model is an extension of the initial version developed by Susan-Resiga et al [1], to include the contributions of non-negligible radial velocity and of the variable rothalpy. Simple analytical expressions are derived for these additional data from three-dimensional numerical simulations of the Kaplan turbine. The final results, i.e. velocity components profiles, are validated against experimental data at two operating points, with the same Kaplan runner blades opening, but variable discharge.

Kaplan turbine tip vortex cavitation - analysis and prevention

NASA Astrophysics Data System (ADS)

Motycak, L.; Skotak, A.; Kupcik, R.

2012-11-01

The work is focused on one type of Kaplan turbine runner cavitation - a tip vortex cavitation. For detailed description of the tip vortex, the CFD analysis is used. On the basis of this analysis it is possible to estimate the intensity of cavitating vortex core, danger of possible blade surface and runner chamber cavitation pitting. In the paper, the ways how to avoid the pitting effect of the tip vortex are described. In order to prevent the blade surface against pitting, the following possibilities as the change of geometry of the runner blade, dimension of tip clearance and finally the installation of the anti-cavitation lips are discussed. The knowledge of the shape and intensity of the tip vortex helps to design the anti-cavitation lips more sophistically. After all, the results of the model tests of the Kaplan runner with or without anti-cavitation lips and the results of the CFD analysis are compared.

Meier-Gorlin syndrome.

PubMed

de Munnik, Sonja A; Hoefsloot, Elisabeth H; Roukema, Jolt; Schoots, Jeroen; Knoers, Nine V A M; Brunner, Han G; Jackson, Andrew P; Bongers, Ernie M H F

2015-09-17

Meier-Gorlin syndrome (MGS) is a rare autosomal recessive primordial dwarfism disorder, characterized by microtia, patellar applasia/hypoplasia, and a proportionate short stature. Associated clinical features encompass feeding problems, congenital pulmonary emphysema, mammary hypoplasia in females and urogenital anomalies, such as cryptorchidism and hypoplastic labia minora and majora. Typical facial characteristics during childhood comprise a small mouth with full lips and micro-retrognathia. During ageing, a narrow, convex nose becomes more prominent. The diagnosis MGS should be considered in patients with at least two of the three features of the clinical triad of microtia, patellar anomalies, and pre- and postnatal growth retardation. In patients with short stature and/or microtia, the patellae should be assessed with care by ultrasonography before age 6 or radiography thereafter. Mutations in one of five genes (ORC1, ORC4, ORC6, CDT1, and CDC6) of the pre-replication complex, involved in DNA-replication, are detected in approximately 67-78% of patients with MGS. Patients with ORC1 and ORC4 mutations appear to have the most severe short stature and microcephaly. Management should be directed towards in-depth investigation, treatment and prevention of associated problems, such as growth retardation, feeding problems, hearing loss, luxating patellae, knee pain, gonarthrosis, and possible pulmonary complications due to congenital pulmonary emphysema with or without broncho- or laryngomalacia. Growth hormone treatment is ineffective in most patients with MGS, but may be effective in patients in whom growth continues to decrease after the first year of life (usually growth velocity normalizes after the first year) and with low levels of IGF1. At present, few data is available about reproduction of females with MGS, but the risk of premature labor might be increased. Here, we propose experience-based guidelines for the regular care and treatment of MGS patients.

Understanding the gendered patterns of substance use initiation among adolescents living in rural, central Mexico

PubMed Central

Ayers, Stephanie; Marsiglia, Flavio; Hoffman, Steven; Urbaeva, Zhyldyz

2012-01-01

Background Little is known about the age of initiation and gender differences in substance use among adolescents in rural, central Mexico. Methods The cross-sectional data were collected from students enrolled in the Videobachillerato (VIBA) (video high school) program in Guanajuato, Mexico. Questionnaires asked students about the age at which they had used alcohol, cigarettes, or marijuana for the first time. Kaplan-Meier Survival Functions were used to estimate if males and females were significantly different in their cumulative probabilities of initiating substances over time. Results On average, alcohol is initiated at 14.7 years of age, cigarettes at 15.1 years of age, and marijuana at 16.5 years of age. Over time, males had a significantly higher probability of initiating alcohol (Kaplan-Meier Failure Curve: Χ2=26.35, p<0.001), cigarettes (Kaplan-Meier Failure Curve: Χ2=41.90, p<0.001), and marijuana (Kaplan-Meier Failure Curve: Χ2=38.01, p<0.001) compared to females. Conclusions These results highlight the gendered patterns of substance use initiation among adolescents in rural, central Mexico and underscore the need for gendered substance use prevention interventions with these adolescents. By putting forth efforts to understand substance use initiation patterns of adolescents living in rural, central Mexico, culturally specific and efficacious prevention efforts can be tailor-made to create lasting differences. PMID:22421555

Persistent fatigue in young athletes: measuring the clinical course and identifying variables affecting clinical recovery.

PubMed

Locke, S; Osborne, M; O'Rourke, P

2011-02-01

The objective of this paper is to measure the clinical course (months) in young athletes with persistent fatigue and to identify any covariates affecting the duration of recovery. This was a prospective longitudinal study of 68 athletes; 87% were elite (42 males, 26 females), aged 20.5±3.74 years (SD), who presented with the symptom of persistent fatigue. The collective duration to full clinical recovery was estimated using Kaplan-Meier product-limit curves, and covariates associated with prolonging recovery were identified from Cox proportional hazard models. The median recovery was 5 months (range 1-60 months). The range of presenting symptom duration was 0.5-36 months. The covariates identified were an increased duration of presenting symptoms [hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.02-1.12; P=0.005] and the response of serum cortisol concentration to a standard exercise challenge (HR, 1.92; 95% CI, 1.09-3.38; P=0.03). Delay in recovery was not associated with categories of fatigue that included medical, training-related diagnoses, or other causes. In conclusion, the fatigued athlete represents a significant clinical problem with a median recovery of 5 months, whose collective clinical course to recovery can be estimated by Kaplan-Meier curves and appears to be a continuum. © 2009 John Wiley & Sons A/S.

Comparison of Exposure in the Kaplan Versus the Kocher Approach in the Treatment of Radial Head Fractures.

PubMed

Barnes, Leslie Fink; Lombardi, Joseph; Gardner, Thomas R; Strauch, Robert J; Rosenwasser, Melvin P

2018-01-01

The aim of this study was to compare the complete visible surface area of the radial head, neck, and coronoid in the Kaplan and Kocher approaches to the lateral elbow. The hypothesis was that the Kaplan approach would afford greater visibility due to the differential anatomy of the intermuscular planes. Ten cadavers were dissected with the Kaplan and Kocher approaches, and the visible surface area was measured in situ using a 3-dimensional digitizer. Six measurements were taken for each approach by 2 surgeons, and the mean of these measurements were analyzed. The mean surface area visible with the lateral collateral ligament (LCL) preserved in the Kaplan approach was 616.6 mm 2 in comparison with the surface area of 136.2 mm 2 visible in the Kocher approach when the LCL was preserved. Using a 2-way analysis of variance, the difference between these 2 approaches was statistically significant. When the LCL complex was incised in the Kocher approach, the average visible surface area of the Kocher approach was 456.1 mm 2 and was statistically less than the Kaplan approach. The average surface area of the coronoid visible using a proximally extended Kaplan approach was 197.8 mm 2 . The Kaplan approach affords significantly greater visible surface area of the proximal radius than the Kocher approach.

The number of seizures needed in the EMU

PubMed Central

Struck, Aaron F.; Cole, Andrew J.; Cash, Sydney S.; Westover, M. Brandon

2016-01-01

Summary Objective The purpose of this study was to develop a quantitative framework to estimate the likelihood of multifocal epilepsy based on the number of unifocal seizures observed in the epilepsy monitoring unit (EMU). Methods Patient records from the EMU at Massachusetts General Hospital (MGH) from 2012 to 2014 were assessed for the presence of multifocal seizures as well the presence of multifocal interictal discharges and multifocal structural imaging abnormalities during the course of the EMU admission. Risk factors for multifocal seizures were assessed using sensitivity and specificity analysis. A Kaplan-Meier survival analysis was used to estimate the risk of multifocal epilepsy for a given number of consecutive seizures. To overcome the limits of the Kaplan-Meier analysis, a parametric survival function was fit to the EMU subjects with multifocal seizures and this was used to develop a Bayesian model to estimate the risk of multifocal seizures during an EMU admission. Results Multifocal interictal discharges were a significant predictor of multifocal seizures within an EMU admission with a p < 0.01, albeit with only modest sensitivity 0.74 and specificity 0.69. Multifocal potentially epileptogenic lesions on MRI were not a significant predictor p = 0.44. Kaplan-Meier analysis was limited by wide confidence intervals secondary to significant patient dropout and concern for informative censoring. The Bayesian framework provided estimates for the number of unifocal seizures needed to predict absence of multifocal seizures. To achieve 90% confidence for the absence of multifocal seizure, three seizures are needed when the pretest probability for multifocal epilepsy is 20%, seven seizures for a pretest probability of 50%, and nine seizures for a pretest probability of 80%. Significance These results provide a framework to assist clinicians in determining the utility of trying to capture a specific number of seizures in EMU evaluations of candidates for

Individualism, Nationalism, and Universalism: The Educational Ideals of Mordecai M. Kaplan's Philosophy of Jewish Education

ERIC Educational Resources Information Center

Ackerman, Ari

2008-01-01

This article will examine educational ideals by exploring the relation between the individual, the collective, and humanity in Kaplan's Jewish and educational philosophy. Generally the goals of individualism, nationalism, and universalism are seen as mutually exclusive. By contrast, Kaplan argues for the symbiotic relationship between…

Numerical investigation of hub clearance flow in a Kaplan turbine

NASA Astrophysics Data System (ADS)

Wu, H.; Feng, J. J.; Wu, G. K.; Luo, X. Q.

2012-11-01

In this paper, the flow field considering the hub clearance flow in a Kaplan turbine has been investigated through using the commercial CFD code ANSYS CFX based on high-quality structured grids generated by ANSYS ICEM CFD. The turbulence is simulated by k-ω based shear stress transport (SST) turbulence model together with automatic near wall treatments. Four kinds of simulations have been conducted for the runner geometry without hub clearance, with only the hub front clearance, with only the rear hub clearance, and with both front and rear clearance. The analysis of the obtained results is focused on the flow structure of the hub clearance flow, the effect on the turbine performance including hydraulic efficiency and cavitation performance, which can improve the understanding on the flow field in a Kaplan turbine.

Survival analysis in telemetry studies: The staggered entry design

USGS Publications Warehouse

Pollock, K.H.; Winterstein, S.R.; Bunck, C.M.; Curtis, P.D.

1989-01-01

A simple description of the Kaplan-Meier procedure is presented with an example using northern bobwhite quail survival data. The Kaplan- Meier procedure was then generalized to allow gradual (or staggered) entry of animals into the study, allowing animals being lost (or censored) due to radio failure, radio loss, or emigration of the animal from the study area. Additionally, the applicability and generalization of the log rank test, a test to compare two survival distributions, was demonstrated. Computer program was developed and is available from authors.

Median nitrate concentrations in groundwater in the New Jersey Highlands Region estimated using regression models and land-surface characteristics

USGS Publications Warehouse

Baker, Ronald J.; Chepiga, Mary M.; Cauller, Stephen J.

2015-01-01

The Kaplan-Meier method of estimating summary statistics from left-censored data was applied in order to include nondetects (left-censored data) in median nitrate-concentration calculations. Median concentrations also were determined using three alternative methods of handling nondetects. Treatment of the 23 percent of samples that were nondetects had little effect on estimated median nitrate concentrations because method detection limits were mostly less than median values.

Postoperative evaluation of palatoplasty using the modified Kaplan method.

PubMed

Isago, Tsukasa; Nozaki, Motohiro; Honda, Takashi; Kikuchi, Yuji

2005-01-01

Bilateral buccal mucosal flaps were used for a pushback operation of the nasal mucosa as well as the oral mucosa. Two flaps from the buccal mucosal areas were inserted into the nasal mucosal raw surface at the hard and soft palatal border to achieve nasal mucosal pushback. Forty-four children with cleft palates were retrospectively studied to investigate the velopharyngeal function, articulation, and craniofacial morphology following primary palatoplasty using the modified Kaplan method. 72.7% showed good velopharyngeal function. Articulation disorders were found in 26 of the 44 subjects (59.1%). A craniofacial morphological analysis revealed no major changes in the SNA (sella-nasion point A angle) and SNB (sella-nasion point B angle) and no cases of a marked loss of maxillary mandibular balance. In addition, no significant differences were observed in the maxillary length and width. The results of these palatoplasties by the modified Kaplan method indicated that the use of bilateral buccal mucosal flaps for the pushback of the nasal mucosa was effective in preventing the contraction of the maxillary and mandibular corpal lengths.

Research on the cavitation characteristic of Kaplan turbine under sediment flow condition

NASA Astrophysics Data System (ADS)

Weili, L.; Jinling, L.; Xingqi, L.; Yuan, L.

2010-08-01

The sediment concentration in many rivers in our world is very high, and the Kaplan turbine running in these rivers are usually seriously abraded. Since the existence of sand, the probability of cavitation is greatly enhanced. Under the joint action and mutual promotion of cavitation and sand erosion, serious abrasion could be made, the hydraulic performance of the Kaplan turbine may be descended, and the safety and stability of turbine are greatly threatened. Therefore, it is very important and significant to investigate the cavitation characteristic of Kaplan turbine under sediment flow condition. In this paper, numerical simulation of cavitation characteristic in pure water and solid-liquid two-phase flow in Kaplan turbine was performed. The solid-liquid two-fluid model were adopted in the numerical simulation, and the pressure, velocity and particle concentration distributive regularity on turbine blade surface under different diameter and concentration was revealed. Particle trajectory model was used to investigate the region and degree of runner blade abrasion in different conditions. The results showed that serious sand abrasion could be found near the blade head and outlet in large flow rate working condition. Relatively slight abrasion may be found near blade flange in small flow rate working condition. The more the sediment concentration and the large the sand diameter, the serious the runner is abraded, and the greater the efficiency is decreased. further analysis of the combined effects of wear and abrasion was performed. The result shows that the cavitation in silt flow is more serious than in pure water. The runner cavitation performance become worse under high sand concentration and large particle diameter, and the efficiency decrease greatly with the increase of sediment concentration.

Coupled skinny baker's maps and the Kaplan-Yorke conjecture

NASA Astrophysics Data System (ADS)

Gröger, Maik; Hunt, Brian R.

2013-09-01

The Kaplan-Yorke conjecture states that for ‘typical’ dynamical systems with a physical measure, the information dimension and the Lyapunov dimension coincide. We explore this conjecture in a neighborhood of a system for which the two dimensions do not coincide because the system consists of two uncoupled subsystems. We are interested in whether coupling ‘typically’ restores the equality of the dimensions. The particular subsystems we consider are skinny baker's maps, and we consider uni-directional coupling. For coupling in one of the possible directions, we prove that the dimensions coincide for a prevalent set of coupling functions, but for coupling in the other direction we show that the dimensions remain unequal for all coupling functions. We conjecture that the dimensions prevalently coincide for bi-directional coupling. On the other hand, we conjecture that the phenomenon we observe for a particular class of systems with uni-directional coupling, where the information and Lyapunov dimensions differ robustly, occurs more generally for many classes of uni-directionally coupled systems (also called skew-product systems) in higher dimensions.

Numerical simulation of turbulence flow in a Kaplan turbine -Evaluation on turbine performance prediction accuracy-

NASA Astrophysics Data System (ADS)

Ko, P.; Kurosawa, S.

2014-03-01

The understanding and accurate prediction of the flow behaviour related to cavitation and pressure fluctuation in a Kaplan turbine are important to the design work enhancing the turbine performance including the elongation of the operation life span and the improvement of turbine efficiency. In this paper, high accuracy turbine and cavitation performance prediction method based on entire flow passage for a Kaplan turbine is presented and evaluated. Two-phase flow field is predicted by solving Reynolds-Averaged Navier-Stokes equations expressed by volume of fluid method tracking the free surface and combined with Reynolds Stress model. The growth and collapse of cavitation bubbles are modelled by the modified Rayleigh-Plesset equation. The prediction accuracy is evaluated by comparing with the model test results of Ns 400 Kaplan model turbine. As a result that the experimentally measured data including turbine efficiency, cavitation performance, and pressure fluctuation are accurately predicted. Furthermore, the cavitation occurrence on the runner blade surface and the influence to the hydraulic loss of the flow passage are discussed. Evaluated prediction method for the turbine flow and performance is introduced to facilitate the future design and research works on Kaplan type turbine.

Further insight into the phenotype associated with a mutation in the ORC6 gene, causing Meier-Gorlin syndrome 3.

PubMed

Shalev, Stavit Allon; Khayat, Morad; Etty, Daniel-Spiegl; Elpeleg, Orly

2015-03-01

Mutations in genes encoding the origin recognition complex subunits cause Meier-Gorlin syndrome. The disease manifests a triad of short stature, small ears, and small and/or absent patellae with variable expressivity. We report on the identification of a homozygous deleterious mutation in the ORC6 gene in previously described fetuses at the severe end of the Meier-Gorlin spectrum. The phenotype included severe intrauterine growth retardation, dislocation of knees, gracile bones, clubfeet, and small mandible and chest. To date, the clinical presentation of ORC6-associated Meier-Gorlin syndrome has been mild compared to other the phenotype associated with other loci. The present report expands the clinical phenotype associated with ORC6 mutations to include severely abnormal embryological development suggesting a possible genotype-phenotype correlation. © 2015 Wiley Periodicals, Inc.

Anterolateral Knee Extra-articular Stabilizers: A Robotic Sectioning Study of the Anterolateral Ligament and Distal Iliotibial Band Kaplan Fibers.

PubMed

Geeslin, Andrew G; Chahla, Jorge; Moatshe, Gilbert; Muckenhirn, Kyle J; Kruckeberg, Bradley M; Brady, Alex W; Coggins, Ashley; Dornan, Grant J; Getgood, Alan M; Godin, Jonathan A; LaPrade, Robert F

2018-05-01

The individual kinematic roles of the anterolateral ligament (ALL) and the distal iliotibial band Kaplan fibers in the setting of anterior cruciate ligament (ACL) deficiency require further clarification. This will improve understanding of their potential contribution to residual anterolateral rotational laxity after ACL reconstruction and may influence selection of an anterolateral extra-articular reconstruction technique, which is currently a matter of debate. Hypothesis/Purpose: To compare the role of the ALL and the Kaplan fibers in stabilizing the knee against tibial internal rotation, anterior tibial translation, and the pivot shift in ACL-deficient knees. We hypothesized that the Kaplan fibers would provide greater tibial internal rotation restraint than the ALL in ACL-deficient knees and that both structures would provide restraint against internal rotation during a simulated pivot-shift test. Controlled laboratory study. Ten paired fresh-frozen cadaveric knees (n = 20) were used to investigate the effect of sectioning the ALL and the Kaplan fibers in ACL-deficient knees with a 6 degrees of freedom robotic testing system. After ACL sectioning, sectioning was randomly performed for the ALL and the Kaplan fibers. An established robotic testing protocol was utilized to assess knee kinematics when the specimens were subjected to a 5-N·m internal rotation torque (0°-90° at 15° increments), a simulated pivot shift with 10-N·m valgus and 5-N·m internal rotation torque (15° and 30°), and an 88-N anterior tibial load (30° and 90°). Sectioning of the ACL led to significantly increased tibial internal rotation (from 0° to 90°) and anterior tibial translation (30° and 90°) as compared with the intact state. Significantly increased internal rotation occurred with further sectioning of the ALL (15°-90°) and Kaplan fibers (15°, 60°-90°). At higher flexion angles (60°-90°), sectioning the Kaplan fibers led to significantly greater internal rotation

Meier-Gorlin syndrome mutations disrupt an Orc1 CDK inhibitory domain and cause centrosome reduplication.

PubMed

Hossain, Manzar; Stillman, Bruce

2012-08-15

Like DNA replication, centrosomes are licensed to duplicate once per cell division cycle to ensure genetic stability. In addition to regulating DNA replication, the Orc1 subunit of the human origin recognition complex controls centriole and centrosome copy number. Here we report that Orc1 harbors a PACT centrosome-targeting domain and a separate domain that differentially inhibits the protein kinase activities of Cyclin E-CDK2 and Cyclin A-CDK2. A cyclin-binding motif (Cy motif) is required for Orc1 to bind Cyclin A and inhibit Cyclin A-CDK2 kinase activity but has no effect on Cyclin E-CDK2 kinase activity. In contrast, Orc1 inhibition of Cyclin E-CDK2 kinase activity occurs by a different mechanism that is affected by Orc1 mutations identified in Meier-Gorlin syndrome patients. The cyclin/CDK2 kinase inhibitory domain of Orc1, when tethered to the PACT domain, localizes to centrosomes and blocks centrosome reduplication. Meier-Gorlin syndrome mutations that disrupt Cyclin E-CDK2 kinase inhibition also allow centrosome reduplication. Thus, Orc1 contains distinct domains that control centrosome copy number and DNA replication. We suggest that the Orc1 mutations present in some Meier-Gorlin syndrome patients contribute to the pronounced microcephaly and dwarfism observed in these individuals by altering centrosome duplication in addition to DNA replication defects.

Grassland productivity limited by multiple nutrients.

PubMed

Fay, Philip A; Prober, Suzanne M; Harpole, W Stanley; Knops, Johannes M H; Bakker, Jonathan D; Borer, Elizabeth T; Lind, Eric M; MacDougall, Andrew S; Seabloom, Eric W; Wragg, Peter D; Adler, Peter B; Blumenthal, Dana M; Buckley, Yvonne M; Chu, Chengjin; Cleland, Elsa E; Collins, Scott L; Davies, Kendi F; Du, Guozhen; Feng, Xiaohui; Firn, Jennifer; Gruner, Daniel S; Hagenah, Nicole; Hautier, Yann; Heckman, Robert W; Jin, Virginia L; Kirkman, Kevin P; Klein, Julia; Ladwig, Laura M; Li, Qi; McCulley, Rebecca L; Melbourne, Brett A; Mitchell, Charles E; Moore, Joslin L; Morgan, John W; Risch, Anita C; Schütz, Martin; Stevens, Carly J; Wedin, David A; Yang, Louie H

2015-07-06

Terrestrial ecosystem productivity is widely accepted to be nutrient limited(1). Although nitrogen (N) is deemed a key determinant of aboveground net primary production (ANPP)(2,3), the prevalence of co-limitation by N and phosphorus (P) is increasingly recognized(4-8). However, the extent to which terrestrial productivity is co-limited by nutrients other than N and P has remained unclear. Here, we report results from a standardized factorial nutrient addition experiment, in which we added N, P and potassium (K) combined with a selection of micronutrients (K+μ), alone or in concert, to 42 grassland sites spanning five continents, and monitored ANPP. Nutrient availability limited productivity at 31 of the 42 grassland sites. And pairwise combinations of N, P, and K+μ co-limited ANPP at 29 of the sites. Nitrogen limitation peaked in cool, high latitude sites. Our findings highlight the importance of less studied nutrients, such as K and micronutrients, for grassland productivity, and point to significant variations in the type and degree of nutrient limitation. We suggest that multiple-nutrient constraints must be considered when assessing the ecosystem-scale consequences of nutrient enrichment.

Adding gauge fields to Kaplan's fermions

NASA Astrophysics Data System (ADS)

Blum, T.; Kärkkäinen, Leo

1994-04-01

We experiment with adding dynamical gauge field to Kaplan (defect) fermions. In the case of U (1) gauge theory we use an inhomogenous Higgs mechanism to restrict the 3d gauge dynamics to a planar 2d defect. In our simulations the 3d theory produce the correct 2d gauge dynamics. We measure fermion propagators with dynamical gauge fields. They posses the correct chiral structure. The fermions at the boundary of the support of the gauge field (waveguide) are non-chiral, and have a mass two times heavier than the chiral modes. Moreover, these modes cannot be excited by a source at the defect; implying that they are dynamically decoupled. We have also checked that the anomaly relation is fullfilled for the case of a smooth external gauge field.

Numerical and in-situ investigations of water hammer effects in Drava river Kaplan turbine hydropower plants

NASA Astrophysics Data System (ADS)

Bergant, A.; Gregorc, B.; Gale, J.

2012-11-01

This paper deals with critical flow regimes that may induce unacceptable water hammer in Kaplan turbine hydropower plants. Water hammer analysis should be performed for normal, emergency and catastrophic operating conditions. Hydropower plants with Kaplan turbines are usually comprised of relatively short inlet and outlet conduits. The rigid water hammer theory can be used for this case. For hydropower plants with long penstocks the elastic water hammer should be used. Some Kaplan turbine units are installed in systems with long open channels. In this case, water level oscillations in the channels should be carefully investigated. Computational results are compared with results of measurements in recently rehabilitated seven Drava river hydroelectric power plants in Slovenia. Water hammer in the six power plants is controlled by appropriate adjustment of the wicket gates and runner blades closing/opening manoeuvres. Due to very long inflow and outflow open channels in Zlatoličje HPP a special vaned pressure regulating device attenuates extreme pressures in Kaplan turbine flow-passage system and controls unsteady flow in both open channels. Comparisons of results include normal operating regimes. The agreement between computed and measured results is reasonable.

Pesticide mixtures in the Swedish streams: Environmental risks, contributions of individual compounds and consequences of single-substance oriented risk mitigation.

PubMed

Gustavsson, Mikael; Kreuger, Jenny; Bundschuh, Mirco; Backhaus, Thomas

2017-11-15

This paper presents the ecotoxicological assessment and environmental risk evaluation of complex pesticide mixtures occurring in freshwater ecosystems in southern Sweden. The evaluation is based on exposure data collected between 2002 and 2013 by the Swedish pesticide monitoring program and includes 1308 individual samples, detecting mixtures of up to 53 pesticides (modal=8). Pesticide mixture risks were evaluated using three different scenarios for non-detects (best-case, worst-case and using the Kaplan-Meier method). The risk of each scenario was analyzed using Swedish Water Quality Objectives (WQO) and trophic-level specific environmental thresholds. Using the Kaplan-Meier method the environmental risk of 73% of the samples exceeded acceptable levels, based on an assessment using Concentration-Addition and WQOs for the individual pesticides. Algae were the most sensitive organism group. However, analytical detection limits, especially for insecticides, were insufficient to analyze concentrations at or near their WQO's. Thus, the risk of the analyzed pesticide mixtures to crustaceans and fish is systematically underestimated. Treating non-detects as being present at their individual limit of detection increased the estimated risk by a factor 100 or more, compared to the best-case or the Kaplan-Meier scenario. Pesticide mixture risks are often driven by only 1-3 compounds. However, the risk-drivers (i.e., individual pesticides explaining the largest share of potential effects) differ substantially between sites and samples, and 83 of the 141 monitored pesticides need to be included in the assessment to account for 95% of the risk at all sites and years. Single-substance oriented risk mitigation measures that would ensure that each individual pesticide is present at a maximum of 95% of its individual WQO, would also reduce the mixture risk, but only from a median risk quotient of 2.1 to a median risk quotient of 1.8. Also, acceptable total risk levels would still

The number of seizures needed in the EMU.

PubMed

Struck, Aaron F; Cole, Andrew J; Cash, Sydney S; Westover, M Brandon

2015-11-01

The purpose of this study was to develop a quantitative framework to estimate the likelihood of multifocal epilepsy based on the number of unifocal seizures observed in the epilepsy monitoring unit (EMU). Patient records from the EMU at Massachusetts General Hospital (MGH) from 2012 to 2014 were assessed for the presence of multifocal seizures as well the presence of multifocal interictal discharges and multifocal structural imaging abnormalities during the course of the EMU admission. Risk factors for multifocal seizures were assessed using sensitivity and specificity analysis. A Kaplan-Meier survival analysis was used to estimate the risk of multifocal epilepsy for a given number of consecutive seizures. To overcome the limits of the Kaplan-Meier analysis, a parametric survival function was fit to the EMU subjects with multifocal seizures and this was used to develop a Bayesian model to estimate the risk of multifocal seizures during an EMU admission. Multifocal interictal discharges were a significant predictor of multifocal seizures within an EMU admission with a p < 0.01, albeit with only modest sensitivity 0.74 and specificity 0.69. Multifocal potentially epileptogenic lesions on MRI were not a significant predictor p = 0.44. Kaplan-Meier analysis was limited by wide confidence intervals secondary to significant patient dropout and concern for informative censoring. The Bayesian framework provided estimates for the number of unifocal seizures needed to predict absence of multifocal seizures. To achieve 90% confidence for the absence of multifocal seizure, three seizures are needed when the pretest probability for multifocal epilepsy is 20%, seven seizures for a pretest probability of 50%, and nine seizures for a pretest probability of 80%. These results provide a framework to assist clinicians in determining the utility of trying to capture a specific number of seizures in EMU evaluations of candidates for epilepsy surgery. Wiley Periodicals, Inc. © 2015

Challenges in risk estimation using routinely collected clinical data: The example of estimating cervical cancer risks from electronic health-records.

PubMed

Landy, Rebecca; Cheung, Li C; Schiffman, Mark; Gage, Julia C; Hyun, Noorie; Wentzensen, Nicolas; Kinney, Walter K; Castle, Philip E; Fetterman, Barbara; Poitras, Nancy E; Lorey, Thomas; Sasieni, Peter D; Katki, Hormuzd A

2018-06-01

Electronic health-records (EHR) are increasingly used by epidemiologists studying disease following surveillance testing to provide evidence for screening intervals and referral guidelines. Although cost-effective, undiagnosed prevalent disease and interval censoring (in which asymptomatic disease is only observed at the time of testing) raise substantial analytic issues when estimating risk that cannot be addressed using Kaplan-Meier methods. Based on our experience analysing EHR from cervical cancer screening, we previously proposed the logistic-Weibull model to address these issues. Here we demonstrate how the choice of statistical method can impact risk estimates. We use observed data on 41,067 women in the cervical cancer screening program at Kaiser Permanente Northern California, 2003-2013, as well as simulations to evaluate the ability of different methods (Kaplan-Meier, Turnbull, Weibull and logistic-Weibull) to accurately estimate risk within a screening program. Cumulative risk estimates from the statistical methods varied considerably, with the largest differences occurring for prevalent disease risk when baseline disease ascertainment was random but incomplete. Kaplan-Meier underestimated risk at earlier times and overestimated risk at later times in the presence of interval censoring or undiagnosed prevalent disease. Turnbull performed well, though was inefficient and not smooth. The logistic-Weibull model performed well, except when event times didn't follow a Weibull distribution. We have demonstrated that methods for right-censored data, such as Kaplan-Meier, result in biased estimates of disease risks when applied to interval-censored data, such as screening programs using EHR data. The logistic-Weibull model is attractive, but the model fit must be checked against Turnbull non-parametric risk estimates. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

XRF and XANES Data for Kaplan U Paper

EPA Pesticide Factsheets

The dataset contains two XRF images of iron and uranium distribution on plant roots and a database of XANES data used to produce XANES spectra figure for Figure 7 in the published paper.This dataset is associated with the following publication:Kaplan, D., R. Kukkadapu, J. Seaman, B. Arey, A. Dohnalkova, S. Buettner, D. Li, T. Varga, K. Scheckel, and P. Jaffe. Iron Mineralogy and Uranium-Binding Environment in the Rhizosphere of a Wetland Soil. D. Barcelo SCIENCE OF THE TOTAL ENVIRONMENT. Elsevier BV, AMSTERDAM, NETHERLANDS, 569: 53-64, (2016).

A capture-recapture survival analysis model for radio-tagged animals

USGS Publications Warehouse

Pollock, K.H.; Bunck, C.M.; Winterstein, S.R.; Chen, C.-L.; North, P.M.; Nichols, J.D.

1995-01-01

In recent years, survival analysis of radio-tagged animals has developed using methods based on the Kaplan-Meier method used in medical and engineering applications (Pollock et al., 1989a,b). An important assumption of this approach is that all tagged animals with a functioning radio can be relocated at each sampling time with probability 1. This assumption may not always be reasonable in practice. In this paper, we show how a general capture-recapture model can be derived which allows for some probability (less than one) for animals to be relocated. This model is not simply a Jolly-Seber model because it is possible to relocate both dead and live animals, unlike when traditional tagging is used. The model can also be viewed as a generalization of the Kaplan-Meier procedure, thus linking the Jolly-Seber and Kaplan-Meier approaches to survival estimation. We present maximum likelihood estimators and discuss testing between submodels. We also discuss model assumptions and their validity in practice. An example is presented based on canvasback data collected by G. M. Haramis of Patuxent Wildlife Research Center, Laurel, Maryland, USA.

14 CFR 21.142 - Production limitation record.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Production limitation record. 21.142 Section 21.142 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... limitation record. The FAA issues a production limitation record as part of a production certificate. The...

14 CFR 21.142 - Production limitation record.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Production limitation record. 21.142 Section 21.142 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... limitation record. The FAA issues a production limitation record as part of a production certificate. The...

14 CFR 21.142 - Production limitation record.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Production limitation record. 21.142 Section 21.142 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... limitation record. The FAA issues a production limitation record as part of a production certificate. The...

Influence of the vibro-acoustic sensor position on cavitation detection in a Kaplan turbine

NASA Astrophysics Data System (ADS)

Schmidt, H.; Kirschner, O.; Riedelbauch, S.; Necker, J.; Kopf, E.; Rieg, M.; Arantes, G.; Wessiak, M.; Mayrhuber, J.

2014-03-01

Hydraulic turbines can be operated close to the limits of the operating range to meet the demand of the grid. When operated close to the limits, the risk increases that cavitation phenomena may occur at the runner and / or at the guide vanes of the turbine. Cavitation in a hydraulic turbine can cause material erosion on the runner and other turbine parts and reduce the durability of the machine leading to required outage time and related repair costs. Therefore it is important to get reliable information about the appearance of cavitation during prototype operation. In this experimental investigation the high frequency acoustic emissions and vibrations were measured at 20 operating points with different cavitation behaviour at different positions in a large prototype Kaplan turbine. The main goal was a comparison of the measured signals at different sensor positions to identify the sensitivity of the location for cavitation detection. The measured signals were analysed statistically and specific values were derived. Based on the measured signals, it is possible to confirm the cavitation limit of the examined turbine. The result of the investigation shows that the position of the sensors has a significant influence on the detection of cavitation.

Simplified tools for measuring retention in care in antiretroviral treatment program in Ethiopia: cohort and current retention in care.

PubMed

Assefa, Yibeltal; Worku, Alemayehu; Wouters, Edwin; Koole, Olivier; Haile Mariam, Damen; Van Damme, Wim

2012-01-01

Patient retention in care is a critical challenge for antiretroviral treatment programs. This is mainly because retention in care is related to adherence to treatment and patient survival. It is therefore imperative that health facilities and programs measure patient retention in care. However, the currently available tools, such as Kaplan Meier, for measuring retention in care have a lot of practical limitations. The objective of this study was to develop simplified tools for measuring retention in care. Retrospective cohort data were collected from patient registers in nine health facilities in Ethiopia. Retention in care was the primary outcome for the study. Tools were developed to measure "current retention" in care during a specific period of time for a specific "ART-age group" and "cohort retention" in care among patients who were followed for the last "Y" number of years on ART. "Probability of retention" based on the tool for "cohort retention" in care was compared with "probability of retention" based on Kaplan Meier. We found that the new tools enable to measure "current retention" and "cohort retention" in care. We also found that the tools were easy to use and did not require advanced statistical skills. Both "current retention" and "cohort retention" are lower among patients in the first two "ART-age groups" and "ART-age cohorts" than in subsequent "ART-age groups" and "ART-age cohorts". The "probability of retention" based on the new tools were found to be similar to the "probability of retention" based on Kaplan Meier. The simplified tools for "current retention" and "cohort retention" will enable practitioners and program managers to measure and monitor rates of retention in care easily and appropriately. We therefore recommend that health facilities and programs start to use these tools in their efforts to improve retention in care and patient outcomes.

Measuring survival time: a probability-based approach useful in healthcare decision-making.

PubMed

2011-01-01

In some clinical situations, the choice between treatment options takes into account their impact on patient survival time. Due to practical constraints (such as loss to follow-up), survival time is usually estimated using a probability calculation based on data obtained in clinical studies or trials. The two techniques most commonly used to estimate survival times are the Kaplan-Meier method and the actuarial method. Despite their limitations, they provide useful information when choosing between treatment options.

Production of N2 Vegard-Kaplan and Lyman-Birge-Hopfield emissions on Pluto

NASA Astrophysics Data System (ADS)

Jain, Sonal Kumar; Bhardwaj, Anil

2015-01-01

We have developed a model to calculate the emission intensities of various vibrational transitions of N2 triplet band and Lyman-Birge-Hopfield (LBH) band emissions in the dayglow of Pluto for solar minimum, moderate, and maximum conditions. The calculated overhead intensities of Vegard-Kaplan (A3Σu+ -X1 Σg+) , First Positive (B3Πg -A3 Σu+), Second Positive (C3Πu -B3Πg) , Wu-Benesch (W3Δu -B3Πg) , Reverse First Positive, and LBH (a1Πg -X1 Σg+) bands of N2 are 17 (74), 14.8 (64), 2.4 (10.8), 2.9 (12.7), 2.9 (12.5), and 2.3 (10) R, respectively, for solar minimum (maximum) condition. We have predicted the overhead and limb intensities of VK (150-190 nm) and LBH (120-190 nm) bands of N2 on Pluto for the New Horizons (NH) flyby condition that can be observed by ALICE: the ultraviolet imaging spectrograph also know as P-ALICE. The predicted limb intensities of VK and LBH bands peak at radial distance of ∼2000 km with the value of about 5 (13) and 9.5 (22) R for solar zenith angle 60° (0°), respectively. We have also calculated overhead and limb intensities of few prominent transition of CO Fourth Positive bands for NH flyby condition.

Grassland productivity limited by multiple nutrients

USDA-ARS?s Scientific Manuscript database

Limitation of aboveground net primary productivity (ANPP) by nitrogen (N) is widely accepted, but the roles of phosphorus (P), potassium (K) and their combinations remain unclear. Thus we may underestimate nutrient limitation of primary productivity. We conducted standardized sampling of ANPP and ...

Rediscovery of Trust: Erikson, Kaplan, and the Myth of Foster Care.

ERIC Educational Resources Information Center

Ocasio, Jeannette; Knight, Janette

Trust, in much the same way as hope, represents one of the essential components of a healthy upbringing. This article investigates the concept of trust as set forth in Eric Erikson's and Louise Kaplan's theories of basic trust, with particular emphasis on definition and development. The article analyzes some of the criteria that have been…

A cyclostationary multi-domain analysis of fluid instability in Kaplan turbines

NASA Astrophysics Data System (ADS)

Pennacchi, P.; Borghesani, P.; Chatterton, S.

2015-08-01

Hydraulic instabilities represent a critical problem for Francis and Kaplan turbines, reducing their useful life due to increase of fatigue on the components and cavitation phenomena. Whereas an exhaustive list of publications on computational fluid-dynamic models of hydraulic instability is available, the possibility of applying diagnostic techniques based on vibration measurements has not been investigated sufficiently, also because the appropriate sensors seldom equip hydro turbine units. The aim of this study is to fill this knowledge gap and to exploit fully, for this purpose, the potentiality of combining cyclostationary analysis tools, able to describe complex dynamics such as those of fluid-structure interactions, with order tracking procedures, allowing domain transformations and consequently the separation of synchronous and non-synchronous components. This paper will focus on experimental data obtained on a full-scale Kaplan turbine unit, operating in a real power plant, tackling the issues of adapting such diagnostic tools for the analysis of hydraulic instabilities and proposing techniques and methodologies for a highly automated condition monitoring system.

Further delineation of the ear, patella, short stature syndrome (Meier-Gorlin syndrome).

PubMed

Boles, R G; Teebi, A S; Schwartz, D; Harper, J F

1994-07-01

Two daughters of phenotypically normal parents are described with severe proportional dwarfism with microcephaly, peculiar craniofacial anomalies, microtia, absent patellae, joint hyperextensibility, and other anomalies. Intrafamilial variability is minimal. This combination of anomalies has many similarities to the six cases previously described with the Ear, Patellae, Short stature syndrome (Meier-Gorlin syndrome), which is distinguished by the triad of microtia, absent patellae and growth retardation. Autosomal recessive inheritance is strongly suggested by the presence of two pairs of affected siblings and the equal sex ratio.

Air injection test on a Kaplan turbine: prototype - model comparison

NASA Astrophysics Data System (ADS)

Angulo, M.; Rivetti, A.; Díaz, L.; Liscia, S.

2016-11-01

Air injection is a very well-known resource to reduce pressure pulsation magnitude in turbines, especially on Francis type. In the case of large Kaplan designs, even when not so usual, it could be a solution to mitigate vibrations arising when tip vortex cavitation phenomenon becomes erosive and induces structural vibrations. In order to study this alternative, aeration tests were performed on a Kaplan turbine at model and prototype scales. The research was focused on efficiency of different air flow rates injected in reducing vibrations, especially at the draft tube and the discharge ring and also in the efficiency drop magnitude. It was found that results on both scales presents the same trend in particular for vibration levels at the discharge ring. The efficiency drop was overestimated on model tests while on prototype were less than 0.2 % for all power output. On prototype, air has a beneficial effect in reducing pressure fluctuations up to 0.2 ‰ of air flow rate. On model high speed image computing helped to quantify the volume of tip vortex cavitation that is strongly correlated with the vibration level. The hydrophone measurements did not capture the cavitation intensity when air is injected, however on prototype, it was detected by a sonometer installed at the draft tube access gallery.

Is early limited surgery associated with a more benign disease course in Crohn’s disease?

PubMed Central

Golovics, Petra Anna; Lakatos, Laszlo; Nagy, Attila; Pandur, Tunde; Szita, Istvan; Balogh, Mihaly; Molnar, Csaba; Komaromi, Erzsebet; Lovasz, Barbara Dorottya; Mandel, Michael; Veres, Gabor; Kiss, Lajos S; Vegh, Zsuzsanna; Lakatos, Peter Laszlo

2013-01-01

AIM: To analyze the difference in disease course and need for surgery in patients with Crohn’s disease (CD). METHODS: Data of 506 patients with incident CD were analyzed (age at diagnosis: 31.5 ± 13.8 years). Both hospital and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database, which includes incident CD patients diagnosed between January 1, 1977 and December 31, 2008. Follow-up data were collected until December 31, 2009. All patients included had at least 1 year of follow-up available. Patients with indeterminate colitis at diagnosis were excluded from the analysis. RESULTS: Overall, 73 patients (14.4%) required resective surgery within 1 year of diagnosis. Steroid exposure and need for biological therapy were lower in patients with early limited surgery (P < 0.001 and P = 0.09). In addition, surgery rates during follow-up in patients with and without early surgery differed significantly after matching on propensity scores (P < 0.001, HR = 0.23). The need for reoperation was also lower in patients with early limited resective surgery (P = 0.038, HR = 0.42) in a Kaplan-Meier and multivariate Cox regression (P = 0.04) analysis. However, this advantage was not observed after matching on propensity scores (PLogrank = 0.656, PBreslow = 0.498). CONCLUSION: Long-term surgery rates and overall exposure to steroids and biological agents were lower in patients with early limited resective surgery, but reoperation rates did not differ. PMID:24282358

The prognostic implications of growth-related gene product β in laryngeal squamous cell carcinoma.

PubMed

Tang, Mingming; Xu, Xinjiang; Chen, Juanjuan; Huang, Jiangfei; Jiang, Bin; Han, Liang

2017-09-01

Growth-related gene product β (GROβ) is an angiogenic chemokine that belongs to the CXC chemokine family, and a number of studies have suggested that GROβ is associated with tumor development and progression. However, a number of studies have investigated the association between GROβ expression and the clinical attributes of laryngeal squamous cell carcinoma (LSCC). In the present study, one-step quantitative polymerase chain reaction and immunohistochemistry analysis were used to detect GROβ expression and evaluate the association between its expression and the clinicopathological characteristics of LSCC. The results demonstrated that the GROβ mRNA and protein expression levels were significantly increased in LSCC compared with the corresponding non-cancerous tissues. GROβ protein expression in LSCC was associated with tumor-node-metastasis stage, lymph node metastasis and histopathological grade. The Kaplan-Meier method and Cox multi-factor analysis indicated that high GROβ expression, lymph node metastasis and histopathological grade were significantly associated with poor survival of patients with LSCC. These data indicated that GROβ may be a novel prognostic biomarker of LSCC.

Going Large or Going Small in Plant Design: Comparison between a P.P. with three small Kaplan turbines and a P.P. with just one Large Kaplan turbine

NASA Astrophysics Data System (ADS)

Castro-Otero, C.

2017-04-01

Very often small turbine manufacturers are requested to produce sizeable turbines, too large in terms of physical dimensions, power or designing capacity. In these cases clever alternative solutions should be found to meet customers’ needs. For instance: in the old times twin runner Francis turbines were an option instead of one large machine, or if a too large Pelton turbine cannot be manufactured or designed, a good option is to install a medium size Francis and a small Pelton. Likewise, a similar approach needs to be taken should the manufacturer be asked for a too large Kaplan. Facing this situation a good option is to install three or more small Kaplan turbines. This particular case was studied in depth and after all the considerations had been made, the following question arouse: Is this a way out for the manufacturer or is it really the best option for the customer? The choice made as a way out for the manufacturer became the best option for the customer and a success for both parties. This paper aims to encourage developers and engineering firms to search for more options than the traditional one to find the best option in plant design.

Relationship of employee-reported work limitations to work productivity.

PubMed

Lerner, Debra; Amick, Benjamin C; Lee, Jennifer C; Rooney, Ted; Rogers, William H; Chang, Hong; Berndt, Ernst R

2003-05-01

Work limitation rates are crucial indicators of the health status of working people. If related to work productivity, work limitation rates may also supply important information about the economic burden of illness. Our objective was to assess the productivity impact of on-the-job work limitations due to employees' physical or mental health problems. Subjects were asked to complete a self-administered survey on the job during 3 consecutive months. Using robust regression analysis, we tested the relationship of objectively-measured work productivity to employee-reported work limitations. We attempted to survey employees of a large firm within 3 different jobs. The survey response rate was 2245 (85.9%). Full survey and productivity data were available for 1827 respondents. Each survey included a validated self-report instrument, the Work Limitations Questionnaire (WLQ). The firm provided objective, employee-level work productivity data. In adjusted regression analyses (n = 1827), employee work productivity (measured as the log of units produced/hour) was significantly associated with 3 dimensions of work limitations: limitations handling the job's time and scheduling demands (P = 0.003), physical job demands (P = 0.001), and output demands (P = 0.006). For every 10% increase in on-the-job work limitations reported on each of the 3 WLQ scales, work productivity declined approximately 4 to 5%. Employee work limitations have a negative impact on work productivity. Employee assessments of their work limitations supply important proxies for the economic burden of health problems.

The limits of crop productivity

NASA Technical Reports Server (NTRS)

Bugbee, Bruce; Monje, Oscar

1992-01-01

The component processes that govern yield limits in food crops are reviewed and how each process can be individually measured is described. The processes considered include absorption of photosynthetic radiation by green tissue, carbon-fixation efficiency in photosynthesis, carbon use efficiency in respiration, biomass allocation to edible products, and efficiency of photosynthesis and respiration. The factors limiting yields in optimal environments are considered.

Gamma Knife radiosurgery for intracranial hemangioblastoma.

PubMed

Silva, Danilo; Grabowski, Mathew M; Juthani, Rupa; Sharma, Mayur; Angelov, Lilyana; Vogelbaum, Michael A; Chao, Samuel; Suh, John; Mohammadi, Alireza; Barnett, Gene H

2016-09-01

Gamma knife radiosurgery (GKRS) has become a treatment option for intracranial hemangioblastomas, especially in patients with poor clinical status and also high-risk surgical candidates. The objective of this study was to analyze clinical outcome and tumor control rates. Retrospective chart review revealed 12 patients with a total of 20 intracranial hemangioblastomas treated with GKRS from May 1998 until December 2014. Kaplan-Meier plots were used to calculate the actuarial local tumor control rates and rate of recurrence following GKRS. Univariate analysis, including log rank test and Wilcoxon test were used on the Kaplan-Meier plots to evaluate the predictors of tumor progression. Two-tailed p value of <0.05 was considered as significant. Median follow-up was 64months (2-184). Median tumor volume pre-GKRS was 946mm(3) (79-15970), while median tumor volume post-GKRS was 356mm(3) (30-5404). Complications were seen in two patients. Tumor control rates were 100% at 1year, 90% at 3years, and 85% at 5years, using the Kaplan-Meier method. There were no statistically significant univariate predictors of progression identified, although there was a trend towards successful tumor control in solid tumors (p=0.07). GKRS is an effective and safe option for treating intracranial hemangioblastoma with favorable tumor control rates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical outcomes in patients with node-negative breast cancer treated based on the recurrence score results: evidence from a large prospectively designed registry.

PubMed

Stemmer, Salomon M; Steiner, Mariana; Rizel, Shulamith; Soussan-Gutman, Lior; Ben-Baruch, Noa; Bareket-Samish, Avital; Geffen, David B; Nisenbaum, Bella; Isaacs, Kevin; Fried, Georgeta; Rosengarten, Ora; Uziely, Beatrice; Svedman, Christer; McCullough, Debbie; Maddala, Tara; Klang, Shmuel H; Zidan, Jamal; Ryvo, Larisa; Kaufman, Bella; Evron, Ella; Karminsky, Natalya; Goldberg, Hadassah; Shak, Steven; Liebermann, Nicky

2017-01-01

The 21-gene Recurrence Score® (RS) assay is a validated prognostic/predictive tool in ER + early-stage breast cancer. However, clinical outcome data from prospective studies in RS ≥ 11 patients are lacking, as are relevant real-life clinical practice data. In this retrospective analysis of a prospectively designed registry, we evaluated treatments/clinical outcomes in patients undergoing RS-testing through Clalit Health Services. The analysis included N0 ER + HER2-negative breast cancer patients who were RS-tested from 1/2006 through 12/2010. Medical records were reviewed to verify treatments/recurrences/survival. The cohort included 1801 patients (median follow-up, 6.2 years). Median age was 60 years, 50.4% were grade 2 and 81.1% had invasive ductal carcinoma; 48.9% had RS < 18, 40.7% RS 18-30, and 10.4% RS ≥ 31, with chemotherapy use of 1.4, 23.7, and 87.2%, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 0.8, 3.0, and 8.6%, for patients with RS < 18, RS 18-30 and RS ≥ 31, respectively; the corresponding 5-year Kaplan-Meier estimates for breast cancer death were 0.0, 0.9, and 6.2%. Chemotherapy-untreated patients with RS < 11 ( n  = 304) and 11-25 ( n  = 1037) (TAILORx categorizatio n ) had 5-year Kaplan-Meier estimates for distant recurrence risk/breast cancer death of 1.0%/0.0% and 1.3%/0.4%, respectively. Our results extend those of the prospective TAILORx trial: the 5-year Kaplan-Meier estimates for distant recurrence and breast cancer death rate for the RS < 18 patients were very low supporting the use of endocrine therapy alone. Furthermore, in chemotherapy-untreated patients with RS 11-25 (where TAILORx patients were randomized to chemoendocrine or endocrine therapy alone), 5-year distant recurrence rates were also very low, suggesting that chemotherapy would not have conferred clinically meaningful benefit.

Analyzing hydro abrasive erosion in Kaplan turbine: A case study from India

NASA Astrophysics Data System (ADS)

Rai, Anant Kr.; Kumar, Arun

2016-10-01

Sediment flow through hydro turbine causes erosion of hydraulic components resulting in drop of turbine efficiency, particularly in hydropower plants of the Himalayan region. The measurement of erosion and monitoring of sediment flow in turbine are major concerns in erosion study. Attempts have been made to study erosion mainly in Pelton and Francis turbines. In this study, a simple and effective method has been presented to measure erosion in a Kaplan turbine of a run-of-river scheme Chilla hydropower plant in foothills of Himalaya. Recent techniques were used to measure sediment parameters like concentration, size, shape and mineral content. A standard erosion model is applied to estimate the erosion in Kaplan turbine blade, runner chamber and draft tube cone. A calibration factor has been proposed to apply the erosion model for site specific conditions. It has been found that the outer trailing edges of the turbine blade and upper runner chamber are most erosion prone zones. Sediment analysis revealed that effective operation can reduce erosion in turbine components. The estimated erosion values from model are found to be consistent with measured values. Finally, suggestions for design improvements and effective operation of erosion affected hydropower plants are given.

High serum uric acid concentration predicts poor survival in patients with breast cancer.

PubMed

Yue, Cai-Feng; Feng, Pin-Ning; Yao, Zhen-Rong; Yu, Xue-Gao; Lin, Wen-Bin; Qian, Yuan-Min; Guo, Yun-Miao; Li, Lai-Sheng; Liu, Min

2017-10-01

Uric acid is a product of purine metabolism. Recently, uric acid has gained much attraction in cancer. In this study, we aim to investigate the clinicopathological and prognostic significance of serum uric acid concentration in breast cancer patients. A total of 443 female patients with histopathologically diagnosed breast cancer were included. After a mean follow-up time of 56months, survival was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of uric acid concentrations, univariate and multivariate Cox regression analyses were applied. Of the clinicopathological parameters, uric acid concentration was associated with age, body mass index, ER status and PR status. Univariate analysis identified that patients with increased uric acid concentration had a significantly inferior overall survival (HR 2.13, 95% CI 1.15-3.94, p=0.016). In multivariate analysis, we found that high uric acid concentration is an independent prognostic factor predicting death, but insufficient to predict local relapse or distant metastasis. Kaplan-Meier analysis indicated that high uric acid concentration is related to the poor overall survival (p=0.013). High uric acid concentration predicts poor survival in patients with breast cancer, and might serve as a potential marker for appropriate management of breast cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Predictive value of initial FDG-PET features for treatment response and survival in esophageal cancer patients treated with chemo-radiation therapy using a random forest classifier.

PubMed

Desbordes, Paul; Ruan, Su; Modzelewski, Romain; Pineau, Pascal; Vauclin, Sébastien; Gouel, Pierrick; Michel, Pierre; Di Fiore, Frédéric; Vera, Pierre; Gardin, Isabelle

2017-01-01

compared to the Mann-Whitney U test and the univariate Kaplan-Meier survival analysis when applied to several tens of features in a limited patient database.

Evaluation of Revascularization Subtypes in Octogenarians Undergoing Coronary Artery Bypass Grafting

PubMed Central

Aziz, Abdulhameed; Lee, Anson M.; Pasque, Michael K.; Lawton, Jennifer S.; Moazami, Nader; Damiano, Ralph J.; Moon, Marc R.

2009-01-01

Background Recent data suggest that octogenarians’ long-term survival after complete CABG revascularization is superior to incomplete revascularization. Discriminating between variable definitions of “complete” complicates interpretation of survival data. We aimed to clarify octogenarian long-term survival rates by stratifying revascularization subtypes. Methods and Results From 1986 to 2007, 580 patients 80 to 94 years of age underwent CABG. Functional complete revascularization was defined as at least one graft to all diseased coronary vessels with greater than 50% stenosis. Traditional complete revascularization was defined as one graft to each major arterial system with at least 50% stenosis. Incomplete revascularization was defined as leaving diseased, ungrafted regions. Revascularization was functional in 279 (48%), traditional in 181 (31%), and incomplete in 120 (21%). Long-term survival was evaluated by Kaplan-Meier analysis. Of 537 operative survivors, there were 402 late deaths. Cumulative long-term survival totaled 2,890 patient-years. Late survival (Kaplan-Meier) was similar between functional (6.8 years, mean) and traditional (6.7 years) groups (p=0.51), but diminished with incomplete (4.2 years) revascularization (p=0.007). Survival by group at 5 years was: 59±3% functional, 57±4% traditional, and 45±5% incomplete. Survival at 8 years was: 40±3% functional, 37±4% traditional, and 26±5% incomplete. To minimize selection bias in patients with limited life expectancy, Kaplan-Meier analysis was repeated including only patients with survival greater than 12 months. Survival was again impaired with incomplete revascularization (p=0.04), and there was no difference between functional and traditional complete revascularization (p=0.73). Conclusions Bypassing all diseased arterial vessels after revascularization does not afford significant long-term survival advantage compared to a traditional approach. Incomplete revascularization, related to more

Repair of Kaplan turbine shaft sealing based on evaluation of hydraulic conditions

NASA Astrophysics Data System (ADS)

Lakatos, K.; Szamosi, Z.; Bereczkei, S.

2012-11-01

This paper has been written to call attention to a potential danger what may occur in Kaplan turbine refurbishments. In Tiszalök hydropower plant, Hungary, the shaft sealing of the refurbished turbine was damaged. In searching for the reasons it was assumed that due to increased internal velocities in the turbine, the pressure at the hub clearance became lower than the atmospheric pressure, and therefore the sealing, which always operated satisfactorily before the refurbishment, had uncertain water supply, dry-running occurred, and after some time the sealing was burnt. First the flow conditions in the turbine and the pressure at the hub clearance were calculated by a one-dimensional flow model. Later this was refined by a two-dimensional approach. The above conclusion was also justified by the data acquisition system and by observing the operation of the small dewatering pump. When the turbine operated at a larger discharge than a certain limit value, then the dewatering pump remained standstill, indicating that no water passed through the shaft sealing. External water supply was then applied, and after this the turbine operated all right.

Robustness of survival estimates from radio-telemetry studies with uncertain relocation of individuals

USGS Publications Warehouse

Bunck, C.M.; Chen, C.-L.; Pollock, K.H.

1995-01-01

Traditional methods of estimating survival from radio-telemetry studies use either the Trent-Rongstad approach (Trent and Rongstad 1974, Heisey and Fuller 1985) or the Kaplan-Meier approach (Kaplan and Meier 1958; Pollock et al. 1989a,b). Both methods appear to require the assumption that relocation probability for animals with a functioning radio is 1. In practice this may not always be reasonable and, in fact, is unnecessary. The number of animals at risk (i.e., risk set) can be modified to account for uncertain relocation of individuals. This involves including only relocated animals in the risk set instead of also including animals not relocated but that were seen later. Simulation results show that estimators and tests for comparing survival curves should be based on this modification.

Numerical investigation of tip clearance cavitation in Kaplan runners

NASA Astrophysics Data System (ADS)

Nikiforova, K.; Semenov, G.; Kuznetsov, I.; Spiridonov, E.

2016-11-01

There is a gap between the Kaplan runner blade and the shroud that makes for a special kind of cavitation: cavitation in the tip leakage flow. Two types of cavitation caused by the presence of clearance gap are known: tip vortex cavitation that appears at the core of the rolled up vortex on the blade suction side and tip clearance cavitation that appears precisely in the gap between the blade tip edge and the shroud. In the context of this work numerical investigation of the model Kaplan runner has been performed taking into account variable tip clearance for several cavitation regimes. The focus is put on investigation of structure and origination of mechanism of cavitation in the tip leakage flow. Calculations have been performed with the help of 3-D unsteady numerical model for two-phase medium. Modeling of turbulent flow in this work has been carried out using full equations of Navier-Stokes averaged by Reynolds with correction for streamline curvature and system rotation. For description of this medium (liquid-vapor) simplification of Euler approach is used; it is based on the model of interpenetrating continuums, within the bounds of this two- phase medium considered as a quasi-homogeneous mixture with the common velocity field and continuous distribution of density for both phases. As a result, engineering techniques for calculation of cavitation conditioned by existence of tip clearance in model turbine runner have been developed. The detailed visualization of the flow was carried out and vortex structure on the suction side of the blade was reproduced. The range of frequency with maximum value of pulsation was assigned and maximum energy frequency was defined; it is based on spectral analysis of the obtained data. Comparison between numerical computation results and experimental data has been also performed. The location of cavitation zone has a good agreement with experiment for all analyzed regimes.

Applications of statistics to medical science, IV survival analysis.

PubMed

Watanabe, Hiroshi

2012-01-01

The fundamental principles of survival analysis are reviewed. In particular, the Kaplan-Meier method and a proportional hazard model are discussed. This work is the last part of a series in which medical statistics are surveyed.

Nested Cohort - R software package

Cancer.gov

NestedCohort is an R software package for fitting Kaplan-Meier and Cox Models to estimate standardized survival and attributable risks for studies where covariates of interest are observed on only a sample of the cohort.

Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis.

PubMed

Fenwick, Aimee L; Kliszczak, Maciej; Cooper, Fay; Murray, Jennie; Sanchez-Pulido, Luis; Twigg, Stephen R F; Goriely, Anne; McGowan, Simon J; Miller, Kerry A; Taylor, Indira B; Logan, Clare; Bozdogan, Sevcan; Danda, Sumita; Dixon, Joanne; Elsayed, Solaf M; Elsobky, Ezzat; Gardham, Alice; Hoffer, Mariette J V; Koopmans, Marije; McDonald-McGinn, Donna M; Santen, Gijs W E; Savarirayan, Ravi; de Silva, Deepthi; Vanakker, Olivier; Wall, Steven A; Wilson, Louise C; Yuregir, Ozge Ozalp; Zackai, Elaine H; Ponting, Chris P; Jackson, Andrew P; Wilkie, Andrew O M; Niedzwiedz, Wojciech; Bicknell, Louise S

2016-07-07

DNA replication precisely duplicates the genome to ensure stable inheritance of genetic information. Impaired licensing of origins of replication during the G1 phase of the cell cycle has been implicated in Meier-Gorlin syndrome (MGS), a disorder defined by the triad of short stature, microtia, and a/hypoplastic patellae. Biallelic partial loss-of-function mutations in multiple components of the pre-replication complex (preRC; ORC1, ORC4, ORC6, CDT1, or CDC6) as well as de novo stabilizing mutations in the licensing inhibitor, GMNN, cause MGS. Here we report the identification of mutations in CDC45 in 15 affected individuals from 12 families with MGS and/or craniosynostosis. CDC45 encodes a component of both the pre-initiation (preIC) and CMG helicase complexes, required for initiation of DNA replication origin firing and ongoing DNA synthesis during S-phase itself, respectively, and hence is functionally distinct from previously identified MGS-associated genes. The phenotypes of affected individuals range from syndromic coronal craniosynostosis to severe growth restriction, fulfilling diagnostic criteria for Meier-Gorlin syndrome. All mutations identified were biallelic and included synonymous mutations altering splicing of physiological CDC45 transcripts, as well as amino acid substitutions expected to result in partial loss of function. Functionally, mutations reduce levels of full-length transcripts and protein in subject cells, consistent with partial loss of CDC45 function and a predicted limited rate of DNA replication and cell proliferation. Our findings therefore implicate the preIC as an additional protein complex involved in the etiology of MGS and connect the core cellular machinery of genome replication with growth, chondrogenesis, and cranial suture homeostasis. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

The Educational Philosophies of Mordecai Kaplan and Michael Rosenak: Surprising Similarities and Illuminating Differences

ERIC Educational Resources Information Center

Schein, Jeffrey; Caplan, Eric

2014-01-01

The thoughts of Mordecai Kaplan and Michael Rosenak present surprising commonalities as well as illuminating differences. Similarities include the perception that Judaism and Jewish education are in crisis, the belief that Jewish peoplehood must include commitment to meaningful content, the need for teachers to teach from a position of…

Ultra-processed foods and the limits of product reformulation.

PubMed

Scrinis, Gyorgy; Monteiro, Carlos Augusto

2018-01-01

The nutritional reformulation of processed food and beverage products has been promoted as an important means of addressing the nutritional imbalances in contemporary dietary patterns. The focus of most reformulation policies is the reduction in quantities of nutrients-to-limit - Na, free sugars, SFA, trans-fatty acids and total energy. The present commentary examines the limitations of what we refer to as 'nutrients-to-limit reformulation' policies and practices, particularly when applied to ultra-processed foods and drink products. Beyond these nutrients-to-limit, there are a range of other potentially harmful processed and industrially produced ingredients used in the production of ultra-processed products that are not usually removed during reformulation. The sources of nutrients-to-limit in these products may be replaced with other highly processed ingredients and additives, rather than with whole or minimally processed foods. Reformulation policies may also legitimise current levels of consumption of ultra-processed products in high-income countries and increased levels of consumption in emerging markets in the global South.

Clozapine, Diabetes Mellitus, Cardiovascular Risk and Mortality: Results of a 21-year Naturalistic Study in Patients with Schizophrenia and Schizoaffective Disorder.

PubMed

Nemani, Katlyn L; Greene, M Claire; Ulloa, Melissa; Vincenzi, Brenda; Copeland, Paul M; Al-Khadari, Sulaiman; Henderson, David C

2017-11-22

The goal of this 21-year naturalistic study of clozapine treated patients was to examine the cardiovascular risk factors following clozapine initiation and resultant mortality estimates from cardiovascular disease. Data was collected from medical records of clozapine treated patients with schizophrenia or schizoaffective disorder from January 1992 to February 2012. Demographics, clozapine dosage and laboratory results were extracted at 12-month intervals. At clozapine initiation, the mean age of 96 patients was 36.4 years ±7.6 years; N=27(28%) were women. The mean duration of clozapine use was 13 years. The Kaplan-Meier estimate for 21-year cardiovascular events was 29%, while the Kaplan-Meier estimate for 21-year mortality from cardiovascular disease was 10%. The mean cardiovascular risk increased during the first ten years (p<.01), while a slight decrease occurred beyond ten years (p<.01). Patients involved in cardiometabolic research showed a greater decrease in cardiovascular risk factors over 21 years (p = .05). The Kaplan-Meier estimate for 21-year all-cause mortality was 22%. Forty-one patients were diagnosed with diabetes (42.7%), compared to a nationwide prevalence of 13.7% in a similar age group. These results support the hypothesis that clozapine-treated patients are at risk for cardiovascular events and death secondary to an increased risk of medical disorders. Interventions that target weight loss, smoking cessation, and lipid profile improvement may alleviate the increased risk of cardiovascular mortality.

Competing approaches to analysis of failure times with competing risks.

PubMed

Farley, T M; Ali, M M; Slaymaker, E

2001-12-15

For the analysis of time to event data in contraceptive studies when individuals are subject to competing causes for discontinuation, some authors have recently advocated the use of the cumulative incidence rate as a more appropriate measure to summarize data than the complement of the Kaplan-Meier estimate of discontinuation. The former method estimates the rate of discontinuation in the presence of competing causes, while the latter is a hypothetical rate that would be observed if discontinuations for the other reasons could not occur. The difference between the two methods of analysis is the continuous time equivalent of a debate that took place in the contraceptive literature in the 1960s, when several authors advocated the use of net (adjusted or single decrement life table rates) rates in preference to crude rates (multiple decrement life table rates). A small simulation study illustrates the interpretation of the two types of estimate - the complement of the Kaplan-Meier estimate corresponds to a hypothetical rate where discontinuations for other reasons did not occur, while the cumulative incidence gives systematically lower estimates. The Kaplan-Meier estimates are more appropriate when estimating the effectiveness of a contraceptive method, but the cumulative incidence estimates are more appropriate when making programmatic decisions regarding contraceptive methods. Other areas of application, such as cancer studies, may prefer to use the cumulative incidence estimates, but their use should be determined according to the application. Copyright 2001 John Wiley & Sons, Ltd.

Load variation effects on the pressure fluctuations exerted on a Kaplan turbine runner

NASA Astrophysics Data System (ADS)

Amiri, K.; Mulu, B.; Raisee, M.; Cervantes, M. J.

2014-03-01

Introduction of intermittent electricity production systems like wind power and solar systems to electricity market together with the consumption-based electricity production resulted in numerous start/stops, load variations and off-design operation of water turbines. The hydropower systems suffer from the varying loads exerted on the stationary and rotating parts of the turbines during load variations which they are not designed for. On the other hand, investigations on part load operation of single regulated turbines, i.e., Francis and propeller, proved the formation of rotating vortex rope (RVR) in the draft tube. The RVR induces oscillating flow both in plunging and rotating modes which results in oscillating force with two different frequencies on the runner blades, bearings and other rotating parts of the turbine. The purpose of this study is to investigate the effect of transient operations on the pressure fluctuations on the runner and mechanism of the RVR formation/mitigation. Draft tube and runner blades of the Porjus U9 model, a Kaplan turbine, were equipped with pressure sensors. The model was run in off-cam mode during different load variation conditions to check the runner performance under unsteady condition. The results showed that the transients between the best efficiency point and the high load happens in a smooth way while transitions to/from the part load, where rotating vortex rope (RVR) forms in the draft tube induces high level of fluctuations with two frequencies on the runner; plunging and rotating mode of the RVR.

A Meier-Gorlin syndrome mutation impairs the ORC1-nucleosome association.

PubMed

Zhang, Wei; Sankaran, Saumya; Gozani, Or; Song, Jikui

2015-05-15

Recent studies have identified several genetic mutations within the BAH domain of human Origin Recognition Complex subunit 1 (hORC1BAH), including the R105Q mutation, implicated in Meier-Gorlin Syndrome (MGS). However, the pathological role of the hORC1 R105Q mutation remains unclear. In this study, we have investigated the interactions of the hORC1BAH domain with histone H4K20me2, DNA, and the nucleosome core particle labeled with H4Kc20me2, a chemical analog of H4K20me2. Our study revealed a nucleosomal DNA binding site for hORC1BAH. The R105Q mutation reduces the hORC1BAH-DNA binding affinity, leading to impaired hORC1BAH-nucleosome interaction, which likely influences DNA replication initiation and MGS pathogenesis. This study provides an etiologic link between the hORC1 R105Q mutation and MGS.

Reactivity of TNT & TNT - Microbial Reduction Products with Soil Components

DTIC Science & Technology

1983-07-01

TECHNICAL REPORT REACTIVITY OF N TNT & TNT - MICROBIAL REDUCTION PRODUCTS WITH SOIL COMPONENTS BY D. L.KAPLAN ANDDTI C A. M. KAPLAN APPPoVrD FOPJUY1S...3. RECIPIENT’S CATALOG NUMBER NATICK TR-83/041 / 5c ’_______________ 4. TITLE (and Subtitle) S. TYPE OF REPORT & PERIOD -COVERED REACTIVITY OF TNT... REACTIVITY OF TNT AND TNT-MICROBIAL REDUCTION PRODUCTS WITH SOIL COMPONENTS INTRODUCTION Contamination of soils by hazardous wastes (toxic

Comparative pathogenicity of Vibrio spp., Photobacterium damselae ssp. damselae and five isolates of Aeromonas salmonicida ssp. achromogenes in juvenile Atlantic halibut (Hippoglossus hippoglossus).

PubMed

Bowden, T J; Bricknell, I R; Preziosi, B M

2018-01-01

Juvenile Atlantic halibut (~100 mg, Hippoglossus hippoglossus) were exposed to Vibrio proteolyticus, a Vibrio spp. isolate, Photobacterium damselae ssp. damselae and five different isolates of Aeromonas salmonicida ssp. achromogenes via an hour-long bath immersion to ascertain their variation in pathogenicity to this fish species. Results were analysed using Kaplan-Meier survival analysis. Analysis of the data from challenges using A. salmonicida ssp. achromogenes revealed three survival values of zero and a spread of values from 0 to 28.43. Challenges using a Vibrio spp isolate, V. proteolyticus and P. damselae resulted in Kaplan-Meier survival estimates of 31.21, 50.41 and 57.21, respectively. As all bacterial species tested could induce juvenile halibut mortalities, they must all be considered as potential pathogens. However, the degree of pathogenicity of A. salmonicida is isolate dependent. © 2017 John Wiley & Sons Ltd.

Parental consanguineous marriages and clinical response to chemotherapy in locally advanced breast cancer patients.

PubMed

Saadat, Mostafa; Khalili, Maryam; Omidvari, Shahpour; Ansari-Lari, Maryam

2011-03-28

The main aim of the present study was investigating the association between parental consanguinity and clinical response to chemotherapy in females affected with locally advanced breast cancer. A consecutive series of 92 patients were prospectively included in this study. Clinical assessment of treatment was accomplished by comparing initial tumor size with preoperative tumor size using revised RECIST guideline (version 1.1). Clinical response defined as complete response, partial response and no response. The Kaplan-Meier survival analysis were used to evaluate the association of parental marriages (first cousin vs unrelated marriages) and clinical response to chemotherapy (complete and partial response vs no response). Number of courses of chemotherapy was considered as time, in the analysis. Kaplan-Meier analysis revealed that offspring of unrelated marriages had poorer response to chemotherapy (log rank statistic=5.10, df=1, P=0.023). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

An evaluation of treatment strategies for head and neck cancer in an African American population.

PubMed

Ignacio, D N; Griffin, J J; Daniel, M G; Serlemitsos-Day, M T; Lombardo, F A; Alleyne, T A

2013-07-01

This study evaluated treatment strategies for head and neck cancers in a predominantly African American population. Data were collected utilizing medical records and the tumour registry at the Howard University Hospital. Kaplan-Meier method was used for survival analysis and Cox proportional hazards regression analysis predicted the hazard of death. Analysis revealed that the main treatment strategy was radiation combined with platinum for all stages except stage I. Cetuximab was employed in only 1% of cases. Kaplan-Meier analysis revealed stage II patients had poorer outcome than stage IV while Cox proportional hazard regression analysis (p = 0.4662) showed that stage I had a significantly lower hazard of death than stage IV (HR = 0.314; p = 0.0272). Contributory factors included tobacco and alcohol but body mass index (BMI) was inversely related to hazard of death. There was no difference in survival using any treatment modality for African Americans.

Attrition of U.S. military enlistees with waivers for hearing deficiency, 1995-2004.

PubMed

Niebuhr, David W; Li, Yuanzhang; Powers, Timothy E; Krauss, Margot R; Chandler, David; Helfer, Thomas

2007-01-01

Hearing deficiency is the condition for which accession medical waivers are most commonly granted. The retention of individuals entering service with a waiver for hearing deficiency has not been previously studied. Military retention among new enlistees with a medical waiver for hearing deficiency was compared with that among a matched comparison group of fully qualified enlistees. Comparisons according to branch of service over the first 3 years of service were performed with the Kaplan-Meier product-limit method and proportional-hazards model. Army subjects had significantly lower retention rates than did their fully qualified counterparts. In the adjusted model, Army and Navy enlistees with a waiver for hearing deficiency had a significantly lower likelihood of retention than did their matched counterparts. The increased likelihood of medical attrition in enlistees with a waiver for hearing loss provides no evidence to make the hearing accession standard more lenient and validates a selective hearing loss waiver policy.

The TP53 gene polymorphisms and survival of sporadic breast cancer patients.

PubMed

Bišof, V; Salihović, M Peričić; Narančić, N Smolej; Skarić-Jurić, T; Jakić-Razumović, J; Janićijević, B; Rudan, P

2012-06-01

The TP53 gene polymorphisms, Arg72Pro and PIN3 (+16 bp), can have prognostic and predictive value in different cancers including breast cancer. The aim of the present study is to investigate a potential association between different genotypes of these polymorphisms and clinicopathological variables with survival of breast cancer patients in Croatian population. Ninety-four women with sporadic breast cancer were retrospectively analyzed. Median follow-up period was 67.9 months. The effects of basic clinical and histopathological characteristics of tumor on survival were tested by Cox's proportional hazards regression analysis. The TNM stage was associated with overall survival by Kaplan-Meier analysis, univariate, and multivariate Cox's proportional hazards regression analysis, while grade was associated with survival by Kaplan-Meier analysis and univariate Cox's proportional hazards regression analysis. Different genotypes of the Arg72Pro and PIN3 (+16 bp) polymorphisms had no significant impact on survival in breast cancer patients. However, in subgroup of patients treated with chemotherapy without anthracycline, the A2A2 genotype of the PIN3 (+16 bp) polymorphism was associated with poorer overall survival than other genotypes by Kaplan-Meier analysis (P = 0.048). The TP53 polymorphisms, Arg72Pro and PIN3 (+16 bp), had no impact on survival in unselected sporadic breast cancer patients in Croatian population. However, the results support the role of the A2A2 genotype of the PIN3 (+16 bp) polymorphism as a marker for identification of patients that may benefit from anthracycline-containing chemotherapy.

Comparative Study of Barotrauma Risk during Fish Passage through Kaplan Turbines

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

Richmond, Marshall C.; Romero-Gomez, Pedro; Serkowski, John A.

Rapid pressure changes in hydroelectric turbine flows can cause barotrauma that can be hazardous to the passage of fish, in particular migratory juvenile salmonids. Although numerous laboratory tests have evaluated the effect of rapid decompression in fish species of relevance, numerical modeling studies offer the advantage of predicting, for new turbine designs, the potential risks of mortality and injury from rapid pressure change during turbine passage. However, rapid pressure change is only one of several hydraulic risks encountered by fish during turbine passage in addition to blade strike, shear, and turbulence. To better understand the role of rapid pressure changes,more » the present work focuses on the application of a computational fluid dynamics based method for evaluating the risk of pressure-related mortality to fish passing through an early 1960s era original hydroelectric Kaplan turbine at Wanapum Dam (Columbia River, Washington), and a modern advanced Kaplan turbine installed in 2005. The results show that the modeling approach acceptably reproduced the nadir pressure distributions compared to field data previously collected at the site using an autonomous sensor. Our findings show that the new advanced-design unit performs better, in terms of reduced barotrauma risk to fish from exposure to low pressures, than the original turbine unit. The outcomes allow for comparative analyses of turbine designs and operations prior to installation, an advantage that can potentially be integrated in the process of designing new turbine units to achieve superior environmental performance. Overall, the results show that modern turbine designs can achieve the multiple objectives of increasing power generation, lowering cavitation potential, and reducing barotrauma risks to passing fish.« less

Twenty-year follow-up study of long-term survival of limited-stage small-cell lung cancer and overview of prognostic and treatment factors.

PubMed

Tai, Patricia; Tonita, Jon; Yu, Edward; Skarsgard, David

2003-07-01

To predict the long-term survival results of clinical trials earlier than using actuarial methods and to assess the factors predictive of long-term cure in patients with limited-stage small-cell lung cancer. Between 1981 and 1998, 1417 new cases of small-cell lung cancer were diagnosed in Saskatchewan, Canada, of which 244 were limited stage and treated with curative intent. They were followed to the end of February 2002. A parametric lognormal statistical model was retrospectively validated to determine whether long-term survival rates could be estimated several years earlier than is possible using the standard life-table actuarial method. The survival time of the uncured group followed a lognormal distribution. Four 2-year periods of diagnosis were combined, and patients were followed as a cohort for an additional 2 years. The estimated 10-year cause-specific survival rate was 13% by the lognormal model. The Kaplan-Meier calculation for 10-year cause-specific survival rate was 15% +/- 3%. The data also showed that the absence of mediastinal lymphadenopathy and higher chest radiotherapy dose were significant prognostic factors on multivariate analysis (p < 0.05). Among the 163 patients given prophylactic cranial irradiation, a higher biologically effective dose to the brain did not improve survival or decrease the incidence of brain metastases. The lognormal model has been validated for the estimation of survival in patients with limited-stage small-cell lung cancer. A higher biologically effective dose to the brain did not improve survival or decrease the incidence of brain metastases.

Comparison of extended colectomy and limited resection in patients with Lynch syndrome.

PubMed

Natarajan, Nagendra; Watson, Patrice; Silva-Lopez, Edibaldo; Lynch, Henry T

2010-01-01

The purpose of the study was to determine the advantages and disadvantages of prophylactic/extended colectomy (subtotal colectomy) in patients with Lynch syndrome who manifest colorectal cancer. A retrospective cohort using Creighton University's hereditary cancer database was used to identify cases and controls. Cases are patients who underwent subtotal colectomy, either with no colorectal cancer diagnosis (prophylactic) or at diagnosis of first colorectal cancer; controls for these 2 types of cases were, respectively, patients who underwent no colon surgery or those having limited resection at time of diagnosis of first colorectal cancer. The Kaplan-Meier and proportional hazard regression models from the Statistical Analysis Software program was used to calculate the difference in survival, time to subsequent colorectal cancer, and subsequent abdominal surgery between cases and controls. The event-free survival of our study did not reach 50%, so we used the event-free survival at 5 years as our parameter to compare the 2 groups. The event-free survival for subsequent colorectal cancer, subsequent abdominal surgery, and death was 94%, 84%, and 93%, respectively, for cases and 74%, 63%, and 88%, respectively, for controls. Times to subsequent colorectal cancer and subsequent abdominal surgery were significantly shorter in the control group (P < .006 and P < .04, respectively). No significant difference was identified with respect to survival time between the cases and controls. Even though no survival benefit was identified between the cases and controls the increased incidence of metachronous colorectal cancer and increased abdominal surgeries among controls warrant the recommendation of subtotal colectomy in patients with Lynch syndrome.

Unsteady numerical simulation of the flow in the U9 Kaplan turbine model

NASA Astrophysics Data System (ADS)

Javadi, Ardalan; Nilsson, Håkan

2014-03-01

The Reynolds-averaged Navier-Stokes equations with the RNG k-ε turbulence model closure are utilized to simulate the unsteady turbulent flow throughout the whole flow passage of the U9 Kaplan turbine model. The U9 Kaplan turbine model comprises 20 stationary guide vanes and 6 rotating blades (696.3 RPM), working at best efficiency load (0.71 m3/s). The computations are conducted using a general finite volume method, using the OpenFOAM CFD code. A dynamic mesh is used together with a sliding GGI interface to include the effect of the rotating runner. The clearance is included in the guide vane. The hub and tip clearances are also included in the runner. An analysis is conducted of the unsteady behavior of the flow field, the pressure fluctuation in the draft tube, and the coherent structures of the flow. The tangential and axial velocity distributions at three sections in the draft tube are compared against LDV measurements. The numerical result is in reasonable agreement with the experimental data, and the important flow physics close to the hub in the draft tube is captured. The hub and tip vortices and an on-axis forced vortex are captured. The numerical results show that the frequency of the forced vortex in 1/5 of the runner rotation.

[Indication for limited surgery on small lung cancer tumors measuring 1cm or less in diameter on preoperative computed tomography and long-term results].

PubMed

Togashi, K; Koike, T; Emura, I; Usuda, H

2008-07-01

Non-invasive lung cancers showed a good prognosis after limited surgery. But it is still uncertain about invasive lung cancers. We investigated the indications for limited surgery for small lung cancer tumors measuring 1 cm or less in diameter on preoperative computed tomography (CT). This study retrospectively analyzed of 1,245 patients who underwent complete resection of lung cancer between 1989 and 2004 in our hospital. Sixty-two patients (5%) had tumors measuring 1 cm or less in diameter. The probability of survival was calculated using the Kaplan-Meier method. All diseases were detected by medical checkup, 52 % of the patients were not definitively diagnosed with lung cancer before surgery. Adenocarcinoma was histologically diagnosed in 49 patients (79%). Other histologic types included squamous cell carcinoma (8), large cell carcinoma (1), small cell carcinoma (1), carcinoid (2), and adenosquamous cell carcinoma (1). Fifty-seven patients (92%) showed pathologic stage IA. The other stages were IB (2), IIA (1), and IIIB (2). There were 14 bronchioloalveolar carcinomas (25% of IA diseases). The 5-year survival rates of IA patients were 90%. The 5-year survival rate of patients with tumors measuring 1cm or less diameter was 91% after lobectomy or pneumonectomy, and 90% after wedge resection or segmentectomy. There were 3 deaths from cancer recurrence, while there were no deaths in 14 patients with bronchioloalveolar carcinoma After limited surgery, non-invasive cancer showed good long-term results, while invasive cancer showed a recurrence rate of 2.3% to 79% even though the tumor measured 1 cm or less in diameter on preoperative CT.

A Meier-Gorlin syndrome mutation in a conserved C-terminal helix of Orc6 impedes origin recognition complex formation.

PubMed

Bleichert, Franziska; Balasov, Maxim; Chesnokov, Igor; Nogales, Eva; Botchan, Michael R; Berger, James M

2013-10-08

In eukaryotes, DNA replication requires the origin recognition complex (ORC), a six-subunit assembly that promotes replisome formation on chromosomal origins. Despite extant homology between certain subunits, the degree of structural and organizational overlap between budding yeast and metazoan ORC has been unclear. Using 3D electron microscopy, we determined the subunit organization of metazoan ORC, revealing that it adopts a global architecture very similar to the budding yeast complex. Bioinformatic analysis extends this conservation to Orc6, a subunit of somewhat enigmatic function. Unexpectedly, a mutation in the Orc6 C-terminus linked to Meier-Gorlin syndrome, a dwarfism disorder, impedes proper recruitment of Orc6 into ORC; biochemical studies reveal that this region of Orc6 associates with a previously uncharacterized domain of Orc3 and is required for ORC function and MCM2-7 loading in vivo. Together, our results suggest that Meier-Gorlin syndrome mutations in Orc6 impair the formation of ORC hexamers, interfering with appropriate ORC functions. DOI:http://dx.doi.org/10.7554/eLife.00882.001.

Habitat, not resource availability, limits consumer production in lake ecosystems

USGS Publications Warehouse

Craig, Nicola; Jones, Stuart E.; Weidel, Brian C.; Solomon, Christopher T.

2015-01-01

Food web productivity in lakes can be limited by dissolved organic carbon (DOC), which reduces fish production by limiting the abundance of their zoobenthic prey. We demonstrate that in a set of 10 small, north temperate lakes spanning a wide DOC gradient, these negative effects of high DOC concentrations on zoobenthos production are driven primarily by availability of warm, well-oxygenated habitat, rather than by light limitation of benthic primary production as previously proposed. There was no significant effect of benthic primary production on zoobenthos production after controlling for oxygen, even though stable isotope analysis indicated that zoobenthos do use this resource. Mean whole-lake zoobenthos production was lower in high-DOC lakes with reduced availability of oxygenated habitat, as was fish biomass. These insights improve understanding of lake food webs and inform management in the face of spatial variability and ongoing temporal change in lake DOC concentrations.

Public injury prevention system in the Italian manufacturing sector: What types of inspection are more effective?

PubMed

Farina, Elena; Bena, Antonella; Fedeli, Ugo; Mastrangelo, Giuseppe; Veronese, Michela; Agnesi, Roberto

2016-04-01

Literature suggests that more research is needed to clarify the effect of workplace inspections by governmental officers on injury rates. This paper aims to compare comprehensive and partial inspections in Italian manufacturing companies. Survival analysis was applied to the period free from injuries following inspection by means of the Kaplan-Meier method and of Cox models. Kaplan-Meier curves show that, compared to companies with a partial inspection, companies which had a comprehensive inspection had a higher survival through the entire period. Adjusting for confounders, the Cox model confirms a significant preventive effect of comprehensive inspection for companies with 10-30 employees, but not for those with >30 employees. The results suggest that the effect on injuries is greater if all aspects of safety are addressed during the inspection instead of focusing on a single aspect. These findings are interesting because they can help in planning effective prevention activities. © 2016 Wiley Periodicals, Inc.

The risk of revision in total knee arthroplasty is not affected by previous high tibial osteotomy

PubMed Central

Badawy, Mona; Fenstad, Anne M; Indrekvam, Kari; Havelin, Leif I; Furnes, Ove

2015-01-01

Background and purpose — Previous studies have found different outcomes after revision of knee arthroplasties performed after high tibial osteotomy (HTO). We evaluated the risk of revision of total knee arthroplasty with or without previous HTO in a large registry material. Patients and methods — 31,077 primary TKAs were compared with 1,399 TKAs after HTO, using Kaplan-Meier 10-year survival percentages and adjusted Cox regression analysis. Results — The adjusted survival analyses showed similar survival in the 2 groups. The Kaplan-Meier 10-year survival was 93.8% in the primary TKA group and 92.6% in the TKA-post-HTO group. Adjusted RR was 0.97 (95% CI: 0.77–1.21; p = 0.8). Interpretation — In this registry-based study, previous high tibial osteotomy did not appear to compromise the results regarding risk of revision after total knee arthroplasty compared to primary knee arthroplasty. PMID:26058747

Survival Analysis of Patients with End Stage Renal Disease

NASA Astrophysics Data System (ADS)

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.

Nutritional limitations to increased production on pasture-based systems.

PubMed

Kolver, Eric S

2003-05-01

The constraints to high levels of milk production imposed by a high-quality-pasture diet, and development of feeding strategies to overcome these limitations, were examined by modelling the nutritional status of New Zealand Friesian and North American Holstein-Friesian dairy cows grazing high-quality pasture. The Cornell Net Carbohydrate and Protein System (CNCPS) was used to predict sensitivity of milk production to a 10% change in the composition of pasture nutrients. The rate at which fibre and protein were degraded in the rumen and the value given to effective fibre and lignin content significantly affected the supply of metabolisable energy and protein, and the profile of amino acid supply. The first limiting factor in milk production when only high-quality pasture was fed was metabolisable energy supply, while specific amino acids, particularly methionine and lysine, limited milk production when > 20 g/kg diet consisted of a grain supplement. Compared with cows fed a total mixed ration in confinement, North American Holstein-Friesians grazing all pasture produced less milk (29.6 v. 44.1 kg/d). Of the difference in milk production 61% could be attributed to a lower DM intake (19 kg/d v. 23.4 kg/d). Predictions using the CNCPS indicated that supply of metabolisable energy was the first-limiting factor for milk production from high-quality pasture (251 g crude protein (N x 6.25)/kg, 432 g neutral-detergent fibre/kg, 77% in vitro DM digestibility), rather than metabolisable protein or amino acids. In addition, these nutritional limitations imposed by pasture diets will be greater for dairy cow genotypes that have not been selected for high performance within a pasture system.

[Estimation of survival rates: technics used (author's transl)].

PubMed

Rodary, C; Laplanche, A; Comnougue, C; Flamant, R

1979-01-01

The direct method and life-table methods (actuarial and Kaplan-Meier) for estimating survival rates are described here. The difference between direct method and lifetable method is the use of information about the patients who are still alive. Practical examples of calculation are given with recommandations for graphical displays.

Community Music during the New Deal: The Contributions of Willem Van de Wall and Max Kaplan

ERIC Educational Resources Information Center

Krikun, Andrew

2010-01-01

Willem Van de Wall (1887-1953) and Max Kaplan (1911-98) built careers spanning music performance, music education, adult education, sociology, social work, music therapy and community music. Willem Van de Wall was a seminal influence on the development of the fields of music therapy and adult education--researching the role of music in…

Metabolic acidosis status and mortality in patients on the end stage of renal disease.

PubMed

Raikou, Vaia D

2016-12-01

Uncorrected metabolic acidosis leads to higher death risk in dialysis patients. We observed the relationship between metabolic acidosis status and mortality rate in patients on renal replacement therapy during a median follow up time of 60 months. We studied 76 patients on an on-line hemodiafiltration. The dialysis adequacy was defined by Kt/V for urea. The Framingham risk score (FRS) points were used to determine the 10-year risk for coronary heart disease. We examined the impact of high or low serum bicarbonate concentrations on mortality rate and on 10-year risk for coronary heart disease via the Kaplan-Meier method. Cox's model was used to evaluate a combination of prognostic variables, such as dialysis adequacy defined by Kt/V for urea, age and serum bicarbonate concentrations. We divided the enrolled patients in three groups according to serum bicarbonate concentrations (< 20 mmol/L, 20-22 mmol/L and > 22 mmol/L). Kaplan-Meier survival curve for the impact of serum bicarbonate concentrations on overall mortality was found significant (log-rank = 7.8, P = 0.02). The prevalence of serum bicarbonate less or more than 20 mmol/L on high FRS (> 20%) by Kaplan-Meier curve was also found significant (log-rank = 4.9, P = 0.02). Cox's model revealed the significant predictive effect of serum bicarbonate on overall mortality ( P = 0.006, OR = 1.5, 95% CI = 1.12-1.98) in combination to Kt/V for urea and age. Uncorrected severe metabolic acidosis, defined by serum bicarbonate concentrations less than 20 mmol/L, is associated with a 10-year risk for coronary heart disease more than 20% and high overall mortality in patients on renal replacement therapy.

A gap analysis approach to assess patient persistence with glaucoma medication.

PubMed

Lee, Paul P; Walt, John G; Chiang, Tina H; Guckian, Angela; Keener, John

2007-10-01

To develop an alternative method for analysis of patient persistence with prescribed medications using the prostaglandin class of intraocular pressure (IOP)-lowering drugs as a model. A retrospective study of prescription refill patterns. Patients with a pharmacy claim for a 2.5 ml bottle of latanoprost, travoprost, or bimatoprost between September 1, 2002 and December 31, 2002 were identified from a retail pharmacy database and were followed up for 12 months. Three separate analyses defined gaps in therapy as spans in excess of 45, 60, or 120 days without a refill for the same medication. Patients were categorized by the number of gaps in therapy and the cumulative length of gaps. A Kaplan-Meier analysis was conducted using a 120-day allowable refill period. For refill periods of 45, 60, and 120 days, 10.6%, 28.6%, and 77.5% of patients, respectively, had no gaps in therapy, and 32.6%, 53.4%, and 86.5%, respectively, had 30 days or fewer off therapy annually. According to the 45-day threshold analysis, 50.7% of patients had three or more gaps vs 18.5% in the 60-day analysis and none in the 120-day analysis. The Kaplan-Meier curve shows 88.6% and 76.1% of patients were persistent for 120 days and one year, respectively. Compared with Kaplan-Meier survival curves, the gap analysis approach may better parallel clinical experience with patient persistence, in which patients stop and restart medications for a variety of reasons over time. This method also may help to identify avenues for investigation of lack of persistency among many patients.

Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles.

PubMed Central

de Wit, R.; van den Berg, H.; Burghouts, J.; Nortier, J.; Slee, P.; Rodenburg, C.; Keizer, J.; Fonteyn, M.; Verweij, J.; Wils, J.

1998-01-01

We have reported previously that the anti-emetic efficacy of single agent 5HT3 antagonists is not maintained when analysed with the measurement of cumulative probabilities. Presently, the most effective anti-emetic regimen is a combination of a 5HT3 antagonist plus dexamethasone. We, therefore, assessed the sustainment of efficacy of such a combination in 125 patients, scheduled to receive cisplatin > or = 70 mg m(-2) either alone or in combination with other cytotoxic drugs. Anti-emetic therapy was initiated with 10 mg of dexamethasone and 3 mg of granisetron intravenously, before cisplatin. On days 1-6, patients received 8 mg of dexamethasone and 1 mg of granisetron twice daily by oral administration. Protection was assessed during all cycles and calculated based on cumulative probability analyses using the method of Kaplan-Meier and a model for transitional probabilities. Irrespective of the type of analysis used, the anti-emetic efficacy of granisetron/dexamethasone decreased over cycles. The initial complete acute emesis protection rate of 66% decreased to 30% according to the method of Kaplan-Meier and to 39% using the model for transitional probabilities. For delayed emesis, the initial complete protection rate of 52% decreased to 21% (Kaplan-Meier) and to 43% (transitional probabilities). In addition, we observed that protection failure in the delayed emesis period adversely influenced the acute emesis protection in the next cycle. We conclude that the anti-emetic efficacy of a 5HT3 antagonist plus dexamethasone is not maintained over multiple cycles of highly emetogenic chemotherapy, and that the acute emesis protection is adversely influenced by protection failure in the delayed emesis phase. PMID:9652766

Coexpression of aPKCλ/ι and IL-6 in prostate cancer tissue correlates with biochemical recurrence.

PubMed

Ishiguro, Hitoshi; Akimoto, Kazunori; Nagashima, Yoji; Kagawa, Eriko; Sasaki, Takeshi; Sano, Jin-yu; Takagawa, Ryo; Fujinami, Kiyoshi; Sasaki, Kazunori; Aoki, Ichiro; Ohno, Shigeo; Kubota, Yoshinobu; Uemura, Hiroji

2011-08-01

Atypical protein kinase C λ/ι (aPKCλ/ι) and interleukin-6 (IL-6) have been implicated in prostate cancer progression, the mechanisms of which have been demonstrated both in vitro and in vivo. However, the clinical significance of the correlation between the expressions of these factors remains to be clarified. In the present study, we report a significant correlation between aPKCλ/ι and IL-6 proteins in prostate cancer tissue by immunohistochemical staining. We evaluated the association of both proteins by analyzing clinicopathological parameters using chi-square test, Kaplan-Meier with log-rank test, and a Cox proportional hazard regression model in univariate and multivariate analyses. The results again showed that the expression of aPKCλ/ι and IL-6 correlates in prostate cancer tissue (P < 0.001). Atypical protein kinase C λ/ι was also found to correlate with the Gleason score (P < 0.001) and with biochemical recurrence after prostatectomy (P = 0.02). Furthermore, aPKCλ/ι correlated with biochemical recurrence in a Kaplan-Meier and log-rank test (P = 0.01) and Cox analysis (P = 0.02 in the univariate analysis, P = 0.02 in the multivariate analysis). The coexpression of aPKCλ/ι and IL-6 also correlated with biochemical recurrence by Kaplan-Meier and log-rank test (P = 0.005) and Cox analysis (P = 0.01 in the univariate analysis, P = 0.03 in the multivariate analysis). These results indicate a strong correlation between aPKCλ/ι and IL-6 in prostate tumors, and that the aPKCλ/ι-IL-6 axis is a reliable prognostic factor for the biochemical recurrence of this cancer. © 2011 Japanese Cancer Association.

Physiology limits commercially viable photoautotrophic production of microalgal biofuels.

PubMed

Kenny, Philip; Flynn, Kevin J

2017-01-01

Algal biofuels have been offered as an alternative to fossil fuels, based on claims that microalgae can provide a highly productive source of compounds as feedstocks for sustainable transport fuels. Life cycle analyses identify algal productivity as a critical factor affecting commercial and environmental viability. Here, we use mechanistic modelling of the biological processes driving microalgal growth to explore optimal production scenarios in an industrial setting, enabling us to quantify limits to algal biofuels potential. We demonstrate how physiological and operational trade-offs combine to restrict the potential for solar-powered algal-biodiesel production in open ponds to a ceiling of ca. 8000 L ha -1 year -1 . For industrial-scale operations, practical considerations limit production to ca. 6000 L ha -1 year -1 . According to published economic models and life cycle analyses, such production rates cannot support long-term viable commercialisation of solar-powered cultivation of natural microalgae strains exclusively as feedstock for biofuels. The commercial viability of microalgal biofuels depends critically upon limitations in microalgal physiology (primarily in rates of C-fixation); we discuss the scope for addressing this bottleneck concluding that even deployment of genetically modified microalgae with radically enhanced characteristics would leave a very significant logistical if not financial burden.

21 CFR 211.111 - Time limitations on production.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Time limitations on production. 211.111 Section 211.111 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Production and...

21 CFR 211.111 - Time limitations on production.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Time limitations on production. 211.111 Section 211.111 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Production and...

21 CFR 211.111 - Time limitations on production.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Time limitations on production. 211.111 Section 211.111 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Production and...

Estimating prefledging survival: Allowing for brood mixing and dependence among brood mates

USGS Publications Warehouse

Flint, Paul L.; Pollock, Kenneth H.; Thomas, Dana; Sedinger, James S.

1995-01-01

Estimates of juvenile survival from hatch to fledging provide important information on waterfowl productivity. We develop a model for estimating survival of young waterfowl from hatch to fledging. Our model enables interchange of individuals among broods and relaxes the assumption that individuals within broods have independent survival probabilities. The model requires repeated observations of individually identifiable adults and their offspring that are not individually identifiable. A modified Kaplan-Meier procedure (Pollock et al. 1989a,b) and a modified Mayfield procedure (Mayfield 1961, 1975; Johnson 1979) can be used under this general modeling framework, and survival rates and corresponding variances of the point estimators can be determined.

ASURV: Astronomical SURVival Statistics

NASA Astrophysics Data System (ADS)

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.

Liposome production by microfluidics: potential and limiting factors.

PubMed

Carugo, Dario; Bottaro, Elisabetta; Owen, Joshua; Stride, Eleanor; Nastruzzi, Claudio

2016-05-19

This paper provides an analysis of microfluidic techniques for the production of nanoscale lipid-based vesicular systems. In particular we focus on the key issues associated with the microfluidic production of liposomes. These include, but are not limited to, the role of lipid formulation, lipid concentration, residual amount of solvent, production method (including microchannel architecture), and drug loading in determining liposome characteristics. Furthermore, we propose microfluidic architectures for the mass production of liposomes with a view to potential industrial translation of this technology.

40 CFR Table 1 to Subpart C - VOC Content Limits by Product Category

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 5 2011-07-01 2011-07-01 false VOC Content Limits by Product Category... PRODUCTS National Volatile Organic Compound Emission Standards for Consumer Products Pt. 59, Subpt. C, Table 1 Table 1 to Subpart C—VOC Content Limits by Product Category Product category VOC content limit...

40 CFR Table 1 to Subpart C - VOC Content Limits by Product Category

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 6 2012-07-01 2012-07-01 false VOC Content Limits by Product Category... PRODUCTS National Volatile Organic Compound Emission Standards for Consumer Products Pt. 59, Subpt. C, Table 1 Table 1 to Subpart C—VOC Content Limits by Product Category Product category VOC content limit...

40 CFR Table 1 to Subpart C - VOC Content Limits by Product Category

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 5 2010-07-01 2010-07-01 false VOC Content Limits by Product Category... PRODUCTS National Volatile Organic Compound Emission Standards for Consumer Products Pt. 59, Subpt. C, Table 1 Table 1 to Subpart C—VOC Content Limits by Product Category Product category VOC content limit...

[Small-diameter portosystemic shunts: indications and limitations].

PubMed

Angel Mercado, M; Granados-García, J; Barradas, F; Chan, C; Contreras, J L; Orozco, H; Angel-Mercado, M

1998-01-01

Low diameter porto-systemic shunts for the treatment of portal hypertension bleeding have emerged as a consequence of the technical development of vascular grafts (PTFE) that allow the use of a narrow lumen. The experience with this kind of operation at the Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City during a 6-year period is reported. There were twenty-seven patients with good liver function (Child-Pugh A-B) were operated or electively, average Age 47.5 years (range 17-71), twenty three patients with liver cirrhosis, one with portal fibrosis and three with idiopathic portal hypertension. Operative mortality: 4%. Rebleeding: 14%. Postoperative encephalopathy was observed in 14 of 27, three of them being grade III-IV (11%). In the remaining 11 cases, it was mild and easily controlled. Postoperative angiography showed shunt patency in 81% of the cases; in 33% of the cases, portal vein diameter reduction was shown, as well as two cases with portal vein thrombosis. In 77% of the cases, adequate postoperative quality of life was observed. Survival (Kaplan-Meier): 86% at 12 months and 56% at 60 months. These kinds of shunts are a good alternate choice for patients considered for surgery, in which other portal blood flow preserving procedures (selective shunts, devascularization with transection) are not feasible.

Characterization and Analysis of Liquid Waste from Marcellus Shale Gas Development.

PubMed

Shih, Jhih-Shyang; Saiers, James E; Anisfeld, Shimon C; Chu, Ziyan; Muehlenbachs, Lucija A; Olmstead, Sheila M

2015-08-18

Hydraulic fracturing of shale for gas production in Pennsylvania generates large quantities of wastewater, the composition of which has been inadequately characterized. We compiled a unique data set from state-required wastewater generator reports filed in 2009-2011. The resulting data set, comprising 160 samples of flowback, produced water, and drilling wastes, analyzed for 84 different chemicals, is the most comprehensive available to date for Marcellus Shale wastewater. We analyzed the data set using the Kaplan-Meier method to deal with the high prevalence of nondetects for some analytes, and compared wastewater characteristics with permitted effluent limits and ambient monitoring limits and capacity. Major-ion concentrations suggested that most wastewater samples originated from dilution of brines, although some of our samples were more concentrated than any Marcellus brines previously reported. One problematic aspect of this wastewater was the very high concentrations of soluble constituents such as chloride, which are poorly removed by wastewater treatment plants; the vast majority of samples exceeded relevant water quality thresholds, generally by 2-3 orders of magnitude. We also examine the capacity of regional regulatory monitoring to assess and control these risks.

Liposome production by microfluidics: potential and limiting factors

PubMed Central

Carugo, Dario; Bottaro, Elisabetta; Owen, Joshua; Stride, Eleanor; Nastruzzi, Claudio

2016-01-01

This paper provides an analysis of microfluidic techniques for the production of nanoscale lipid-based vesicular systems. In particular we focus on the key issues associated with the microfluidic production of liposomes. These include, but are not limited to, the role of lipid formulation, lipid concentration, residual amount of solvent, production method (including microchannel architecture), and drug loading in determining liposome characteristics. Furthermore, we propose microfluidic architectures for the mass production of liposomes with a view to potential industrial translation of this technology. PMID:27194474

Axial U(1) current in Grabowska and Kaplan's formulation

NASA Astrophysics Data System (ADS)

Hamada, Yu; Kawai, Hikaru

2017-06-01

Recently, Grabowska and Kaplan [Phys. Rev. Lett. 116, 211602 (2016); Phys. Rev. D 94, 114504 (2016)] suggested a nonperturbative formulation of a chiral gauge theory, which consists of the conventional domain-wall fermion and a gauge field that evolves by gradient flow from one domain wall to the other. We introduce two sets of domain-wall fermions belonging to complex conjugate representations so that the effective theory is a 4D vector-like gauge theory. Then, as a natural definition of the axial-vector current, we consider a current that generates simultaneous phase transformations for the massless modes in 4 dimensions. However, this current is exactly conserved and does not reproduce the correct anomaly. In order to investigate this point precisely, we consider the mechanism of the conservation. We find that this current includes not only the axial current on the domain wall but also a contribution from the bulk, which is nonlocal in the sense of 4D fields. Therefore, the local current is obtained by subtracting the bulk contribution from it.

The Factor Structure and Age-Related Factorial Invariance of the Delis-Kaplan Executive Function System (D-KEFS)

ERIC Educational Resources Information Center

Latzman, Robert D.; Markon, Kristian E.

2010-01-01

There has been an increased interest in the structure of and relations among executive functions.The present study examined the factor structure as well as age-related factorial invariance of the Delis-Kaplan Executive Function System (D-KEFS), a widely used inventory aimed at assessing executive functions. Analyses were first conducted using data…

4 out of 5 Students Surveyed Would Recommend this Activity (Comparing Chewing Gum Flavor Durations)

ERIC Educational Resources Information Center

Richardson, Mary; Rogness, Neal; Gajewski, Byron

2005-01-01

This paper describes an interactive activity developed for illustrating hypothesis tests on the mean for paired or matched samples. The activity is extended to illustrate assessing normality, the Wilcoxon signed rank test, Kaplan-Meier survival functions, two-way analysis of variance, and the randomized block design. (Contains 6 tables and 13…

Pressure pulsation in Kaplan turbines: Prototype-CFD comparison

NASA Astrophysics Data System (ADS)

Rivetti, A.; Lucino1, C.; Liscia, S.; Muguerza, D.; Avellan, F.

2012-11-01

Pressure pulsation phenomena in a large Kaplan turbine are investigated by means of numerical simulations (CFD) and prototype measurements in order to study the dynamic behavior of flow due to the blade passage and its interaction with other components of the turbine. Numerical simulations are performed with the commercial software Ansys CFX code, solving the incompressible Unsteady Reynolds-Averaged-Navier Stokes equations under a finite volume scheme. The computational domain involves the entire machine at prototype scale. Special care is taken in the discretization of the wicket gate overhang and runner blade gap. Prototype measurements are performed using pressure transducers at different locations among the wicket gate outlet and the draft tube inlet. Then, CFD results are compared with temporary signals of prototype measurements at identical locations to validate the numerical model. A detailed analysis was focused on the tip gap flow and the pressure field at the discharge ring. From a rotating reference frame perspective, it is found that the mean pressure fluctuates accordingly the wicket gate passage. Moreover, in prototype measurements the pressure frequency that reveals the presence of modulated cavitation at the discharge ring is distinguished, as also verified from the shape of erosion patches in concordance with the number of wicket gates.

Native wildflower seed production with limited subsurface drip irrigation

Treesearch

Clinton C. Shock; Erik B. G. Feibert; Lamont D. Saunders; Nancy Shaw

2010-01-01

Native wildflower seed is needed to restore rangelands of the Intermountain West. Commercial seed production is necessary to provide the quantity of seed needed for restoration efforts. A major limitation to economically viable commercial production of native wildflower (forb) seed is stable and consistent seed productivity over years. Variations in spring rainfall and...

Native wildflower seed production with limited subsurface drip irrigation

Treesearch

Clint C. Shock; Erik Feibert; Lamont Saunders; Nancy Shaw

2009-01-01

Native wildflower seed is needed to restore rangelands of the Intermountain West. Commercial seed production is necessary to provide the quantity of seed needed for restoration efforts. A major limitation to economically viable commercial production of native wildflower (forb) seed is stable and consistent seed productivity over years. Variations in spring rainfall and...

Socialization into a Civilization: The Dewey-Kaplan Synthesis in American Jewish Schooling in the Early 20th Century

ERIC Educational Resources Information Center

Jacobs, Benjamin M.

2009-01-01

This historical study focuses on how John Dewey's theory of education as socialization and Mordecai Kaplan's theory of Judaism as a civilization together served as an ideological base and pedagogical framework for the creation of "progressive," "reconstructed" American Jewish school programs in the early 20th century…

The theoretical limit to plant productivity.

PubMed

DeLucia, Evan H; Gomez-Casanovas, Nuria; Greenberg, Jonathan A; Hudiburg, Tara W; Kantola, Ilsa B; Long, Stephen P; Miller, Adam D; Ort, Donald R; Parton, William J

2014-08-19

Human population and economic growth are accelerating the demand for plant biomass to provide food, fuel, and fiber. The annual increment of biomass to meet these needs is quantified as net primary production (NPP). Here we show that an underlying assumption in some current models may lead to underestimates of the potential production from managed landscapes, particularly of bioenergy crops that have low nitrogen requirements. Using a simple light-use efficiency model and the theoretical maximum efficiency with which plant canopies convert solar radiation to biomass, we provide an upper-envelope NPP unconstrained by resource limitations. This theoretical maximum NPP approached 200 tC ha(-1) yr(-1) at point locations, roughly 2 orders of magnitude higher than most current managed or natural ecosystems. Recalculating the upper envelope estimate of NPP limited by available water reduced it by half or more in 91% of the land area globally. While the high conversion efficiencies observed in some extant plants indicate great potential to increase crop yields without changes to the basic mechanism of photosynthesis, particularly for crops with low nitrogen requirements, realizing such high yields will require improvements in water use efficiency.

Statistical analysis of water-quality data containing multiple detection limits II: S-language software for nonparametric distribution modeling and hypothesis testing

USGS Publications Warehouse

Lee, L.; Helsel, D.

2007-01-01

Analysis of low concentrations of trace contaminants in environmental media often results in left-censored data that are below some limit of analytical precision. Interpretation of values becomes complicated when there are multiple detection limits in the data-perhaps as a result of changing analytical precision over time. Parametric and semi-parametric methods, such as maximum likelihood estimation and robust regression on order statistics, can be employed to model distributions of multiply censored data and provide estimates of summary statistics. However, these methods are based on assumptions about the underlying distribution of data. Nonparametric methods provide an alternative that does not require such assumptions. A standard nonparametric method for estimating summary statistics of multiply-censored data is the Kaplan-Meier (K-M) method. This method has seen widespread usage in the medical sciences within a general framework termed "survival analysis" where it is employed with right-censored time-to-failure data. However, K-M methods are equally valid for the left-censored data common in the geosciences. Our S-language software provides an analytical framework based on K-M methods that is tailored to the needs of the earth and environmental sciences community. This includes routines for the generation of empirical cumulative distribution functions, prediction or exceedance probabilities, and related confidence limits computation. Additionally, our software contains K-M-based routines for nonparametric hypothesis testing among an unlimited number of grouping variables. A primary characteristic of K-M methods is that they do not perform extrapolation and interpolation. Thus, these routines cannot be used to model statistics beyond the observed data range or when linear interpolation is desired. For such applications, the aforementioned parametric and semi-parametric methods must be used.

The limited benefit of "product-by-process" claim.

PubMed

Chang, Bao-Chi; Wang, Shyh-Jen

2016-10-02

A product-by-process claim was initially developed when the invention could not otherwise be adequately defined. In the US, a patent applicant can use a product-by-process claim for a new product, no matter whether the product can also be defined by using structure features. However, the applicant mainly bears the burden to establish the novelty between the claimed product and the prior art product. Moreover, in terms of infringement, the very recent CAFC cases indicate that the product must be made by a process recited in the claim to infringe a product-by-process claim. Thus, an assignee almost can not take advantage from product-by-process claims during the patent enforcement by comparing with process claims. From the points of the burden during patent prosecution and confined scope in determining infringement, the benefit of using a product-by-process claim would be very limited.

Lymphovascular invasion in clear cell renal cell carcinoma--association with disease-free and cancer-specific survival.

PubMed

Belsante, Michael; Darwish, Oussama; Youssef, Ramy; Bagrodia, Aditya; Kapur, Payal; Sagalowsky, Arthur I; Lotan, Yair; Margulis, Vitaly

2014-01-01

The objective is to evaluate the effect of lymphovascular invasion (LVI) on disease-free survival (DFS) and cancer-specific survival (CSS) in patients with clinically localized clear cell renal cell carcinoma (ccRCC). Patients with ccRCC who were treated surgically in 1997 to 2010 were identified. Retrospective chart review was performed to identify clinical outcomes. Independent pathologic re-review was performed by a single pathologist to confirm LVI status. Pathologic features were correlated with clinical outcomes using Kaplan-Meier and Cox regression analyses. Four hundred and nineteen patients with nonmetastatic ccRCC comprised the study cohort. Three hundred and thirty-three of these patients had an organ-confined (pT1-2, N any, and M0) disease. LVI was present in 14.3% of all nonmetastatic patients. In all patients with nonmetastatic ccRCC, presence of LVI was correlated with significantly shorter DFS (P <0.001) and CSS (P = 0.001) on Kaplan-Meier analysis. In cases of organ-confined, nonmetastatic ccRCC, presence of LVI was a significant predictor of DFS (hazard ratio = 4.0, P = 0.026) and CSS (hazard ratio = 12.7, P = 0.01) on multivariate analysis. Patients with organ-confined RCC who were LVI positive had similar DFS (P = 0.957) and CSS (P = 0.799) to patients with locally advanced tumors (pT3-pT4, N any, and M0) on Kaplan-Meier analysis. The presence of LVI is an independent predictor of both DFS and CSS in organ-confined, nonmetastatic ccRCC. LVI positivity in patients with otherwise pathologically organ-confined ccRCC confers oncologic outcomes similar to those of patients with locally advanced disease. If confirmed by others, future revisions to the tumor-node-metastasis staging system may incorporate LVI status into the prognostic algorithm of patients with RCC. Copyright © 2014 Elsevier Inc. All rights reserved.

Defibrotide for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome following nontransplant-associated chemotherapy: Final results from a post hoc analysis of data from an expanded-access program.

PubMed

Kernan, Nancy A; Richardson, Paul G; Smith, Angela R; Triplett, Brandon M; Antin, Joseph H; Lehmann, Leslie; Messinger, Yoav; Liang, Wei; Hume, Robin; Tappe, William; Soiffer, Robert J; Grupp, Stephan A

2018-06-06

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially fatal complication of conditioning for hematopoietic stem cell transplantation (HSCT) but can occur after nontransplant-associated chemotherapy. Following HSCT, VOD/SOS with multi-organ dysfunction (MOD) may be associated with >80% mortality. Defibrotide is approved to treat severe hepatic VOD/SOS post-HSCT in patients aged >1 month in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Prior to US approval, defibrotide was available to treat VOD/SOS through an expanded-access treatment (T-IND) program. A post hoc analysis of nontransplant-associated VOD/SOS patients treated with defibrotide initiated within 30 days of starting chemotherapy and followed for 70 days is presented. Patients were diagnosed by Baltimore or modified Seattle criteria or biopsy, and received defibrotide 25 mg/kg/day in four divided doses (≥21 days recommended). Of the 1,154 patients in the T-IND, 137 had nontransplant-associated VOD/SOS, 82 of whom developed VOD/SOS within 30 days of starting chemotherapy. Of them, 66 (80.5%) were aged ≤16 years. Across all the 82 patients, Kaplan-Meier estimated day +70 survival was 74.1%, 65.8% in patients with MOD (n = 38), and 81.3% in patients without MOD (n = 44). By age group, Kaplan-Meier estimated day +70 survival was 80.1% in pediatric patients (n = 66) and 50.0% in adults (n = 16). Treatment-related adverse events occurred in 26.8%. In this post hoc analysis of 82 patients initiating defibrotide within 30 days of starting chemotherapy, Kaplan-Meier estimated survival was 74.1% at 70 days after defibrotide initiation. Safety profile was consistent with prior defibrotide studies. © 2018 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.

Long-Term Survivors Using Intraoperative Radiotherapy for Recurrent Gynecologic Malignancies

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

Tran, Phuoc T.; Su Zheng; Hara, Wendy

2007-10-01

Purpose: To analyze the outcomes of therapy and identify prognostic factors for patients treated with surgery followed by intraoperative radiotherapy (IORT) for gynecologic malignancies at a single institution. Methods and Materials: We performed a retrospective review of 36 consecutive patients treated with IORT to 44 sites with mean follow-up of 50 months. The primary site was the cervix in 47%, endometrium in 31%, vulva in 14%, vagina in 6%, and fallopian tubes in 3%. Previous RT had failed in 72% of patients, and 89% had recurrent disease. Of 38 IORT sessions, 84% included maximal cytoreductive surgery, including 18% exenterations. Themore » mean age was 52 years (range, 30-74), mean tumor size was 5 cm (range, 0.5-12), previous disease-free interval was 32 months (range, 0-177), and mean IORT dose was 1,152 cGy (range, 600-1,750). RT and systemic therapy after IORT were given to 53% and 24% of the cohort, respectively. The outcomes measured were locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and treatment-related complications. Results: The Kaplan-Meier 5-year LRC, DMFS, and DSS probability for the whole group was 44%, 51%, and 47%, respectively. For cervical cancer patients, the Kaplan-Meier 5-year LRC, DMFS, and DSS estimate was 45%, 60%, and 46%, respectively. The prognostic factors found on multivariate analysis (p {<=} 0.05) were the disease-free interval for LRC, tumor size for DMFS, and cervical primary, previous surgery, and locoregional relapse for DSS. Our cohort had 10 Grade 3-4 complications associated with treatment (surgery and IORT) and a Kaplan-Meier 5-year Grade 3-4 complication-free survival rate of 72%. Conclusions: Survival for pelvic recurrence of gynecologic cancer is poor (range, 0-25%). IORT after surgery seems to confer long-term local control in carefully selected patients.« less

Mixture models for undiagnosed prevalent disease and interval-censored incident disease: applications to a cohort assembled from electronic health records.

PubMed

Cheung, Li C; Pan, Qing; Hyun, Noorie; Schiffman, Mark; Fetterman, Barbara; Castle, Philip E; Lorey, Thomas; Katki, Hormuzd A

2017-09-30

For cost-effectiveness and efficiency, many large-scale general-purpose cohort studies are being assembled within large health-care providers who use electronic health records. Two key features of such data are that incident disease is interval-censored between irregular visits and there can be pre-existing (prevalent) disease. Because prevalent disease is not always immediately diagnosed, some disease diagnosed at later visits are actually undiagnosed prevalent disease. We consider prevalent disease as a point mass at time zero for clinical applications where there is no interest in time of prevalent disease onset. We demonstrate that the naive Kaplan-Meier cumulative risk estimator underestimates risks at early time points and overestimates later risks. We propose a general family of mixture models for undiagnosed prevalent disease and interval-censored incident disease that we call prevalence-incidence models. Parameters for parametric prevalence-incidence models, such as the logistic regression and Weibull survival (logistic-Weibull) model, are estimated by direct likelihood maximization or by EM algorithm. Non-parametric methods are proposed to calculate cumulative risks for cases without covariates. We compare naive Kaplan-Meier, logistic-Weibull, and non-parametric estimates of cumulative risk in the cervical cancer screening program at Kaiser Permanente Northern California. Kaplan-Meier provided poor estimates while the logistic-Weibull model was a close fit to the non-parametric. Our findings support our use of logistic-Weibull models to develop the risk estimates that underlie current US risk-based cervical cancer screening guidelines. Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA. Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Isolated Complete Heart Block in the Fetus.

PubMed

Ho, Andrew; Gordon, Patrick; Rosenthal, Eric; Simpson, John; Miller, Owen; Sharland, Gurleen

2015-07-01

Isolated congenital complete heart block (CCHB) is a rare disease with significant associated morbidity and mortality. A diagnosis is often made in fetal life, but data regarding long-term outcomes are limited, and fetal therapy to improve prognosis is controversial. In our institution, 85 fetuses were diagnosed with CCHB from 1981 to 2013 in 80 mothers. There were 37 anti-Ro-positive pregnancies, 36 both anti-Ro and anti-La positive, 10 antibody negative, and 2 of unknown antibody status. Antenatal treatments were given in 14 fetuses, with 8 given fluorinated steroids, 4 beta sympathomimetics, and both in 2. Of the original 85, 74 babies survived to delivery. Fetal hydrops was the only risk factor found to be significantly associated with intrauterine death (p <0.001). Four babies died before pacemaker implantation, 56 have had pacemakers implanted, and 14 are pacemaker free. The Kaplan-Meier estimate for median time to pacemaker implantation was 2.6 years, with 15 implanted in the neonatal period. There have been 14 postnatal deaths, with a Kaplan-Meier estimate of survival at 30 years of 76.8% (95% confidence interval 65% to 90%). Dilated cardiomyopathy was uncommon, occurring in 6 patients. Prematurity and hydrops were associated with increased postnatal mortality (p = 0.02 and 0.005, respectively). In conclusion, we present the largest single-unit experience of prenatally diagnosed CCHB in the published literature. Our cohort was conservatively managed, with survival similar to those previously published. These data offer insight into the long-term natural history of CCHB. Copyright © 2015 Elsevier Inc. All rights reserved.

Treatment of benign and malignant tracheobronchial obstruction with metal wire stents: experience with a balloon-expandable and a self-expandable stent type.

PubMed

Rieger, Johannes; Hautmann, Hubert; Linsenmaier, Ulrich; Weber, Cristoph; Treitl, Markus; Huber, Rudolf Maria; Pfeifer, Klaus-Jürgen

2004-01-01

Over the last few years various types of metal wire stents have been increasingly employed in the treatment of both malignant and benign tracheobronchial obstruction. To date, however, few studies have investigated the in vivo properties of different stent types. We implanted 26 balloon-expandable tantalum Strecker stents (18 patients) and 18 self-expandable Wallstents (16 patients) into the tracheobronchial system of 30 patients with combined stenting in 4 patients. Mean age was 51 years (range: 0.5-79 years). Malignant disease was present in 23 patients, benign disease in seven patients. Both patients and individual stents were monitored clinically and radiographically. The probability of stents remaining within the tracheobronchial system, and of their remaining undislocated and uncompressed was calculated using Kaplan-Meier analysis for both stent types. Average stent follow-up time was 112 days until explantation and 115 days until patients' death or discharge. Kaplan-Meier analysis revealed a higher probability for the Wallstent to remain within the tracheobronchial system. Dislocation and compression occurred more rarely. Explantation, however, if desired, was more difficult compared to the Strecker stent. The Wallstent also led to the formation of granulation tissue, especially at the proximal stent end, frequently requiring reintervention. Both stent types proved to be effective therapeutic options in the management of obstructive tracheobronchial disease. The mechanical properties of the Strecker stent seem to be less favorable compared to the Wallstent but removal is easy. For benign disease, however, the Wallstent reveals limitations due to significant side effects.

Incidence of Mastitis in the Neonatal Period in a Traditional Breastfeeding Society: Results of a Cohort Study.

PubMed

Khanal, Vishnu; Scott, Jane A; Lee, Andy H; Binns, Colin W

2015-12-01

Mastitis is a painful problem experienced by breastfeeding women, especially in the first few weeks postpartum. There have been limited studies of the incidence of mastitis from traditionally breastfeeding societies in South Asia. This study investigated the incidence, determinants, and management of mastitis in the first month postpartum, as well as its association with breastfeeding outcomes at 4 and 6 months postpartum, in western Nepal. Subjects were a subsample of 338 mothers participating in a larger prospective cohort study conducted in 2014 in western Nepal. Mothers were interviewed during the first month postpartum and again at 4 and 6 months to obtain information on breastfeeding practices. The association of mastitis and determinant variables was investigated using multivariable logistic regression, and the association with breastfeeding duration was examined using Kaplan-Meier estimation. The incidence of mastitis was 8.0% (95% confidence interval, 5.1%, 10.8%) in the first month postpartum. Prelacteal feeding (adjusted odds ratio = 2.76; 95% confidence interval, 1.03, 7.40) and cesarean section (adjusted odds ratio = 3.52; 95% confidence interval, 1.09, 11.42) were associated with a higher likelihood of mastitis. Kaplan-Meier estimation showed no significant difference in the duration of exclusive breastfeeding among the mothers who experienced an episode of mastitis and those who did not. Roughly one in 10 (8.0%) women experienced mastitis in the first month postpartum, and there appeared to be little effect of mastitis on breastfeeding outcomes. Traditional breastfeeding practices should be encouraged, and the management of mastitis should be included as a part of lactation promotion.

Decreased expression of FOXF2 as new predictor of poor prognosis in stage I non-small cell lung cancer.

PubMed

Kong, Peng-Zhou; Li, Guang-Ming; Tian, Yin; Song, Bin; Shi, RuYi

2016-08-23

Forkhead box F2 (FOXF2) is relatively limited to the adult lung, but its contribution to non-small cell lung cancer (NSCLC) prognosis is unclear. FOXF2 mRNA levels in NSCLC were lower than that in paired normal lung tissues (P = 0.012). The FOXF2low patients had shorter survival time than the FOXF2high patients (P = 0.024) especially in stage I (P = 0.002), chemotherapy (P = 0.018) and < 60 age groups (P = 0.002). Lower FOXF2 mRNA levels could independently predict poorer survival for patients with NSCLC (HR = 2.384, 95% CI = 1.241-4.577; P = 0.009), especially in stage I (HR =4.367, 95% CI =1.599-11.925; P = 0.004). The two independent datasets confirmed our findings. We examined FOXF2 mRNA levels in 84 primary NSCLC and 8 normal lung tissues using qRT-PCR. Rank-sum tests and chi-square tests were used to assess the differences among groups with various clinicopathological factors. Kaplan-Meier tests were used to compare survival status in patients with different FOXF2 mRNA levels. Cox proportional hazards regression model was used to evaluate the predictive value of FOXF2 mRNA level in NSCLC patients. Independent validation was performed using an independent dataset (98 samples) and an online survival analysis software Kaplan-Meier plotter (1928 samples). Our results demonstrated that decreased FOXF2 expression is an independent predictive factor for poor prognosis of patients with NSCLC, especially in stage I NSCLC.

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.

PubMed

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.

An identifiable model for informative censoring

USGS Publications Warehouse

Link, W.A.; Wegman, E.J.; Gantz, D.T.; Miller, J.J.

1988-01-01

The usual model for censored survival analysis requires the assumption that censoring of observations arises only due to causes unrelated to the lifetime under consideration. It is easy to envision situations in which this assumption is unwarranted, and in which use of the Kaplan-Meier estimator and associated techniques will lead to unreliable analyses.

Decoupling production from growth by magnesium sulfate limitation boosts de novo limonene production.

PubMed

Willrodt, Christian; Hoschek, Anna; Bühler, Bruno; Schmid, Andreas; Julsing, Mattijs K

2016-06-01

The microbial production of isoprenoids has recently developed into a prime example for successful bottom-up synthetic biology or top-down systems biology strategies. Respective fermentation processes typically rely on growing recombinant microorganisms. However, the fermentative production of isoprenoids has to compete with cellular maintenance and growth for carbon and energy. Non-growing but metabolically active E. coli cells were evaluated in this study as alternative biocatalyst configurations to reduce energy and carbon loss towards biomass formation. The use of non-growing cells in an optimized fermentation medium resulted in more than fivefold increased specific limonene yields on cell dry weight and glucose, as compared to the traditional growing-cell-approach. Initially, the stability of the resting-cell activity was limited. This instability was overcome via the optimization of the minimal fermentation medium enabling high and stable limonene production rates for up to 8 h and a high specific yield of ≥50 mg limonene per gram cell dry weight. Omitting MgSO4 from the fermentation medium was very promising to prohibit growth and allow high productivities. Applying a MgSO4 -limitation also improved limonene formation by growing cells during non-exponential growth involving a reduced biomass yield on glucose and a fourfold increase in specific limonene yields on biomass as compared to non-limited cultures. The control of microbial growth via the medium composition was identified as a key but yet underrated strategy for efficient isoprenoid production. Biotechnol. Bioeng. 2016;113: 1305-1314. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Tumor histology predicts mediastinal nodal status and may be used to guide limited lymphadenectomy in patients with clinical stage I non-small cell lung cancer.

PubMed

Cheng, Xinghua; Zheng, Difan; Li, Yuan; Li, Hang; Sun, Yihua; Xiang, Jiaqing; Chen, Haiquan

2018-06-01

Methods to minimize surgical trauma from mediastinal lymphadenectomy in patients with early-stage lung cancer are still immature. This study aimed to identify predictors of negative pathologic N2, which may be used to select patients for limited mediastinal lymphadenectomy. Clinicopathologic features of 1430 patients with resected clinical stage I non-small cell lung cancer and complete mediastinal lymphadenectomy were retrospectively analyzed for variables associated with negative N2 nodal metastasis (2008-2015). Overall and recurrence-free survival in patients after complete or limited mediastinal lymphadenectomy were assessed via Kaplan-Meier survival analysis and log-rank testing. The accuracy of frozen section diagnosis for predicting final pathology was retrospectively assessed in 126 randomly selected patients after the surgery. Multivariable analysis revealed that tumor size ≤2 cm, negative pN1, lymphovascular invasion, and lepidic adenocarcinoma were associated with negative mediastinal nodal metastasis. Notably, none of the patients with histology of adenocarcinoma in situ, minimally invasive adenocarcinoma, or lepidic pattern-predominant adenocarcinoma on final pathology had pN2 disease, and the 5-year overall and recurrence free-survival of these patients (99.3% and 99.3%, respectively) was not different from those after limited mediastinal lymphadenectomy (98.7% and 100%, P = .582 and .511, respectively). If these subtypes were classified together as the low-risk group, the concordance rate between frozen section and final pathology diagnosis was 88.9% in the retrospective test cohort. Tumor histology may predict negative mediastinal metastasis in patients with early-stage lung cancer. Future prospective studies are merited to validate the feasibility of using frozen section to select patients for limited mediastinal lymphadenectomy. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

[Application of Competing Risks Model in Predicting Smoking Relapse Following Ischemic Stroke].

PubMed

Hou, Li-Sha; Li, Ji-Jie; Du, Xu-Dong; Yan, Pei-Jing; Zhu, Cai-Rong

2017-07-01

To determine factors associated with smoking relapse in men who survived from their first stroke. Data were collected through face to face interviews with stroke patients in the hospital, and then repeated every three months via telephone over the period from 2010 to 2014. Kaplan-Meier method and competing risk model were adopted to estimate and predict smoking relapse rates. The Kaplan-Meier method estimated a higher relapse rate than the competing risk model. The four-year relapse rate was 43.1% after adjustment of competing risk. Exposure to environmental tobacco smoking outside of home and workplace (such as bars and restaurants) ( P =0.01), single ( P <0.01), and prior history of smoking at least 20 cigarettes per day ( P =0.02) were significant predictors of smoking relapse. When competing risks exist, competing risks model should be used in data analyses. Smoking interventions should give priorities to those without a spouse and those with a heavy smoking history. Smoking ban in public settings can reduce smoking relapse in stroke patients.

Maternal smoking during pregnancy and the risk of pediatric cardiovascular diseases of the offspring: A population-based cohort study with up to 18-years of follow up.

PubMed

Leybovitz-Haleluya, Noa; Wainstock, Tamar; Landau, Daniella; Sheiner, Eyal

2018-06-01

Cigarette smoke is a well-known reproductive toxicant. We aimed to study the long-term effect of cigarette smoking during pregnancy on the risk for childhood cardiovascular morbidity of the offspring. A population-based cohort analysis was performed comparing total and subtypes of cardiovascular related pediatric hospitalizations among offspring of smoking mothers versus offspring of non-smoking mothers. The analysis included all singletons born between the years 1999-2014.A Kaplan-Meier survival curve was used to compare the cumulative cardiovascular morbidity, and a Cox proportional hazards model was constructed to adjust for confounders. The study population included 242,342 newborns which met inclusion criteria; among them 2861 were born to smoking mothers. Offspring of smoking mothers had higher rates of cardiovascular-related hospitalizations (1.3% vs. 0.6%, OR 2.1, 95% CI 1.5-2.9; p < 0.001; Kaplan-Meier log-rank test p < 0.001). Smoking exposure during pregnancy is associated with an increased risk for long-term pediatric cardiovascular morbidity of the offspring. Copyright © 2018 Elsevier Inc. All rights reserved.

Nonparametric Discrete Survival Function Estimation with Uncertain Endpoints Using an Internal Validation Subsample

PubMed Central

Zee, Jarcy; Xie, Sharon X.

2015-01-01

Summary When a true survival endpoint cannot be assessed for some subjects, an alternative endpoint that measures the true endpoint with error may be collected, which often occurs when obtaining the true endpoint is too invasive or costly. We develop an estimated likelihood function for the situation where we have both uncertain endpoints for all participants and true endpoints for only a subset of participants. We propose a nonparametric maximum estimated likelihood estimator of the discrete survival function of time to the true endpoint. We show that the proposed estimator is consistent and asymptotically normal. We demonstrate through extensive simulations that the proposed estimator has little bias compared to the naïve Kaplan-Meier survival function estimator, which uses only uncertain endpoints, and more efficient with moderate missingness compared to the complete-case Kaplan-Meier survival function estimator, which uses only available true endpoints. Finally, we apply the proposed method to a dataset for estimating the risk of developing Alzheimer's disease from the Alzheimer's Disease Neuroimaging Initiative. PMID:25916510

Climate seasonality limits leaf carbon assimilation and wood productivity in tropical forests

DOE PAGES

Wagner, Fabien H.; Hérault, Bruno; Bonal, Damien; ...

2016-04-28

Here, the seasonal climate drivers of the carbon cycle in tropical forests remain poorly known, although these forests account for more carbon assimilation and storage than any other terrestrial ecosystem. Based on a unique combination of seasonal pan-tropical data sets from 89 experimental sites (68 include aboveground wood productivity measurements and 35 litter productivity measurements), their associated canopy photosynthetic capacity (enhanced vegetation index, EVI) and climate, we ask how carbon assimilation and aboveground allocation are related to climate seasonality in tropical forests and how they interact in the seasonal carbon cycle. We found that canopy photosynthetic capacity seasonality responds positivelymore » to precipitation when rainfall is < 2000 mm yr -1 (water-limited forests) and to radiation otherwise (light-limited forests). On the other hand, independent of climate limitations, wood productivity and litterfall are driven by seasonal variation in precipitation and evapotranspiration, respectively. Consequently, light-limited forests present an asynchronism between canopy photosynthetic capacity and wood productivity. First-order control by precipitation likely indicates a decrease in tropical forest productivity in a drier climate in water-limited forest, and in current light-limited forest with future rainfall < 2000 mm yr -1.« less

Climate seasonality limits leaf carbon assimilation and wood productivity in tropical forests

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

Wagner, Fabien H.; Hérault, Bruno; Bonal, Damien

Here, the seasonal climate drivers of the carbon cycle in tropical forests remain poorly known, although these forests account for more carbon assimilation and storage than any other terrestrial ecosystem. Based on a unique combination of seasonal pan-tropical data sets from 89 experimental sites (68 include aboveground wood productivity measurements and 35 litter productivity measurements), their associated canopy photosynthetic capacity (enhanced vegetation index, EVI) and climate, we ask how carbon assimilation and aboveground allocation are related to climate seasonality in tropical forests and how they interact in the seasonal carbon cycle. We found that canopy photosynthetic capacity seasonality responds positivelymore » to precipitation when rainfall is < 2000 mm yr -1 (water-limited forests) and to radiation otherwise (light-limited forests). On the other hand, independent of climate limitations, wood productivity and litterfall are driven by seasonal variation in precipitation and evapotranspiration, respectively. Consequently, light-limited forests present an asynchronism between canopy photosynthetic capacity and wood productivity. First-order control by precipitation likely indicates a decrease in tropical forest productivity in a drier climate in water-limited forest, and in current light-limited forest with future rainfall < 2000 mm yr -1.« less

Dual oxidase 1: A predictive tool for the prognosis of hepatocellular carcinoma patients.

PubMed

Chen, Shengsen; Ling, Qingxia; Yu, Kangkang; Huang, Chong; Li, Ning; Zheng, Jianming; Bao, Suxia; Cheng, Qi; Zhu, Mengqi; Chen, Mingquan

2016-06-01

Dual oxidase 1 (DUOX1), which is the main source of reactive oxygen species (ROS) production in the airway, can be silenced in human lung cancer and hepatocellular carcinomas. However, the prognostic value of DUOX1 expression in hepatocellular carcinoma patients is still unclear. We investigated the prognostic value of DUOX1 expression in liver cancer patients. DUOX1 mRNA expression was determined in tumor tissues and non-tumor tissues by real‑time PCR. For evaluation of the prognostic value of DUOX1 expression, Kaplan-Meier method and Cox's proportional hazards model (univariate analysis and multivariate analysis) were employed. A simple risk score was devised by using significant variables obtained from the Cox's regression analysis to further predict the HCC patient prognosis. We observed a reduced DUOX1 mRNA level in the cancer tissues in comparison to the non‑cancer tissues. More importantly, Kaplan-Meier analysis showed that patients with high DUOX1 expression had longer disease-free survival and overall survival compared with those with low expression of DUOX1. Cox's regression analysis indicated that DUOX1 expression, age, and intrahepatic metastasis may be significant prognostic factors for disease-free survival and overall survival. Finally, we found that patients with total scores of >2 and >1 were more likely to relapse and succumb to the disease than patients whose total scores were ≤2 and ≤1. In conclusion, DUOX1 expression in liver tumors is a potential prognostic tool for patients. The risk scoring system is useful for predicting the survival of liver cancer patients after tumor resection.

A conversation with Drs. Kaplan and Moser about conflicting data, confusing results, and some recent treatment recommendations for the management of hypertension.

PubMed

Post, Wendy; Moser, Marvin; Kaplan, Norman

2005-10-01

Following a hypertension symposium in Baltimore, MD, on June 1, 2005, Dr. Wendy Post from the Johns Hopkins University School of Medicine, Baltimore, MD, had the opportunity to interview two of the outstanding hypertension experts in the United States on several controversial issues in hypertension management. Dr. Norman Kaplan is Clinical Professor of Medicine at the Southwestern Health Science Center in Dallas, TX, and Dr. Marvin Moser is Clinical Professor of Medicine at the Yale University School of Medicine, New Haven, CT. Both have been leaders in the field of hypertension treatment and education for more than 40 years. Dr. Kaplan's book Clinical Hypertension has been a standard textbook since 1973 and is now in its ninth edition. Dr. Marvin Moser was the Senior Medical Consultant to the National High Blood Pressure Education Program from 1974 to 2002 and was Chairman of the first Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure and a member of the six subsequent committees. His book Clinical Management of Hypertension is in its seventh edition. Drs. Moser and Kaplan were corecipients of the 2004 International Society of Hypertension Award for Outstanding Contributions to Hypertension Treatment and Education and have lectured extensively throughout the United States and overseas.

Lack of pollinators limits fruit production in commercial blueberry (Vaccinium corymbosum).

PubMed

Benjamin, Faye E; Winfree, Rachael

2014-12-01

Modern agriculture relies on domesticated pollinators such as the honey bee (Apis mellifera L.), and to a lesser extent on native pollinators, for the production of animal-pollinated crops. There is growing concern that pollinator availability may not keep pace with increasing agricultural production. However, whether crop production is in fact pollen-limited at the field scale has rarely been studied. Here, we ask whether commercial highbush blueberry (Vaccinium corymbosum L.) production in New Jersey is limited by a lack of pollination even when growers provide honey bees at recommended densities. We studied two varieties of blueberry over 3 yr to determine whether blueberry crop production is pollen-limited and to measure the relative contributions of honey bees and native bees to blueberry pollination. We found two lines of evidence for pollen limitation. First, berries receiving supplemental hand-pollination were generally heavier than berries receiving ambient pollination. Second, mean berry mass increased significantly and nonasymptotically with honey bee flower visitation rate. While honey bees provided 86% of pollination and thus drove the findings reported above, native bees still contributed 14% of total pollination even in our conventionally managed, high-input agricultural system. Honey bees and native bees were also similarly efficient as pollinators on a per-visit basis. Overall, our study shows that pollination can be a limiting factor in commercial fruit production. Yields might increase with increased honey bee stocking rates and improved dispersal of hives within crop fields, and with habitat restoration to increase pollination provided by native bees.

Development of low head Kaplan turbine for power station rehabilitation project

NASA Astrophysics Data System (ADS)

Lim, S. M.; Ohtake, N.; Kurosawa, S.; Suzuki, T.; Yamasaki, T.; Nishi, H.

2012-11-01

This paper presents the latest Kaplan turbine rehabilitation project for Funagira Power Station in Japan completed by J-POWER Group in collaboration with Toshiba Corporation. Area of rehabilitation was restricted to guide vane and runner. The main goal of the rehabilitation project was to expand the operating range of the existing turbine in terms of discharge and power with high operational stability, low noise as well as high cavitation performance. Computational Fluids Dynamics and model test were used to optimize the shape of guide vane and runner in development stage. Finally, field tests and runner inspection were carried out to confirm the performance of the new turbine. It was found that the new turbine has excellent performance in efficiency, power output, operational stability compared with existing turbine. Moreover, no sign of cavitation on the runner blade surface was observed after 5078 hours of operation near 100% load.

Total-reflection X-ray fluorescence studies of trace elements in biomedical samples

NASA Astrophysics Data System (ADS)

Kubala-Kukuś, A.; Braziewicz, J.; Pajek, M.

2004-08-01

Application of the total-reflection X-ray fluorescence (TXRF) analysis in the studies of trace element contents in biomedical samples is discussed in the following aspects: (i) a nature of trace element concentration distributions, (ii) censoring approach to the detection limits, and (iii) a comparison of two sets of censored data. The paper summarizes the recent results achieved in this topics, in particular, the lognormal, or more general logstable, nature of concentration distribution of trace elements, the random left-censoring and the Kaplan-Meier approach accounting for detection limits and, finally, the application of the logrank test to compare the censored concentrations measured for two groups. These new aspects, which are of importance for applications of the TXRF in different fields, are discussed here in the context of TXRF studies of trace element in various samples of medical interest.

Implementation of pressurized air injection system in a Kaplan prototype for the reduction of vibration caused by tip vortex cavitation

NASA Astrophysics Data System (ADS)

Rivetti, A.; Angulo, M.; Lucino, C.; Hene, M.; Capezio, O.; Liscia, S.

2016-11-01

Blade tip cavitation is a well-known phenomenon that affects the performance of large-diameter Kaplan turbines and induces structural vibration. Injection of pressurized air has been found to yield promising results in reducing those damaging effects. In this work, the results of an experimental test of air injection on a 9.5-m-diameter Kaplan turbine are reported. Experiments were performed for several load conditions and for two different net heads. Accelerations, pressure pulsation and noise emission were monitored for every tested condition. Results show that, at the expense of a maximum efficiency drop of 0.2%, air injection induces a decrease on the level of vibration from 57% up to 84%, depending on the load condition. Such decrease is seen to be proportional to the air flow rate, in the range from 0.06 to 0.8‰ (respect to the discharge at the best efficiency point).

New product forecasting with limited or no data

NASA Astrophysics Data System (ADS)

Ismai, Zuhaimy; Abu, Noratikah; Sufahani, Suliadi

2016-10-01

In the real world, forecasts would always be based on historical data with the assumption that the behaviour be the same for the future. But how do we forecast when there is no such data available? New product or new technologies normally has limited amount of data available. Knowing that forecasting is valuable for decision making, this paper presents forecasting of new product or new technologies using aggregate diffusion models and modified Bass Model. A newly launched Proton car and its penetration was chosen to demonstrate the possibility of forecasting sales demand where there is limited or no data available. The model was developed to forecast diffusion of new vehicle or an innovation in the Malaysian society. It is to represent the level of spread on the new vehicle among a given set of the society in terms of a simple mathematical function that elapsed since the introduction of the new product. This model will forecast the car sales volume. A procedure of the proposed diffusion model was designed and the parameters were estimated. Results obtained by applying the proposed diffusion model and numerical calculation shows that the model is robust and effective for forecasting demand of the new vehicle. The results reveal that newly developed modified Bass diffusion of demand function has significantly contributed for forecasting the diffusion of new Proton car or new product.

Burden of systemic lupus erythematosus on employment and work productivity: data from a large cohort in the southeastern United States.

PubMed

Drenkard, Cristina; Bao, Gaobin; Dennis, Greg; Kan, Hong J; Jhingran, Priti M; Molta, Charles T; Lim, S Sam

2014-06-01

To examine the burden of systemic lupus erythematosus (SLE) on work loss, unemployment, and work productivity impairment in an SLE cohort from the southeastern US. We examined 689 SLE patients ages 18-64 years from the Georgians Organized Against Lupus (GOAL) cohort. GOAL is a longitudinal cohort predominantly derived from the Georgia Lupus Registry, a population-based registry established in metropolitan Atlanta. We used the Kaplan-Meier method to assess the proportion of patients who self-reported work loss since diagnosis. We compared unemployment between SLE patients and the general population from the same geographic area, calculating the standardized unemployment ratio (SUR) within demographic and disease strata. We also calculated the percentage of work productivity impairment by disease outcomes. Of 511 patients employed at diagnosis, 249 (49%) experienced work loss within an average disease duration of 13 years. The proportion of patients who lost their jobs since diagnosis was almost twice for African Americans than for whites. However, the SURs were similar across demographic characteristics, including race. Patients with severe disease activity and severe organ damage had the highest SUR at 4.4 and 5.6, respectively. Among those that remained employed, patients with severe fatigue, neurocognitive symptoms, and musculoskeletal symptoms had the highest impairment of work productivity. SLE imposes a substantial toll on individuals and burden on society. Major factors that negatively impact work outcomes are fatigue, disease activity, and organ damage. More effective treatments along with coping strategies at the workplace are needed to reduce the burden of SLE on work outcomes. Copyright © 2014 by the American College of Rheumatology.

Predicting the onset of psychosis in patients at clinical high risk: practical guide to probabilistic prognostic reasoning.

PubMed

Fusar-Poli, P; Schultze-Lutter, F

2016-02-01

Prediction of psychosis in patients at clinical high risk (CHR) has become a mainstream focus of clinical and research interest worldwide. When using CHR instruments for clinical purposes, the predicted outcome is but only a probability; and, consequently, any therapeutic action following the assessment is based on probabilistic prognostic reasoning. Yet, probabilistic reasoning makes considerable demands on the clinicians. We provide here a scholarly practical guide summarising the key concepts to support clinicians with probabilistic prognostic reasoning in the CHR state. We review risk or cumulative incidence of psychosis in, person-time rate of psychosis, Kaplan-Meier estimates of psychosis risk, measures of prognostic accuracy, sensitivity and specificity in receiver operator characteristic curves, positive and negative predictive values, Bayes' theorem, likelihood ratios, potentials and limits of real-life applications of prognostic probabilistic reasoning in the CHR state. Understanding basic measures used for prognostic probabilistic reasoning is a prerequisite for successfully implementing the early detection and prevention of psychosis in clinical practice. Future refinement of these measures for CHR patients may actually influence risk management, especially as regards initiating or withholding treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Limiting factors in the production of deep microstructures

NASA Astrophysics Data System (ADS)

Tolfree, David W. L.; O'Neill, William; Tunna, Leslie; Sutcliffe, Christopher

1999-10-01

Microsystems increasingly require precision deep microstructures that can be cost-effectively designed and manufactured. New products must be able to meet the demands of the rapidly growing markets for microfluidic, micro- optical and micromechanical devices in industrial sectors which include chemicals, pharmaceuticals, biosciences, medicine and food. The realization of such products, first requires an effective process to design and manufacture prototypes. Two process methods used for the fabrication of high aspect-ratio microstructures are based on X-ray beam lithography with electroforming processes and direct micromachining with a frequency multiplied Nd:YAG laser using nanosecond pulse widths. Factors which limit the efficiency and precision obtainable using such processes are important parameters when deciding on the best fabrication method to use. A basic microstructure with narrow channels suitable for a microfluidic mixer have been fabricated using both these techniques and comparisons made of the limitations and suitability of the processes in respect of fast prototyping and manufacture or working devices.

One-Year Incidence, Time Trends, and Predictors of Recurrent Ischemic Stroke in Sweden From 1998 to 2010: An Observational Study.

PubMed

Bergström, Lisa; Irewall, Anna-Lotta; Söderström, Lars; Ögren, Joachim; Laurell, Katarina; Mooe, Thomas

2017-08-01

Recent data on the incidence, time trends, and predictors of recurrent ischemic stroke are limited for unselected patient populations. Data for ischemic stroke patients were obtained from The Swedish Stroke Register (Riksstroke) between 1998 and 2009 and merged with The Swedish National Inpatient Register. A reference group of patients was created by Statistics Sweden. The ischemic stroke patient cohort was divided into 4 time periods. Recurrent ischemic stroke within 1 year was recorded until 2010. Kaplan-Meier and Cox regression analyses were performed to study time trends and predictors of ischemic stroke recurrence. Of 196 765 patients with ischemic stroke, 11.3% had a recurrent ischemic stroke within 1 year. The Kaplan-Meier estimates of the 1-year cumulative incidence of recurrent ischemic stroke decreased from 15.0% in 1998 to 2001 to 12.0% in 2007 to 2010 in the stroke patient cohort while the cumulative incidence of ischemic stroke decreased from 0.7% to 0.4% in the reference population. Age >75 years, prior ischemic stroke or myocardial infarction, atrial fibrillation without warfarin treatment, diabetes mellitus, and treatment with β-blockers or diuretics were associated with a higher risk while warfarin treatment for atrial fibrillation, lipid-lowering medication, and antithrombotic treatment (acetylsalicylic acid, dipyridamole) were associated with a reduced risk of recurrent ischemic stroke. The risk of recurrent ischemic stroke decreased from 1998 to 2010. Well-known risk factors for stroke were associated with a higher risk of ischemic stroke recurrence; whereas, secondary preventive medication was associated with a reduced risk, emphasizing the importance of secondary preventive treatment. © 2017 American Heart Association, Inc.

Patency of the Internal Iliac Artery after Placement of Common and External Iliac Artery Stents.

PubMed

Vinogradova, Margie; Lee, Hye Joon; Armstrong, Ehrin J; Laird, John; Humphries, Misty D

2017-01-01

Treatment of severe aortoiliac occlusive disease (AIOD) frequently requires long-segment stenting of the common and external iliac arteries (CIA and EIA, respectively). This study aims to analyze the patency of the internal iliac artery (IIA) after placement of a CIA and EIA stents across the orifice. A retrospective analysis of all patients who underwent de novo ipsilateral stent placement in the CIA and EIA between 2006 and 2013 was performed. Kaplan-Meier analysis was used to analyze patency of the IIA, and Cox proportional hazard models were used to identify characteristics associated with occlusion. We identified 77 patients and 93 limbs where ipsilateral CIA and EIA stents were placed. Preintervention angiographic review found 52 cases of a patent ipsilateral IIA where stents were placed across the origin of the IIA in 31 cases and staggered across the orifice in 20 limbs. Kaplan-Meier analysis demonstrated a 37% patency in limbs where the stent covered the IIA orifice compared to 78% patency in uncovered arteries (P = 0.04). New-onset buttock claudication developed in 4 patients, 2 with patent IIAs and 2 with occluded. New-onset impotence also developed in 3 patients with occluded IIA and 5 patients with patent IIAs. Placement of stents across the origin of the IIA may not result in immediate occlusion, but long-term patency of covered IIAs is decreased compared to uncovered IIAs. This study is limited by a small sample size, but when treating AIOD, coverage of the internal iliac origin should be avoided to maintain patency of the pelvic circulation. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2016-01-01

Objective 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. Methods 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). Results 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). Conclusions 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. PMID:27019825

Combination therapy with thalidomide, temozolomide and tamoxifen improves quality of life in patients with malignant astrocytomas.

PubMed

Rabbani, Golam; Benzil, Deborah; Wallam, Mohammed N; Chen, Benjamin; Hoang, Albert; Kancherla, Ram; Ahmed, Tauseef

2007-01-01

Patients with malignant astrocytomas (MA) have a poor survival rate despite surgery, radiation therapy (RT), and chemotherapy (CT). Patients deteriorate rapidly with decreasing quality of life (QoL). The purpose of the current study was to determine the safety and efficacy, including QoL evaluation, of oral therapy with temozolomide, thalidomide, and tamoxifen (TTT) in patients with MA in an Institutional Review Board (IRB)-approved, prospective trial. Twenty-three patients met the eligibility requirements and were enrolled after informed consent was signed. After baseline testing, patients received temozolomide 75 mg/m2 orally (p.o.) for the first 21 days, thalidomide 100 mg p.o. daily, and tamoxifen 100 mg p.o. daily for each 28-day cycle. Treatment continued until disease progression. Primary outcome measurements were survival (Kaplan-Meier analysis), response to treatment, toxicity (National Cancer Institute's Common Toxicity Criterion) and QoL evaluation. The Kaplan-Meier analysis showed that survival time from diagnosis was 78.4+/-15 weeks with a median survival of 54.6 weeks and from date of enrollment was 46.1+/-10 weeks with median survival of 33.3 weeks. Toxicity was limited to 5 patients with deep venous thrombosis (DVT), 2 of whom had pulmonary emboli (PE). All recovered with anticoagulation therapy and none suffered long term sequelae. Several QoL measures, including the global health status scores (p=0.003), were significantly improved after 2 cycles of treatment compared to the baseline assessment. The combination of temozolomide, thalidomide and tamoxifen administered as outpatient oral therapy resulted in significantly improved QoL for patients with MA without significant toxicity.

Revision total knee arthroplasty for septic versus aseptic failure.

PubMed

Rajgopal, Ashok; Vasdev, Attique; Gupta, Himanshu; Dahiya, Vivek

2013-12-01

To compare the medium-term outcome of revision total knee arthroplasty (TKA) for septic versus aseptic failure. Records of 142 patients who underwent revision TKA by a single senior surgeon for septic (n=65) or aseptic (n=77) failure were reviewed. In the septic group, 67 knees in 42 women and 23 men were included. In the aseptic group, 88 knees in 51 women and 26 men were included. The Knee Society Score was measured. The Kaplan Meier survival curve at months 36, 60, and 95 was plotted, with revision as the end point. The survival rates at each specific time point between the 2 groups were compared using the Z test. The Knee Society Scores improved 18% from 51 to 69 in the septic group and 18% from 52 to 70 in the aseptic group (p=0.72). The range of motion improved 30% from 72 to 102 degrees in the septic group and 39% from 62 to 100 degrees in the aseptic group (p<0.001). Results of the 2 groups were similar in terms of the Knee Society Score, range of motion, and the Kaplan-Meier survivorship.

Metastatic volume: an old oncologic concept and a new prognostic factor for stage IV melanoma patients.

PubMed

Panasiti, V; Curzio, M; Roberti, V; Lieto, P; Devirgiliis, V; Gobbi, S; Naspi, A; Coppola, R; Lopez, T; di Meo, N; Gatti, A; Trevisan, G; Londei, P; Calvieri, S

2013-01-01

The last melanoma staging system of the 2009 American Joint Committee on Cancer takes into account, for stage IV disease, the serum levels of lactate dehydrogenase (LDH) and the site of distant metastases. Our aim was to compare the significance of metastatic volume, as evaluated at the time of stage IV melanoma diagnosis, with other clinical predictors of prognosis. We conducted a retrospective multicentric study. To establish which variables were statistically correlated both with death and survival time, contingency tables were evaluated. The overall survival curves were compared using the Kaplan-Meier method. Metastatic volume and number of affected organs were statistically related to death. In detail, patients with a metastatic volume >15 cm(3) had a worse prognosis than those with a volume lower than this value (survival probability at 60 months: 6.8 vs. 40.9%, respectively). The Kaplan-Meier method confirmed that survival time was significantly related to the site(s) of metastases, to elevated LDH serum levels and to melanoma stage according to the latest system. Our results suggest that metastatic volume may be considered as a useful prognostic factor for survival among melanoma patients.

Suspended-Sediment Impacts on Light-limited Productivity in the Delaware Estuary

NASA Astrophysics Data System (ADS)

McSweeney, J.; Chant, R. J.; Wilkin, J.; Sommerfield, C. K.

2016-12-01

The Delaware Estuary has a history of high anthropogenic nutrient loadings, but has been classified as a high-nutrient, low-growth system due persistent light limitations caused by turbidity. While the biogeochemical implications of light limitation in turbid estuaries has been well-studied, there has been minimal effort focused on the connectivity between hydrodynamics, sediment dynamics, and light-limitation. Our understanding of sediment dynamics in the Delaware Estuary has advanced significantly in the last decade, and this study provides insight about how the spatiotemporal variability of the estuarine turbidity maximum controls the light available for primary productivity. This analysis uses data from eight along-estuary cruises from March, June, September, and December 2010 and 2011 to look at the seasonality of suspended sediment and chlorophyll distributions. By estimating the absorption due to sediment under a range of environmental conditions, we describe how the movement of the turbidity maximum affects light availability. We also use an idealized 2-dimensional Regional Ocean Modeling System (ROMS) numerical model to evaluate how river discharge and spring-neap variability modulate the location of phytoplankton blooms. We conclude that high river flows and neap tides can drive stratification that is strong enough to prevent sediment from being resuspended into the surface layer, thus providing light conditions favorable for primary productivity. This study sheds light on the importance of sediment in the limiting primary productivity, and the role of stratification in promoting production, highlighting the potential limitations of biogeochemical models that do not account for sediment absorption.

Entropy production of a Brownian ellipsoid in the overdamped limit.

PubMed

Marino, Raffaele; Eichhorn, Ralf; Aurell, Erik

2016-01-01

We analyze the translational and rotational motion of an ellipsoidal Brownian particle from the viewpoint of stochastic thermodynamics. The particle's Brownian motion is driven by external forces and torques and takes place in an heterogeneous thermal environment where friction coefficients and (local) temperature depend on space and time. Our analysis of the particle's stochastic thermodynamics is based on the entropy production associated with single particle trajectories. It is motivated by the recent discovery that the overdamped limit of vanishing inertia effects (as compared to viscous fricion) produces a so-called "anomalous" contribution to the entropy production, which has no counterpart in the overdamped approximation, when inertia effects are simply discarded. Here we show that rotational Brownian motion in the overdamped limit generates an additional contribution to the "anomalous" entropy. We calculate its specific form by performing a systematic singular perturbation analysis for the generating function of the entropy production. As a side result, we also obtain the (well-known) equations of motion in the overdamped limit. We furthermore investigate the effects of particle shape and give explicit expressions of the "anomalous entropy" for prolate and oblate spheroids and for near-spherical Brownian particles.

MEKK1 is a Novel Regulator of the Dmp1-Arf-p53 Pathway and Prognostic Indicator in Breast Cancer

DTIC Science & Technology

2012-12-01

hDMP1, INK4a/ARF, p53 or Hdm2 amplification. Kaplan -Meier analyses have been conducted to study the impact for the impact of loss or gain of each locus on...Palma P, Pellegrini S, Fina P et al. Mdm2 gene alterations and mdm2 protein expression in breast carcinomas. J Pathol 1995; 175: 31–38. 21 Turbin DA

Survival analysis: Part I — analysis of time-to-event

PubMed Central

2018-01-01

Length of time is a variable often encountered during data analysis. Survival analysis provides simple, intuitive results concerning time-to-event for events of interest, which are not confined to death. This review introduces methods of analyzing time-to-event. The Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazards regression modeling method are described with examples of hypothetical data. PMID:29768911

One-Carbon Metabolism and Breast Cancer Survival in a Population-Based Study

DTIC Science & Technology

2008-06-01

the dietary intake of one- carbon-related micronutrients /compounds (e.g. folate, methionine, chioline, B vitamins, alcohol, etc) in relation to...examine the dietary intake of one-carbon-related micronutrients /compounds (e.g. folate, methionine, chioline, B vitamins, alcohol, etc) in relation to...of dietary methyl content and overall survival. Some descriptive statistical analysis has been reported in previous annual report. The Kaplan-Meier

Impact of phosphate limitation on PHA production in a feast-famine process.

PubMed

Korkakaki, Emmanouela; van Loosdrecht, Mark C M; Kleerebezem, Robbert

2017-12-01

Double-limitation systems have shown to induce polyhydroxyalkanoates (PHA) production in chemostat studies limited in e.g. carbon and phosphate. In this work the impact of double substrate limitation on the enrichment of a PHA producing community was studied in a sequencing batch process. Enrichments at different C/P concentration ratios in the influent were established and the effect on the PHA production capacity and the enrichment community structure was investigated. Experimental results demonstrated that when a double substrate limitation is imposed at a C/P ratio in the influent in a range of 150 (C-mol/mol), the P-content of the biomass and the specific substrate uptake rates decreased. Nonetheless, the PHA storage capacity remained high (with a maximum of 84 wt%). At a C/P ratio of 300, competition in the microbial community is based on phosphate uptake, and the PHA production capacity is lost. Biomass specific substrate uptake rates are a linear function of the cellular P-content, offering advantages for scaling-up the PHA production process due to lower oxygen requirements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adenosine triphosphate stress myocardial perfusion imaging for risk stratification of patients aged 70 years and older with suspected coronary artery disease.

PubMed

Yao, Zhiming; Zhu, Hui; Li, Wenchan; Chen, Congxia; Wang, Hua; Shi, Lei; Zhang, Wenjie

2017-04-01

We investigated the cardiac risk stratification value of adenosine triphosphate stress myocardial perfusion imaging (ATP-MPI) in patients aged 70 years and older with suspected coronary artery disease (CAD). We identified a series of 415 consecutive patients aged 70 years and older with suspected CAD, who had undergone ATP-MPI with 99m Tc-MIBI. The presence of a fixed and/or reversible perfusion defect was considered as an abnormal MPI. Follow-up was available in 399 patients (96.1%) over 3.45 ± 1.71 years after excluding 16 patients who underwent early coronary revascularization <60 days after MPI. The major adverse cardiac events (MACE), including cardiac death, nonfatal infarction, and late coronary revascularization, were recorded. One hundred twenty-five (31.3%) patients had abnormal MPI and the remaining had normal MPI. A multivariable analysis using Cox regression demonstrated that abnormal MPI was independently associated with MACE (hazard ratio 19.50 and 95% confidence interval 5.91-64.31, P value .000). The patients with SSS > 8 had significantly higher cumulative MACE rate than patients with SSS ≤ 8 had (37.8% vs 5.2%, respectively, P < .001). The Kaplan-Meier cumulative MACE-free survival in patients with abnormal MPI (57.0%) was significantly lower than that in patients with normal MPI (89.6%), P < .0001. Among patients with SSS > 8, the Kaplan-Meier cumulative MACE-free survival were 36.9% in patients ≥80 years old and 49.5% in patients 70-79 years old, respectively, P < .05. However, among patients with SSS ≤ 8, there was no difference between the Kaplan-Meier cumulative MACE-free survivals of these two age groups. ATP-MPI data are useful for the prediction of major adverse cardiac events in patients aged 70 years and older with suspected CAD.

How do knee implants perform past the second decade? Nineteen- to 25-year followup of the Press-fit Condylar design TKA.

PubMed

Patil, Shantanu; McCauley, Julie C; Pulido, Pamela; Colwell, Clifford W

2015-01-01

At 14- to 17-year followup, we reported successful outcomes of the Press-fit Condylar total knee arthroplasty (TKA) system in 160 TKAs performed between 1986 and 1989. However, there are few published reports on TKA survivorship and patient function that include patients evaluated into the third decade after surgery. The study purpose was to determine (1) the survivorship of the implant; and (2) knee function in patients with this TKA system at a mean 20-year followup. We ascertained revision status of all living patients (42 of 160 knees) and all patients (22 knees) who died since the previous study. Among patients alive at the latest followup, Knee Society function scores were obtained and radiographs were evaluated. Kaplan-Meier survivorship analysis with 95% confidence intervals was performed with revision for any reason and aseptic loosening as endpoints. A competing risks analysis with 95% confidence intervals was also performed for revision for any reason as the endpoint. At the mean 20-year (range, 19-25 years) followup, all living patients retained their original implants from the index TKA, exclusive of three polyethylene exchanges. This study demonstrates an 87% Kaplan-Meier survivorship for revision for any reason (95% confidence interval [CI], 80%-92%) and a 98% Kaplan-Meier survivorship for revision for aseptic loosening (95% CI, 93%-99%). Competing risks survivorship was 79% (95% CI, 70%-85%) at 25 years for revision for any reason. Mean Knee Society function score was 46.9. Since the previous study, three revisions have been performed, all for polyethylene wear. The Press-fit Condylar implant system continues to be successful, maintaining longevity up to 25-year followup. This is one of the longest followup studies, reporting continued successes over 20 years, and should serve as a benchmark for current-generation implants. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

The prognostic value of tumor-infiltrating neutrophils in gastric adenocarcinoma after resection.

PubMed

Zhao, Jing-jing; Pan, Ke; Wang, Wei; Chen, Ju-gao; Wu, Yan-heng; Lv, Lin; Li, Jian-jun; Chen, Yi-bing; Wang, Dan-dan; Pan, Qiu-zhong; Li, Xiao-dong; Xia, Jian-chuan

2012-01-01

Several pieces of evidence indicate that tumor-infiltrating neutrophils (TINs) are correlated to tumor progression. In the current study, we explore the relationship between TINs and clinicopathological features of gastric adenocarcinoma patients. Furthermore, we investigated the prognostic value of TINs. The study was comprised of two groups, training group (115 patients) and test group (97 patients). Biomarkers (intratumoral CD15+ neutrophils) were assessed by immunohistochemistry. The relationship between clinicopathological features and patient outcome were evaluated using Cox regression and Kaplan-Meier analysis. Immunohistochemical detection showed that the tumor-infiltrating neutrophils (TINs) in the training group ranged from 0.00-115.70 cells/high-power microscopic field (HPF) and the median number was 21.60 cells/HPF. Based on the median number, the patients were divided into high and low TINs groups. Chi-square test analysis revealed that the density of CD15+ TINs was positively associated with lymph node metastasis (p = 0.024), distance metastasis (p = 0.004) and UICC (International Union Against Cancer) staging (p = 0.028). Kaplan-Meier analysis showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.002). Multivariate Cox's analysis showed that the density of CD15+ TINs was an independent prognostic factor for overall survival of gastric adenocarcinoma patients. Using another 97 patients as a test group and basing on the median number of TINs (21.60 cells/HPF) coming from the training group, Kaplan-Meier analysis also showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.032). The results verify that the number of CD15+ TINs can predict the survival of gastric adenocarcinoma surgical patients. The presence of CD15+ TINs is an independent and unfavorable factor in the prognosis of gastric

The Prognostic Value of Tumor-Infiltrating Neutrophils in Gastric Adenocarcinoma after Resection

PubMed Central

Wang, Wei; Chen, Ju-gao; Wu, Yan-heng; Lv, Lin; Li, Jian-jun; Chen, Yi-bing; Wang, Dan-dan; Pan, Qiu-zhong; Li, Xiao-dong; Xia, Jian-chuan

2012-01-01

Background Several pieces of evidence indicate that tumor-infiltrating neutrophils (TINs) are correlated to tumor progression. In the current study, we explore the relationship between TINs and clinicopathological features of gastric adenocarcinoma patients. Furthermore, we investigated the prognostic value of TINs. Patients and Methods The study was comprised of two groups, training group (115 patients) and test group (97 patients). Biomarkers (intratumoral CD15+ neutrophils) were assessed by immunohistochemistry. The relationship between clinicopathological features and patient outcome were evaluated using Cox regression and Kaplan-Meier analysis. Results Immunohistochemical detection showed that the tumor-infiltrating neutrophils (TINs) in the training group ranged from 0.00–115.70 cells/high-power microscopic field (HPF) and the median number was 21.60 cells/HPF. Based on the median number, the patients were divided into high and low TINs groups. Chi-square test analysis revealed that the density of CD15+ TINs was positively associated with lymph node metastasis (p = 0.024), distance metastasis (p = 0.004) and UICC (International Union Against Cancer) staging (p = 0.028). Kaplan-Meier analysis showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.002). Multivariate Cox's analysis showed that the density of CD15+ TINs was an independent prognostic factor for overall survival of gastric adenocarcinoma patients. Using another 97 patients as a test group and basing on the median number of TINs (21.60 cells/HPF) coming from the training group, Kaplan-Meier analysis also showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.032). The results verify that the number of CD15+ TINs can predict the survival of gastric adenocarcinoma surgical patients. Conclusions The presence of CD15+ TINs is an independent and

Aggravated phosphorus limitation on biomass production under increasing nitrogen loading: a meta-analysis.

PubMed

Li, Yong; Niu, Shuli; Yu, Guirui

2016-02-01

Nitrogen (N) and phosphorus (P), either individually or in combination, have been demonstrated to limit biomass production in terrestrial ecosystems. Field studies have been extensively synthesized to assess global patterns of N impacts on terrestrial ecosystem processes. However, to our knowledge, no synthesis has been done so far to reveal global patterns of P impacts on terrestrial ecosystems, especially under different nitrogen (N) levels. Here, we conducted a meta-analysis of impacts of P addition, either alone or with N addition, on aboveground (AGB) and belowground biomass production (BGB), plant and soil P concentrations, and N : P ratio in terrestrial ecosystems. Overall, our meta-analysis quantitatively confirmed existing notions: (i) colimitation of N and P on biomass production and (ii) more P limitation in tropical forest than other ecosystems. More importantly, our analysis revealed new findings: (i) P limitation on biomass production was aggravated by N enrichment and (ii) plant P concentration was a better indicator of P limitation than soil P availability. Specifically, P addition increased AGB and BGB by 34% and 13%, respectively. The effect size of P addition on biomass production was larger in tropical forest than grassland, wetland, and tundra and varied with P fertilizer forms, P addition rates, or experimental durations. The P-induced increase in biomass production and plant P concentration was larger under elevated than ambient N. Our findings suggest that the global limitation of P on biomass production will become severer under increasing N fertilizer and deposition in the future. © 2015 John Wiley & Sons Ltd.

40 CFR Table 1 to Subpart E of... - Product-Weighted Reactivity Limits by Coating Category

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 6 2012-07-01 2012-07-01 false Product-Weighted Reactivity Limits by... Pt. 59, Subpt. E, Table 1 Table 1 to Subpart E of Part 59—Product-Weighted Reactivity Limits by Coating Category Coating category Category code a Reactivity limit(g O3/g product) Clear Coatings CCP 1.50...

40 CFR Table 1 to Subpart E of... - Product-Weighted Reactivity Limits by Coating Category

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 6 2013-07-01 2013-07-01 false Product-Weighted Reactivity Limits by... Pt. 59, Subpt. E, Table 1 Table 1 to Subpart E of Part 59—Product-Weighted Reactivity Limits by Coating Category Coating category Category code a Reactivity limit(g O3/g product) Clear Coatings CCP 1.50...

Comparison of numerical and experimental results of the flow in the U9 Kaplan turbine model

NASA Astrophysics Data System (ADS)

Petit, O.; Mulu, B.; Nilsson, H.; Cervantes, M.

2010-08-01

The present work compares simulations made using the OpenFOAM CFD code with experimental measurements of the flow in the U9 Kaplan turbine model. Comparisons of the velocity profiles in the spiral casing and in the draft tube are presented. The U9 Kaplan turbine prototype located in Porjus and its model, located in Älvkarleby, Sweden, have curved inlet pipes that lead the flow to the spiral casing. Nowadays, this curved pipe and its effect on the flow in the turbine is not taken into account when numerical simulations are performed at design stage. To study the impact of the inlet pipe curvature on the flow in the turbine, and to get a better overview of the flow of the whole system, measurements were made on the 1:3.1 model of the U9 turbine. Previously published measurements were taken at the inlet of the spiral casing and just before the guide vanes, using the laser Doppler anemometry (LDA) technique. In the draft tube, a number of velocity profiles were measured using the LDA techniques. The present work extends the experimental investigation with a horizontal section at the inlet of the draft tube. The experimental results are used to specify the inlet boundary condition for the numerical simulations in the draft tube, and to validate the computational results in both the spiral casing and the draft tube. The numerical simulations were realized using the standard k-e model and a block-structured hexahedral wall function mesh.

Effect of delayed toxicity of chemical barriers to control Argentine ants (Hymenoptera: Formicidae).

PubMed

Soeprono, Andrew M; Rust, Michael K

2004-12-01

Brief exposures of Argentine ants to four different insecticide treatments, bifenthrin, beta-cyfluthrin, bifenthrin + beta-cyfluthrin, and fipronil, were conducted to determine Kaplan-Meier product limit survivorship percentiles (SPs) at 21-23 and 27-29 degrees C. Bifenthrin, beta-cyfluthrin, and bifenthrin + beta-cyfluthrin provided rapid kill at 21-23 degrees C with SP10 values ranging from 11.2 to 33.7 min. Fipronil provided delayed toxicity at 21-23 degrees C with SP10 values ranging from 270 to 960 min. At 27-29 degrees C, all of the SP10 values significantly decreased. Field tests in which Argentine ants were induced to forage across insecticide-treated surfaces were used to determine the effect that speed of action has on foraging and recruitment ability, and whether these insecticides are repellent. The slower-acting fipronil allowed a greater amount of foraging and consequently a greater fraction of the colony to be exposed, whereas fast-acting bifenthrin, beta-cyfluthrin, and bifenthrin + beta-cyfluthrin inhibited recruitment, resulting in fewer ants being exposed and killed. Implications for controlling ants by using perimeter barrier treatments are discussed.

How Do We Defend Democratic Education? Lois Weiner and Andy Kaplan Respond to Diane Ravitch's "The Reign of Error"

ERIC Educational Resources Information Center

Weiner, Lois; Kaplan, Andy

2014-01-01

In this commentary, Andy Kaplan discusses with Lois Weiner, Diane Ravitch's latest book "The Reign of Error," which combines scholarly argument and scrupulous research in defense of democratic education. Weiner notes, the book will prove an important resource in the ongoing struggle for the survival of public schooling. Weiner adds,…

Zebrafish cdc6 hypomorphic mutation causes Meier-Gorlin syndrome-like phenotype.

PubMed

Yao, Likun; Chen, Jing; Wu, Xiaotong; Jia, Shunji; Meng, Anming

2017-11-01

Cell Division Cycle 6 (Cdc6) is a component of pre-replicative complex (preRC) forming on DNA replication origins in eukaryotes. Recessive mutations in ORC1, ORC4, ORC6, CDT1 or CDC6 of the preRC in human cause Meier-Gorlin syndrome (MGS) that is characterized by impaired post-natal growth, short stature and microcephaly. However, vertebrate models of MGS have not been reported. Through N-ethyl-N-nitrosourea mutagenesis and Cas9 knockout, we generate several cdc6 mutant lines in zebrafish. Loss-of-function mutations of cdc6, as manifested by cdc6tsu4305 and cdc6tsu7cd mutants, lead to embryonic lethality due to cell cycle arrest at the S phase and extensive apoptosis. Embryos homozygous for a cdc6 hypomorphic mutation, cdc6tsu21cd, develop normally during embryogenesis. Later on, compared with their wild-type (WT) siblings, cdc6tsu21cd mutant fish show growth retardation, and their body weight and length in adulthood are greatly reduced, which resemble human MGS. Surprisingly, cdc6tsu21cd mutant fish become males with a short life and fail to mate with WT females, suggesting defective reproduction. Overexpression of Cdc6 mutant forms, which mimic human CDC6(T323R) mutation found in a MGS patient, in zebrafish cdc6tsu4305 mutant embryos partially represses cell death phenotype, suggesting that the human CDC6(T323R) mutation is a hypomorph. cdc6tsu21cd mutant fish will be useful to detect more tissue defects and develop medical treatment strategies for MGS patients. © The Author 2017. Published by Oxford University Press.

Zebrafish cdc6 hypomorphic mutation causes Meier-Gorlin syndrome-like phenotype

PubMed Central

Yao, Likun; Chen, Jing; Wu, Xiaotong; Jia, Shunji; Meng, Anming

2017-01-01

Abstract Cell Division Cycle 6 (Cdc6) is a component of pre-replicative complex (preRC) forming on DNA replication origins in eukaryotes. Recessive mutations in ORC1, ORC4, ORC6, CDT1 or CDC6 of the preRC in human cause Meier-Gorlin syndrome (MGS) that is characterized by impaired post-natal growth, short stature and microcephaly. However, vertebrate models of MGS have not been reported. Through N-ethyl-N-nitrosourea mutagenesis and Cas9 knockout, we generate several cdc6 mutant lines in zebrafish. Loss-of-function mutations of cdc6, as manifested by cdc6tsu4305 and cdc6tsu7cd mutants, lead to embryonic lethality due to cell cycle arrest at the S phase and extensive apoptosis. Embryos homozygous for a cdc6 hypomorphic mutation, cdc6tsu21cd, develop normally during embryogenesis. Later on, compared with their wild-type (WT) siblings, cdc6tsu21cd mutant fish show growth retardation, and their body weight and length in adulthood are greatly reduced, which resemble human MGS. Surprisingly, cdc6tsu21cd mutant fish become males with a short life and fail to mate with WT females, suggesting defective reproduction. Overexpression of Cdc6 mutant forms, which mimic human CDC6(T323R) mutation found in a MGS patient, in zebrafish cdc6tsu4305 mutant embryos partially represses cell death phenotype, suggesting that the human CDC6(T323R) mutation is a hypomorph. cdc6tsu21cd mutant fish will be useful to detect more tissue defects and develop medical treatment strategies for MGS patients. PMID:28985365

77 FR 24656 - Extension of Port Limits of Indianapolis, IN

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-25

...-0118. FOR FURTHER INFORMATION CONTACT: Roger Kaplan, Office of Field Operations, U.S. Customs and Border Protection, (202) 325-4543, or by email at Roger.Kaplan@dhs.gov . SUPPLEMENTARY INFORMATION: I...

Runaway transient simulation of a model Kaplan turbine

NASA Astrophysics Data System (ADS)

Liu, S.; Zhou, D.; Liu, D.; Wu, Y.; Nishi, M.

2010-08-01

The runaway transient is a typical transient process of a hydro power unit, where the rotational speed of a turbine runner rapidly increases up to the runaway speed under a working head as the guide vanes cannot be closed due to some reason at the load rejection. In the present paper, the characteristics of the runaway transient of a model Kaplan turbine having ns = 479(m-kW) is simulated by using a time-dependent CFD technique where equation of rotational motion of runner, continuity equation and unsteady RANS equations with RNG k-epsilon turbulence model are solved iteratively. In the calculation, unstructured mesh is used to the whole flow passage, which consists of several sub-domains: entrance, casing, stay vanes + guide vanes, guide section, runner and draft tube. And variable speed sliding mesh technique is used to exchange interface flow information between moving part and stationary part, and three-dimensional unstructured dynamic mesh technique is also adopted to ensure mesh quality. Two cases were treated in the simulation of runaway transient characteristics after load rejection: one is the rated operating condition as the initial condition, and the other is the condition at the maximum head. Regarding the runaway speed, the experimental speed is 1.45 times the initial speed and the calculation is 1.47 times the initial for the former case. In the latter case, the experiment and the calculation are 1.67 times and 1.69 times respectively. From these results, it is recognized that satisfactorily prediction will be possible by using the present numerical method. Further, numerical results show that the swirl in the draft-tube flow becomes stronger in the latter part of the transient process so that a vortex rope will occur in the draft tube and its precession will cause the pressure fluctuations which sometimes affect the stability of hydro power system considerably.

Clinical and Economic Evaluation of Treatment Strategies for T1N0 Anal Canal Cancer.

PubMed

Deshmukh, Ashish A; Zhao, Hui; Das, Prajnan; Chiao, Elizabeth Y; You, Yi-Qian Nancy; Franzini, Luisa; Lairson, David R; Swartz, Michael D; Giordano, Sharon H; Cantor, Scott B

2018-07-01

A comparative assessment of treatment alternatives for T1N0 anal canal cancer has never been conducted. We compared the outcomes associated with the treatment alternatives-chemoradiotherapy (CRT), radiotherapy (RT), and surgery or ablation techniques (surgery/ablation)-for T1N0 anal canal cancer. This retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results (SEER) registries linked with Medicare longitudinal data (SEER-Medicare database). Analysis included 190 patients who were treated for T1N0 anal canal cancer using surgery/ablation (n=44), RT (n=50), or CRT (n=96). The outcomes were reported in terms of survival and hazards ratios using Kaplan-Meier and Cox proportional hazards modeling, respectively; lifetime costs; and cost-effectiveness measured in terms of incremental cost-effectiveness ratio, that is, the ratio of the difference in costs between the 2 alternatives to the difference in effectiveness between the same 2 alternatives. There was no significant difference in the survival duration between the treatment groups as predicted by the Kaplan-Meier curves. After adjusting for patient characteristics and propensity score, the hazard ratio of death for the patients who received CRT compared with surgery/ablation was 1.742 (95% confidence interval, 0.793-3.829) and RT was 2.170 (95% confidence interval, 0.923-5.101); however, the relationship did not reach statistical significance. Surgery/ablation resulted in lower lifetime cost than RT or CRT. The incremental cost-effectiveness ratio associated with CRT compared with surgery/ablation was $142,883 per life year gained. There was no statistically significant difference in survival among the treatment alternatives for T1N0 anal canal cancer. Given that surgery/ablation costs less than RT or CRT and might be cost-effective compared with RT and CRT, it is crucial to explore this finding further in this era of limited health care resources.

Different electrophysiological profiles and treatment response in 'typical' and 'atypical' chronic inflammatory demyelinating polyneuropathy.

PubMed

Kuwabara, Satoshi; Isose, Sagiri; Mori, Masahiro; Mitsuma, Satsuki; Sawai, Setsu; Beppu, Minako; Sekiguchi, Yukari; Misawa, Sonoko

2015-10-01

Chronic inflammatory demyelinating polyneuropathy (CIDP) is currently classified into 'typical' CIDP and 'atypical' subtypes such as multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). To assess the frequency of CIDP subtypes, and to elucidate clinical and electrophysiological features, and treatment response in each subtype. We reviewed data from 100 consecutive patients fulfilling criteria for CIDP proposed by the European Federation of Neurological Societies and the Peripheral Nerve Society. The Kaplan-Meier curve was used to estimate long-term outcome. Patients were classified as having typical CIDP (60%), MADSAM (34%), demyelinating acquired distal symmetric neuropathy (8%) or pure sensory CIDP (1%). Compared with patients with MADSAM, patients with typical CIDP showed more rapid progression and severe disability, and demyelination predominant in the distal nerve segments. MADSAM was characterised by multifocal demyelination in the nerve trunks. Abnormal median-normal sural sensory responses were more frequently found for typical CIDP (53% vs 13%). Patients with typical CIDP invariably responded to corticosteroids, immunoglobulin or plasmapheresis, whereas patients with MADSAM were more refractory to these treatments. The Kaplan-Meier analyses showed that 64% of patients with typical CIDP and 41% of patients with MADSAM had a clinical remission 5 years later (p=0.02). Among the CIDP spectrum, typical CIDP and MADSAM are the major subtypes, and their pathophysiology appears to be distinct. In typical CIDP, the distal nerve terminals and possibly the nerve roots, where the blood-nerve barrier is anatomically deficient, are preferentially affected, raising the possibility of antibody-mediated demyelination, whereas cellular immunity with breakdown of the barrier may be important in MADSAM neuropathy. 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.

Long-term pediatric skin eruption-related hospitalizations in offspring conceived via fertility treatment.

PubMed

Krieger, Yuval; Wainstock, Tamar; Sheiner, Eyal; Harlev, Avi; Landau, Daniella; Horev, Amir; Bogdanov-Berezovsky, Alexander; Walfisch, Asnat

2018-03-01

Although concerns have been raised regarding the long-term health risks of offspring conceived following fertility treatments, limited information is available regarding their health status beyond the neonatal period. We aimed to evaluate the risk of long-term eruptive dermatological morbidity among children born following fertility treatments as compared to those conceived spontaneously. A population-based cohort study was conducted, including all singleton deliveries occurring between the years 1991 and 2014 at a single tertiary medical center. Fetuses with congenital malformations and multiple gestations were excluded. Children delivered following fertility treatment pregnancies and spontaneous pregnancies were compared. Hospitalizations of the offspring up to the age of 18 years involving cutaneous eruptions were evaluated. A Kaplan-Meier survival curve was used to compare cumulative morbidity incidence and a Cox regression model to control for confounders. During the study period, 242,187 singleton deliveries met the inclusion criteria, 1.8% of which were following fertility treatments (n = 4324). Eruptive dermatological morbidity of the offspring up to the age of 18 years was significantly more common in the fertility treatment group (1.5%) as compared to spontaneous pregnancies (1.1%; P = 0.023). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of eruptive dermatological morbidity following fertility treatments (log-rank P = 0.007). Using the Cox regression model, while controlling for multiple confounders, fertility treatment was noted as an independent risk factor for long-term pediatric eruptive dermatological morbidity (adjusted HR = 1.43, CI 1.12-1.83, P = 0.004). Singletons conceived via fertility treatments appear to be at an increased risk for long-term eruptive dermatological morbidity. © 2018 The International Society of Dermatology.

Exercise Capacity and the Obesity Paradox in Heart Failure: The FIT (Henry Ford Exercise Testing) Project.

PubMed

McAuley, Paul A; Keteyian, Steven J; Brawner, Clinton A; Dardari, Zeina A; Al Rifai, Mahmoud; Ehrman, Jonathan K; Al-Mallah, Mouaz H; Whelton, Seamus P; Blaha, Michael J

2018-05-03

To assess the influence of exercise capacity and body mass index (BMI) on 10-year mortality in patients with heart failure (HF) and to synthesize these results with those of previous studies. This large biracial sample included 774 men and women (mean age, 60±13 years; 372 [48%] black) with a baseline diagnosis of HF from the Henry Ford Exercise Testing (FIT) Project. All patients completed a symptom-limited maximal treadmill stress test from January 1, 1991, through May 31, 2009. Patients were grouped by World Health Organization BMI categories for Kaplan-Meier survival analyses and stratified by exercise capacity (<4 and ≥4 metabolic equivalents [METs] of task). Associations of BMI and exercise capacity with all-cause mortality were assessed using multivariable-adjusted Cox proportional hazards models. During a mean follow-up of 10.1±4.6 years, 380 patients (49%) died. Kaplan-Meier survival plots revealed a significant positive association between BMI category and survival for exercise capacity less than 4 METs (log-rank, P=.05), but not greater than or equal to 4 METs (P=.76). In the multivariable-adjusted models, exercise capacity (per 1 MET) was inversely associated, but BMI was not associated, with all-cause mortality (hazard ratio, 0.89; 95% CI, 0.85-0.94; P<.001 and hazard ratio, 0.99; 95% CI, 0.97-1.01; P=.16, respectively). Maximal exercise capacity modified the relationship between BMI and long-term survival in patients with HF, upholding the presence of an exercise capacity-obesity paradox dichotomy as observed over the short-term in previous studies. Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Heart transplant outcomes in recipients of Centers for Disease Control (CDC) high risk donors.

PubMed

Tsiouris, Athanasios; Wilson, Lynn; Sekar, Rajesh B; Mangi, Abeel A; Yun, James J

2016-12-01

A lack of donor hearts remains a major limitation of heart transplantation. Hearts from Centers for Disease Control (CDC) high-risk donors can be utilized with specific recipient consent. However, outcomes of heart transplantation with CDC high-risk donors are not well known. We sought to define outcomes, including posttransplant hepatitis and human immunodeficiency virus (HIV) status, in recipients of CDC high-risk donor hearts at our institution. All heart transplant recipients from August 2010 to December 2014 (n = 74) were reviewed. Comparison of 1) CDC high-risk donor (HRD) versus 2) standard-risk donor (SRD) groups were performed using chi-squared tests for nominal data and Wilcoxon two-sample tests for continuous variables. Survival was estimated with Kaplan-Meier curves. Of 74 heart transplant recipients reviewed, 66 (89%) received a SRD heart and eight (11%) received a CDC HRD heart. We found no significant differences in recipient age, sex, waiting list 1A status, pretransplant left ventricular assist device (LVAD) support, cytomegalovirus (CMV) status, and graft ischemia times (p = NS) between the HRD and SRD groups. All of the eight HRD were seronegative at the time of transplant. Postoperatively, there was no significant difference in rejection rates at six and 12 months posttransplant. Importantly, no HRD recipients acquired hepatitis or HIV. Survival in HRD versus SRD recipients was not significantly different by Kaplan-Meier analysis (log rank p = 0.644) at five years posttransplant. Heart transplants that were seronegative at the time of transplant had similar posttransplant graft function, rejection rates, and five-year posttransplant survival versus recipients of SRD hearts. At our institution, no cases of hepatitis or HIV occurred in HRD recipients in early follow-up. © 2016 Wiley Periodicals, Inc.

78 FR 54755 - Extension of Port Limits of Indianapolis, IN

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-06

... INFORMATION CONTACT: Roger Kaplan, Office of Field Operations, U.S. Customs and Border Protection, by phone at (202) 325- 4543, or by email at Roger.Kaplan@dhs.gov . SUPPLEMENTARY INFORMATION: I. Background In a...

A clinical and pathologic comparison between stage-matched endometrial intraepithelial carcinoma and uterine serous carcinoma: is there a difference?

PubMed

Hou, June Y; McAndrew, Thomas C; Goldberg, Gary L; Whitney, Kathleen; Shahabi, Shohreh

2014-04-01

Endometrial intraepithelial carcinoma (EIC) is a rare pathologic variant of uterine serous carcinoma (USC). Our aim is to distinguish patterns of clinic-pathologic outcomes in patients with EIC and USC for disease limited to the endometrium (stage 1A) as well as with distant metastasis (stage 4B). Surgically staged patients were retrospectively identified and relevant variables were extracted and compared. Kaplan-Meier was used to generate the survival data. More USC (n = 29) exhibited lymphovascular invasion (stage 4, P = .01) and expressed higher levels of estrogen receptor-α than EIC (P = .0009 and .063 for stages 1 and 4, respectively). The survival is comparable, with 1 recurrence in each group for stage 1A disease. For stage 4 EIC and USC, the progression-free survival (14 vs10 months) and overall survival (19 vs 20 months) are similar to what is previously published. In conclusion, EIC, whether limited to the endometrium, or widely metastatic, imparts similar outcomes and should be treated comparably with stage-matched USC.

40 CFR Table 1 to Subpart E of... - Product-Weighted Reactivity Limits by Coating Category

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Product-Weighted Reactivity Limits by... CONSUMER AND COMMERCIAL PRODUCTS National Volatile Organic Compound Emission Standards for Aerosol Coatings Pt. 59, Subpt. E, Table 1 Table 1 to Subpart E of Part 59—Product-Weighted Reactivity Limits by...

Statistical evaluation of a project to estimate fish trajectories through the intakes of Kaplan hydropower turbines

NASA Astrophysics Data System (ADS)

Sutton, Virginia Kay

This paper examines statistical issues associated with estimating paths of juvenile salmon through the intakes of Kaplan turbines. Passive sensors, hydrophones, detecting signals from ultrasonic transmitters implanted in individual fish released into the preturbine region were used to obtain the information to estimate fish paths through the intake. Aim and location of the sensors affects the spatial region in which the transmitters can be detected, and formulas relating this region to sensor aiming directions are derived. Cramer-Rao lower bounds for the variance of estimators of fish location are used to optimize placement of each sensor. Finally, a statistical methodology is developed for analyzing angular data collected from optimally placed sensors.

Correcting for dependent censoring in routine outcome monitoring data by applying the inverse probability censoring weighted estimator.

PubMed

Willems, Sjw; Schat, A; van Noorden, M S; Fiocco, M

2018-02-01

Censored data make survival analysis more complicated because exact event times are not observed. Statistical methodology developed to account for censored observations assumes that patients' withdrawal from a study is independent of the event of interest. However, in practice, some covariates might be associated to both lifetime and censoring mechanism, inducing dependent censoring. In this case, standard survival techniques, like Kaplan-Meier estimator, give biased results. The inverse probability censoring weighted estimator was developed to correct for bias due to dependent censoring. In this article, we explore the use of inverse probability censoring weighting methodology and describe why it is effective in removing the bias. Since implementing this method is highly time consuming and requires programming and mathematical skills, we propose a user friendly algorithm in R. Applications to a toy example and to a medical data set illustrate how the algorithm works. A simulation study was carried out to investigate the performance of the inverse probability censoring weighted estimators in situations where dependent censoring is present in the data. In the simulation process, different sample sizes, strengths of the censoring model, and percentages of censored individuals were chosen. Results show that in each scenario inverse probability censoring weighting reduces the bias induced in the traditional Kaplan-Meier approach where dependent censoring is ignored.

Prior history of non-melanoma skin cancer is associated with increased mortality in patients with chronic lymphocytic leukemia

PubMed Central

Toro, Jorge R.; Blake, Patrick W.; Björkholm, Magnus; Kristinsson, Sigurdur Y.; Wang, Zhuoqiao; Landgren, Ola

2009-01-01

We investigated whether a previous diagnosis of non-melanoma skin cancer among chronic lymphocytic leukemia patients is a predictor of poor outcome. Using the Swedish Cancer Registry, we conducted a population-based study to evaluate the survival patterns among chronic lymphocytic leukemia patients with and without non-melanoma skin cancer. Cox proportional hazards regression models were used and Kaplan-Meier curves were constructed. Of a total of 12,041 chronic lymphocytic leukemia cases identified, 236 cases, including 111 squamous cell cancer, had a prior history of non-melanoma skin cancer. Chronic lymphocytic leukemia patients with a prior history of non-melanoma skin cancer had a 1.29-fold (95% CI 1.10–1.52; p=0.0024) increased risk of dying; and those with a history of squamous cell cancer had a further elevated 1.86-fold (95% CI 1.46–2.36; p<0.0001) risk of dying. Kaplan-Meier plots showed that patients with a history of non-melanoma skin cancer, particularly those with squamous cell cancer, had significantly poorer survival than chronic lymphocytic leukemia patients without non-melanoma skin cancer (p<0.0001; log-rank test). Non-melanoma skin cancer may be a novel clinical predictor of worse chronic lymphocytic leukemia outcome. PMID:19794092

[Expression and clinical significance of 5hmC in bladder urothelial carcinoma].

PubMed

Li, Jie; Xu, Yuqiao; Zhang, Zhiwen; Zhang, Ming; Zhang, Zhekai; Zhang, Feng; Li, Qing

2016-02-01

To investigate the expression of 5-hydroxymethylcytosine (5hmC) in bladder urothelial carcinoma (UC) and its clinical significance. The expression of 5hmC in 21 cases of UC tissues and pericarcinous urinary tract epithelium was detected by immunohistochemical staining. Then the expression of 5hmC in the surgical resection of UC tissues in 92 cases was also surveyed. Non parametric U Mann-Whitney test was used to analyze the correlation between 5hmC expression and clinical data. Single factor survival analysis was performed by Kaplan-Meier test. The expression of 5hmC in normal urinary tract epithelium and UC tissues was significantly different, but there was no significant difference in the expression of 5hmC between low and high grades of UC tissues as well as between different TNM grades. Kaplan-Meier single factor survival analysis showed that there was no significant correlation between the 5hmC expression level and the survival rate or the recurrence-free survival of UC patients. The expression level of 5hmC in UC tissues is significantly lower than that in pericarcinous urinary tract epithelium. There is no correlation between the 5hmC expression and the progression, prognosis and recurrence of UC.

Evaluation of the TRPM2 channel as a biomarker in breast cancer using public databases analysis.

PubMed

Sumoza-Toledo, Adriana; Espinoza-Gabriel, Mario Iván; Montiel-Condado, Dvorak

Breast cancer is one of the most common malignancies affecting women. Recent investigations have revealed a major role of ion channels in cancer. The transient receptor potential melastatin-2 (TRPM2) is a plasma membrane and lysosomal channel with important roles in cell migration and cell death in immune cells and tumor cells. In this study, we investigated the prognostic value of TRPM2 channel in breast cancer, analyzing public databases compiled in Oncomine™ (Thermo Fisher, Ann Arbor, MI) and online Kaplan-Meier Plotter platforms. The results revealed that TRPM2 mRNA overexpression is significant in situ and invasive breast carcinoma compared to normal breast tissue. Furthermore, multi-gene validation using Oncomine™ showed that this channel is coexpressed with proteins related to cellular migration, transformation, and apoptosis. On the other hand, Kaplan-Meier analysis exhibited that low expression of TRPM2 could be used to predict poor outcome in ER- and HER2+ breast carcinoma patients. TRPM2 is a promising biomarker for aggressiveness of breast cancer, and a potential target for the development of new therapies. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Talent in Female Gymnastics: a Survival Analysis Based upon Performance Characteristics.

PubMed

Pion, J; Lenoir, M; Vandorpe, B; Segers, V

2015-11-01

This study investigated the link between the anthropometric, physical and motor characteristics assessed during talent identification and dropout in young female gymnasts. 3 cohorts of female gymnasts (n=243; 6-9 years) completed a test battery for talent identification. Performance-levels were monitored over 5 years of competition. Kaplan-Meier and Cox Proportional Hazards analyses were conducted to determine the survival rate and the characteristics that influence dropout respectively. Kaplan-Meier analysis indicated that only 18% of the female gymnasts that passed the baseline talent identification test survived at the highest competition level 5 years later. The Cox Proportional Hazards Model indicated that gymnasts with a score in the best quartile for a specific characteristic significantly increased chances of survival by 45-129%. These characteristics being: basic motor skills (129%), shoulder strength (96%), leg strength (53%) and 3 gross motor coordination items (45-73%). These results suggest that tests batteries commonly used for talent identification in young female gymnasts may also provide valuable insights into future dropout. Therefore, multidimensional test batteries deserve a prominent place in the selection process. The individual test results should encourage trainers to invest in an early development of basic physical and motor characteristics to prevent attrition. © Georg Thieme Verlag KG Stuttgart · New York.

Downregulation of SASH1 correlates with poor prognosis in cervical cancer.

PubMed

Xie, J; Zhang, W; Zhang, J; Lv, Q-Y; Luan, Y-F

2017-10-01

The aim of this study was to analyze the association of SASH1 expression with clinicopathological features and prognosis in patients suffering cervical cancer. The expressions of SASH1 mRNA and protein in cervical cancer tissues and matched normal cervical tissues were detected by Real-time PCR and Immunohistochemistry. Based on the above findings, the association among SASH1 expression and clinicopathological features was analyzed. Overall survival was evaluated using the Kaplan-Meier method. The variables were used in univariate and multivariate analysis by the Cox proportional hazards model. The results demonstrated that both SASH1 mRNA and proteins were downregulated in cervical cancer tissues compared with those in matched normal tissues (both p < 0.05). Also, decreased SASH1 expression in cervical cancer was found to be significantly associated with high FIGO Stage (p = 0.001), lymph nodes metastasis (p = 0.003) and differentiation (p = 0.018). Furthermore, Kaplan-Meier analysis demonstrated that low SASH1 expression level was associated with poorer overall survival (p < 0.01). Univariate and multivariate analyses indicated that status of SASH1 was an independent prognostic factor for patients with cervical cancer. These findings suggested that SASH1 can be useful as a new prognostic marker and therapeutic target in cervical cancer patients.

Some insight on censored cost estimators.

PubMed

Zhao, H; Cheng, Y; Bang, H

2011-08-30

Censored survival data analysis has been studied for many years. Yet, the analysis of censored mark variables, such as medical cost, quality-adjusted lifetime, and repeated events, faces a unique challenge that makes standard survival analysis techniques invalid. Because of the 'informative' censorship imbedded in censored mark variables, the use of the Kaplan-Meier (Journal of the American Statistical Association 1958; 53:457-481) estimator, as an example, will produce biased estimates. Innovative estimators have been developed in the past decade in order to handle this issue. Even though consistent estimators have been proposed, the formulations and interpretations of some estimators are less intuitive to practitioners. On the other hand, more intuitive estimators have been proposed, but their mathematical properties have not been established. In this paper, we prove the analytic identity between some estimators (a statistically motivated estimator and an intuitive estimator) for censored cost data. Efron (1967) made similar investigation for censored survival data (between the Kaplan-Meier estimator and the redistribute-to-the-right algorithm). Therefore, we view our study as an extension of Efron's work to informatively censored data so that our findings could be applied to other marked variables. Copyright © 2011 John Wiley & Sons, Ltd.

Skin autofluorescence and all-cause mortality in stage 3 CKD.

PubMed

Fraser, Simon D S; Roderick, Paul J; McIntyre, Natasha J; Harris, Scott; McIntyre, Christopher W; Fluck, Richard J; Taal, Maarten W

2014-08-07

Novel markers may help to improve risk prediction in CKD. One potential candidate is tissue advanced glycation end product accumulation, a marker of cumulative metabolic stress, which can be assessed by a simple noninvasive measurement of skin autofluorescence. Skin autofluorescence correlates with higher risk of cardiovascular events and mortality in people with diabetes or people requiring RRT, but its role in earlier CKD has not been studied. A prospective cohort of 1741 people with CKD stage 3 was recruited from primary care between August 2008 and March 2010. Participants underwent medical history, clinical assessment, blood and urine sampling for biochemistry, and measurement of skin autofluorescence. Kaplan-Meier plots and multivariate Cox proportional hazards models were used to investigate associations between skin autofluorescence (categorical in quartiles) and all-cause mortality. In total, 1707 participants had skin autofluorescence measured; 170 (10%) participants died after a median of 3.6 years of follow-up. The most common cause of death was cardiovascular disease (41%). Higher skin autofluorescence was associated significantly with poorer survival (all-cause mortality, P<0.001) on Kaplan-Meier analysis. Univariate and age/sex-adjusted Cox proportional hazards models showed that the highest quartile of skin autofluorescence was associated with all-cause mortality (hazard ratio, 2.64; 95% confidence interval, 1.71 to 4.08; P<0.001 and hazard ratio, 1.84; 95% confidence interval, 1.18 to 2.86; P=0.003, respectively, compared with the lowest quartile). This association was not maintained after additional adjustment to include cardiovascular disease, diabetes, smoking, body mass index, eGFR, albuminuria, and hemoglobin. Skin autofluorescence was not independently associated with all-cause mortality in this study. Additional research is needed to clarify whether it has a role in risk prediction in CKD. Copyright © 2014 by the American Society of

Evaluation of blade-strike models for estimating the biological performance of large Kaplan hydro turbines

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

Deng, Z.; Carlson, T. J.; Ploskey, G. R.

2005-11-01

Bio-indexing of hydro turbines has been identified as an important means to optimize passage conditions for fish by identifying operations for existing and new design turbines that minimize the probability of injury. Cost-effective implementation of bio-indexing requires the use of tools such as numerical and physical turbine models to generate hypotheses for turbine operations that can be tested at prototype scales using live fish. Blade strike has been proposed as an index variable for the biological performance of turbines. Report reviews an evaluation of the use of numerical blade-strike models as a means with which to predict the probability ofmore » blade strike and injury of juvenile salmon smolt passing through large Kaplan turbines on the mainstem Columbia River.« less

Limitations for current production in Geobacter sulfurreducens biofilms.

PubMed

Bonanni, P Sebastian; Bradley, Dan F; Schrott, Germán D; Busalmen, Juan Pablo

2013-04-01

Devices that exploit electricity produced by electroactive bacteria such as Geobacter sulfurreducens have not yet been demonstrated beyond the laboratory scale. The current densities are far from the maximum that the bacteria can produce because fundamental properties such as the mechanism of extracellular electron transport and factors limiting cell respiration remain unclear. In this work, a strategy for the investigation of electroactive biofilms is presented. Numerical modeling of the response of G. sulfurreducens biofilms cultured on a rotating disk electrode has allowed for the discrimination of different limiting steps in the process of current production within a biofilm. The model outputs reveal that extracellular electron transport limits the respiration rate of the cells furthest from the electrode to the extent that cell division is not possible. The mathematical model also demonstrates that recent findings such as the existence of a redox gradient in actively respiring biofilms can be explained by an electron hopping mechanism but not when considering metallic-like conductivities. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bedrock composition limits mountain ecosystem productivity and landscape evolution (Invited)

NASA Astrophysics Data System (ADS)

Riebe, C. S.; Hahm, W.; Lukens, C.

2013-12-01

We used measurements of bedrock geochemistry, forest productivity and cosmogenic nuclides to explore connections among lithology, ecosystem productivity and landscape evolution across a lithosequence of 21 sites in the Sierra Nevada Batholith, California. Our sites span a narrow range in elevations and thus share similar climatic conditions. Meanwhile, underlying bedrock varies from granite to diorite and spans nearly the entire range of geochemical compositions observed in Cordilleran granitoids. Land cover varies markedly, from groves of Giant Sequoia, the largest trees on Earth, to pluton-spanning swaths of little or no soil and vegetative cover. This is closely reflected in measures of forest productivity, such as remotely sensed tree-canopy cover, which varies by more than an order of magnitude across our sites and often changes abruptly at mapped contacts between rock types. We find that tree-canopy cover is closely correlated with the concentrations in bedrock of major and minor elements, including several plant-essential nutrients. For example, tree-canopy cover is virtually zero where there is less than 0.3 mg/g phosphorus in bedrock. Erosion rates from these nearly vegetation-free, nutrient deserts are more than 2.5 times slower on average than they are from surrounding, relatively nutrient-rich, soil-mantled bedrock. Thus by influencing soil and forest cover, bedrock nutrient concentrations may provoke weathering-limited erosion and thus may strongly regulate landscape evolution. Our analysis suggests that variations in bedrock nutrient concentrations can also provoke an intrinsic limitation on primary productivity. These limitations appear to apply across all our sites. To the extent that they are broadly representative of conditions in granitic landscapes elsewhere around the world, our results are consistent with widespread, but previously undocumented lithologic control of the distribution and diversity of vegetation in mountainous terrain.

Switch-backs associated with generic drugs approved using product-specific determinations of therapeutic equivalence.

PubMed

Gagne, Joshua J; Polinski, Jennifer M; Jiang, Wenlei; Dutcher, Sarah K; Xie, Jing; Lii, Joyce; Fulchino, Lisa A; Kesselheim, Aaron S

2016-08-01

US Food and Drug Administration approval for generic drugs relies on demonstrating pharmaceutical equivalence and bioequivalence; however, some drug products have unique attributes that necessitate product-specific approval pathways. We evaluated rates of patients' switching back to brand-name versions from generic versions of four drugs approved via such approaches. We used data from Optum LifeSciences Research Database to identify patients using a brand-name version of a study drug (acarbose tablets, salmon calcitonin nasal spray, enoxaparin sodium injection, and venlafaxine extended release tablets) or a control drug. We followed patients to identify switching to generic versions and then followed those who switched to identify whether they switched back to brand-name versions. We calculated switch and switch-back rates and used Kaplan-Meier and log-rank tests to compare rates between study and control drugs. Our cohort included 201 959 eligible patients. Brand-to-generic switch rates ranged from 66 to 106 switches per 100 person-years for study drugs and 80 to 110 for control drugs. Rates of switch-back to brand-name versions ranged from 5 to 37 among study drugs and 3 to 53 among control drugs. Switch-back rates were higher for venlafaxine vs. sertraline (p < 0.01) and calcitonin vs. alendronate (p = 0.01). Switch-back rates were lower for venlafaxine vs. paroxetine (p < 0.01) and acarbose vs. nateglinide (p < 0.01). Rates were similar for acarbose vs. glimepiride (p = 0.97) and for enoxaparin vs. fondiparinux (p = 0.11). As compared to control drugs, patients were not more likely to systematically switch back from generic to brand-name versions of the four study drugs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

General circulation model response to production-limited fossil fuel emission estimates.

NASA Astrophysics Data System (ADS)

Bowman, K. W.; Rutledge, D.; Miller, C.

2008-12-01

The differences in emissions scenarios used to drive IPCC climate projections are the largest sources of uncertainty in future temperature predictions. These estimates are critically dependent on oil, gas, and coal production where the extremal variations in fossil fuel production used in these scenarios is roughly 10:1 after 2100. The development of emission scenarios based on production-limited fossil fuel estimates, i.e., total fossil fuel reserves can be reliably predicted from cumulative production, offers the opportunity to significantly reduce this uncertainty. We present preliminary results of the response of the NASA GISS atmospheric general circulation model to input forcings constrained by production-limited cumulative future fossil-fuel CO2 emissions estimates that reach roughly 500 GtC by 2100, which is significantly lower than any of the IPCC emission scenarios. For climate projections performed from 1958 through 2400 and a climate sensitivity of 5C/2xCO2, the change in globally averaged annual mean temperature relative to fixed CO2 does not exceed 3C with most changes occurring at high latitudes. We find that from 2100-2400 other input forcings such as increased in N2O play an important role in maintaining increase surface temperatures.

Estimating the mean and standard deviation of environmental data with below detection limit observations: Considering highly skewed data and model misspecification.

PubMed

Shoari, Niloofar; Dubé, Jean-Sébastien; Chenouri, Shoja'eddin

2015-11-01

In environmental studies, concentration measurements frequently fall below detection limits of measuring instruments, resulting in left-censored data. Some studies employ parametric methods such as the maximum likelihood estimator (MLE), robust regression on order statistic (rROS), and gamma regression on order statistic (GROS), while others suggest a non-parametric approach, the Kaplan-Meier method (KM). Using examples of real data from a soil characterization study in Montreal, we highlight the need for additional investigations that aim at unifying the existing literature. A number of studies have examined this issue; however, those considering data skewness and model misspecification are rare. These aspects are investigated in this paper through simulations. Among other findings, results show that for low skewed data, the performance of different statistical methods is comparable, regardless of the censoring percentage and sample size. For highly skewed data, the performance of the MLE method under lognormal and Weibull distributions is questionable; particularly, when the sample size is small or censoring percentage is high. In such conditions, MLE under gamma distribution, rROS, GROS, and KM are less sensitive to skewness. Related to model misspecification, MLE based on lognormal and Weibull distributions provides poor estimates when the true distribution of data is misspecified. However, the methods of rROS, GROS, and MLE under gamma distribution are generally robust to model misspecifications regardless of skewness, sample size, and censoring percentage. Since the characteristics of environmental data (e.g., type of distribution and skewness) are unknown a priori, we suggest using MLE based on gamma distribution, rROS and GROS. Copyright © 2015 Elsevier Ltd. All rights reserved.

40 CFR 63.5984 - What emission limits must I meet for tire production affected sources?

Code of Federal Regulations, 2010 CFR

2010-07-01

... tire production affected sources? 63.5984 Section 63.5984 Protection of Environment ENVIRONMENTAL... POLLUTANTS FOR SOURCE CATEGORIES National Emissions Standards for Hazardous Air Pollutants: Rubber Tire Manufacturing Emission Limits for Tire Production Affected Sources § 63.5984 What emission limits must I meet...

Survival of blood transfusion recipients identified by a look-back investigation.

PubMed

Dorsey, Kerri A; Moritz, Erin D; Notari, Edward P; Schonberger, Lawrence B; Dodd, Roger Y

2014-01-01

Survival of blood transfusion recipients is a critical consideration in assessing the outcomes of transfusion. Data from the USA on the short- and long-term survival of recipients are limited. Blood product recipients were identified through a look-back study of Creutzfeldt-Jakob disease. Survival data were obtained from searches of the National Death Index or the Social Security Death Master File. Short- and long-term survival of recipients was analysed through descriptive statistics, Kaplan-Meier survival analysis, and stratified Cox proportional hazard modelling. This study includes data from 575 blood product recipients. One half of the recipients died within the first year of transfusion and the median time to death was 1.1 years. Survival rates at 5, 10, 15, 20, and 25 years after transfusion were 32%, 22%, 15%, 12%, and 9%, respectively. Survival rates varied with age at transfusion and type of component received, but not by gender. Survival after transfusion varied by year of transfusion, with recipients transfused in 1980-1989 having longer post-transfusion survival than those transfused in 2000-2010 (p=0.049). In multivariate models, the type of component transfused, but not the year of transfusion, was a significant predictor of survival among recipients; this effect varied by age. We provide an estimate of survival time from a geographically diverse sample of blood product recipients in the USA. Predictors of post-transfusion survival are numerous and complex, and may include year of transfusion and type of component transfused.

The mechanism of improved pullulan production by nitrogen limitation in batch culture of Aureobasidium pullulans.

PubMed

Wang, Dahui; Chen, Feifei; Wei, Gongyuan; Jiang, Min; Dong, Mingsheng

2015-08-20

Batch culture of Aureobasidium pullulans CCTCC M 2012259 for pullulan production at different concentrations of ammonium sulfate and yeast extract was investigated. Increased pullulan production was obtained under nitrogen-limiting conditions, as compared to that without nitrogen limitation. The mechanism of nitrogen limitation favoring to pullulan overproduction was revealed by determining the activity as well as gene expression of key enzymes, and energy supply for pullulan biosynthesis. Results indicated that nitrogen limitation increased the activities of α-phosphoglucose mutase and glucosyltransferase, up-regulated the transcriptional levels of pgm1 and fks genes, and supplied more ATP intracellularly, which were propitious to further pullulan biosynthesis. The economic analysis of batch pullulan production indicated that nitrogen limitation could reduce more than one third of the cost of raw materials when glucose was supplemented to a total concentration of 70 g/L. This study also helps to understand the mechanism of other polysaccharide overproduction by nitrogen limitation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Applications and Limitations of Micropropagation for the Production of Underwater Grasses

DTIC Science & Technology

2006-01-01

ERDC/TN SAV-06-1 January 2006 Applications and Limitations of Micropropagation for the Production of Underwater Grasses by Steve Ailstock and...Deborah Shafer DEFINITION: Micropropagation is a technique that manipulates small quantities of axenic plant mate- rial, ranging from single cells to...plant structures. Micropropagation , on the other hand, allows the year-round production of new plants at rates significantly higher than that

40 CFR 63.1299 - Standards for slabstock flexible polyurethane foam production-source-wide emission limitation.

Code of Federal Regulations, 2014 CFR

2014-07-01

... polyurethane foam production-source-wide emission limitation. 63.1299 Section 63.1299 Protection of Environment... Pollutants for Flexible Polyurethane Foam Production § 63.1299 Standards for slabstock flexible polyurethane foam production—source-wide emission limitation. Each owner or operator of a new or existing slabstock...

40 CFR 63.1299 - Standards for slabstock flexible polyurethane foam production-source-wide emission limitation.

Code of Federal Regulations, 2013 CFR

2013-07-01

... polyurethane foam production-source-wide emission limitation. 63.1299 Section 63.1299 Protection of Environment... Pollutants for Flexible Polyurethane Foam Production § 63.1299 Standards for slabstock flexible polyurethane foam production—source-wide emission limitation. Each owner or operator of a new or existing slabstock...

Overexpression of Pofut1 and activated Notch1 may be associated with poor prognosis in breast cancer.

PubMed

Wan, Guoxing; Tian, Lin; Yu, Yuandong; Li, Fang; Wang, Xuanbin; Li, Chen; Deng, Shouheng; Yu, Xiongjie; Cai, Xiaojun; Zuo, Zhigang; Cao, Fengjun

2017-09-09

The present study was to evaluate the prognostic value of protein expression of Pofut1 and Notch1 signaling in breast cancer. Formalin-fixed paraffin-embedded 314 breast specimens including 174 infiltrating ductal carcinoma(IDC), 50 ductal carcinoma in situ(DCIS) and 90 adjacent normal tissue(ANT) were immunohistochemically examined to evaluate the protein expression of Pofut1, activated Notch1(N1IC) and Slug on specimens. Survival analysis was performed by Kaplan-Meier method and Cox's proportional-hazards model. A online database was computationally used to further explore the prognostic role of Pofut1 and Notch1 mRNA expression by Kaplan-Meier Plotter. Pofut1, Slug and N1IC expression were significantly increased in IDC compared to ANT(all p < 0.05). High expression of Pofut1, Slug and N1IC were associated with tumor aggressiveness including lymph node metastasis (LNM: p = 0.005 for Pofut1, p < 0.001 for N1IC, p = 0.017 for Slug), advanced stage(p = 0.039 for Pofut1, p = 0.025 for N1IC) and higher histological grade(p = 0.001 for N1IC). Additionally, high expression of Pofut1 was found to be significantly associated with high expressions of N1IC and Slug in IDC(r = 0.244, p = 0.001; r = 0.374, p < 0.001, respectively), similar correlation was also observed between high N1IC and Slug expression(r = 0.496, p < 0.001). Moreover, Kaplan-Meier and Cox's regression analysis indicated the significant prognostic value of elevated Pofut1, N1IC, Slug expressions, positive LNM and advanced tumor stage for the prediction of a shorter disease-free survival (DFS) and overall survival(OS). The web-based analysis also suggested a significant association of high Pofut1 and Notch1 mRNA expression with worse survival outcome. Our findings suggested that overexpression of Pofut1 and activated Notch1 signaling may be associated with a poor prognosis in breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

The Short-Term and Intermediate-Term Risk of Second Neoplasms After Diagnosis and Treatment of Unilateral Vestibular Schwannoma: Analysis of 9460 Cases

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

Carlson, Matthew L., E-mail: carlson.matthew@mayo.edu; Department of Neurologic Surgery, Mayo Clinic School of Medicine, Rochester, Minnesota; Glasgow, Amy E.

Purpose: To determine the incidence of second intracranial neoplasms after the diagnosis and treatment of sporadic vestibular schwannoma (VS). Methods and Materials: Analysis of the Surveillance, Epidemiology, and End Results (SEER) database including all patients identified with a diagnosis of VS and a second intracranial tumor. The Kaplan-Meier method was used to determine the incidence of second tumors while allowing for censoring at loss to follow-up or death. Multivariable associations between treatment modality and second tumor formation were explored using Cox proportional hazards regression analysis. Two illustrative cases are also presented. Results: In all, 9460 patients with unilateral VS weremore » identified between 2004 and 2012. Overall, 66 (0.7%) patients experienced a separate intracranial tumor, benign or malignant, after treatment of VS. Kaplan-Meier estimates for time to second neoplasm at 1, 3, and 5 years were 0.3%, 0.7%, and 0.8%, respectively. Multivariable comparison between VS treatment modalities revealed that the risk of second tumor formation was similar between radiation and surgery (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.36-1.51; P=.93) but greater for tumors managed with observation alone compared with radiation (HR 2.48; 95% CI 1.31-4.71; P<.01). A total of 6 (0.06%) intracranial malignancies were diagnosed after VS treatment. Kaplan-Meier estimates for time to malignancy at 1, 3, and 5 years were 0%, 0.1%, and 0.1%, respectively. After adjustment for age at diagnosis, sex, and treatment modality, the probability of malignancy after radiation was not greater than after observation alone or microsurgery (HR 4.88; 95% CI 0.85-28.14; P=.08) during the study period. Conclusions: The risk for the development of a second intracranial neoplasm, benign or malignant, at 5 years after treatment of unilateral VS is approximately 0.8%, whereas the risk of acquiring a separate malignancy is 0.1%, or approximately 1 per 1000

Targeting the Prometastatic Microenvironment of the Involuting Mammary Gland

DTIC Science & Technology

2014-09-01

analyses. To assess expression of Ltbp1 in breast cancer we began by mining in silico data using database available online specifically Kaplan-Meier... Dermatology , New York University School of Medicine, 550 First Ave, New York, NY 10016, USA Full list of author information is available at the end of the...1Department of Cell Biology, New York University School of Medicine, New York, NY, USA. 2The Ronald O Perelman Department of Dermatology , New York

Aldo-keto Reductase Family 1 B10 as a Novel Target for Breast Cancer Treatment

DTIC Science & Technology

2010-08-01

overexpressed in tested human breast cancer tissues and mediates acetyl-CoA carboxylase-α ( ACCA ) stability, affecting fatty acid de novo synthesis and...9703; Fax. 217-545-3227; E-mail: dcao@siumed.edu Running title: AKR1B10 as a new risk factor for breast cancer Abbreviations used: ACCA , acetyl...The effect of AKR1B10 expression in cancer tissue on patient survival was evaluated with Kaplan - Meier plots, and results showed that AKR1B10

Improve T Cell Therapy in Neuroblastoma

DTIC Science & Technology

2015-09-01

bioluminescence was then measured overtime. The graph is representative of one of 4 experiments using CMV-CTLs from 4 donors. Panel E. Kaplan-Meier...whole-cell vaccine expressing the iC9 gene and labeled with an enhanced firefly luciferase. Tumor growth was measured by in vivo imaging. Panel E...down regulation in LTE -T cells is not caused by specific culture conditions. T lymphocytes were activated with immobilized OKT3 (1 μg ml) and

The productivity limit of manufacturing blood cell therapy in scalable stirred bioreactors

PubMed Central

Bayley, Rachel; Ahmed, Forhad; Glen, Katie; McCall, Mark; Stacey, Adrian

2017-01-01

Abstract Manufacture of red blood cells (RBCs) from progenitors has been proposed as a method to reduce reliance on donors. Such a process would need to be extremely efficient for economic viability given a relatively low value product and high (2 × 1012) cell dose. Therefore, the aim of these studies was to define the productivity of an industry standard stirred‐tank bioreactor and determine engineering limitations of commercial red blood cells production. Cord blood derived CD34+ cells were cultured under erythroid differentiation conditions in a stirred micro‐bioreactor (Ambr™). Enucleated cells of 80% purity could be created under optimal physical conditions: pH 7.5, 50% oxygen, without gas‐sparging (which damaged cells) and with mechanical agitation (which directly increased enucleation). O2 consumption was low (~5 × 10–8 μg/cell.h) theoretically enabling erythroblast densities in excess of 5 × 108/ml in commercial bioreactors and sub‐10 l/unit production volumes. The bioreactor process achieved a 24% and 42% reduction in media volume and culture time, respectively, relative to unoptimized flask processing. However, media exchange limited productivity to 1 unit of erythroblasts per 500 l of media. Systematic replacement of media constituents, as well as screening for inhibitory levels of ammonia, lactate and key cytokines did not identify a reason for this limitation. We conclude that the properties of erythroblasts are such that the conventional constraints on cell manufacturing efficiency, such as mass transfer and metabolic demand, should not prevent high intensity production; furthermore, this could be achieved in industry standard equipment. However, identification and removal of an inhibitory mediator is required to enable these economies to be realized. Copyright © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd. PMID:27696710

Enhanced limonene production in cyanobacteria reveals photosynthesis limitations.

PubMed

Wang, Xin; Liu, Wei; Xin, Changpeng; Zheng, Yi; Cheng, Yanbing; Sun, Su; Li, Runze; Zhu, Xin-Guang; Dai, Susie Y; Rentzepis, Peter M; Yuan, Joshua S

2016-12-13

Terpenes are the major secondary metabolites produced by plants, and have diverse industrial applications as pharmaceuticals, fragrance, solvents, and biofuels. Cyanobacteria are equipped with efficient carbon fixation mechanism, and are ideal cell factories to produce various fuel and chemical products. Past efforts to produce terpenes in photosynthetic organisms have gained only limited success. Here we engineered the cyanobacterium Synechococcus elongatus PCC 7942 to efficiently produce limonene through modeling guided study. Computational modeling of limonene flux in response to photosynthetic output has revealed the downstream terpene synthase as a key metabolic flux-controlling node in the MEP (2-C-methyl-d-erythritol 4-phosphate) pathway-derived terpene biosynthesis. By enhancing the downstream limonene carbon sink, we achieved over 100-fold increase in limonene productivity, in contrast to the marginal increase achieved through stepwise metabolic engineering. The establishment of a strong limonene flux revealed potential synergy between photosynthate output and terpene biosynthesis, leading to enhanced carbon flux into the MEP pathway. Moreover, we show that enhanced limonene flux would lead to NADPH accumulation, and slow down photosynthesis electron flow. Fine-tuning ATP/NADPH toward terpene biosynthesis could be a key parameter to adapt photosynthesis to support biofuel/bioproduct production in cyanobacteria.

Exploring the limits of crop productivity: beyond the limits of tipburn in lettuce

NASA Technical Reports Server (NTRS)

Frantz, Jonathan M.; Ritchie, Glen; Cometti, Nilton N.; Robinson, Justin; Bugbee, Bruce

2004-01-01

The productivity of lettuce in a combination of high light, high temperature, and elevated CO2 has not been commonly studied because rapid growth usually causes a calcium deficiency in meristems called tipburn, which greatly reduces quality and marketability. We eliminated tipburn by blowing air directly onto the meristem, which allowed us to increase the photosynthetic photon flux (PPF) to 1000 micromoles m-2 s-1 (57.6 mol m-2 d-1); two to three times higher than normally used for lettuce. Eliminating tipburn doubled edible yield at the highest PPF level. In addition to high PPF, CO2 was elevated to 1200 micromoles m-2 mol-1, which increased the temperature optimum from 25 to 30 degrees C. The higher temperature increased leaf expansion rate, which improved radiation capture and more than doubled yield. Photosynthetic efficiency, measured as canopy quantum yield in a whole-plant gas exchange system, steadily increased up to the highest temperature of 32 degrees C in high CO2. The highest productivity was 19 g m-2 d-1 of dry biomass (380 g d-1 fresh mass) averaged over the 23 days the plants received light. Without the limitation of tipburn, the combination of high PPF, high temperature, and elevated CO2 resulted in a 4-fold increase in growth rate over productivity in conventional environments.

Numerical Investigation of the Flow Structure in a Kaplan Draft Tube at Part Load

NASA Astrophysics Data System (ADS)

Maddahian, R.; Cervantes, M. J.; Sotoudeh, N.

2016-11-01

This research presents numerical simulation of the unsteady flow field inside the draft tube of a Kaplan turbine at part load condition. Due to curvature of streamlines, the ordinary two-equations turbulence models fail to predict the flow features. Therefore, a modification of the Shear Stress Transport (SST-SAS) model is utilized to approximate the turbulent stresses. A guide vane, complete runner and draft tube are considered to insure the real boundary conditions at the draft tube inlet. The outlet boundary is assumed to discharge into the atmosphere. The obtained pressure fluctuations inside the draft tube are in good agreement with available experimental data. In order to further investigate the RVR formation and its movement, the λ2 criterion, relating the position of the vortex core and strength to the second largest Eigen value of the velocity gradient tensor, is employed. The method used for vortex identification shows the flow structure and vortex motion inside the draft tube accurately.

Herbal Products: Benefits, Limits, and Applications in Chronic Liver Disease

PubMed Central

Del Prete, Anna; Scalera, Antonella; Iadevaia, Maddalena Diana; Miranda, Agnese; Zulli, Claudio; Gaeta, Laura; Tuccillo, Concetta; Federico, Alessandro; Loguercio, Carmelina

2012-01-01

Complementary and alternative medicine soughts and encompasses a wide range of approaches; its use begun in ancient China at the time of Xia dynasty and in India during the Vedic period, but thanks to its long-lasting curative effect, easy availability, natural way of healing, and poor side-effects it is gaining importance throughout the world in clinical practice. We conducted a review describing the effects and the limits of using herbal products in chronic liver disease, focusing our attention on those most known, such as quercetin or curcumin. We tried to describe their pharmacokinetics, biological properties, and their beneficial effects (as antioxidant role) in metabolic, alcoholic, and viral hepatitis (considering that oxidative stress is the common pathway of chronic liver diseases of different etiology). The main limit of applicability of CAM comes from the lacking of randomized, placebo-controlled clinical trials giving a real proof of efficacy of those products, so that anecdotal success and personal experience are frequently the driving force for acceptance of CAM in the population. PMID:22991573

Limitation of egg production in Calanus finmarchicus in the field: A stoichiometric analysis

NASA Astrophysics Data System (ADS)

Mayor, Daniel J.; Anderson, Thomas R.; Pond, David W.; Irigoien, Xabier

2009-11-01

The egg production of marine copepods correlates with a range of variables, including the availability of organic carbon (C), nitrogen (N) and the polyunsaturated fatty acids (PUFAs) 20:5( n-3) (EPA) and 22:6( n-3) (DHA). However, an understanding of which substrates limit egg production in the natural environment has yet to be reached. The quantities of C, N, EPA and DHA ingested, derived from parental biomass, and invested in eggs by female Calanus finmarchicus during a 5-day incubation experiment were examined using stoichiometric theory to determine which substrate was limiting. The majority of each substrate was derived from parental biomass, and therefore the existing stoichiometric theory is developed to include this route of supply. The females were essentially devoid of lipid reserves, as evidenced by the lack of the storage fatty acids 20:1( n-9) and 22:1( n-11), and carbon limitation was predicted under most of the scenarios examined. Nitrogen limitation was only apparent when carbon and nitrogen utilisation efficiencies were assumed to be high (0.5) and low (0.4) respectively. PUFAs were assumed to be utilised with high efficiency (0.9), and were never predicted to limit production. This work highlights the need for a more detailed understanding of the maintenance requirements that marine copepods have for C, N, EPA, and DHA and hence the efficiencies with these substrates can be utilised for growth.

Stem-cell therapy for dilated cardiomyopathy: a pilot study evaluating retrograde coronary venous delivery.

PubMed

Pogue, B; Estrada, A H; Sosa-Samper, I; Maisenbacher, H W; Lamb, K E; Mincey, B D; Erger, K E; Conlon, T J

2013-07-01

To evaluate retrograde coronary venous stem-cell delivery for Dobermanns with dilated cardiomyopathy. Retrograde coronary venous delivery of adipose-derived mesenchymal stem cells transduced with tyrosine mutant adeno-associated virus 2 to express stromal-derived factor-1 was performed in Dobermanns with dilated cardiomyopathy. Cases were followed for 2 years and electrocardiograms (ECG), echocardiograms and Holter monitoring were performed. Delivery of cells was feasible in 15 of 15 dogs. One dog died following the development of ventricular fibrillation 24 hours after cell delivery. The remaining 14 dogs were discharged the following day without complications. Echocardiographic measurements of left ventricular size and function showed continued progression of disease. On the basis of Kaplan-Meier product limit estimates, median survival for dogs following stem-cell delivery was 620 days (range of 1-799 days). When including only the occult-dilated cardiomyopathy population and excluding those dogs already in congestive heart failure, median survival was 652 days (range of 46-799 days). Retrograde venous delivery of tyrosine mutant adeno-associated virus 2-stromal-derived factor-1 adipose-derived mesenchymal stem cells appears safe. Stem-cell therapy in dogs with occult-dilated cardiomyopathy does not appear to offer advantage compared to recently published survival data in similarly affected Dobermanns. © 2013 British Small Animal Veterinary Association.

Prognostic value of MLH1 promoter methylation in male patients with esophageal squamous cell carcinoma.

PubMed

Wu, Dongping; Chen, Xiaoying; Xu, Yan; Wang, Haiyong; Yu, Guangmao; Jiang, Luping; Hong, Qingxiao; Duan, Shiwei

2017-04-01

The DNA mismatch repair (MMR) gene MutL homolog 1 ( MLH1 ) is critical for the maintenance of genomic integrity. Methylation of the MLH1 gene promoter was identified as a prognostic marker for numerous types of cancer including glioblastoma, colorectal, ovarian and gastric cancer. The present study aimed to determine whether MLH1 promoter methylation was associated with survival in male patients with esophageal squamous cell carcinoma (ESCC). Formalin-fixed, paraffin-embedded ESCC tissues were collected from 87 male patients. MLH1 promoter methylation was assessed using the methylation-specific polymerase chain reaction approach. Kaplan-Meier survival curves and log-rank tests were used to evaluate the association between MLH1 promoter methylation and overall survival (OS) in patients with ESCC. Cox regression analysis was used to obtain crude and multivariate hazard ratios (HR), and 95% confidence intervals (CI). The present study revealed that MLH1 promoter methylation was observed in 53/87 (60.9%) of male patients with ESCC. Kaplan-Meier survival analysis demonstrated that MLH1 promoter hypermethylation was significantly associated with poorer prognosis in patients with ESCC (P=0.048). Multivariate survival analysis revealed that MLH1 promoter hypermethylation was an independent predictor of poor OS in male patients with ESCC (HR=1.716; 95% CI=1.008-2.921). Therefore, MLH1 promoter hypermethylation may be a predictor of prognosis in male patients with ESCC.

Results of press-fit stems in revision knee arthroplasties.

PubMed

Wood, Gavin C; Naudie, Douglas D R; MacDonald, Steven J; McCalden, Richard W; Bourne, Robert B

2009-03-01

The ideal method of stem fixation in revision knee arthroplasty is controversial with advantages and disadvantages for cemented and press-fit designs. Studies have suggested cemented revision knee stems may provide better long-term survival. The aim of this study was to report our experience with press-fit uncemented stems and metaphyseal cement fixation in a selected series of patients undergoing revision total knee arthroplasty. One hundred twenty-seven patients (135 knees) who underwent revision total knee arthroplasty using a press-fit technique (press-fit diaphyseal fixation and cemented metaphyseal fixation) were reviewed. Minimum followup was 2 years (mean, 5 years; range, 2-12 years). A Kaplan-Meier survivorship analysis using an end point of revision surgery or radiographic loosening was used to determine probability of survival at 5 and 10 years. Of the 127 patients (135 knees), 31 patients (36 knees) died and two patients (two knees) were lost to followup. Six patients (six knees) had revisions at a mean of 3.5 years (range, 1-8 years). Kaplan-Meier survivorship analysis revealed a probability of survival free of revision for aseptic loosening of 98% at 12 years. Survivorship of press-fit stems for revision knee arthroplasty is comparable to reported survivorship of cemented stem revision knee arthroplasty. Radiographic analysis has shown continued satisfactory appearances regardless of constraint, stem size, and augmentations.

Prognostic significance of hemoglobin level in patients with congestive heart failure and normal ejection fraction.

PubMed

Varadarajan, Padmini; Gandhi, Siddharth; Sharma, Sanjay; Umakanthan, Branavan; Pai, Ramdas G

2006-10-01

Previous studies have shown low hemoglobin (Hb) to have an adverse effect on survival in patients with congestive heart failure (CHF) and reduced left ventricular (LV) ejection fraction (EF); but its effect on survival in patients with CHF and normal EF is not known. This study sought to determine whether low Hb has an effect on survival in patients with both CHF and normal EF. Detailed chart reviews were performed by medical residents on 2,246 patients (48% with normal EF) with a discharge diagnosis of CHF in a large tertiary care hospital from 1990 to 1999. The CHF diagnosis was validated using the Framingham criteria. Mortality data were obtained from the National Death Index. Survival analysis was performed using Kaplan-Meier and Cox regression models. By Kaplan-Meier analysis, low Hb (< 12 gm/dl) compared with normal hemoglobin was associated with a lower 5-year survival in patients with CHF and both normal (38 vs. 50%, p = 0.0008) and reduced (35 vs. 48%, p = 0.0009) EF. Using the Cox regression model, low Hb was an independent predictor of mortality after adjusting for age, gender, renal dysfunction, diabetes mellitus, hypertension, and EF in both groups of patients. Low Hb has an independent adverse effect on survival in patients with CHF and both normal and reduced EF in both groups of patients.

Single Versus Double Lung Retransplantation Does Not Affect Survival Based on Previous Transplant Type.

PubMed

Schumer, Erin M; Rice, Jonathan D; Kistler, Amanda M; Trivedi, Jaimin R; Black, Matthew C; Bousamra, Michael; van Berkel, Victor

2017-01-01

Survival following retransplantation with a single lung is worse than after double lung transplant. We sought to characterize survival of patients who underwent lung retransplantation based on the type of their initial transplant, single or double. The United Network for Organ Sharing database was queried for adult patients who underwent lung retransplantation from 2005 onward. Patients were excluded if they underwent more than one retransplantation. The patient population was divided into 4 groups based on first followed by second transplant type, respectively: single then single, double then single, double then double, and single then double. Descriptive analysis and Kaplan-Meier survival analysis were performed. A p value less than 0.05 was considered significant. A total of 410 patients underwent retransplantation in the study time period. Overall mean survival for all patients who underwent retransplantation was 1,213 days. Kaplan-Meier survival analysis demonstrated no difference in graft survival between the 4 study groups (p = 0.146). There was no significant difference in graft survival between recipients of retransplant with single or double lungs when stratified by previous transplant type. These results suggest that when retransplantation is performed, single lung retransplantation should be considered, regardless of previous transplant type, in an effort to maximize organ resources. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Incident and prevalent cohorts with pulmonary arterial hypertension: insight from SERAPHIN.

PubMed

Simonneau, Gérald; Channick, Richard N; Delcroix, Marion; Galiè, Nazzareno; Ghofrani, Hossein-Ardeschir; Jansa, Pavel; Le Brun, Franck-Olivier; Mehta, Sanjay; Perchenet, Loic; Pulido, Tomás; Sastry, B K S; Sitbon, Olivier; Souza, Rogério; Torbicki, Adam; Rubin, Lewis J

2015-12-01

In SERAPHIN, a long-term, randomised, controlled trial (NCT00660179) in pulmonary arterial hypertension (PAH), macitentan significantly reduced the risk of morbidity/mortality and PAH-related death/hospitalisation. We evaluated disease progression and the effect of macitentan in treatment-naïve incident and prevalent cohorts.Patients allocated to placebo, or macitentan 3 mg or 10 mg were classified by time from diagnosis to enrolment as incident (≤6 months; n=110) or prevalent (>6 months; n=157). The risk of morbidity/mortality and PAH-related death/hospitalisation was determined using Cox regression.The risk of morbidity/mortality (Kaplan-Meier estimates at month 12: 54.4% versus 26.7%; p=0.006) and PAH-related death/hospitalisation (Kaplan-Meier estimates at month 12: 47.3% versus 19.9%; p=0.006) were significantly higher for incident versus prevalent patients receiving placebo, respectively. There was no significant difference in the risk of all-cause death between incident and prevalent cohorts (p=0.587). Macitentan 10 mg significantly reduced the risk of morbidity/mortality and PAH-related death/hospitalisation versus placebo in incident and prevalent cohorts.Incident patients had a higher risk for PAH progression compared with prevalent patients but not a higher risk of death. Macitentan delayed disease progression in both incident and prevalent PAH patients. Copyright ©ERS 2015.

The effect of preoperative serum triglycerides and high-density lipoprotein-cholesterol levels on the prognosis of breast cancer.

PubMed

Li, Xing; Tang, Hailin; Wang, Jin; Xie, Xinhua; Liu, Peng; Kong, Yanan; Ye, Feng; Shuang, Zeyu; Xie, Zeming; Xie, Xiaoming

2017-04-01

Although dyslipidemia has been documented to be associated with several types of cancer including breast cancer, it remains uncertainty the prognostic value of serum lipid in breast cancer. The purpose of this study is to evaluate the association between the preoperative plasma lipid profile and the prognostic of breast cancer patients. The levels of preoperative serum lipid profile (including cholesterol [CHO], Triglycerides [TG], high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C], apolipoprotein A-I [ApoAI], and apolipoprotein B [ApoB]) and the clinical data were retrospectively collected and reviewed in 1044 breast cancer patients undergoing operation. Kaplan-Meier method and the Cox proportional hazards regression model were used in analyzing the overall survival [OS] and disease-free survival [DFS]. Combining the receiver-operating characteristic and Kaplan-Meier analysis, we found that preoperative lower TG and HDL-C level were risk factors of breast cancer patients. In multivariate analyses, a decreased HDL-C level showed significant association with worse OS (HR: 0.528; 95% CI: 0.302-0.923; P = 0.025), whereas a decreased TG level showed significant association with worse DFS (HR: 0.569; 95% CI: 0.370-0.873; P = 0.010). Preoperative serum levels of TG and HDL-C may be independent factor to predict outcome in breast cancer patient. Copyright © 2016 Elsevier Ltd. All rights reserved.

Investigation of standardized administration of anti-platelet drugs and its effect on the prognosis of patients with coronary heart disease.

PubMed

Ding, Chao; Zhang, Jianhua; Li, Rongcheng; Wang, Jiacai; Hu, Yongcang; Chen, Yanyan; Li, Xiannan; Xu, Yan

2017-10-01

The aim of the present study was to explore the effect of adherence to standardized administration of anti-platelet drugs on the prognosis of patients with coronary heart disease. A total of 144 patients newly diagnosed with coronary heart disease at Lu'an Shili Hospital of Anhui Province (Lu'an, China) between June 2010 and June 2012 were followed up. Kaplan-Meier curves and the Cox regression model were used to evaluate the effects of standardized administration of anti-platelet drugs on primary and secondary end-point events. Of the patients with coronary heart disease, 109 (76%) patients took standard anti-platelet drugs following discharge. Kaplan-Meier curve and Cox regression analysis showed that standardized administration of anti-platelet drugs reduced the risk of primary end-point events (including all-cause mortality, non-lethal myocardial infarction and stroke) of patients with coronary heart disease [hazard ratio (HR)=0.307; 95% confidence interval (CI): 0.099-0.953; P=0.041) and all-cause mortality (HR=0.162; 95% CI: 0.029-0.890; P=0.036); however, standardized administration had no predictive value with regard to secondary end-point events. Standardized administration of anti-platelet drugs obviously reduced the risk of primary end-point events in patients with coronary heart disease, and further analysis showed that only all-cause mortality exhibited a statistically significant reduction.

Heparin for clearance of peripherally inserted central venous catheter in newborns: an in vitro study

PubMed Central

Balaminut, Talita; Venturini, Danielle; da Silva, Valéria Costa Evangelista; Rossetto, Edilaine Giovanini; Zani, Adriana Valongo

2015-01-01

Objective: To compare the efficacy of two concentrations of heparin to clear the lumen of in vitro clotted neonatal peripherally inserted central catheters (PICCs). Methods: This is an in vitro, experimental quantitative study of 76 neonatal 2.0-Fr PICCs coagulated in vitro. The catheters were divided into two groups of 38 PICCs each. In both groups an infusion of low molecular weight heparin was administered with a dose of 25IU/mL for Group 1 and 50IU/mL for Group 2. The negative pressure technique was applied to the catheters of both groups at 5, 15 and 30min and at 4h to test their permeability. Kaplan-Meier survival analysis was used to verify the outcome of the groups according to time intervals. Results: The comparison between both groups in the first 5min showed that more catheters from Group 2 were cleared compared to Group 1 (57.9 vs. 21.1%, respectively). Kaplan-Meier survival analysis showed that less time was needed to clear catheters treated with 50IU/mL of heparin (p<0.001). Conclusions: The use of low molecular weight heparin at a concentration of 50IU/mL was more effective in restoring the permeability of neonatal PICCs occluded in vitro by a clot, and the use of this concentration is within the safety margin indicated by scientific literature. PMID:26116325

Reduced miR-300 expression predicts poor prognosis in patients with laryngeal squamous cell carcinoma.

PubMed

He, F-Y; Liu, H-J; Guo, Q; Sheng, J-L

2017-02-01

miR-300 has been demonstrated to play an important role in the progression of several tumors, but its role in tumorigenesis of laryngeal squamous cell carcinoma (LSCC) is still unclear. The purpose of this study was to explore miR-300 expression in LSCC patients and analyze its association with clinicopathological factors and prognosis. In the present study, we measured the expression level of miR-300 in LSCC tissues by RT-PCR. Associations between miRNA-300 expressions and various clinicopathological characteristics were analyzed. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. The univariate and multivariate analysis were performed using the Cox proportional hazard analysis. miR-300 expression was significantly increased in LSCC tissues compared with that in adjacent non-cancerous tissues (p < 0.01). In addition, lymph node metastasis (p = 0.004) and TNM stage (p = 0.001) were obvious influence factors for the expression of miR-300. More importantly, Kaplan-Meier analysis showed that LSCC patients with low miR-300 expression tended to have shorter overall survival (p < 0.001). Finally, multivariate analysis revealed that miR-300 expression was an independent prognostic factor for LSCC patients. Our results pointed to miR-300 as a powerful prognostic marker in LSCC and as a novel target for tumor-suppressive therapy.

Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy.

PubMed

Gerami, Pedram; Cook, Robert W; Russell, Maria C; Wilkinson, Jeff; Amaria, Rodabe N; Gonzalez, Rene; Lyle, Stephen; Jackson, Gilchrist L; Greisinger, Anthony J; Johnson, Clare E; Oelschlager, Kristen M; Stone, John F; Maetzold, Derek J; Ferris, Laura K; Wayne, Jeffrey D; Cooper, Chelsea; Obregon, Roxana; Delman, Keith A; Lawson, David

2015-05-01

A gene expression profile (GEP) test able to accurately identify risk of metastasis for patients with cutaneous melanoma has been clinically validated. We aimed for assessment of the prognostic accuracy of GEP and sentinel lymph node biopsy (SLNB) tests, independently and in combination, in a multicenter cohort of 217 patients. Reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the expression of 31 genes from primary melanoma tumors, and SLNB outcome was determined from clinical data. Prognostic accuracy of each test was determined using Kaplan-Meier and Cox regression analysis of disease-free, distant metastasis-free, and overall survivals. GEP outcome was a more significant and better predictor of each end point in univariate and multivariate regression analysis, compared with SLNB (P < .0001 for all). In combination with SLNB, GEP improved prognostication. For patients with a GEP high-risk outcome and a negative SLNB result, Kaplan-Meier 5-year disease-free, distant metastasis-free, and overall survivals were 35%, 49%, and 54%, respectively. Within the SLNB-negative cohort of patients, overall risk of metastatic events was higher (∼30%) than commonly found in the general population of patients with melanoma. In this study cohort, GEP was an objective tool that accurately predicted metastatic risk in SLNB-eligible patients. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Intrathecal oligoclonal bands synthesis in multiple sclerosis: is it always a prognostic factor?

PubMed

Frau, Jessica; Villar, Luisa Maria; Sardu, Claudia; Secci, Maria Antonietta; Schirru, Lucia; Ferraro, Diana; Coghe, Giancarlo; Lorefice, Lorena; Fenu, Giuseppe; Bedin, Roberta; Sola, Patrizia; Marrosu, Maria Giovanna; Cocco, Eleonora

2018-02-01

Oligoclonal IgM (OCMB) and IgG (OCGB) bands were found to be associated with poor multiple sclerosis (MS) prognosis. We aimed to evaluate the prognostic value of OCMB/OCGB in a cohort of Sardinian MS patients. We recruited patients from the University of Cagliari. They underwent lumbar puncture for diagnostic purposes. Demographic and the following clinical data were recorded: clinical course; time to reach EDSS 3 and 6; EDSS at last follow-up; and MS treatments. The influence of gender, clinical course, age at onset, treatments, and OCGB/OCMB on reaching EDSS 3 was analysed using Cox regression. Kaplan-Meier curves were used to study the time to reach EDSS 3 considering OCMB/OCGB and therapies. The enrolled number of subjects was 503. The variables influencing the achievement of EDSS 3.0 were: male gender (p = 0.005); progressive course (p = 0.001); age at onset (p < 0.001); and disease-modifying drugs (p < 0.001). The OCGB/OCMB status was not significant. Kaplan-Meier analysis showed no difference in time to reach EDSS 3 for patients with and without OCGB or OCMB in both treated and non-treated groups. Our study did not confirm the poor prognostic value of OCMB/OCGB. These results may be influenced by the peculiar genetic background associated with the risk of MS in Sardinians.

Overexpression of epithelial cell adhesion molecule protein is associated with favorable prognosis in an unselected cohort of ovarian cancer patients.

PubMed

Battista, Marco Johannes; Cotarelo, Cristina; Jakobi, Sina; Steetskamp, Joscha; Makris, Georgios; Sicking, Isabel; Weyer, Veronika; Schmidt, Marcus

2014-07-01

The aim of this study was to evaluate the prognostic influence of epithelial cell adhesion molecule (EpCAM) in an unselected cohort of ovarian cancer (OC) patients. Expression of EpCAM was determined by immunohistochemistry in an unselected cohort of 117 patients with OC. Univariable and multivariable Cox regression analyses adjusted for age, tumor stage, histological grading, histological subtype, postoperative tumor burden and completeness of chemotherapy were performed in order to determine the prognostic influence of EpCAM. The Kaplan-Meier method is used to estimate survival rates. Univariable Cox regression analysis showed that overexpression of EpCAM is associated with favorable prognosis in terms of progression-free survival (PFS) (p = 0.011) and disease-specific survival (DSS) (p = 0.003). In multivariable Cox regression analysis, overexpression of EpCAM retains its significance independent of established prognostic factors for longer PFS [hazard ratios (HR) 0.408, 95 % confidence interval (CI) 0.197-0.846, p = 0.003] but not for PFS (HR 0.666, 95 % CI 0.366-1.212, p = 0.183). Kaplan-Meier plots demonstrate an influence on 5-year PFS rates (0 vs. 27.6 %, p = 0.048) and DSS rates (11.8 vs. 54.0 %, p = 0.018). These findings support the hypothesis that the expression of EpCAM is associated with favorable prognosis in OC.

Clinical Significance of SASH1 Expression in Glioma

PubMed Central

Yang, Liu; Zhang, Haitao; Yao, Qi; Yan, Yingying; Wu, Ronghua; Liu, Mei

2015-01-01

Objective. SAM and SH3 domain containing 1 (SASH1) is a recently discovered tumor suppressor gene. The role of SASH1 in glioma has not yet been described. We investigated SASH1 expression in glioma cases to determine its clinical significance on glioma pathogenesis and prognosis. Methods. We produced tissue microarrays using 121 patient-derived glioma samples and 30 patient-derived nontumor cerebral samples. Immunohistochemistry and Western blotting were used to evaluate SASH1 expression. We used Fisher's exact tests to determine relationships between SASH1 expression and clinicopathological characteristics; Cox regression analysis to evaluate the independency of different SASH1 expression; Kaplan-Meier analysis to determine any correlation of SASH1 expression with survival rate. Results. SASH1 expression was closely correlated with the WHO glioma grade. Of the 121 cases, 66.9% with low SASH1 expression were mostly grade III-IV cases, whereas 33.1% with high SASH1 expression were mostly grades I-II. Kaplan-Meier analysis revealed a significant positive correlation between SASH1 expression and postoperative survival. Conclusions. SASH1 was widely expressed in normal and low-grade glioma tissues. SASH1 expression strongly correlated with glioma grades, showing higher expression at a lower grade, which decreased significantly as grade increased. Furthermore, SASH1 expression was positively correlated with better postoperative survival in patients with glioma. PMID:26424902

Clinical Significance of SASH1 Expression in Glioma.

PubMed

Yang, Liu; Zhang, Haitao; Yao, Qi; Yan, Yingying; Wu, Ronghua; Liu, Mei

2015-01-01

SAM and SH3 domain containing 1 (SASH1) is a recently discovered tumor suppressor gene. The role of SASH1 in glioma has not yet been described. We investigated SASH1 expression in glioma cases to determine its clinical significance on glioma pathogenesis and prognosis. We produced tissue microarrays using 121 patient-derived glioma samples and 30 patient-derived nontumor cerebral samples. Immunohistochemistry and Western blotting were used to evaluate SASH1 expression. We used Fisher's exact tests to determine relationships between SASH1 expression and clinicopathological characteristics; Cox regression analysis to evaluate the independency of different SASH1 expression; Kaplan-Meier analysis to determine any correlation of SASH1 expression with survival rate. SASH1 expression was closely correlated with the WHO glioma grade. Of the 121 cases, 66.9% with low SASH1 expression were mostly grade III-IV cases, whereas 33.1% with high SASH1 expression were mostly grades I-II. Kaplan-Meier analysis revealed a significant positive correlation between SASH1 expression and postoperative survival. SASH1 was widely expressed in normal and low-grade glioma tissues. SASH1 expression strongly correlated with glioma grades, showing higher expression at a lower grade, which decreased significantly as grade increased. Furthermore, SASH1 expression was positively correlated with better postoperative survival in patients with glioma.

Decreased graft survival in liver transplant recipients of donors with positive blood cultures: a review of the United Network for Organ Sharing dataset.

PubMed

Huaman, Moises A; Vilchez, Valery; Mei, Xiaonan; Shah, Malay B; Daily, Michael F; Berger, Jonathan; Gedaly, Roberto

2017-06-01

Liver transplantation using blood culture positive donors (BCPD) has allowed a significant expansion of the donor pool. We aimed to characterize BCPD and assess the outcomes of BCPD liver transplant recipients. We retrieved data from the United Network for Organ Sharing (UNOS) registry on all adults who underwent primary, single-organ deceased-donor liver transplantation in the USA between 2008 and 2013. Patients were classified into two cohorts: the BCPD cohort and the non-BCPD cohort. One-year graft and patient survival were compared between cohorts using Kaplan-Meier estimates and Cox models. A total of 28 961 patients were included. There were 2316 (8.0%) recipients of BCPD. BCPD were more likely to be older, female, black, diabetic, hypertensive, and obese compared to non-BCPD. Graft survival was significantly lower in BCPD recipients compared to non-BCPD recipients (Kaplan-Meier, 0.85 vs. 0.87; P = 0.009). Results remained significant in propensity-matched analysis (P = 0.038). BCPD was independently associated with decreased graft survival (adjusted HR; 1.10, 95% CI 1.01-1.20; P = 0.04). There were no significant differences in patient survival between study groups. BCPD was associated with decreased graft survival in liver transplant recipients. Studies are needed to identify subgroups of BCPD with the highest risk of graft failure and characterize the underlying pathogenic mechanisms. © 2016 Steunstichting ESOT.

Increased expression of Nlp, a potential oncogene in ovarian cancer, and its implication in carcinogenesis.

PubMed

Qu, Danni; Qu, Hongyan; Fu, Ming; Zhao, Xuelian; Liu, Rong; Sui, Lihua; Zhan, Qimin

2008-08-01

Nlp (Ninein-like protein), a novel centrosome protein involved in microtubule nucleation, has been studied extensively in our laboratory, and its overexpression has been found in some human tumors. To understand the role of Nlp in human ovarian cancer development, we studied the correlation of Nlp expression with clinicopathological parameters and survival in epithelial ovarian cancer, and the impact of Nlp overexpression on ovarian cancer cells. Nlp expression in normal, borderline, benign and malignant epithelial ovarian tissues was examined by immunohistochemistry. The correlation between Nlp expression and tumor grade, FIGO stage and histological type was also evaluated. Survival was calculated using Kaplan-Meier estimates. Cell proliferation and apoptosis were assayed after stable transfection of pEGFP-C3-Nlp or empty vector in human ovarian cancer cell line SKOV3. Nlp was positive in 1 of 10 (10%) normal ovarian tissues, 5 of 34 (14.7%) benign tumors, 9 of 26 (34.6%) borderline tumors and 73 of 131 (56.0%) ovarian tumors. Nlp immunoreactivity intensity significantly correlated with tumor grade, but not with FIGO stage or histological type. Kaplan-Meier curves showed that Nlp overexpression was marginally associated with decreased overall survival. Overexpression of Nlp enhanced proliferation and inhibited apoptosis induced by paclitaxel in the SKOV3 cell line. Overexpression of Nlp in ovarian tumors raises the possibility that Nlp may play a role in ovarian carcinogenesis.

Stent placement with the monorail technique for treatment of mesenteric artery stenosis.

PubMed

Schaefer, Philipp J; Schaefer, Fritz K W; Hinrichsen, Holger; Jahnke, Thomas; Charalambous, Nikolas; Heller, Martin; Mueller-Huelsbeck, Stefan

2006-04-01

To analyze the immediate and midterm success of stenting of mesenteric arteries by a monorail technique in patients with chronic mesenteric ischemia. In this prospective case series, 19 patients (11 male, 8 female; mean age, 62.9 +/- 10.4 y; range, 36-82 y) with 23 symptomatic stenoses of mesenteric arteries were treated with stent placement by a monorail technique in a radiologic intervention center over a period of 4.5 years. Clinical examinations and duplex sonography were used to evaluate the stents' patency and clinical success. Kaplan-Meier graphs were calculated to analyze the patency and freedom-from-symptom rate. Initial technical success rate was 22/23 (96%). Mean follow-up was 17 months (range, 1-58 mo). Primary patency and primary clinical success rates were 82% and 78%, respectively. According to Kaplan-Meier tables, the patency rates were 96%, 87%, 76%, and 61% at 0, 1, 15, and 24 months, respectively, and the freedom-from-symptom rates were 95%, 90%, 72%, and 54% at 0, 1, 24, and 30 months, respectively. No peri-interventional complications occurred. Two patients died of cardiac failure in the hospital within 30 days after intervention; deaths were not related to the intervention. Stent placement by a monorail technique in mesenteric arteries is an effective and safe treatment for symptomatic stenoses in patients with chronic mesenteric ischemia after a mean follow-up of 17 months.

Validation of long-term survival prediction for scheduled abdominal aortic aneurysm repair with an independent calculator using only pre-operative variables.

PubMed

Carlisle, J B; Danjoux, G; Kerr, K; Snowden, C; Swart, M

2015-06-01

We observed survival after scheduled repair of abdominal aortic aneurysm in 1096 patients for a median (IQR [range]) of 3.0 (1.5-5.8 [0-15]) years: 943 patients had complete data, 250 of whom died. We compared discrimination and calibration of an external model with the Kaplan-Meier model generated from the study data. Integrated Brier misclassification scores for both models at 1-5 postoperative years were 0.04, 0.08, 0.11, 0.13 and 0.16, respectively. Harrel's concordance index at 1-5 postoperative years was 0.73, 0.71, 0.68, 0.67 and 0.66, respectively. Groups with median 5-year predicted mortality of 40% (n = 251), 18% (n = 414) and 8% (n = 164) had lower observed mortality than 114 patients with 70% predicted mortality, hazard ratio (95% CI): 0.58 (0.37-0.76), p = 0.0031; 0.30 (0.19-0.48), p = 1.7 × 10(-12) and 0.19 (0.13-0.27), p = 1.3 × 10(-10) , respectively, test for trend p = 5.6 × 10(-15) . Survival predicted by the external calculator was similar to the Kaplan-Meier estimate. © 2015 The Association of Anaesthetists of Great Britain and Ireland.

PRIMARY ACQUIRED MELANOSIS OF THE CONJUNCTIVA: EXPERIENCE WITH 311 EYES

PubMed Central

Shields, Jerry A.; Shields, Carol L.; Mashayekhi, Arman; Marr, Brian P.; Benavides, Raquel; Thangappan, Archana; Phan, Laura; Eagle, Ralph C.

2007-01-01

Purpose To evaluate clinical features and risks for transformation of conjunctival primary acquired melanosis (PAM) into melanoma. Methods Retrospective chart review and Kaplan-Meier estimates of times to PAM enlargement, recurrence, and transformation into melanoma. Main outcome measures: PAM enlargement, recurrence, and transformation into melanoma. Results The mean patient age at diagnosis of PAM was 56 years; 62% were female and 96% Caucasian. The conjunctival quadrant(s) affected by PAM and its extent in clock hours were recorded. Initial management included observation in 62%, biopsy combined with cryotherapy in 34%, and other methods in 4%. Of PAM that was observed, Kaplan-Meier estimates at 10 years revealed PAM enlargement in 35% and transformation into melanoma in 12%. Of those that underwent incisional or excisional biopsy, 10-year estimates of PAM recurrence and transformation into melanoma were 58% and 11%, respectively. Progression to melanoma occurred in 0% of PAM without atypia, 0% of PAM with mild atypia, and 13% of PAM with severe atypia. Multivariable analysis revealed that the most significant factor for both PAM recurrence and progression to melanoma was extent of PAM in clock hours. Conclusion PAM without atypia or with mild atypia shows 0% progression into melanoma, whereas PAM with severe atypia shows progression into melanoma in 13%. The greater the extent of PAM in clock hours, the greater the risk for transformation into melanoma. PMID:18427595

40 CFR 63.5986 - What emission limits must I meet for tire cord production affected sources?

Code of Federal Regulations, 2010 CFR

2010-07-01

... tire cord production affected sources? 63.5986 Section 63.5986 Protection of Environment ENVIRONMENTAL... POLLUTANTS FOR SOURCE CATEGORIES National Emissions Standards for Hazardous Air Pollutants: Rubber Tire Manufacturing Emission Limits for Tire Cord Production Affected Sources § 63.5986 What emission limits must I...

Enhanced limonene production in cyanobacteria reveals photosynthesis limitations

PubMed Central

Wang, Xin; Liu, Wei; Xin, Changpeng; Zheng, Yi; Cheng, Yanbing; Sun, Su; Li, Runze; Zhu, Xin-Guang; Dai, Susie Y.; Rentzepis, Peter M.; Yuan, Joshua S.

2016-01-01

Terpenes are the major secondary metabolites produced by plants, and have diverse industrial applications as pharmaceuticals, fragrance, solvents, and biofuels. Cyanobacteria are equipped with efficient carbon fixation mechanism, and are ideal cell factories to produce various fuel and chemical products. Past efforts to produce terpenes in photosynthetic organisms have gained only limited success. Here we engineered the cyanobacterium Synechococcus elongatus PCC 7942 to efficiently produce limonene through modeling guided study. Computational modeling of limonene flux in response to photosynthetic output has revealed the downstream terpene synthase as a key metabolic flux-controlling node in the MEP (2-C-methyl-d-erythritol 4-phosphate) pathway-derived terpene biosynthesis. By enhancing the downstream limonene carbon sink, we achieved over 100-fold increase in limonene productivity, in contrast to the marginal increase achieved through stepwise metabolic engineering. The establishment of a strong limonene flux revealed potential synergy between photosynthate output and terpene biosynthesis, leading to enhanced carbon flux into the MEP pathway. Moreover, we show that enhanced limonene flux would lead to NADPH accumulation, and slow down photosynthesis electron flow. Fine-tuning ATP/NADPH toward terpene biosynthesis could be a key parameter to adapt photosynthesis to support biofuel/bioproduct production in cyanobacteria. PMID:27911807

Digital Humanitarians: How Big Data Is Changing the Face of Humanitarian Response : Patrick Meier, 2015, CRC Press (Boca Raton, FL, 978-1-4822-4839-5, 259 pp.).

PubMed

Dave, Anushree

2017-12-01

This is a review of Patrick Meier's 2015 book, Digital Humanitarians: How Big Data Is Changing the Face of Humanitarian Response. The book explores the role of technologies such as high-resolution satellite imagery, online social media, drones, and artificial intelligence in humanitarian responses during disasters such as the 2010 Haiti earthquake. In this analysis, the book is examined using a humanitarian health ethics perspective.

Estimation of the Ratio of Scale Parameters in the Two Sample Problem with Arbitrary Right Censorship.

DTIC Science & Technology

1980-06-01

70. AWST RC 7 Coeittu an rewwase ati of nee*aa.ean mimDdentify by black n,.mboJ T two-sample version of the Cram~ r -von Mines statistic for right...estimator for exponential distributions. KEY WORDS: Cram~ r -von Mtses distance; Kaplan-Meier estimators; Right censorship; Scale parameter; lodgea and...suppose that two positive random variables ’i 2 S0 and ’ r differ in distribution only by their scale parameters. That is, there exists a positive

Survival and movements of molting male black ducks in Labrador

USGS Publications Warehouse

Bowman, Timothy D.; Longcore, J.R.

1989-01-01

We marked 26 flightless male American black ducks with transmitters during the post-nuptial molt in northern Labrabor to determine survival and movements. Twelve ducks remained in the watershed where marked and 11 ducks moved to different watersheds. The period survival rate (PSR) for these flightless males was 0.89 using the Kaplan-Meier estimator. Only 2 ducks were killed by predators. Death of these 2 ducks might have been influenced by our disturbance, thus we considered the PSR minimal.

40 CFR 63.5987 - What are my alternatives for meeting the emission limits for tire cord production affected sources?

Code of Federal Regulations, 2010 CFR

2010-07-01

... the emission limits for tire cord production affected sources? 63.5987 Section 63.5987 Protection of... Pollutants: Rubber Tire Manufacturing Emission Limits for Tire Cord Production Affected Sources § 63.5987 What are my alternatives for meeting the emission limits for tire cord production affected sources? You...

[A boy with Meier-Gorlin syndrome carrying a novel ORC6 mutation and uniparental disomy of chromosome 16].

PubMed

Li, Juan; Ding, Yu; Chang, Guoying; Cheng, Qing; Li, Xin; Wang, Jian; Wang, Xiumin; Shen, Yiping

2017-02-10

To identify the genetic cause for a 11-year-old Chinese boy with Meier-Gorlin syndrome (MGS). Chromosomal microarray analysis (CMA) was used to detect potential variations, while whole exome sequencing (WES) was used to identify sequence variants. Sanger sequencing was used to confirm the suspected variants. The boy has featured short stature, microtia, small patella, slender body build, craniofacial anomalies, and small testes with normal gonadotropin. A complete uniparental disomy of chromosome 16 was revealed by CMA. WES has identified a novel homozygous mutation c.67A>G (p.Lys23Glu) in ORC6 gene mapped to chromosome 16. As predicted by Alamut functional software, the mutation may affect the function of structural domain of the ORC6 protein. The patient is probably the first diagnosed MGS case in China, who carried a novel homozygous mutation of the ORC6 gene and uniparental disomy of chromosome 16. The effect of this novel mutation on the growth and development needs to be further investigated.

Meier-Gorlin syndrome: growth and secondary sexual development of a microcephalic primordial dwarfism disorder.

PubMed

de Munnik, Sonja A; Otten, Barto J; Schoots, Jeroen; Bicknell, Louise S; Aftimos, Salim; Al-Aama, Jumana Y; van Bever, Yolande; Bober, Michael B; Borm, George F; Clayton-Smith, Jill; Deal, Cheri L; Edrees, Alaa Y; Feingold, Murray; Fryer, Alan; van Hagen, Johanna M; Hennekam, Raoul C; Jansweijer, Maaike C E; Johnson, Diana; Kant, Sarina G; Opitz, John M; Ramadevi, A Radha; Reardon, Willie; Ross, Alison; Sarda, Pierre; Schrander-Stumpel, Constance T R M; Sluiter, A Erik; Temple, I Karen; Terhal, Paulien A; Toutain, Annick; Wise, Carol A; Wright, Michael; Skidmore, David L; Samuels, Mark E; Hoefsloot, Lies H; Knoers, Nine V A M; Brunner, Han G; Jackson, Andrew P; Bongers, Ernie M H F

2012-11-01

Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia. Recently, mutations in the ORC1, ORC4, ORC6, CDT1, and CDC6 genes, encoding components of the pre-replication complex, have been identified. This complex is essential for DNA replication and therefore mutations are expected to impair cell proliferation and consequently could globally reduce growth. However, detailed growth characteristics of MGS patients have not been reported, and so this is addressed here through study of 45 MGS patients, the largest cohort worldwide. Here, we report that growth velocity (length) is impaired in MGS during pregnancy and first year of life, but, thereafter, height increases in paralleled normal reference centiles, resulting in a mean adult height of -4.5 standard deviations (SD). Height is dependent on ethnic background and underlying molecular cause, with ORC1 and ORC4 mutations causing more severe short stature and microcephaly. Growth hormone therapy (n = 9) was generally ineffective, though in two patients with significantly reduced IGF1 levels, growth was substantially improved by GH treatment, with 2SD and 3.8 SD improvement in height. Growth parameters for monitoring growth in future MGS patients are provided and as well we highlight that growth is disproportionately affected in certain structures, with growth related minor genital abnormalities (42%) and mammary hypoplasia (100%) frequently present, in addition to established effects on ears and patellar growth. Copyright © 2012 Wiley Periodicals, Inc.

Distinct roles of two anaplerotic pathways in glutamate production induced by biotin limitation in Corynebacterium glutamicum.

PubMed

Sato, Hiroki; Orishimo, Keita; Shirai, Tomokazu; Hirasawa, Takashi; Nagahisa, Keisuke; Shimizu, Hiroshi; Wachi, Masaaki

2008-07-01

Corynebacterium glutamicum is a biotin auxotrophic bacterium in which glutamate production is induced under biotin-limited conditions. During glutamate production, anaplerotic reactions catalyzed by phosphoenolpyruvate carboxylase (PEPC) and a biotin-containing enzyme pyruvate carboxylase (PC) are believed to play an important role in supplying oxaloacetate in the tricarboxylic acid cycle. To understand the distinct roles of PEPC and PC on glutamate production by C. glutamicum, we observed glutamate production induced under biotin-limited conditions in the disruptants of the genes encoding PEPC (ppc) and PC (pyc), respectively. The pyc disruptant retained the ability to produce high amounts of glutamate, and lactate was simultaneously produced probably due to the increased intracellular pyruvate levels. On the other hand, the ppc knockout mutant could not produce glutamate. Additionally, glutamate production in the pyc disruptant was enhanced by overexpression of ppc rather than disruption of the lactate dehydrogenase gene (ldh), which is involved in lactate production. Metabolic flux analysis based on the 13C-labeling experiment and measurement of 13C-enrichment in glutamate using nuclear magnetic resonance spectroscopy revealed that the flux for anaplerotic reactions in the pyc disruptant was lower than that in the wild type, concomitantly increasing the flux for lactate formation. Moreover, overexpression of ppc increased this flux in both the pyc disruptant and the wild type. Our results suggest that the PEPC-catalyzed anaplerotic reaction is necessary for glutamate production induced under biotin-limited conditions, because PC is not active during glutamate production, and overexpression of ppc effectively enhances glutamate production under biotin-limited conditions.

Internal Migration and Sexual Initiation among Never Married Youths in Nigeria

PubMed Central

Mberu, Blessing Uchenna; White, Michael J

2013-01-01

The high rates of youth migration to urban and economic centers, in the context of persistent poverty and devastating HIV/AIDS burden, raises intricate social policy challenges in developing countries. This study examines patterns of internal migration and sexual initiation among Nigerian youths, using the 2003 Nigeria DHS data, descriptive statistics, Kaplan-Meier survival curves and discrete-time hazard regression models. Migrants generally show stronger association than non-migrants, and urban-urban migrants show the strongest independent association to early sexual initiation. These outcomes underscore that loss of social capital and exposure to sexually lenient urban environment increase youth's propensity to sexual engagement. Other significant covariates are age, gender, ethnic origin, education, independent living arrangement and formal employment. The findings highlight the inadequacy of policy perspectives that neglect complex contextual nuances across groups and the need to address limited livelihood opportunities that fuel youth migration to urban destinations. PMID:21435767

A Clinical and Pathologic Comparison Between Stage-Matched Endometrial Intraepithelial Carcinoma and Uterine Serous Carcinoma

PubMed Central

Hou, June Y.; McAndrew, Thomas C.; Goldberg, Gary L.; Whitney, Kathleen

2014-01-01

Endometrial intraepithelial carcinoma (EIC) is a rare pathologic variant of uterine serous carcinoma (USC). Our aim is to distinguish patterns of clinic–pathologic outcomes in patients with EIC and USC for disease limited to the endometrium (stage 1A) as well as with distant metastasis (stage 4B). Surgically staged patients were retrospectively identified and relevant variables were extracted and compared. Kaplan-Meier was used to generate the survival data. More USC (n = 29) exhibited lymphovascular invasion (stage 4, P = .01) and expressed higher levels of estrogen receptor-α than EIC (P = .0009 and .063 for stages 1 and 4, respectively). The survival is comparable, with 1 recurrence in each group for stage 1A disease. For stage 4 EIC and USC, the progression-free survival (14 vs10 months) and overall survival (19 vs 20 months) are similar to what is previously published. In conclusion, EIC, whether limited to the endometrium, or widely metastatic, imparts similar outcomes and should be treated comparably with stage-matched USC. PMID:24023030

40 CFR 49.128 - Rule for limiting particulate matter emissions from wood products industry sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... emissions from wood products industry sources. 49.128 Section 49.128 Protection of Environment ENVIRONMENTAL... Rule for limiting particulate matter emissions from wood products industry sources. (a) What is the... certain wood products industry sources operating within the Indian reservation to control ground-level...

A review and comparison of methods for recreating individual patient data from published Kaplan-Meier survival curves for economic evaluations: a simulation study.

PubMed

Wan, Xiaomin; Peng, Liubao; Li, Yuanjian

2015-01-01

In general, the individual patient-level data (IPD) collected in clinical trials are not available to independent researchers to conduct economic evaluations; researchers only have access to published survival curves and summary statistics. Thus, methods that use published survival curves and summary statistics to reproduce statistics for economic evaluations are essential. Four methods have been identified: two traditional methods 1) least squares method, 2) graphical method; and two recently proposed methods by 3) Hoyle and Henley, 4) Guyot et al. The four methods were first individually reviewed and subsequently assessed regarding their abilities to estimate mean survival through a simulation study. A number of different scenarios were developed that comprised combinations of various sample sizes, censoring rates and parametric survival distributions. One thousand simulated survival datasets were generated for each scenario, and all methods were applied to actual IPD. The uncertainty in the estimate of mean survival time was also captured. All methods provided accurate estimates of the mean survival time when the sample size was 500 and a Weibull distribution was used. When the sample size was 100 and the Weibull distribution was used, the Guyot et al. method was almost as accurate as the Hoyle and Henley method; however, more biases were identified in the traditional methods. When a lognormal distribution was used, the Guyot et al. method generated noticeably less bias and a more accurate uncertainty compared with the Hoyle and Henley method. The traditional methods should not be preferred because of their remarkable overestimation. When the Weibull distribution was used for a fitted model, the Guyot et al. method was almost as accurate as the Hoyle and Henley method. However, if the lognormal distribution was used, the Guyot et al. method was less biased compared with the Hoyle and Henley method.

A Review and Comparison of Methods for Recreating Individual Patient Data from Published Kaplan-Meier Survival Curves for Economic Evaluations: A Simulation Study

PubMed Central

Wan, Xiaomin; Peng, Liubao; Li, Yuanjian

2015-01-01

Background In general, the individual patient-level data (IPD) collected in clinical trials are not available to independent researchers to conduct economic evaluations; researchers only have access to published survival curves and summary statistics. Thus, methods that use published survival curves and summary statistics to reproduce statistics for economic evaluations are essential. Four methods have been identified: two traditional methods 1) least squares method, 2) graphical method; and two recently proposed methods by 3) Hoyle and Henley, 4) Guyot et al. The four methods were first individually reviewed and subsequently assessed regarding their abilities to estimate mean survival through a simulation study. Methods A number of different scenarios were developed that comprised combinations of various sample sizes, censoring rates and parametric survival distributions. One thousand simulated survival datasets were generated for each scenario, and all methods were applied to actual IPD. The uncertainty in the estimate of mean survival time was also captured. Results All methods provided accurate estimates of the mean survival time when the sample size was 500 and a Weibull distribution was used. When the sample size was 100 and the Weibull distribution was used, the Guyot et al. method was almost as accurate as the Hoyle and Henley method; however, more biases were identified in the traditional methods. When a lognormal distribution was used, the Guyot et al. method generated noticeably less bias and a more accurate uncertainty compared with the Hoyle and Henley method. Conclusions The traditional methods should not be preferred because of their remarkable overestimation. When the Weibull distribution was used for a fitted model, the Guyot et al. method was almost as accurate as the Hoyle and Henley method. However, if the lognormal distribution was used, the Guyot et al. method was less biased compared with the Hoyle and Henley method. PMID:25803659

Gas Transfer Controls Carbon Limitation During Biomass Production by Marine Microalgae.

PubMed

Tamburic, Bojan; Evenhuis, Christian R; Suggett, David J; Larkum, Anthony W D; Raven, John A; Ralph, Peter J

2015-08-24

This study presents the first in-depth analysis of CO2 limitation on the biomass productivity of the biofuel candidate marine microalga Nannochloropsis oculata. Net photosynthesis decreased by 60% from 125 to 50 μmol O2 L(-1)h(-1) over a 12 h light cycle as a direct result of carbon limitation. Continuous dissolved O2 and pH measurements were used to develop a detailed diurnal mechanism for the interaction between photosynthesis, gas exchange and carbonate chemistry in the photo-bioreactor. Gas exchange determined the degree of carbon limitation experienced by the algae. Carbon limitation was confirmed by delivering more CO2 , which increased net photosynthesis back to its steady-state maximum. This study highlights the importance of maintaining replete carbon concentrations in photo-bioreactors and other culturing facilities, either by constant pH operation or preferably by designing a feedback loop based on the dissolved O2 concentration. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Predictive Factors for Visual Field Conversion: Comparison of Scanning Laser Polarimetry and Optical Coherence Tomography.

PubMed

Diekmann, Theresa; Schrems-Hoesl, Laura M; Mardin, Christian Y; Laemmer, Robert; Horn, Folkert K; Kruse, Friedrich E; Schrems, Wolfgang A

2018-02-01

The purpose of this study was to compare the ability of scanning laser polarimetry (SLP) and spectral-domain optical coherence tomography (SD-OCT) to predict future visual field conversion of subjects with ocular hypertension and early glaucoma. All patients were recruited from the Erlangen glaucoma registry and examined using standard automated perimetry, 24-hour intraocular pressure profile, and optic disc photography. Peripapillary retinal nerve fiber layer thickness (RNFL) measurements were obtained by SLP (GDx-VCC) and SD-OCT (Spectralis OCT). Positive and negative predictive values (PPV, NPV) were calculated for morphologic parameters of SLP and SD-OCT. Kaplan-Meier survival curves were plotted and log-rank tests were performed to compare the survival distributions. Contingency tables and Venn-diagrams were calculated to compare the predictive ability. The study included 207 patients-75 with ocular hypertension, 85 with early glaucoma, and 47 controls. Median follow-up was 4.5 years. A total of 29 patients (14.0%) developed visual field conversion during follow-up. SLP temporal-inferior RNFL [0.667; 95% confidence interval (CI), 0.281-0.935] and SD-OCT temporal-inferior RNFL (0.571; 95% CI, 0.317-0.802) achieved the highest PPV; nerve fiber indicator (0.923; 95% CI, 0.876-0.957) and SD-OCT mean (0.898; 95% CI, 0.847-0.937) achieved the highest NPV of all investigated parameters. The Kaplan-Meier curves confirmed significantly higher survival for subjects within normal limits of measurements of both devices (P<0.001). Venn diagrams tested with McNemar test statistics showed no significant difference for PPV (P=0.219) or NPV (P=0.678). Both GDx-VCC and SD-OCT demonstrate comparable results in predicting future visual field conversion if taking typical scans for GDx-VCC. In addition, the likelihood ratios suggest that GDx-VCC's nerve fiber indicator<30 may be the most useful parameter to confirm future nonconversion. (http://www.ClinicalTrials.gov number, NTC

The long-term outcomes of epilepsy surgery

PubMed Central

Keller, Simon; Nicolson, Andrew; Biswas, Shubhabrata; Smith, David; Osman Farah, Jibril; Eldridge, Paul; Wieshmann, Udo

2018-01-01

Objective Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. Methods This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. Results We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1–27). Kaplan-Meier estimates showed that 47% (95% CI 40–58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31–45) at 10 years after surgery. 74% (95% CI 69–80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64–77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. Conclusion The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with

Determining the sample size required to establish whether a medical device is non-inferior to an external benchmark.

PubMed

Sayers, Adrian; Crowther, Michael J; Judge, Andrew; Whitehouse, Michael R; Blom, Ashley W

2017-08-28

The use of benchmarks to assess the performance of implants such as those used in arthroplasty surgery is a widespread practice. It provides surgeons, patients and regulatory authorities with the reassurance that implants used are safe and effective. However, it is not currently clear how or how many implants should be statistically compared with a benchmark to assess whether or not that implant is superior, equivalent, non-inferior or inferior to the performance benchmark of interest.We aim to describe the methods and sample size required to conduct a one-sample non-inferiority study of a medical device for the purposes of benchmarking. Simulation study. Simulation study of a national register of medical devices. We simulated data, with and without a non-informative competing risk, to represent an arthroplasty population and describe three methods of analysis (z-test, 1-Kaplan-Meier and competing risks) commonly used in surgical research. We evaluate the performance of each method using power, bias, root-mean-square error, coverage and CI width. 1-Kaplan-Meier provides an unbiased estimate of implant net failure, which can be used to assess if a surgical device is non-inferior to an external benchmark. Small non-inferiority margins require significantly more individuals to be at risk compared with current benchmarking standards. A non-inferiority testing paradigm provides a useful framework for determining if an implant meets the required performance defined by an external benchmark. Current contemporary benchmarking standards have limited power to detect non-inferiority, and substantially larger samples sizes, in excess of 3200 procedures, are required to achieve a power greater than 60%. It is clear when benchmarking implant performance, net failure estimated using 1-KM is preferential to crude failure estimated by competing risk models. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No

The long-term outcomes of epilepsy surgery.

PubMed

Mohan, Midhun; Keller, Simon; Nicolson, Andrew; Biswas, Shubhabrata; Smith, David; Osman Farah, Jibril; Eldridge, Paul; Wieshmann, Udo

2018-01-01

Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1-27). Kaplan-Meier estimates showed that 47% (95% CI 40-58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31-45) at 10 years after surgery. 74% (95% CI 69-80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64-77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with hippocampal sclerosis or those who had anterior temporal

40 CFR 49.128 - Rule for limiting particulate matter emissions from wood products industry sources.

Code of Federal Regulations, 2013 CFR

2013-07-01

... emissions from wood products industry sources. 49.128 Section 49.128 Protection of Environment ENVIRONMENTAL... Region 10 § 49.128 Rule for limiting particulate matter emissions from wood products industry sources. (a... emitted from certain wood products industry sources operating within the Indian reservation to control...

40 CFR 49.128 - Rule for limiting particulate matter emissions from wood products industry sources.

Code of Federal Regulations, 2012 CFR

2012-07-01

... emissions from wood products industry sources. 49.128 Section 49.128 Protection of Environment ENVIRONMENTAL... Region 10 § 49.128 Rule for limiting particulate matter emissions from wood products industry sources. (a... emitted from certain wood products industry sources operating within the Indian reservation to control...

40 CFR 49.128 - Rule for limiting particulate matter emissions from wood products industry sources.

Code of Federal Regulations, 2011 CFR

2011-07-01

... emissions from wood products industry sources. 49.128 Section 49.128 Protection of Environment ENVIRONMENTAL... Region 10 § 49.128 Rule for limiting particulate matter emissions from wood products industry sources. (a... emitted from certain wood products industry sources operating within the Indian reservation to control...

Reduced detrital resources limit Pycnopsyche gentilis (Trichoptera: Limnephilidae) production and growth

Treesearch

Susan L. Eggert; J. Bruce Wallace

2003-01-01

Leaf inputs in temperate forest streams may limit caddisfly production because leaf detritus serves both as a food and case-material resource. We estimated Pycnopsyche gentilis produdion in a stream experimentally decoupled fmm its riparian habitat and a reference stream for 8 y in the southern Appalachians. We also examined laboratory survivorship,...

Estimating survival of radio-tagged birds

USGS Publications Warehouse

Bunck, C.M.; Pollock, K.H.; Lebreton, J.-D.; North, P.M.

1993-01-01

Parametric and nonparametric methods for estimating survival of radio-tagged birds are described. The general assumptions of these methods are reviewed. An estimate based on the assumption of constant survival throughout the period is emphasized in the overview of parametric methods. Two nonparametric methods, the Kaplan-Meier estimate of the survival funcrion and the log rank test, are explained in detail The link between these nonparametric methods and traditional capture-recapture models is discussed aloag with considerations in designing studies that use telemetry techniques to estimate survival.

The Emission, Lifetimes, and Formation Threshold of the Vegard-Kaplan Transition of Solid Nitrogen Exposed to Far-ultraviolet Radiation

NASA Astrophysics Data System (ADS)

Lu, Hsiao-Chi; Lo, Jen-Iu; Peng, Yu-Chain; Chou, Sheng-Lung; Lin, Meng-Yeh; Cheng, Bing-Ming

2016-11-01

Irradiation of solid nitrogen at 4 K with far-ultraviolet light from a synchrotron caused excitation to the upper state of the Vegard-Kaplan (VK) system; the emission in that system was simultaneously recorded in wavelength region 200-440 nm. The lifetimes of emission lines for VK (0, 1) to (0, 12) transitions were measured in the range of 2.12 ˜ 2.65 s. The threshold wavelength to observe the VK emission was 175.0 ± 3.5 nm, corresponding to energy 7.08 ± 0.14 eV. This investigation of the generation of icy VK nitrogen enhances our understanding of its photochemistry in space.

Benefits and Limitations of DNA Barcoding and Metabarcoding in Herbal Product Authentication

PubMed Central

Raclariu, Ancuta Cristina; Heinrich, Michael; Ichim, Mihael Cristin

2017-01-01

Abstract Introduction Herbal medicines play an important role globally in the health care sector and in industrialised countries they are often considered as an alternative to mono‐substance medicines. Current quality and authentication assessment methods rely mainly on morphology and analytical phytochemistry‐based methods detailed in pharmacopoeias. Herbal products however are often highly processed with numerous ingredients, and even if these analytical methods are accurate for quality control of specific lead or marker compounds, they are of limited suitability for the authentication of biological ingredients. Objective To review the benefits and limitations of DNA barcoding and metabarcoding in complementing current herbal product authentication. Method Recent literature relating to DNA based authentication of medicinal plants, herbal medicines and products are summarised to provide a basic understanding of how DNA barcoding and metabarcoding can be applied to this field. Results Different methods of quality control and authentication have varying resolution and usefulness along the value chain of these products. DNA barcoding can be used for authenticating products based on single herbal ingredients and DNA metabarcoding for assessment of species diversity in processed products, and both methods should be used in combination with appropriate hyphenated chemical methods for quality control. Conclusions DNA barcoding and metabarcoding have potential in the context of quality control of both well and poorly regulated supply systems. Standardisation of protocols for DNA barcoding and DNA sequence‐based identification are necessary before DNA‐based biological methods can be implemented as routine analytical approaches and approved by the competent authorities for use in regulated procedures. © 2017 The Authors. Phytochemical Analysis Published by John Wiley & Sons Ltd. PMID:28906059

Benefits and Limitations of DNA Barcoding and Metabarcoding in Herbal Product Authentication.

PubMed

Raclariu, Ancuta Cristina; Heinrich, Michael; Ichim, Mihael Cristin; de Boer, Hugo

2018-03-01

Herbal medicines play an important role globally in the health care sector and in industrialised countries they are often considered as an alternative to mono-substance medicines. Current quality and authentication assessment methods rely mainly on morphology and analytical phytochemistry-based methods detailed in pharmacopoeias. Herbal products however are often highly processed with numerous ingredients, and even if these analytical methods are accurate for quality control of specific lead or marker compounds, they are of limited suitability for the authentication of biological ingredients. To review the benefits and limitations of DNA barcoding and metabarcoding in complementing current herbal product authentication. Recent literature relating to DNA based authentication of medicinal plants, herbal medicines and products are summarised to provide a basic understanding of how DNA barcoding and metabarcoding can be applied to this field. Different methods of quality control and authentication have varying resolution and usefulness along the value chain of these products. DNA barcoding can be used for authenticating products based on single herbal ingredients and DNA metabarcoding for assessment of species diversity in processed products, and both methods should be used in combination with appropriate hyphenated chemical methods for quality control. DNA barcoding and metabarcoding have potential in the context of quality control of both well and poorly regulated supply systems. Standardisation of protocols for DNA barcoding and DNA sequence-based identification are necessary before DNA-based biological methods can be implemented as routine analytical approaches and approved by the competent authorities for use in regulated procedures. © 2017 The Authors. Phytochemical Analysis Published by John Wiley & Sons Ltd. © 2017 The Authors. Phytochemical Analysis Published by John Wiley & Sons Ltd.

Large-scale production of kappa-carrageenan droplets for gel-bead production: theoretical and practical limitations of size and production rate.

PubMed

Hunik, J H; Tramper, J

1993-01-01

Immobilization of biocatalysts in kappa-carrageenan gel beads is a widely used technique nowadays. Several methods are used to produce the gel beads. The gel-bead production rate is usually sufficient to make the relatively small quantities needed for bench-scale experiments. The droplet diameter can, within limits, be adjusted to the desired size, but it is difficult to predict because of the non-Newtonian fluid behavior of the kappa-carrageenan solution. Here we present the further scale-up of the extrusion technique with the theory to predict the droplet diameters for non-Newtonian fluids. The emphasis is on the droplet formation, which is the rate-limiting step in this extrusion technique. Uniform droplets were formed by breaking up a capillary jet with a sinusoidal signal of a vibration exciter. At the maximum production rate of 27.6 dm3/h, uniform droplets with a diameter of (2.1 +/- 0.12) x 10(-3) m were obtained. This maximum flow rate was limited by the power transfer of the vibration exciter to the liquid flow. It was possible to get a good prediction of the droplet diameter by estimating the local viscosity from shear-rate calculations and an experimental relation between the shear rate and viscosity. In this way the theory of Newtonian fluids could be used for the non-Newtonian kappa-carrageenan solution. The calculated optimal break-up frequencies and droplet sizes were in good agreement with those found in the experiments.

Improved long-term survival after intra-operative single high-dose ATG-Fresenius induction in renal transplantation: a single centre experience.

PubMed

Kaden, Jürgen; May, Gottfried; Völp, Andreas; Wesslau, Claus

2009-01-01

In organ grafts donor-specific sensitization is initiated immediately after revascularization. Therefore, in 1990 we introduced the intra-operative single high-dose ATG-Fresenius (ATG-F) induction in addition to standard triple drug therapy (TDT) consisting of steroids, azathioprine and cyclosporin. A total of 778 first renal transplantations from deceased donors, performed between 1987 and 1998, were included in this evaluation. This retrospective analysis of clinic records and electronic databases presents data of all recipients of first kidney grafts who received two different ATG-F inductions (1(st) group: 9 mg/kg body weight as single high-dose intra-operatively, n=484; 2(nd) group: 3 mg/kg body weight on 7 or 8 consecutive days as multiple-dose starting also intra-operatively, n=78) and standard TDT alone (3(rd) group: TDT alone, n=216). The 10-year patient survival rates were 72.6+/-2.6% (TDT + ATG-F single high-dose), 79.5+/-5.1% (TDT + ATG-F multiple-dose) and 67.2+/-3.7%% (TDT alone; Kaplan-Meier estimates with standard errors; ATG-F vs TDT alone, p=0.001). The 10-year graft survival rates with censoring of patients that died with a functioning graft were 73.8+/-2.4%, 57.7+/-5.8% and 58.4+/-3.6% (Kaplan-Meier estimates with standard errors; 1(st) vs 2(nd )and 3(rd) group, respectively, p<0.001) and the 10-year graft survival rates with patient death counted as graft failure were 58.3+/-2.7%, 55.7+/-5.8% and 48.2+/-3.5% (Kaplan-Meier estimates with standard errors; ATG-F single high-dose vs TDT, p=0.023). In pre-sensitized recipients there were also significant differences in favour of ATG-F, more notably in the single high-dose ATG-F induction. A total of 69% of the patients in the two cohorts receiving ATG-F did not experience any transplant rejections compared to 56% in patients undergoing TDT alone (p=0.018). The incidence of infectious complications was comparable across all groups. According to evidence obtained from the routine documentation of 778

Retinoblastoma Vitreous Seed Clouds (Class 3): A Comparison of Treatment with Ophthalmic Artery Chemosurgery with or without Intravitreous and Periocular Chemotherapy.

PubMed

Francis, Jasmine H; Iyer, Saipriya; Gobin, Y Pierre; Brodie, Scott E; Abramson, David H

2017-10-01

To compare the efficacy and toxicity of treating class 3 retinoblastoma vitreous seeds with ophthalmic artery chemosurgery (OAC) alone versus OAC with intravitreous chemotherapy. Retrospective cohort study. Forty eyes containing clouds (class 3 vitreous seeds) of 40 retinoblastoma patients (19 treated with OAC alone and 21 treated with OAC plus intravitreous and periocular chemotherapy). Ocular survival, disease-free survival and time to regression of seeds were estimated with Kaplan-Meier estimates. Ocular toxicity was evaluated by clinical findings and electroretinography: 30-Hz flicker responses were compared at baseline and last follow-up visit. Continuous variables were compared with Student t test, and categorical variables were compared with the Fisher exact test. Ocular survival, disease-free survival, and time to regression of seeds. There were no disease- or treatment-related deaths and no patient demonstrated externalization of tumor or metastatic disease. There was no significant difference in the age, laterality, disease, or disease status (treatment naïve vs. previously treated) between the 2 groups. The time to regression of seeds was significantly shorter for eyes treated with OAC plus intravitreous chemotherapy (5.7 months) compared with eyes treated with OAC alone (14.6 months; P < 0.001). The 18-month Kaplan-Meier estimates of disease-free survival were significantly worse for the OAC alone group: 67.1% (95% confidence interval, 40.9%-83.6%) versus 94.1% (95% confidence interval, 65%-99.1%) for the OAC plus intravitreous chemotherapy group (P = 0.05). The 36-month Kaplan-Meier estimates of ocular survival were 83.3% (95% confidence interval, 56.7%-94.3%) for the OAC alone group and 100% for the OAC plus intravitreous chemotherapy group (P = 0.16). The mean change in electroretinography responses was not significantly different between groups, decreasing by 11 μV for the OAC alone group and 22 μV for the OAC plus intravitreous chemotherapy

Microbial lipid production by Rhodosporidium toruloides under sulfate-limited conditions.

PubMed

Wu, Siguo; Zhao, Xin; Shen, Hongwei; Wang, Qian; Zhao, Zongbao K

2011-01-01

Novel biochemical approaches remain to be developed to improve microbial lipid technology. This study demonstrated that sulfate limitation was effective to promote accumulating substantial amounts of intracellular lipid by the oleaginous yeast Rhodosporidium toruloides Y4. When it was cultivated using a medium with an initial carbon-to-sulfur (C/S) molar ratio of 46,750, cellular lipid content reached up to 58.3%. The time courses of cell growth, lipid accumulation and nutrient depletion were analyzed and discussed in terms of lipid biosynthesis. Moreover, lipid accumulation under sulfate-limited conditions was effective regardless of the presence of a high concentration of nitrogen sources. Thus, lipid contents almost held constant at near 57% in the media with an initial C/S molar ratio of 11,380 although the carbon-to-nitrogen molar ratio ranged from 28.3 to 5.7. Taken together, our results established the sulfate-limitation approach to control lipid biosynthesis, which should be valuable to explore nitrogen-rich raw materials as the feedstock for lipid production. Copyright © 2010 Elsevier Ltd. All rights reserved.

16 CFR 1500.88 - Exemptions from lead limits under section 101 of the Consumer Product Safety Improvement Act for...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 101 of the Consumer Product Safety Improvement Act for certain electronic devices. 1500.88 Section... from lead limits under section 101 of the Consumer Product Safety Improvement Act for certain electronic devices. (a) The Consumer Product Safety Improvement Act (CPSIA) provides for specific lead limits...

Prognostic value of inflammation-based markers in patients with pancreatic cancer administered gemcitabine and erlotinib.

PubMed

Lee, Jae Min; Lee, Hong Sik; Hyun, Jong Jin; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Chun, Hoon Jai; Um, Soon Ho; Kim, Chang Duck

2016-07-15

To evaluate the value of systemic inflammation-based markers as prognostic factors for advanced pancreatic cancer (PC). Data from 82 patients who underwent combination chemotherapy with gemcitabine and erlotinib for PC from 2011 to 2014 were collected retrospectively. Data that included the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio, and the C-reactive protein (CRP)-to-albumin (CRP/Alb) ratio were analyzed. Kaplan-Meier curves, and univariate and multivariate Cox proportional hazards regression analyses were used to identify the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). The univariate analysis demonstrated the prognostic value of the NLR (P = 0.049) and the CRP/Alb ratio (P = 0.047) in relation to PFS, and a positive relationship between an increase in inflammation-based markers and a poor prognosis in relation to OS. The multivariate analysis determined that an increased NLR (hazard ratio = 2.76, 95%CI: 1.33-5.75, P = 0.007) is an independent prognostic factor for poor OS. There was no association between the PLR and the patients' prognoses in those who had received chemotherapy that comprised gemcitabine and erlotinib in combination. The Kaplan-Meier method and the log-rank test determined significantly worse outcomes in relation to PFS and OS in patients with an NLR > 5 or a CRP/Alb ratio > 5. Systemic inflammation-based markers, including increases in the NLR and the CRP/Alb ratio, may be useful for predicting PC prognoses.

Assessment of the American Joint Commission on Cancer 8th Edition Staging System for Patients with Pancreatic Neuroendocrine Tumors: A Surveillance, Epidemiology, and End Results analysis.

PubMed

Li, Xiaogang; Gou, Shanmiao; Liu, Zhiqiang; Ye, Zeng; Wang, Chunyou

2018-03-01

Although several staging systems have been proposed for pancreatic neuroendocrine tumors (pNETs), the optimal staging system remains unclear. Here, we aimed to assess the application of the newly revised 8th edition American Joint Committee on Cancer (AJCC) staging system for exocrine pancreatic carcinoma (EPC) to pNETs, in comparison with that of other staging systems. We identified pNETs patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2014). Overall survival was analyzed using Kaplan-Meier curves with the log-rank test. The predictive accuracy of each staging system was assessed by the concordance index (c-index). Cox proportional hazards regression was conducted to calculate the impact of different stages. In total, 2424 patients with pNETs, including 2350 who underwent resection, were identified using SEER data. Patients with different stages were evenly stratified based on the 8th edition AJCC staging system for EPC. Kaplan-Meier curves were well separated in all patients and patients with resection using the 8th edition AJCC staging system for EPC. Moreover, the hazard ratio increased with worsening disease stage. The c-index of the 8th edition AJCC staging system for EPC was similar to that of the other systems. For pNETs patients, the 8th edition AJCC staging system for EPC exhibits good prognostic discrimination among different stages in both all patients and those with resection. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Increased Prognostic Value of Query Amyloid Late Enhancement Score in Light-Chain Cardiac Amyloidosis.

PubMed

Wan, Ke; Sun, Jiayu; Han, Yuchi; Liu, Hong; Yang, Dan; Li, Weihao; Wang, Jie; Cheng, Wei; Zhang, Qing; Zeng, Zhi; Chen, Yucheng

2018-02-23

Late gadolinium enhancement (LGE) pattern is a powerful imaging biomarker for prognosis of cardiac amyloidosis. It is unknown if the query amyloid late enhancement (QALE) score in light-chain (AL) amyloidosis could provide increased prognostic value compared with LGE pattern.Methods and Results:Seventy-eight consecutive patients with AL amyloidosis underwent contrast-enhanced cardiovascular magnetic resonance imaging. Patients with cardiac involvement were grouped by LGE pattern and analyzed using QALE score. Receiver operating characteristic curve was used to identify the optimal cut-off for QALE score in predicting all-cause mortality. Survival of these patients was analyzed with the Kaplan-Meier method and multivariate Cox regression. During a median follow-up of 34 months, 53 of 78 patients died. The optimal cut-off for QALE score to predict mortality at 12-month follow-up was 9.0. On multivariate Cox analysis, QALE score ≥9 (HR, 5.997; 95% CI: 2.665-13.497; P<0.001) and log N-terminal pro-brain natriuretic peptide (HR, 1.525; 95% CI: 1.112-2.092; P=0.009) were the only 2 independent predictors of all-cause mortality. On Kaplan-Meier analysis, patients with subendocardial LGE can be further risk stratified using QALE score ≥9. The QALE scoring system provides powerful independent prognostic value in AL cardiac amyloidosis. QALE score ≥9 has added value to differentiate prognosis in AL amyloidosis patients with a subendocardial LGE pattern.

High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers.

PubMed

Peng, Li; Yuan, Xiao-Qing; Liu, Zhao-Yang; Li, Wen-Ling; Zhang, Chao-Yang; Zhang, Ya-Qin; Pan, Xi; Chen, Jun; Li, Yue-Hui; Li, Guan-Cheng

2017-01-03

Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients.

Differential Expression and Clinical Significance of Transforming Growth Factor-Beta Isoforms in GBM Tumors.

PubMed

Roy, Laurent-Olivier; Poirier, Marie-Belle; Fortin, David

2018-04-08

Glioblastoma (GBM) represents the most common and aggressive malignant primary brain tumors in adults. Response to standard treatment is transitory and the survival of clinical trial cohorts are little more than 14 months. GBM are characterized by excessive proliferation, invasiveness, and radio-/chemoresistance features; which are strongly upregulated by transforming growth factor-beta (TGF-β). We hypothesized that TGF-β gene expression could correlate with overall survival (OS) and serve as a prognostic biomarker. TGF-β₁ and -β₂ expression were analyzed by qPCR in 159 GBM tumor specimens. Kaplan-Meier and multivariate analyses were used to correlate expression with OS and progression-free survival (PFS). In GBM, TGF-β₁ and -β₂ levels were 33- and 11-fold higher respectively than in non-tumoral samples. Kaplan-Meier and multivariate analyses revealed that high to moderate expressions of TGF-β₁ significantly conferred a strikingly poorer OS and PFS in newly diagnosed patients. Interestingly, at relapse, neither isoforms had meaningful impact on clinical evolution. We demonstrate that TGF-β₁ is the dominant isoform in newly diagnosed GBM rather than the previously acknowledged TGF-β₂. We believe our study is the first to unveil a significant relationship between TGF-β₁ expression and OS or PFS in newly diagnosed GBM. TGF-β₁ could serve as a prognostic biomarker or target affecting treatment planning and patient follow-up.

On the importance of accounting for competing risks in pediatric cancer trials designed to delay or avoid radiotherapy: I. Basic concepts and first analyses.

PubMed

Tai, Bee-Choo; Grundy, Richard G; Machin, David

2010-04-01

In trials designed to delay or avoid irradiation among children with malignant brain tumor, although irradiation after disease progression is an important event, patients who have disease progression may decline radiotherapy (RT), or those without disease progression may opt for elective RT. To accurately describe the cumulative need for RT in such instances, it is crucial to account for these distinct events and to evaluate how each contributes to the delay or advancement of irradiation via a competing risks analysis. We describe the summary of competing events in such trials using competing risks methods based on cumulative incidence functions and Gray's test. The results obtained are contrasted with standard survival methods based on Kaplan-Meier curves, cause-specific hazard functions and log-rank test. The Kaplan-Meier method overestimates all event-specific rates. The cause-specific hazard analysis showed reduction in hazards for all events (A: RT after progression; B: no RT after progression; C: elective RT) among children with ependymoma. For event A, a higher cumulative incidence was reported for ependymoma. Although Gray's test failed to detect any difference (p = 0.331) between histologic subtypes, the log-rank test suggested marginal evidence (p = 0.057). Similarly, for event C, the log-rank test found stronger evidence of reduction in hazard among those with ependymoma (p = 0.005) as compared with Gray's test (p = 0.086). To evaluate treatment differences, failing to account for competing risks using appropriate methodology may lead to incorrect interpretations.

High Rab27A expression indicates favorable prognosis in CRC.

PubMed

Shi, Chuanbing; Yang, Xiaojun; Ni, Yijiang; Hou, Ning; Xu, Li; Zhan, Feng; Zhu, Huijun; Xiong, Lin; Chen, Pingsheng

2015-06-13

Rab27A is a peculiar member in Rab family and has been suggested to play essential roles in the development of human cancers. However, the association between Rab27A expression and clinicopathological characteristics of colorectal cancer (CRC) has not been elucidated yet. One-step quantitative real-time polymerase chain reaction (qPCR) test with 18 fresh-frozen CRC samples and immunohistochemistry (IHC) analysis in 112 CRC cases were executed to evaluate the relationship between Rab27A expression and the clinicopathological features of CRC. Cox regression and Kaplan-Meier survival analyses were performed to identify the prognostic factors for 112 CRC patients. The results specified that the expression levels of Rab27A mRNA and protein were significantly higher in CRC tissues than that in matched non-cancerous tissues, in both qPCR test (p = 0.029) and IHC analysis (p = 0.020). The IHC data indicated that the Rab27A protein expression in CRC was statistically correlated with lymph node metastasis (p = 0.022) and TNM stage (p = 0.026). Cox multi-factor analysis and Kaplan-Meier method suggested Rab27A protein expression (p = 0.012) and tumor differentiation (p = 0.004) were significantly associated with the overall survival of CRC patients. The data indicated the differentiate expression of Rab27A in CRC tissues and matched non-cancerous tissues. Rab27A may be used as a valuable prognostic biomarker for CRC patients.

The preoperative plasma fibrinogen level is an independent prognostic factor for overall survival of breast cancer patients who underwent surgical treatment.

PubMed

Wen, Jiahuai; Yang, Yanning; Ye, Feng; Huang, Xiaojia; Li, Shuaijie; Wang, Qiong; Xie, Xiaoming

2015-12-01

Previous studies have suggested that plasma fibrinogen contributes to tumor cell proliferation, progression and metastasis. The current study was performed to evaluate the prognostic relevance of preoperative plasma fibrinogen in breast cancer patients. Data of 2073 consecutive breast cancer patients, who underwent surgery between January 2002 and December 2008 at the Sun Yat-sen University Cancer Center, were retrospectively evaluated. Plasma fibrinogen levels were routinely measured before surgeries. Participants were grouped by the cutoff value estimated by the receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed using Kaplan-Meier analysis, and multivariate Cox proportional hazards regression model was performed to evaluate the independent prognostic value of plasma fibrinogen level. The optimal cutoff value of preoperative plasma fibrinogen was determined to be 2.83 g/L. The Kaplan-Meier analysis showed that patients with high fibrinogen levels had shorter OS than patients with low fibrinogen levels (p < 0.001). Multivariate analysis suggested preoperative plasma fibrinogen as an independent prognostic factor for OS in breast cancer patients (HR = 1.475, 95% confidence interval (CI): 1.177-1.848, p = 0.001). Subgroup analyses revealed that plasma fibrinogen level was an unfavorable prognostic parameter in stage II-III, Luminal subtypes and triple-negative breast cancer patients. Elevated preoperative plasma fibrinogen was independently associated with poor prognosis in breast cancer patients and may serve as a valuable parameter for risk assessment in breast cancer patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Predicting long-term graft survival in adult kidney transplant recipients.

PubMed

Pinsky, Brett W; Lentine, Krista L; Ercole, Patrick R; Salvalaggio, Paolo R; Burroughs, Thomas E; Schnitzler, Mark A

2012-07-01

The ability to accurately predict a population's long-term survival has important implications for quantifying the benefits of transplantation. To identify a model that can accurately predict a kidney transplant population's long-term graft survival, we retrospectively studied the United Network of Organ Sharing data from 13,111 kidney-only transplants completed in 1988- 1989. Nineteen-year death-censored graft survival (DCGS) projections were calculated and compared with the population's actual graft survival. The projection curves were created using a two-part estimation model that (1) fits a Kaplan-Meier survival curve immediately after transplant (Part A) and (2) uses truncated observational data to model a survival function for long-term projection (Part B). Projection curves were examined using varying amounts of time to fit both parts of the model. The accuracy of the projection curve was determined by examining whether predicted survival fell within the 95% confidence interval for the 19-year Kaplan-Meier survival, and the sample size needed to detect the difference in projected versus observed survival in a clinical trial. The 19-year DCGS was 40.7% (39.8-41.6%). Excellent predictability (41.3%) can be achieved when Part A is fit for three years and Part B is projected using two additional years of data. Using less than five total years of data tended to overestimate the population's long-term survival, accurate prediction of long-term DCGS is possible, but requires attention to the quantity data used in the projection method.

Glycolytic activity in breast cancer using 18F-FDG PET/CT as prognostic predictor: A molecular phenotype approach.

PubMed

Garcia Vicente, A M; Soriano Castrejón, A; Amo-Salas, M; Lopez Fidalgo, J F; Muñoz Sanchez, M M; Alvarez Cabellos, R; Espinosa Aunion, R; Muñoz Madero, V

2016-01-01

To explore the relationship between basal (18)F-FDG uptake in breast tumors and survival in patients with breast cancer (BC) using a molecular phenotype approach. This prospective and multicentre study included 193 women diagnosed with BC. All patients underwent an (18)F-FDG PET/CT prior to treatment. Maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N), and the N/T index was obtained in all the cases. Metabolic stage was established. As regards biological prognostic parameters, tumors were classified into molecular sub-types and risk categories. Overall survival (OS) and disease free survival (DFS) were obtained. An analysis was performed on the relationship between semi-quantitative metabolic parameters with molecular phenotypes and risk categories. The effect of molecular sub-type and risk categories in prognosis was analyzed using Kaplan-Meier and univariate and multivariate tests. Statistical differences were found in both SUVT and SUVN, according to the molecular sub-types and risk classifications, with higher semi-quantitative values in more biologically aggressive tumors. No statistical differences were observed with respect to the N/T index. Kaplan-Meier analysis revealed that risk categories were significantly related to DFS and OS. In the multivariate analysis, metabolic stage and risk phenotype showed a significant association with DFS. High-risk phenotype category showed a worst prognosis with respect to the other categories with higher SUVmax in primary tumor and lymph nodes. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Efficacy of prophylactic cranial irradiation in patients with limited-disease small-cell lung cancer who were confirmed to have no brain metastasis via magnetic resonance imaging after initial chemoradiotherapy.

PubMed

Mamesaya, Nobuaki; Wakuda, Kazushige; Omae, Katsuhiro; Miyawaki, Eriko; Kotake, Mie; Fujiwara, Takumi; Kawamura, Takahisa; Kobayashi, Haruki; Nakashima, Kazuhisa; Omori, Shota; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Murakami, Haruyasu; Mori, Keita; Harada, Hideyuki; Endo, Masahiro; Nakajima, Takashi; Takahashi, Toshiaki

2018-04-03

Prophylactic cranial irradiation (PCI) is recommended for patients with limited-disease small-cell lung cancer (LD-SCLC) who achieved good response to definitive chemoradiotherapy. However, most clinical studies lacked brain imaging scans before PCI. Our study aimed to investigate whether PCI has a survival benefit in patients who have no brain metastases (BM) confirmed via magnetic resonance imaging (MRI) before PCI. Eighty patients were included in this study. Sixty patients received PCI (PCI group) and 20 patients did not (non-PCI group). OS was not significantly different between the two groups. The median OS time was 4.3 years (95% CI: 2.6 years-8.6 years) in the PCI group and was not reached (NR) (95% CI: 1.9 years-NR) in the non-PCI group ( p = 0.542). Moreover, no differences were observed in the 3-year rates of PFS (46.2% and 44.4%, p = 0.720) and cumulative incidence of BM (24.0% vs. 27%, p = 0.404). Our result suggests that PCI may not have a survival benefit in patients with LD-SCLC confirmed to have no BM after initial therapy, even if patients achieve a good response to definitive chemoradiotherapy. We retrospectively evaluated patients with LD-SCLC who were confirmed to have no BM via MRI after initial chemoradiotherapy at the Shizuoka Cancer Center between September 2002 and August 2015. The overall survival (OS), progression-free survival (PFS), and cumulative incidence of BM were estimated using the Kaplan-Meier method between patients who received PCI and those who did not. Propensity score matching was used to balance baseline characteristics.

Testing the limits in a greenhouse ocean: Did low nitrogen availability limit marine productivity during the end-Triassic mass extinction?

NASA Astrophysics Data System (ADS)

Schoepfer, Shane D.; Algeo, Thomas J.; Ward, Peter D.; Williford, Kenneth H.; Haggart, James W.

2016-10-01

The end-Triassic mass extinction has been characterized as a 'greenhouse extinction', related to rapid atmospheric warming and associated changes in ocean circulation and oxygenation. The response of the marine nitrogen cycle to these oceanographic changes, and the extent to which mass extinction intervals represent a deviation in nitrogen cycling from other ice-free 'greenhouse' periods of Earth history, remain poorly understood. The well-studied Kennecott Point section in Haida Gwaii, British Columbia, Canada, was deposited in the open Panthalassic Ocean, and is used here as a test case to better understand changes in the nitrogen cycle and marine productivity from the pre-crisis greenhouse of the Rhaetian to the latest-Rhaetian crisis interval. We estimated marine productivity from the late Norian to the early Hettangian using TOC- and P-based paleoproductivity transform equations, and then compared these estimates to records of sedimentary nitrogen isotopes, redox-sensitive trace elements, and biomarker data. Major negative excursions in δ15N (to ≤ 0 ‰) correspond to periods of depressed marine productivity. During these episodes, the development of a stable pycnocline below the base of the photic zone suppressed vertical mixing and limited N availability in surface waters, leading to low productivity and increased nitrogen fixation, as well as ecological stresses in the photic zone. The subsequent shoaling of euxinic waters into the ocean surface layer was fatal for most Triassic marine fauna, although the introduction of regenerated NH4+ into the photic zone may have allowed phytoplankton productivity to recover. These results indicate that the open-ocean nitrogen cycle was influenced by climatic changes during the latest Triassic, despite having existed in a greenhouse state for over 50 million years previously, and that low N availability limited marine productivity for hundreds of thousands of years during the end-Triassic crisis.

Structural limits on force production and shortening of smooth muscle.

PubMed

Siegman, Marion J; Davidheiser, Sandra; Mooers, Susan U; Butler, Thomas M

2013-02-01

This study determined the factors that limit force production and shortening in two smooth muscles having very different relationships between active and passive force as a function of muscle length. The rat anococcygeus muscle develops active force over the range of lengths 0.2-2.0× the optimum length for force production (Lo). Passive tension due to extension of the resting muscle occurs only at lengths exceeding Lo. In contrast, the rabbit taenia coli develops force in the range of lengths 0.4-1.1 Lo, and passive force which is detectable at 0.56 Lo, increases to ~0.45 maximum active force at Lo, and increases sharply with further extension. The anococcygeus muscle can shorten to 0.2 Lo and the taenia coli to 0.4 Lo. Dynamic stiffness and energy usage at short muscle lengths suggest that the limit of shortening in the taenia coli, in contrast to the anococcygeus muscle, is not due to a failure of cross bridge interaction. Phosphorylation of the regulatory myosin light chains in intact muscles decreased to a small extent at short lengths compared to the decrease in force production. The differences in force production and the extent of shortening in the two muscles was maintained even when, following permeabilization, the myosin light chains were irreversibly phosphorylated with ATPγS, indicating that differences in activation played little, if any role. Ultrastructural studies on resting and activated muscles show that the taenia coli, which is rich in connective tissue (unlike the anococcygeus muscle) undergoes marked cellular twisting and contractile filament misalignment at short lengths with compression of the extracellular matrix. As a result, force is not transmitted in the longitudinal axis of the muscle, but is dissipated against an internal load provided by the compressed extracellular matrix. These observations on two very different normal smooth muscles reveal how differences in the relative contribution of active and passive structural elements

Nutrient limitations to aquatic production along an alluvial groundwater connectivity gradient in semi-arid northwest Australia

NASA Astrophysics Data System (ADS)

Iles, Jordan; Pettit, Neil; Grierson, Pauline

2017-04-01

Primary production of intermittent streams in hot arid regions, such as the geologically ancient Pilbara region of northwest Australia, is strongly limited by both water and nutrient availability. Pulses of allochthonous materials can be significant source of nutrients and carbon during short periods of connected flow. However, during interflow periods, which may last months to years, surface water retracts to a series of surface disconnected pools, where hydrological processes including hyporheic exchange and evapo-concentration of ions are of increasing importance in maintaining bioavailable nutrients for primary production. In the Pilbara, the persistence of individual pools during interflow periods is strongly linked to local topography and connectivity to alluvial groundwater. We might thus expect that autochthonous production is greater in pools that become disconnected from groundwater due to increased concentration of nutrients. We thus investigated the importance of nitrogen (N) and phosphorus (P) limitations on aquatic production along an alluvial groundwater connectivity gradient. First, we used in-situ bottle incubations and a 13C-enriched NaHCO3 isotopic tracer to measure rates of charophyte and phytoplankton production in response to nutrient amendments. Second, we paired a nutrient diffusing substrata limitation experiment with high performance liquid chromatography to i) identify which nutrient(s) limit periphyton production, and ii) how the periphyton community structure changes within pools along the alluvial gradient. Charophyte production was 2 mg C g-1 DW h-1 while phytoplankton production was orders of magnitude less (˜0.01 mg C g-1 DW h-1). Although charophytes showed no clear respiration response to short-term nutrient addition, productivity was positively correlated to both charophyte N and P content (R2 = 0.65, p < 0.001 and R2 = 0.41, p < 0.001 respectively). This relationship was stronger in pools which were disconnected from alluvial

Item response theory analyses of the Delis-Kaplan Executive Function System card sorting subtest.

PubMed

Spencer, Mercedes; Cho, Sun-Joo; Cutting, Laurie E

2018-02-02

In the current study, we examined the dimensionality of the 16-item Card Sorting subtest of the Delis-Kaplan Executive Functioning System assessment in a sample of 264 native English-speaking children between the ages of 9 and 15 years. We also tested for measurement invariance for these items across age and gender groups using item response theory (IRT). Results of the exploratory factor analysis indicated that a two-factor model that distinguished between verbal and perceptual items provided the best fit to the data. Although the items demonstrated measurement invariance across age groups, measurement invariance was violated for gender groups, with two items demonstrating differential item functioning for males and females. Multigroup analysis using all 16 items indicated that the items were more effective for individuals whose IRT scale scores were relatively high. A single-group explanatory IRT model using 14 non-differential item functioning items showed that for perceptual ability, females scored higher than males and that scores increased with age for both males and females; for verbal ability, the observed increase in scores across age differed for males and females. The implications of these findings are discussed.

Evaluation of methods for managing censored results when calculating the geometric mean.

PubMed

Mikkonen, Hannah G; Clarke, Bradley O; Dasika, Raghava; Wallis, Christian J; Reichman, Suzie M

2018-01-01

Currently, there are conflicting views on the best statistical methods for managing censored environmental data. The method commonly applied by environmental science researchers and professionals is to substitute half the limit of reporting for derivation of summary statistics. This approach has been criticised by some researchers, raising questions around the interpretation of historical scientific data. This study evaluated four complete soil datasets, at three levels of simulated censorship, to test the accuracy of a range of censored data management methods for calculation of the geometric mean. The methods assessed included removal of censored results, substitution of a fixed value (near zero, half the limit of reporting and the limit of reporting), substitution by nearest neighbour imputation, maximum likelihood estimation, regression on order substitution and Kaplan-Meier/survival analysis. This is the first time such a comprehensive range of censored data management methods have been applied to assess the accuracy of calculation of the geometric mean. The results of this study show that, for describing the geometric mean, the simple method of substitution of half the limit of reporting is comparable or more accurate than alternative censored data management methods, including nearest neighbour imputation methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Overcoming limits set by scarce resources - role of local food production and food imports

NASA Astrophysics Data System (ADS)

Porkka, Miina; Guillaume, Joseph H. A.; Schaphoff, Sibyll; Siebert, Stefan; Gerten, Dieter; Kummu, Matti

2017-04-01

There is a fundamental tension between population growth and carrying capacity, i.e. the population that could potentially be supported using the resources and technologies available at a given time. This makes the assessments of resource use and agricultural productivity central to the debate on future food security. Local carrying capacity can be increased by expanding (e.g. through land conversion and irrigation infrastructure) or intensifying (e.g. through technologies and practices that increase efficiency) the resource use in agriculture. Food imports can be considered another way of overcoming current local limits and continuing growth beyond the local human-carrying capacity. Focusing on water as the key limiting resource, we performed a global assessment of the capacity for food self-sufficiency at sub-national and national scale for 1961-2009, taking into account the availability of both green and blue water as well as technology and management practices affecting water productivity at a given time, and using the hydrology and agriculture model LPJmL as our primary tool. Furthermore, we examined the use of food imports as a strategy to increase carrying capacity in regions where the potential for food self-sufficiency was limited by water availability and productivity. We found that the capacity for food self-sufficiency reduced notably during the study period due to the rapid population growth that outpaced the substantial improvements in water productivity. In 2009 more than a third (2.2 billion people) of the world's population lived in areas where sufficient food production to meet the needs of the population was not possible, and some 800 million people more were approaching this threshold. Food imports have nearly universally been used to overcome these local limits to growth, though the success of this strategy has been highly dependent on economic purchasing power. In the unsuccessful cases, increases in imports and local productivity have not

De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome

PubMed Central

Burrage, Lindsay C.; Charng, Wu-Lin; Eldomery, Mohammad K.; Willer, Jason R.; Davis, Erica E.; Lugtenberg, Dorien; Zhu, Wenmiao; Leduc, Magalie S.; Akdemir, Zeynep C.; Azamian, Mahshid; Zapata, Gladys; Hernandez, Patricia P.; Schoots, Jeroen; de Munnik, Sonja A.; Roepman, Ronald; Pearring, Jillian N.; Jhangiani, Shalini; Katsanis, Nicholas; Vissers, Lisenka E.L.M.; Brunner, Han G.; Beaudet, Arthur L.; Rosenfeld, Jill A.; Muzny, Donna M.; Gibbs, Richard A.; Eng, Christine M.; Xia, Fan; Lalani, Seema R.; Lupski, James R.; Bongers, Ernie M.H.F.; Yang, Yaping

2015-01-01

Meier-Gorlin syndrome (MGS) is a genetically heterogeneous primordial dwarfism syndrome known to be caused by biallelic loss-of-function mutations in one of five genes encoding pre-replication complex proteins: ORC1, ORC4, ORC6, CDT1, and CDC6. Mutations in these genes cause disruption of the origin of DNA replication initiation. To date, only an autosomal-recessive inheritance pattern has been described in individuals with this disorder, with a molecular etiology established in about three-fourths of cases. Here, we report three subjects with MGS and de novo heterozygous mutations in the 5′ end of GMNN, encoding the DNA replication inhibitor geminin. We identified two truncating mutations in exon 2 (the 1st coding exon), c.16A>T (p.Lys6∗) and c.35_38delTCAA (p.Ile12Lysfs∗4), and one missense mutation, c.50A>G (p.Lys17Arg), affecting the second-to-last nucleotide of exon 2 and possibly RNA splicing. Geminin is present during the S, G2, and M phases of the cell cycle and is degraded during the metaphase-anaphase transition by the anaphase-promoting complex (APC), which recognizes the destruction box sequence near the 5′ end of the geminin protein. All three GMNN mutations identified alter sites 5′ to residue Met28 of the protein, which is located within the destruction box. We present data supporting a gain-of-function mechanism, in which the GMNN mutations result in proteins lacking the destruction box and hence increased protein stability and prolonged inhibition of replication leading to autosomal-dominant MGS. PMID:26637980

'What's the ethics of that?' A Conversation with Thomas O. Pyle. Interview by Donald M. Berwick and Madge Kaplan.

PubMed

Pyle, Thomas O

2008-01-01

Thomas O. Pyle served in the top echelons of the Harvard Community Health Plan (HCHP) for nineteen years. In that time, HCHP became the largest health maintenance organization (HMO) in New England, and its reputation for innovation and entrepreneurship rose to the top ranks of the industry. HCHP pioneered the automated medical record, nurse practitioners, quality measurement, and sophisticated disease management. In this interview, Berwick and the Institute for Healthcare Improvement's Madge Kaplan explore Pyle's background, his interpretation of HCHP's evolution and eventual transition to a much different organization, and his recommendations for the future. At the time of this interview, Tom was suffering from advanced pancreatic cancer, from which he died ten weeks later, 18 July 2007.

Pollen source and resource limitation to fruit production in the rare species Eremosparton songoricum (Fabaceae)

USDA-ARS?s Scientific Manuscript database

Eremosparton songoricum (Litv.) Vass. is a rare, central Asian desert species which shows lower fruit set and seed set (<16%) than most hermaphroditic species. We hypothesized that fruit production was limited by pollen and resources. To evaluate potential fruit abortion due to pollen limitation, su...

40 CFR 63.5996 - How do I demonstrate initial compliance with the emission limits for tire production affected...

Code of Federal Regulations, 2010 CFR

2010-07-01

... with the emission limits for tire production affected sources? 63.5996 Section 63.5996 Protection of... Pollutants: Rubber Tire Manufacturing Testing and Initial Compliance Requirements for Tire Production Affected Sources § 63.5996 How do I demonstrate initial compliance with the emission limits for tire...

40 CFR 63.5999 - How do I demonstrate initial compliance with the emission limits for tire cord production...

Code of Federal Regulations, 2010 CFR

2010-07-01

... with the emission limits for tire cord production affected sources? 63.5999 Section 63.5999 Protection... Pollutants: Rubber Tire Manufacturing Testing and Initial Compliance Requirements for Tire Cord Production Affected Sources § 63.5999 How do I demonstrate initial compliance with the emission limits for tire cord...

Information models of software productivity - Limits on productivity growth

NASA Technical Reports Server (NTRS)

Tausworthe, Robert C.

1992-01-01

Research into generalized information-metric models of software process productivity establishes quantifiable behavior and theoretical bounds. The models establish a fundamental mathematical relationship between software productivity and the human capacity for information traffic, the software product yield (system size), information efficiency, and tool and process efficiencies. An upper bound is derived that quantifies average software productivity and the maximum rate at which it may grow. This bound reveals that ultimately, when tools, methodologies, and automated assistants have reached their maximum effective state, further improvement in productivity can only be achieved through increasing software reuse. The reuse advantage is shown not to increase faster than logarithmically in the number of reusable features available. The reuse bound is further shown to be somewhat dependent on the reuse policy: a general 'reuse everything' policy can lead to a somewhat slower productivity growth than a specialized reuse policy.

Influences of age, sex, and LDL-C change on cardiovascular risk reduction with pravastatin treatment in elderly Japanese patients: A post hoc analysis of data from the Pravastatin Anti-atherosclerosis Trial in the Elderly (PATE)

PubMed Central

Ouchi, Yasuyoshi; Ohashi, Yasuo; Ito, Hideki; Saito, Yasushi; Ishikawa, Toshitsugu; Akishita, Masahiro; Shibata, Taro; Nakamura, Haruo; Orimo, Hajime

2006-01-01

Background: The Pravastatin Anti-atherosclerosis Trial in the Elderly (PATE) found that the prevalence of cardiovascular events (CVEs) was significantly lower with standard-dose (10–20 mg/d) pravastatin treatment compared with low-dose (5 mg/d) pravastatin treatment in elderly (aged ⩾ 60 years) Japanese patients with hypercholesterolemia. Small differences in on-treatment total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels between the 2 dose groups in the PATE study were associated with significant differences in CVE prevalence. However, the reasons for these differences have not been determined. How sex and age differences influence the effectiveness of pravastatin also remains unclear. Objectives: The aims of this study were to determine the relationship between reduction in LDL-C level and CVE risk reduction in the PATE study and to assess the effects of sex and age on the effectiveness of pravastatin treatment (assessed using CVE risk reduction). Methods: In this post hoc analysis, Cox regression analysis was performed to study the relationship between on-treatment (pravastatin 5–20 mg/d) LDL-C level and CVE risk reduction using age, sex, smoking status, presence of diabetes mellitus and/or hypertension, history of cardiovascular disease (CVD), and high-density lipoprotein cholesterol level as adjustment factors. To explore risk reduction due to unspecified mechanisms other than LDLrC reduction, an estimated Kaplan-Meier curve from the Cox regression analysis was calculated and compared with the empirical (observed) Kaplan-Meier curve. Results: A total of 665 patients (527 women, 138 men; mean [SD] age, 72.8 [5.7] years) were enrolled in PATE and were followed up for a mean of 3.9 years (range, 3–5 years). Of those patients, 50 men and 173 women were ⩾75 years of age. Data from 619 patients were included in the present analysis. In the calculation of model-based Kaplan-Meier curves, data from an additional 32 patients were

Influences of age, sex, and LDL-C change on cardiovascular risk reduction with pravastatin treatment in elderly Japanese patients: A post hoc analysis of data from the Pravastatin Anti-atherosclerosis Trial in the Elderly (PATE).

PubMed

Ouchi, Yasuyoshi; Ohashi, Yasuo; Ito, Hideki; Saito, Yasushi; Ishikawa, Toshitsugu; Akishita, Masahiro; Shibata, Taro; Nakamura, Haruo; Orimo, Hajime

2006-07-01

The Pravastatin Anti-atherosclerosis Trial in the Elderly (PATE) found that the prevalence of cardiovascular events (CVEs) was significantly lower with standard-dose (10-20 mg/d) pravastatin treatment compared with low-dose (5 mg/d) pravastatin treatment in elderly (aged ⩾ 60 years) Japanese patients with hypercholesterolemia. Small differences in on-treatment total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels between the 2 dose groups in the PATE study were associated with significant differences in CVE prevalence. However, the reasons for these differences have not been determined. How sex and age differences influence the effectiveness of pravastatin also remains unclear. The aims of this study were to determine the relationship between reduction in LDL-C level and CVE risk reduction in the PATE study and to assess the effects of sex and age on the effectiveness of pravastatin treatment (assessed using CVE risk reduction). In this post hoc analysis, Cox regression analysis was performed to study the relationship between on-treatment (pravastatin 5-20 mg/d) LDL-C level and CVE risk reduction using age, sex, smoking status, presence of diabetes mellitus and/or hypertension, history of cardiovascular disease (CVD), and high-density lipoprotein cholesterol level as adjustment factors. To explore risk reduction due to unspecified mechanisms other than LDLrC reduction, an estimated Kaplan-Meier curve from the Cox regression analysis was calculated and compared with the empirical (observed) Kaplan-Meier curve. A total of 665 patients (527 women, 138 men; mean [SD] age, 72.8 [5.7] years) were enrolled in PATE and were followed up for a mean of 3.9 years (range, 3-5 years). Of those patients, 50 men and 173 women were ⩾75 years of age. Data from 619 patients were included in the present analysis. In the calculation of model-based Kaplan-Meier curves, data from an additional 32 patients were excluded from the LDL-C analysis because there were no

30 CFR 250.1159 - May the Regional Supervisor limit my well or reservoir production rates?

Code of Federal Regulations, 2011 CFR

2011-07-01

... reservoir production rates? 250.1159 Section 250.1159 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE... Supervisor limit my well or reservoir production rates? (a) The Regional Supervisor may set a Maximum...

40 CFR 63.1299 - Standards for slabstock flexible polyurethane foam production-source-wide emission limitation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... polyurethane foam production-source-wide emission limitation. 63.1299 Section 63.1299 Protection of Environment... Flexible Polyurethane Foam Production § 63.1299 Standards for slabstock flexible polyurethane foam... procedures in paragraphs (c)(1) through (4) of this section, unless a recovery device is used. Slabstock foam...

40 CFR 63.1299 - Standards for slabstock flexible polyurethane foam production-source-wide emission limitation.

Code of Federal Regulations, 2012 CFR

2012-07-01

... polyurethane foam production-source-wide emission limitation. 63.1299 Section 63.1299 Protection of Environment... Flexible Polyurethane Foam Production § 63.1299 Standards for slabstock flexible polyurethane foam... procedures in paragraphs (c)(1) through (4) of this section, unless a recovery device is used. Slabstock foam...

40 CFR 63.1299 - Standards for slabstock flexible polyurethane foam production-source-wide emission limitation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... polyurethane foam production-source-wide emission limitation. 63.1299 Section 63.1299 Protection of Environment... Flexible Polyurethane Foam Production § 63.1299 Standards for slabstock flexible polyurethane foam... procedures in paragraphs (c)(1) through (4) of this section, unless a recovery device is used. Slabstock foam...

Pre-treatment red blood cell distribution width provides prognostic information in multiple myeloma.

PubMed

Zhou, Di; Xu, Peipei; Peng, Miaoxin; Shao, Xiaoyan; Wang, Miao; Ouyang, Jian; Chen, Bing

2018-06-01

The red blood cell distribution width (RDW), a credible marker for abnormal erythropoiesis, has recently been studied as a prognostic factor in oncology, but its role in multiple myeloma (MM) hasn't been thoroughly investigated. We performed a retrospective study in 162 patients with multiple myeloma. Categorical parameters were analyzed using Pearson chi-squared test. The Mann-Whitney and Wilcoxon tests were used for group comparisons. Comparisons of repeated samples data were analyzed with the general linear model repeated-measures procedure. The Kaplan-Meier product-limit method was used to determine OS and PFS, and the differences were assessed by the log-rank test. High RDW baseline was significantly associated with indexes including haemoglobin, bone marrow plasma cell infiltration, and cytogenetics risk stratification. After chemotherapy, the overall response rate (ORR) decreased as RDW baseline increased. In 24 patients with high RDW baseline, it was revealed RDW value decreased when patients achieved complete remission (CR), but increased when the disease progressed. The normal-RDW baseline group showed both longer overall survival (OS) and progression-free survival (PFS) than the high-RDW baseline group. Our study suggests pre-treatment RDW level is a prognostic factor in MM and should be regarded as an important parameter for assessment of therapeutic efficiency. Copyright © 2018. Published by Elsevier B.V.

Elite athletes: is survival shortened in boxers?

PubMed

Bianco, M; Fabbricatore, C; Sanna, N; Fabiano, C; Palmieri, V; Zeppilli, P

2007-08-01

Moderate exercise and intense physical training are associated with increased life expectancy (LE). Boxing is characterized by intentional and repetitive head blows, sometimes causing brain injury, possibly reducing LE. We examined a sample of male athletes born between 1860 and 1930 selected from the international "hall of fame" inductees in baseball (n = 154), ice hockey (n = 130), tennis (n = 83), football (n = 81), boxing (n = 81), track and field (n = 59), basketball (n = 58), swimming (n = 37) and wrestling (n = 32). In boxing, we analyzed the number of disputed bouts/rounds and career records. Sports were also analyzed according to physiological demand and occurrence and kind of contact (intentional, unintentional). The Kaplan-Meier product limit method was used to compare survival curves (significance: p

The value of local registry data for describing cervical cancer management and outcomes over three decades in Australia.

PubMed

Roder, D; Davy, M; Selva-Nayagam, S; Gowda, R; Paramasivam, S; Adams, J; Keefe, D; Eckert, M; Powell, K; Fusco, K; Buranyi-Trevarton, D; Oehler, M K

2018-01-01

Registry data on invasive cervical cancers (n = 1,274) from four major hospitals (1984-2012) were analysed to determine their value for informing local service delivery in Australia. The methodology comprised disease-specific survival analyses using Kaplan-Meier product-limit estimates and Cox proportional hazards models and treatment analyses using logistic regression. Five- and 10-year survivals were 72% and 68%, respectively, equating with relative survival estimates for Australia and the USA. Most common treatments were surgery and radiotherapy. Systemic therapies increased in recent years, generally with radiotherapy, but were less common for residents from less accessible areas. Surgery was more common for younger women and early-stage disease, and radiotherapy for older women and regional and more advanced disease. The proportion of glandular cancers increased in-step with national trends. Little evidence of variation in risk-adjusted survival presented over time or by Local Health District. The study illustrates the value of local registry data for describing local treatment and outcomes. They show the lower use of systemic therapies among residents of less accessible areas which warrants further investigation. Risk-adjusted treatment and outcomes did not vary by socio-economic status, suggesting equity in service delivery. These data are important for local evaluation and were not available from other sources. © 2017 John Wiley & Sons Ltd.

MCM5: a new actor in the link between DNA replication and Meier-Gorlin syndrome.

PubMed

Vetro, Annalisa; Savasta, Salvatore; Russo Raucci, Annalisa; Cerqua, Cristina; Sartori, Geppo; Limongelli, Ivan; Forlino, Antonella; Maruelli, Silvia; Perucca, Paola; Vergani, Debora; Mazzini, Giuliano; Mattevi, Andrea; Stivala, Lucia Anna; Salviati, Leonardo; Zuffardi, Orsetta

2017-05-01

Meier-Gorlin syndrome (MGORS) is a rare disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia. Recessive mutations in ORC1, ORC4, ORC6, CDT1, CDC6, and CDC45, encoding members of the pre-replication (pre-RC) and pre-initiation (pre-IC) complexes, and heterozygous mutations in GMNN, a regulator of cell-cycle progression and DNA replication, have already been associated with this condition. We performed whole-exome sequencing (WES) in a patient with a clinical diagnosis of MGORS and identified biallelic variants in MCM5. This gene encodes a subunit of the replicative helicase complex, which represents a component of the pre-RC. Both variants, a missense substitution within a conserved domain critical for the helicase activity, and a single base deletion causing a frameshift and a premature stop codon, were predicted to be detrimental for the MCM5 function. Although variants of MCM5 have never been reported in specific human diseases, defect of this gene in zebrafish causes a phenotype of growth restriction overlapping the one associated with orc1 depletion. Complementation experiments in yeast showed that the plasmid carrying the missense variant was unable to rescue the lethal phenotype caused by mcm5 deletion. Moreover cell-cycle progression was delayed in patient's cells, as already shown for mutations in the ORC1 gene. Altogether our findings support the role of MCM5 as a novel gene involved in MGORS, further emphasizing that this condition is caused by impaired DNA replication.

Understanding of polyhydroxybutyrate production under carbon and phosphorus-limited growth conditions in non-axenic continuous culture.

PubMed

Cavaillé, Laëtitia; Albuquerque, Maria; Grousseau, Estelle; Lepeuple, Anne-Sophie; Uribelarrea, Jean-Louis; Hernandez-Raquet, Guillermina; Paul, Etienne

2016-02-01

In a waste into resource strategy, a selection of polyhydroxybutyrate (PHB)-accumulating organisms from activated sludge was achieved in an open continuous culture under acetic acid and phosphorus limitation. Once the microbial population was selected at a dilution rate (D), an increase in phosphorus limitation degree was applied in order to study the intracellular phosphorus plasticity of selected bacteria and the resulting capacity to produce PHB. Whatever D, all selected populations were able to produce PHB. At a D, the phosphorus availability determined the phosphorus-cell content which in turn fixed the amount of cell. All the remaining carbon was thus directed toward PHB. By decreasing D, microorganisms adapted more easily to higher phosphorus limitation leading to higher PHB content. A one-stage continuous reactor operated at D=0.023h(-)(1) gave reliable high PHB productivity with PHB content up to 80%. A two-stage reactor could ensure better productivity while allowing tuning product quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-limiting food conditions for growth and production of the copepod community in a highly productive upwelling zone

NASA Astrophysics Data System (ADS)

Escribano, Rubén; Bustos-Ríos, Evelyn; Hidalgo, Pamela; Morales, Carmen E.

2016-09-01

Zooplankton production is critical for understanding marine ecosystem dynamics. This work estimates copepod growth and production in the coastal upwelling and coastal transition zones off central-southern Chile (~35 to 37°S) during a 3-year time series (2004, 2005, and 2006) at a fixed shelf station, and from spring-summer spatial surveys during the same period. To estimate copepod production (CP), we used species-biomasses and associated C-specific growth rates from temperature dependent equations (food-saturated) for the dominant species, which we assumed were maximal growth rates (gmax). Using chlorophyll-a concentrations as a proxy for food conditions, we determined a size-dependent half-saturation constant with the Michaelis-Menten equation to derive growth rates (g) under the effect of food limitation. These food-dependent C-specific growth rates were much lower (<0.1 d-1) than those observed in the field for the dominant species, while gmax for same species, in the range of 0.19-0.23 d-1 better represented the necessary growth to attain observed adult sizes of at least two copepods, Paracalanus cf. indicus and Calanus chilensis. Copepod biomass (CB) and rates of maximal copepod production (CPmax) obtained with gmax were higher in the coastal upwelling zone (<50 km from shore), and correlated significantly to oceanographic variables associated with upwelling conditions. Both CPmax and gmax exhibited negative trends at the fixed station from 2004 to 2006 in association with increased duration of upwelling in the latter year. Annual CPmax ranged between 24 and 52 g C m-2 y-1 with a mean annual P/B ratio of 7.3. We concluded that interannual variation in copepod production resulted from factors and processes regulating copepod abundance and biomass in the absence of bottom-up control, allowing copepods to grow without limitation due to food resources.

Drosophila model of Meier-Gorlin syndrome based on the mutation in a conserved C-Terminal domain of Orc6.

PubMed

Balasov, Maxim; Akhmetova, Katarina; Chesnokov, Igor

2015-11-01

Meier-Gorlin syndrome (MGS) is an autosomal recessive disorder characterized by microtia, primordial dwarfism, small ears, and skeletal abnormalities. Patients with MGS often carry mutations in the genes encoding the components of the pre-replicative complex such as Origin Recognition Complex (ORC) subunits Orc1, Orc4, Orc6, and helicase loaders Cdt1 and Cdc6. Orc6 is an important component of ORC and has functions in both DNA replication and cytokinesis. Mutation in conserved C-terminal motif of Orc6 associated with MGS impedes the interaction of Orc6 with core ORC. In order to study the effects of MGS mutation in an animal model system we introduced MGS mutation in Orc6 and established Drosophila model of MGS. Mutant flies die at third instar larval stage with abnormal chromosomes and DNA replication defects. The lethality can be rescued by elevated expression of mutant Orc6 protein. Rescued MGS flies are unable to fly and display multiple planar cell polarity defects. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Examining the Latent Structure of the Delis-Kaplan Executive Function System.

PubMed

Karr, Justin E; Hofer, Scott M; Iverson, Grant L; Garcia-Barrera, Mauricio A

2018-05-04

The current study aimed to determine whether the Delis-Kaplan Executive Function System (D-KEFS) taps into three executive function factors (inhibition, shifting, fluency) and to assess the relationship between these factors and tests of executive-related constructs less often measured in latent variable research: reasoning, abstraction, and problem solving. Participants included 425 adults from the D-KEFS standardization sample (20-49 years old; 50.1% female; 70.1% White). Eight alternative measurement models were compared based on model fit, with test scores assigned a priori to three factors: inhibition (Color-Word Interference, Tower), shifting (Trail Making, Sorting, Design Fluency), and fluency (Verbal/Design Fluency). The Twenty Questions, Word Context, and Proverb Tests were predicted in separate structural models. The three-factor model fit the data well (CFI = 0.938; RMSEA = 0.047), although a two-factor model, with shifting and fluency merged, fit similarly well (CFI = 0.929; RMSEA = 0.048). A bifactor model fit best (CFI = 0.977; RMSEA = 0.032) and explained the most variance in shifting indicators, but rarely converged among 5,000 bootstrapped samples. When the three first-order factors simultaneously predicted the criterion variables, only shifting was uniquely predictive (p < .05; R2 = 0.246-0.408). The bifactor significantly predicted all three criterion variables (p < .001; R2 = 0.141-242). Results supported a three-factor D-KEFS model (i.e., inhibition, shifting, and fluency), although shifting and fluency were highly related (r = 0.696). The bifactor showed superior fit, but converged less often than other models. Shifting best predicted tests of reasoning, abstraction, and problem solving. These findings support the validity of D-KEFS scores for measuring executive-related constructs and provide a framework through which clinicians can interpret D-KEFS results.

De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome.

PubMed

Burrage, Lindsay C; Charng, Wu-Lin; Eldomery, Mohammad K; Willer, Jason R; Davis, Erica E; Lugtenberg, Dorien; Zhu, Wenmiao; Leduc, Magalie S; Akdemir, Zeynep C; Azamian, Mahshid; Zapata, Gladys; Hernandez, Patricia P; Schoots, Jeroen; de Munnik, Sonja A; Roepman, Ronald; Pearring, Jillian N; Jhangiani, Shalini; Katsanis, Nicholas; Vissers, Lisenka E L M; Brunner, Han G; Beaudet, Arthur L; Rosenfeld, Jill A; Muzny, Donna M; Gibbs, Richard A; Eng, Christine M; Xia, Fan; Lalani, Seema R; Lupski, James R; Bongers, Ernie M H F; Yang, Yaping

2015-12-03

Meier-Gorlin syndrome (MGS) is a genetically heterogeneous primordial dwarfism syndrome known to be caused by biallelic loss-of-function mutations in one of five genes encoding pre-replication complex proteins: ORC1, ORC4, ORC6, CDT1, and CDC6. Mutations in these genes cause disruption of the origin of DNA replication initiation. To date, only an autosomal-recessive inheritance pattern has been described in individuals with this disorder, with a molecular etiology established in about three-fourths of cases. Here, we report three subjects with MGS and de novo heterozygous mutations in the 5' end of GMNN, encoding the DNA replication inhibitor geminin. We identified two truncating mutations in exon 2 (the 1(st) coding exon), c.16A>T (p.Lys6(∗)) and c.35_38delTCAA (p.Ile12Lysfs(∗)4), and one missense mutation, c.50A>G (p.Lys17Arg), affecting the second-to-last nucleotide of exon 2 and possibly RNA splicing. Geminin is present during the S, G2, and M phases of the cell cycle and is degraded during the metaphase-anaphase transition by the anaphase-promoting complex (APC), which recognizes the destruction box sequence near the 5' end of the geminin protein. All three GMNN mutations identified alter sites 5' to residue Met28 of the protein, which is located within the destruction box. We present data supporting a gain-of-function mechanism, in which the GMNN mutations result in proteins lacking the destruction box and hence increased protein stability and prolonged inhibition of replication leading to autosomal-dominant MGS. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

The density dilemma: limitations on juvenile production in threatened salmon populations

USGS Publications Warehouse

Walters, Annika W.; Copeland, Timothy; Venditti, David A.

2013-01-01

Density-dependent processes have repeatedly been shown to have a central role in salmonid population dynamics, but are often assumed to be negligible for populations at low abundances relative to historical records. Density dependence has been observed in overall spring/summer Snake River Chinook salmon Oncorhynchus tshawytscha production, but it is not clear how patterns observed at the aggregate level relate to individual populations within the basin. We used a Bayesian hierarchical modelling approach to explore the degree of density dependence in juvenile production for nine Idaho populations. Our results indicate that density dependence is ubiquitous, although its strength varies between populations. We also investigated the processes driving the population-level pattern and found density-dependent growth and mortality present for both common life-history strategies, but no evidence of density-dependent movement. Overwinter mortality, spatial clustering of redds and limited resource availability were identified as potentially important limiting factors contributing to density dependence. The ubiquity of density dependence for these threatened populations is alarming as stability at present low abundance levels suggests recovery may be difficult without major changes. We conclude that density dependence at the population level is common and must be considered in demographic analysis and management.

On the semi-classical limit of scalar products of the XXZ spin chain

NASA Astrophysics Data System (ADS)

Jiang, Yunfeng; Brunekreef, Joren

2017-03-01

We study the scalar products between Bethe states in the XXZ spin chain with anisotropy |Δ| > 1 in the semi-classical limit where the length of the spin chain and the number of magnons tend to infinity with their ratio kept finite and fixed. Our method is a natural yet non-trivial generalization of similar methods developed for the XXX spin chain. The final result can be written in a compact form as a contour integral in terms of Faddeev's quantum dilogarithm function, which in the isotropic limit reduces to the classical dilogarithm function.

Evaluation of statistical treatments of left-censored environmental data using coincident uncensored data sets: I. Summary statistics

USGS Publications Warehouse

Antweiler, Ronald C.; Taylor, Howard E.

2008-01-01

The main classes of statistical treatment of below-detection limit (left-censored) environmental data for the determination of basic statistics that have been used in the literature are substitution methods, maximum likelihood, regression on order statistics (ROS), and nonparametric techniques. These treatments, along with using all instrument-generated data (even those below detection), were evaluated by examining data sets in which the true values of the censored data were known. It was found that for data sets with less than 70% censored data, the best technique overall for determination of summary statistics was the nonparametric Kaplan-Meier technique. ROS and the two substitution methods of assigning one-half the detection limit value to censored data or assigning a random number between zero and the detection limit to censored data were adequate alternatives. The use of these two substitution methods, however, requires a thorough understanding of how the laboratory censored the data. The technique of employing all instrument-generated data - including numbers below the detection limit - was found to be less adequate than the above techniques. At high degrees of censoring (greater than 70% censored data), no technique provided good estimates of summary statistics. Maximum likelihood techniques were found to be far inferior to all other treatments except substituting zero or the detection limit value to censored data.

Effect of Cognitive Activity Level on Duration of Post-Concussion Symptoms

PubMed Central

Brown, Naomi J.; Mannix, Rebekah C.; O’Brien, Michael J.; Gostine, David; Collins, Michael W.

2014-01-01

OBJECTIVE: To determine the effect of cognitive activity level on duration of post-concussion symptoms. METHODS: We conducted a prospective cohort study of patients who presented to a Sports Concussion Clinic within 3 weeks of injury between October 2009 and July 2011. At each visit, patients completed a scale that recorded their average level of cognitive activity since the previous visit. The product of cognitive activity level and days between visits (cognitive activity-days) was calculated and divided into quartiles. Kaplan-Meier Product Limit method was used to generate curves of symptom duration based on cognitive activity level. To adjust for other possible predictors of concussion recovery, we constructed a Cox proportional hazard model with cognitive activity-days as the main predictor. RESULTS: Of the 335 patients included in the study, 62% were male, 19% reported a loss of consciousness, and 37% reported experiencing amnesia at the time of injury. The mean age of participants was 15 years (range, 8–23) and the mean number of previous concussions was 0.76; 39% of athletes had sustained a previous concussion. The mean Post-Concussion Symptom Scale score at the initial visit was 30 (SD, 26). The overall mean duration of symptoms was 43 days (SD, 53). Of all variables assessed, only total symptom burden at initial visit and cognitive activity level were independently associated with duration of symptoms. CONCLUSIONS: Increased cognitive activity is associated with longer recovery from concussion. This study supports the use of cognitive rest and adds to the current consensus opinion. PMID:24394679

Exploring the limits of crop productivity: A model to evaluate progress

NASA Technical Reports Server (NTRS)

Bugbee, Bruce

1990-01-01

The goal was to determine the limits of crop productivity when all environmental constraints were removed. Researchers define productivity as food output per unit of input. Researchers evaluated cultivars of wheat with reduced leaf size and number to decrease the leaf area index at high plant densities. These cultivars may also have an improved harvest index. Hydroponic studies indicate that 1 mM nitrate in solution is adequate to support maximum growth in these systems, provided iron nutrition is adequate. Wheat does not accumulate nitrate in leaves even when the solution nitrate concentration is 15 mM. Long-term photosynthetic efficiency (g mol (exp -1) of photons) and harvest index were not altered by photoperiod (16, 20, or 24 hours). Wheat does not need, nor benefit from, a diurnal dark period.

Comparison of graft survival following penetrating keratoplasty and Descemet's stripping endothelial keratoplasty in eyes with a glaucoma drainage device.

PubMed

Iverson, Shawn M; Spierer, Oriel; Papachristou, George C; Feuer, William J; Shi, Wei; Greenfield, David S; O'Brien, Terrence P

2018-02-01

To compare corneal graft survival rates after penetrating keratoplasty (PK) and Descemet's stripping endothelial keratoplasty (DSEK) in patients with a glaucoma drainage device (GDD) or medically managed glaucoma. A retrospective chart review was conducted on consecutive patients who underwent primary PK or primary DSEK. Inclusion criteria consisted of eyes with a diagnosis of glaucoma prior to corneal transplantation and a minimum of 6 months of follow-up. Graft failure was defined as an edematous cornea with failure to maintain deturgescence lasting beyond a period of 1 month of intense steroid therapy or vascularization and scarring resulting in irreversible loss of central graft clarity. Corneal graft survival was calculated using Kaplan-Meier survival analysis. Patients were divided into four groups: GDD-PK, GDD-DSEK, medical-PK and medical-DSEK. Fifty-six eyes of 56 patients were identified as meeting inclusion criteria. Among eyes with a GDD, there was no difference in the proportion of failures between PK grafts (48%) and DSEK grafts (50%) (p = 0.90). Failure occurred earlier in DSEK recipients compared to PK recipients, 5.82 ± 6.77 months versus 14.40 ± 7.70 months, respectively (p = 0.04). A Kaplan-Meier analysis did not identify a difference between the four groups with respect to graft failure (p = 0.52). There is no significant difference in graft survival rates between medically and surgically treated glaucoma patients for either PK or DSEK grafts. In patients with GDD, graft failure occurs earlier in DSEK compared to PK.

C-reactive protein-to-albumin ratio is a predictor of hepatitis B virus related decompensated cirrhosis: time-dependent receiver operating characteristics and decision curve analysis.

PubMed

Huang, Si-Si; Xie, Dong-Mei; Cai, Yi-Jing; Wu, Jian-Min; Chen, Rui-Chong; Wang, Xiao-Dong; Song, Mei; Zheng, Ming-Hua; Wang, Yu-Qun; Lin, Zhuo; Shi, Ke-Qing

2017-04-01

Hepatitis B virus (HBV) infection remains a major health problem and HBV-related-decompensated cirrhosis (HBV-DC) usually leads to a poor prognosis. Our aim was to determine the utility of inflammatory biomarkers in predicting mortality of HBV-DC. A total of 329 HBV-DC patients were enrolled. Survival estimates for the entire study population were generated using the Kaplan-Meier method. The prognostic values for model for end-stage liver disease (MELD) score, Child-Pugh score, and inflammatory biomarkers neutrophil/lymphocyte ratio, C-reactive protein-to-albumin ratio (CAR), and lymphocyte-to-monocyte ratio (LMR) for HBV-DC were compared using time-dependent receiver operating characteristic curves and time-dependent decision curves. The survival time was 23.1±15.8 months. Multivariate analysis identified age, CAR, LMR, and platelet count as prognostic independent risk factors. Kaplan-Meier analysis indicated that CAR of at least 1.0 (hazard ratio, 7.19; 95% confidence interval, 4.69-11.03), and LMR less than 1.9 (hazard ratio, 2.40; 95% confidence interval, 1.69-3.41) were independently associated with mortality of HBV-DC. The time-dependent receiver operating characteristic indicated that CAR showed the best performance in predicting mortality of HBV-DC compared with LMR, MELD score, and Child-Pugh score. The results were also confirmed by time-dependent decision curves. CAR and LMR were associated with the prognosis of HBV-DC. CAR was superior to LMR, MELD score, and Child-Pugh score in HBV-DC mortality prediction.

High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers

PubMed Central

Peng, Li; Liu, Zhao-Yang; Li, Wen-Ling; Zhang, Chao-Yang; Zhang, Ya-Qin; Pan, Xi; Chen, Jun; Li, Yue-Hui

2017-01-01

Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients. PMID:27926484

Plasma big endothelin-1 levels at admission and future cardiovascular outcomes: A cohort study in patients with stable coronary artery disease.

PubMed

Zhou, Bing-Yang; Guo, Yuan-Lin; Wu, Na-Qiong; Zhu, Cheng-Gang; Gao, Ying; Qing, Ping; Li, Xiao-Lin; Wang, Yao; Dong, Qian; Liu, Geng; Xu, Rui Xia; Cui, Chuan-Jue; Sun, Jing; Li, Jian-Jun

2017-03-01

Big endothelin-1 (ET-1) has been proposed as a novel prognostic indicator of acute coronary syndrome, while its predicting role of cardiovascular outcomes in patients with stable coronary artery disease (CAD) is unclear. A total of 3154 consecutive patients with stable CAD were enrolled and followed up for 24months. The outcomes included all-cause death, non-fatal myocardial infarction, stroke and unplanned revascularization (percutaneous coronary intervention and coronary artery bypass grafting). Baseline big ET-1 was measured using sandwich enzyme immunoassay method. Cox proportional hazard regression analysis and Kaplan-Meier analysis were used to evaluate the prognostic value of big ET-1 on cardiovascular outcomes. One hundred and eighty-nine (5.99%) events occurred during follow-up. Patients were divided into two groups: events group (n=189) and non-events group (n=2965). The results indicated that the events group had higher levels of big ET-1 compared to non-events group. Multivariable Cox proportional hazard regression analysis showed that big ET-1 was positively and statistically correlated with clinical outcomes (Hazard Ratio: 1.656, 95% confidence interval: 1.099-2.496, p=0.016). Additionally, the Kaplan-Meier analysis revealed that patients with higher big ET-1 presented lower event-free survival (p=0.016). The present study firstly suggests that big ET-1 is an independent risk marker of cardiovascular outcomes in patients with stable CAD. And more studies are needed to confirm our findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Collagen Triple Helix Repeat Containing-1 (CTHRC1) Expression in Oral Squamous Cell Carcinoma (OSCC): Prognostic Value and Clinico-Pathological Implications

PubMed Central

Lee, Chia Ee; Vincent-Chong, Vui King; Ramanathan, Anand; Kallarakkal, Thomas George; Karen-Ng, Lee Peng; Ghani, Wan Maria Nabillah; Rahman, Zainal Ariff Abdul; Ismail, Siti Mazlipah; Abraham, Mannil Thomas; Tay, Keng Kiong; Mustafa, Wan Mahadzir Wan; Cheong, Sok Ching; Zain, Rosnah Binti

2015-01-01

BACKGROUND: Collagen Triple Helix Repeat Containing 1 (CTHRC1) is a protein often found to be over-expressed in various types of human cancers. However, correlation between CTHRC1 expression level with clinico-pathological characteristics and prognosis in oral cancer remains unclear. Therefore, this study aimed to determine mRNA and protein expression of CTHRC1 in oral squamous cell carcinoma (OSCC) and to evaluate the clinical and prognostic impact of CTHRC1 in OSCC. METHODS: In this study, mRNA and protein expression of CTHRC1 in OSCCs were determined by quantitative PCR and immunohistochemistry, respectively. The association between CTHRC1 and clinico-pathological parameters were evaluated by univariate and multivariate binary logistic regression analyses. Correlation between CTHRC1 protein expressions with survival were analysed using Kaplan-Meier and Cox regression models. RESULTS: Current study demonstrated CTHRC1 was significantly overexpressed at the mRNA level in OSCC. Univariate analyses indicated a high-expression of CTHRC1 that was significantly associated with advanced stage pTNM staging, tumour size ≥ 4 cm and positive lymph node metastasis (LNM). However, only positive LNM remained significant after adjusting with other confounder factors in multivariate logistic regression analyses. Kaplan-Meier survival analyses and Cox model demonstrated that patients with high-expression of CTHRC1 protein were associated with poor prognosis and is an independent prognostic factor in OSCC. CONCLUSION: This study indicated that over-expression of CTHRC1 potentially as an independent predictor for positive LNM and poor prognosis in OSCC. PMID:26664254

Up-Regulation of Angiotensin-Converting Enzyme (ACE) Enhances Cell Proliferation and Predicts Poor Prognosis in Laryngeal Cancer.

PubMed

Han, Chao-Dong; Ge, Wen-Sheng

2016-11-01

BACKGROUND The angiotensin-converting enzyme (ACE, CD143) gene plays a crucial role in the pathology of many cancers. Previous studies mostly focused on the gene polymorphism, but the other functions of ACE have rarely been reported. The purpose of this study was to investigate the expression of ACE and its biological function, as well as its prognostic value, in laryngeal cancer. MATERIAL AND METHODS The expression of ACE was detected by quantitative real-time polymerase chain reaction (qRT-PCR) analysis in 106 patients with laryngeal cancer and 85 healthy people. Then the cell proliferation was estimated after the cell lines Hep-2 were transfected with pGL3-ACE and empty vector, respectively. In addition, the relationship between ACE expression and clinicopathologic characteristics was analyzed. Finally, Kaplan-Meier analysis was used to evaluate the overall survival of patients with different ACE expression, while Cox regression analysis was conducted to reveal the prognostic value of ACE in laryngeal cancer. RESULTS Our results demonstrate that ACE is over-expressed in laryngeal cancer and thus promotes cell proliferation. The up-regulation of ACE was significantly influenced by tumor stage and lymph node metastasis. Patients with high ACE expression had a shorter overall survival compared with those with low ACE expression according to Kaplan-Meier analysis. The ACE gene was also found to be an important factor in the prognosis of laryngeal cancer. CONCLUSIONS Our study shows that the ACE gene was up-regulated, which promoted the cell proliferation, and it could be an independent prognostic marker in laryngeal cancer.

The Association of Individual and Regional Socioeconomic Status on Initial Peritonitis and Outcomes in Peritoneal Dialysis Patients: A Propensity Score-Matched Cohort Study.

PubMed

Wang, Qin; Hu, Ke-Jie; Ren, Ye-Ping; Dong, Jie; Han, Qing-Feng; Zhu, Tong-Ying; Chen, Jiang-Hua; Zhao, Hui-Ping; Chen, Meng-Hua; Xu, Rong; Wang, Yue; Hao, Chuan-Ming; Zhang, Xiao-Hui; Wang, Mei; Tian, Na; Wang, Hai-Yan

2016-01-01

♦ Research indicates that the socioeconomic status (SES) of individuals and the area where they live are related to initial peritonitis and outcomes in peritoneal dialysis (PD). We conducted a retrospective, multi-center cohort study in China to examine these associations. ♦ Data on 2,171 PD patients were collected from 7 centers, including baseline demographic, socioeconomic, and laboratory data. We explored the potential risk factors for initial peritonitis and outcomes using univariate Cox regression and unadjusted binary logistic regression. Then, we used propensity score matching to balance statistically significant risk factors for initial peritonitis and outcomes, and Kaplan-Meier survival analysis to compare differences in peritonitis-free rates between different groups of participants after matching. ♦ A total of 563 (25.9%) initial episodes of peritonitis occurred during the study period. The Kaplan-Meier peritonitis-free rate curve showed high-income patients had a significantly lower risk than low-income patients (p = 0.007) after matching for age, hemoglobin, albumin, and regional SES and PD center. The risk of treatment failure was significantly lower in the high-income than the low-income group after matching for the organism causing peritonitis and PD center: odds ratio (OR) = 0.27 (0.09 - 0.80, p = 0.018). Regional SES and education were not associated with initial peritonitis and outcomes. ♦ Our study demonstrates low individual income is a risk factor for the initial onset of peritonitis and treatment failure after initial peritonitis. Copyright © 2016 International Society for Peritoneal Dialysis.

One year clinical outcomes in patients with insulin-treated diabetes mellitus and non-insulin-treated diabetes mellitus compared to non-diabetics after deployment of the bio-engineered COMBO stent.

PubMed

Kalkman, Deborah N; Woudstra, Pier; den Heijer, Peter; Menown, Ian B A; Erglis, Andrejs; Suryapranata, Harry; Arkenbout, Karin E; Iñiguez, Andrés; van 't Hof, Arnoud W J; Muller, Philippe; Tijssen, Jan G; de Winter, Robbert J

2017-01-01

The COMBO stent is a novel sirolimus-eluting stent with a luminal anti-CD34+ antibody layer to promote vessel healing. No data is currently available on clinical outcomes after treatment with this novel bio-engineered device in diabetic patients. We evaluate clinical outcomes at twelve months after COMBO stent placement in patients without diabetes mellitus (non-DM), patients with non-insulin-treated diabetes mellitus (nITDM) and patients with insulin-treated diabetes mellitus (ITDM). This study is a pre-specified subgroup analysis of the 1000 patient all-comers REMEDEE Registry. The primary endpoint is target lesion failure (TLF), which is a combined endpoint consisting of cardiac death, target vessel-myocardial infarction (tv-MI) and target lesion revascularization (TLR) at twelve months follow-up. Kaplan Meier method is used with log rank to compare outcomes between groups. This subgroup analysis includes 807 non-DM, 117 nITDM and 67 ITDM. Kaplan-Meier estimates for TLF at twelve months are 4.4% in non-DM, 6.8% in nITDM and 20.3% in ITDM, p<0.001 (non-DM vs nITDM p=0.244, non-DM vs ITDM p<0.001). This study gives the first insight into the impact of insulin-treated diabetes mellitus on clinical outcome of patients treated with the novel COMBO stent. At one year after COMBO stent placement significantly higher rates of target lesion failure are seen in patients with ITDM compared to patients with nITDM and patients without DM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Disciplinary action against physicians: who is likely to get disciplined?

PubMed

Khaliq, Amir A; Dimassi, Hani; Huang, Chiung-Yu; Narine, Lutchmie; Smego, Raymond A

2005-07-01

We sought to determine the characteristics of disciplined physicians at-large and the risk of disciplinary action over time and to report the type and frequency of complaints and the nature of disciplinary actions against allopathic physicians in Oklahoma. Descriptive statistics, Kaplan-Meier analysis, and Cox proportional hazards modeling of publicly available data on physicians licensed by the Oklahoma Board of Medical Licensure and Supervision. Among 14,314 currently or previously licensed physicians, 396 (2.8%) had been disciplined. Using univariate proportional hazards analysis, men (P <0.04), non-whites (P < 0.001), non-board-certified physicians (P < 0.001), and those in family medicine (P < 0.001), psychiatry (P < 0.001), general practice (P < 0.001), obstetrics-gynecology (P < 0.03) and emergency medicine (P < 0.001) were found to be at greater risk of being disciplined than other medical specialty groups. Foreign medical graduates had a higher risk of disciplinary action compared to US medical graduates (P < 0.001), although this finding was not confirmed by multivariate analysis. Kaplan-Meier analysis revealed that the proportion of physicians disciplined increased with each successive 10-year interval since first licensure. Complaints against physicians originated most often from the general public (66%), other physicians (5%), and staff (4%), and the complaints most frequently involved issues related to quality of care (25%), medication/prescription violations (19%), incompetence (18%), and negligence (17%). To improve physician behavior and reduce the need for disciplinary action, medical schools and residency training programs must continue to emphasize both patient care and medical professionalism as critical core competencies.

The Risk of Herpes Zoster in Patients with Non-small Cell Lung Cancer according to Chemotherapy Regimens: Tyrosine Kinase Inhibitors versus Cytotoxic Chemotherapy.

PubMed

Choi, Ji Young; Kim, Miso; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong-Wan; Heo, Dae Seog; Jo, Seong Jin

2018-04-05

Despite the successful use of tyrosine kinase inhibitors (TKIs) in cancer patients, their effect on herpes zoster development has not been studied. The aim of this study was to evaluate and compare the effects of epidermal growth factor receptor (EGFR) TKI and cytotoxic chemotherapy on the risk of herpes zoster development in non-small cell lung cancer (NSCLC) patients. We conducted a medical review of all eligible NSCLC patients in Seoul National University hospital between 2002 and 2015. We classified patients based on whether they previously underwent EGFR TKI therapy into either the TKI group or the cytotoxic group. We compared the incidence rates of herpes zoster during TKI therapy and cytotoxic chemotherapy. Additionally, the longitudinal risk of herpes zoster from TKIs was analyzed using the incidence rate ratio (IRR) of the TKI group to the cytotoxic group and the log-rank test of the Kaplan-Meier method. Of the 2,981 NSCLC patients, 54 patients (1.54%) developed herpes zoster. In the TKI group (2,002 patients), the IRR of herpes zoster during TKI therapy compared to that during cytotoxic chemotherapy was 1.05 (95% confidence interval [CI], 0.53 to 2.09). The IRR of the TKI group compared to the cytotoxic group was 1.33 (95% CI, 0.64 to 2.76). The Kaplan-Meier cumulative risk of both groups was not significantly different. Our results show that the incidence rate of herpes zoster in the TKI group was not statistically different from the incidence in the cytotoxic group during and after chemotherapy in NSCLC patients.

Timing of new black box warnings and withdrawals for prescription medications.

PubMed

Lasser, Karen E; Allen, Paul D; Woolhandler, Steffie J; Himmelstein, David U; Wolfe, Sidney M; Bor, David H

2002-05-01

Recently approved drugs may be more likely to have unrecognized adverse drug reactions (ADRs) than established drugs, but no recent studies have examined how frequently postmarketing surveillance identifies important ADRs. To determine the frequency and timing of discovery of new ADRs described in black box warnings or necessitating withdrawal of the drug from the market. Examination of the Physicians' Desk Reference for all new chemical entities approved by the US Food and Drug Administration between 1975 and 1999, and all drugs withdrawn from the market between 1975 and 2000 (with or without a prior black box warning). Frequency of and time to a new black box warning or drug withdrawal. A total of 548 new chemical entities were approved in 1975-1999; 56 (10.2%) acquired a new black box warning or were withdrawn. Forty-five drugs (8.2%) acquired 1 or more black box warnings and 16 (2.9%) were withdrawn from the market. In Kaplan-Meier analyses, the estimated probability of acquiring a new black box warning or being withdrawn from the market over 25 years was 20%. Eighty-one major changes to drug labeling in the Physicians' Desk Reference occurred including the addition of 1 or more black box warnings per drug, or drug withdrawal. In Kaplan-Meier analyses, half of these changes occurred within 7 years of drug introduction; half of the withdrawals occurred within 2 years. Serious ADRs commonly emerge after Food and Drug Administration approval. The safety of new agents cannot be known with certainty until a drug has been on the market for many years.

Cardiovascular Magnetic Resonance and prognosis in cardiac amyloidosis

PubMed Central

Maceira, Alicia M; Prasad, Sanjay K; Hawkins, Philip N; Roughton, Michael; Pennell, Dudley J

2008-01-01

Background Cardiac involvement is common in amyloidosis and associated with a variably adverse outcome. We have previously shown that cardiovascular magnetic resonance (CMR) can assess deposition of amyloid protein in the myocardial interstitium. In this study we assessed the prognostic value of late gadolinium enhancement (LGE) and gadolinium kinetics in cardiac amyloidosis in a prospective longitudinal study. Materials and methods The pre-defined study end point was all-cause mortality. We prospectively followed a cohort of 29 patients with proven cardiac amyloidosis. All patients underwent biopsy, 2D-echocardiography and Doppler studies, 123I-SAP scintigraphy, serum NT pro BNP assay, and CMR with a T1 mapping method and late gadolinium enhancement (LGE). Results Patients with were followed for a median of 623 days (IQ range 221, 1436), during which 17 (58%) patients died. The presence of myocardial LGE by itself was not a significant predictor of mortality. However, death was predicted by gadolinium kinetics, with the 2 minute post-gadolinium intramyocardial T1 difference between subepicardium and subendocardium predicting mortality with 85% accuracy at a threshold value of 23 ms (the lower the difference the worse the prognosis). Intramyocardial T1 gradient was a better predictor of survival than FLC response to chemotherapy (Kaplan Meier analysis P = 0.049) or diastolic function (Kaplan-Meier analysis P = 0.205). Conclusion In cardiac amyloidosis, CMR provides unique information relating to risk of mortality based on gadolinium kinetics which reflects the severity of the cardiac amyloid burden. PMID:19032744

Long-Term Outcomes of Non-ST-Elevation Myocardial Infarction Without Creatine Kinase Elevation　- The J-MINUET Study.

PubMed

Ishihara, Masaharu; Nakao, Koichi; Ozaki, Yukio; Kimura, Kazuo; Ako, Junya; Noguchi, Teruo; Fujino, Masashi; Yasuda, Satoshi; Suwa, Satoru; Fujimoto, Kazuteru; Nakama, Yasuharu; Morita, Takashi; Shimizu, Wataru; Saito, Yoshihiko; Hirohata, Atsushi; Morita, Yasuhiro; Inoue, Teruo; Okamura, Atsunori; Uematsu, Masaaki; Hirata, Kazuhito; Tanabe, Kengo; Shibata, Yoshisato; Owa, Mafumi; Tsujita, Kenichi; Funayama, Hiroshi; Kokubu, Nobuaki; Kozuma, Ken; Tobaru, Tetsuya; Oshima, Shigeru; Nakai, Michikazu; Nishimura, Kunihiro; Miyamoto, Yoshihiro; Ogawa, Hisao

2017-06-23

According to troponin-based criteria of myocardial infarction (MI), patients without elevation of creatine kinase (CK), formerly classified as unstable angina (UA), are now diagnosed as non-ST-elevation MI (NSTEMI), but little is known about their outcomes.Methods and Results:Between July 2012 and March 2014, 3,283 consecutive patients with MI were enrolled. Clinical follow-up data were obtained up to 3 years. The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure and urgent revascularization for UA. There were 2,262 patients with ST-elevation MI (STEMI), 563 NSTEMI with CK elevation (NSTEMI+CK) and 458 NSTEMI without CK elevation (NSTEMI-CK). From day 0, Kaplan-Meier curves for the primary endpoint began to diverge in favor of NSTEMI-CK for up to 30 days. The 30-day event rate was significantly lower in patients with NSTEMI-CK (3.3%) than in STEMI (8.6%, P<0.001) and NSTEMI+CK (9.9%, P<0.001). Later, the event curves diverged in favor of STEMI. The event rate from 31 days to 3 years was significantly lower in patients with STEMI (19.8%) than in NSTEMI+CK (33.6%, P<0.001) and NSTEMI-CK (34.2%, P<0.001). Kaplan-Meier curves from 31 days to 3 years were almost identical between NSTEMI+CK and NSTEMI-CK (P=0.91). Despite smaller infarct size and better short-term outcomes, long-term outcomes of NSTEMI-CK after convalescence were as poor as those for NSTEMI+CK and worse than for STEMI.

Thyroid status and 6-year mortality in elderly people living in a mildly iodine-deficient area: the aging in the Chianti Area Study.

PubMed

Ceresini, Graziano; Ceda, Gian Paolo; Lauretani, Fulvio; Maggio, Marcello; Usberti, Elisa; Marina, Michela; Bandinelli, Stefania; Guralnik, Jack M; Valenti, Giorgio; Ferrucci, Luigi

2013-06-01

To test the hypothesis that, in older adults, living in a mildly iodine-deficient area, thyroid dysfunction may be associated with mortality independent of potential confounders. Longitudinal. Community-based. Nine hundred fifty-one individuals aged 65 and older. Plasma thyrotropin, free thyroxine, and free triiodothyronine concentrations and demographic features were evaluated in participants of the Invecchiare in Chianti Study aged 65 and older. Participants were classified according to thyroid function test. Kaplan-Meier survival and Cox proportional hazards models adjusted for confounders were used in the analysis. Eight hundred nineteen participants were euthyroid, 83 had subclinical hyperthyroidism (SHyper), and 29 had subclinical hypothyroidism (SHypo). Overt hypo- and hyperthyroidism were found in five and 15 subjects, respectively. During a median of 6 years of follow-up, 210 deaths occurred (22.1%), 98 (46.6%) of which were from cardiovascular causes. Kaplan-Meier analysis revealed higher overall mortality for SHyper (P = .04) than euthyroid subjects. After adjusting for multiple confounders, participants with SHyper (hazard ratio (HR) = 1.65, 95% confidence interval (CI) = 1.02-2.69) had significantly higher all-cause mortality than those with normal thyroid function. No significant association was found between SHyper and cardiovascular mortality. In euthyroid subjects, thyrotropin was found to be predictive of lower risk of all-cause mortality (HR = 0.76, 95% CI = 0.57-0.99). SHyper is an independent risk factor for all-cause mortality in older adults. Low to normal circulating thyrotropin should be carefully monitored in elderly euthyroid individuals. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

Long noncoding RNA SNHG5 is up-regulated and serves as a potential prognostic biomarker in acute myeloid leukemia.

PubMed

Li, J; Sun, C-K

2018-06-01

Growing evidence has demonstrated that the dysregulation of long non-coding RNAs (lncRNAs) may act as an important role in human tumorigenesis. Our present study aimed to explore the expression pattern and prognostic value of a newly discovered lncRNA small nucleolar RNA host gene 5 (SNHG5) in acute myeloid leukemia (AML). The expression of SNHG5 was determined using Real-time reverse transcription-polymerase chain reaction (qRT-PCR) in bone marrow and plasma obtained from AML patients and healthy controls. The correlation between SNHG5 expression and clinical features were statistically analyzed. The association between SNHG5 expression and overall survival was estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed to analyze the prognostic significance of SNHG5 expression. SNHG5 expression levels were consistently higher in the bone marrow and plasma of AML patients than those in the healthy controls (p<0.01). Furthermore, SNHG5 upregulation more frequently occurred in AML patients with advanced FAB classification (p<0.005) and unfavorable cytogenetics (p=0.001). In addition, the data of Kaplan-Meier method revealed that overall patient survival for those with high plasma SNHG5 expression was significantly shorter than those patients with low SNHG5 expression (p<0.0070). Importantly, univariate and multivariate Cox regression analysis identified increased SNHG5 expression as an independent factor predicting poor prognosis for AML patients. Our findings provide evidence that plasma SNHG5 is an independent biomarker for patients with AML, suggesting the potential role of SNHG5 as a highly specific and sensitive biomarker.

Adjuvant radiation therapy and survival for adenoid cystic carcinoma of the breast.

PubMed

Sun, Jia-Yuan; Wu, San-Gang; Chen, Shan-Yu; Li, Feng-Yan; Lin, Huan-Xin; Chen, Yong-Xiong; He, Zhen-Yu

2017-02-01

The assess the clinical value of different types of surgical procedures and further analyze the effect of adjuvant radiation therapy (RT) for adenoid cystic carcinoma (ACC) of the breast. Patients with ACC of the breast were identified using a population-based national registration database (Surveillance, Epidemiology, and End Results, SEER). The Kaplan-Meier method and Cox regression models were performed to determine the impact of the surgical procedures and adjuvant RT associated with cause-specific survival (CSS) and overall survival (OS). A total of 478 patients with ACC of the breast were identified. The median follow-up was 59 months. The 10-year CSS and OS were 87.5% and 75.3%, respectively. For the Kaplan-Meier analysis, the 5-year CSS were 96.1%, 91.8%, 90.2%, and 94.1% in patients that received lumpectomy + adjuvant RT, lumpectomy alone, mastectomy alone, and mastectomy + adjuvant RT, respectively (p = 0.026). In the multivariate Cox analyses, lumpectomy + adjuvant RT was an independent prognostic factor for CSS and OS. Patients that received lumpectomy + adjuvant RT had better survival rates than patients that underwent lumpectomy only (CSS, p = 0.018; OS, p = 0.031) and mastectomy only (CSS, p = 0.010; OS, p = 0.004). ACC of the breast has an excellent prognosis. Breast-conserving surgery is a reasonable alternative for patients with ACC of the breast, and adjuvant RT after lumpectomy improved survival rates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Graft survival of diabetic versus nondiabetic donor tissue after initial keratoplasty.

PubMed

Vislisel, Jesse M; Liaboe, Chase A; Wagoner, Michael D; Goins, Kenneth M; Sutphin, John E; Schmidt, Gregory A; Zimmerman, M Bridget; Greiner, Mark A

2015-04-01

To compare corneal graft survival using tissue from diabetic and nondiabetic donors in patients undergoing initial Descemet stripping automated endothelial keratoplasty (DSAEK) or penetrating keratoplasty (PKP). A retrospective chart review of pseudophakic eyes that underwent DSAEK or PKP was performed. The primary outcome measure was graft failure. Cox proportional hazard regression and Kaplan-Meier survival analyses were used to compare diabetic versus nondiabetic donor tissue for all keratoplasty cases. A total of 183 eyes (136 DSAEK, 47 PKP) were included in the statistical analysis. Among 24 procedures performed using diabetic donor tissue, there were 4 cases (16.7%) of graft failure (3 DSAEK, 1 PKP), and among 159 procedures performed using nondiabetic donor tissue, there were 18 cases (11.3%) of graft failure (12 DSAEK, 6 PKP). Cox proportional hazard ratio of graft failure for all cases comparing diabetic with nondiabetic donor tissue was 1.69, but this difference was not statistically significant (95% confidence interval, 0.56-5.06; P = 0.348). There were no significant differences in Kaplan-Meier curves comparing diabetic with nondiabetic donor tissue for all cases (P = 0.380). Statistical analysis of graft failure by donor diabetes status within each procedure type was not possible because of the small number of graft failure events involving diabetic tissue. We found similar rates of graft failure in all keratoplasty cases when comparing tissue from diabetic and nondiabetic donors, but further investigation is needed to determine whether diabetic donor tissue results in different graft failure rates after DSAEK compared with PKP.

Steroid Avoidance in Pediatric Heart Transplantation Results in Excellent Graft Survival

PubMed Central

Auerbach, Scott R.; Gralla, Jane; Campbell, David N.; Miyamoto, Shelley D.; Pietra, Biagio A.

2018-01-01

Background Maintenance steroid (MS) use in pediatric heart transplantation (HT) varies across centers. The purpose of this study was to evaluate the impact of steroid-free maintenance immunosuppression (SF) on graft outcomes in pediatric HT. Methods Patients younger than 18 years in the United States undergoing a first HT during 1990 to 2010 were analyzed for conditional 30-day graft loss (death or repeat HT) and death based on MS use by multivariable analysis. A propensity score was then given to each patient using a logistic model, and propensity matching was performed using pre-HT risk factors, induction therapy, and nonsteroid maintenance immunosuppression. Kaplan-Meier graft and patient survival probabilities by MS use were then calculated. Results Of 4894 patients, 3962 (81%) were taking MS and 932 (19%) SF. Of the 4530 alive at 30 days after HT, 3694 (82%) and 836 (18%) were in the MS and SF groups, respectively. Unmatched multivariable analysis showed no difference in 30-day conditional graft survival between MS and SF groups (hazard ratio=1.08, 95% confidence interval=0.93-1.24; P=0.33). Propensity matching resulted in 462 patients in each MS and SF group. Propensity-matched Kaplan-Meier survival analysis showed no difference in graft or patient survival between groups (P=0.3 and P=0.16, respectively). Conclusions We found no difference in graft survival between SF patients and those taking MS. An SF regimen in pediatric HT avoids potential complications of steroid use without compromising graft survival, even after accounting for pre-HT risk factors. PMID:24389908

Factors affecting commencement and cessation of smoking behaviour in Malaysian adults

PubMed Central

2012-01-01

Background Tobacco consumption peak in developed countries has passed, however, it is on the increase in many developing countries. Apart from cigarettes, consumption of local hand-rolled cigarettes such as bidi and rokok daun are prevalent in specific communities. Although factors associated with smoking initiation and cessation has been investigated elsewhere, the only available data for Malaysia is on prevalence. This study aims to investigate factors associated with smoking initiation and cessation which is imperative in designing intervention programs. Methods Data were collected from 11,697 adults by trained recording clerks on sociodemographic characteristics, practice of other risk habit and details of smoking such as type, duration and frequency. Smoking commencement and cessation were analyzed using the Kaplan-Meier estimates and log-rank tests. Univariate and multivariate Cox proportional hazard regression models were used to calculate the hazard rate ratios. Results Males had a much higher prevalence of the habit (61.7%) as compared to females (5.8%). Cessation was found to be most common among the Chinese and those regularly consuming alcoholic beverages. Kaplan-Meier plot shows that although males are more likely to start smoking, females are found to be less likely to stop. History of betel quid chewing and alcohol consumption significantly increase the likelihood of commencement (p < 0.0001), while cessation was least likely among Indians, current quid chewers and kretek users (p < 0.01). Conclusions Gender, ethnicity, history of quid chewing and alcohol consumption have been found to be important factors in smoking commencement; while ethnicity, betel quid chewing and type of tobacco smoked influences cessation. PMID:22429627

Elucidation of the Strongest Predictors of Cardiovascular Events in Patients with Heart Failure.

PubMed

Fukuda, Hiroki; Shindo, Kazuhiro; Sakamoto, Mari; Ide, Tomomi; Kinugawa, Shintaro; Fukushima, Arata; Tsutsui, Hiroyuki; Ito, Shin; Ishii, Akira; Washio, Takashi; Kitakaze, Masafumi

2018-06-20

In previous retrospective studies, we identified the 50 most influential clinical predictors of cardiovascular outcomes in patients with heart failure (HF). The present study aimed to use the novel limitless-arity multiple-testing procedure to filter these 50 clinical factors and thus yield combinations of no more than four factors that could potentially predict the onset of cardiovascular events. A Kaplan-Meier analysis was used to investigate the importance of the combinations. In a multi-centre observational trial, we prospectively enrolled 213 patients with HF who were hospitalized because of exacerbation, discharged according to HF treatment guidelines and observed to monitor cardiovascular events. After the observation period, we stratified patients according to whether they experienced cardiovascular events (rehospitalisation or cardiovascular death). Among 77,562 combinations of fewer than five clinical parameters, we identified 151 combinations that could potentially explain the occurrence of cardiovascular events. Of these, 145 combinations included the use of inotropic agents, whereas the remaining 6 included the use of diuretics without bradycardia or tachycardia, suggesting that the high probability of cardiovascular events is exclusively determined by these two clinical factors. Importantly, Kaplan-Meier curves demonstrated that the use of inotropes or of diuretics without bradycardia or tachycardia were independent predictors of a markedly worse cardiovascular prognosis. Patients treated with either inotropic agents or diuretics without bradycardia or tachycardia were at a higher risk of cardiovascular events. The uses of these drugs, regardless of heart rate, are the strongest clinical predictors of cardiovascular events in patients with HF. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Overcoming substrate limitations for improved production of ethylene in E. coli.

PubMed

Lynch, Sean; Eckert, Carrie; Yu, Jianping; Gill, Ryan; Maness, Pin-Ching

2016-01-01

Ethylene is an important industrial compound for the production of a wide variety of plastics and chemicals. At present, ethylene production involves steam cracking of a fossil-based feedstock, representing the highest CO2-emitting process in the chemical industry. Biological ethylene production can be achieved via expression of a single protein, the ethylene-forming enzyme (EFE), found in some bacteria and fungi; it has the potential to provide a sustainable alternative to steam cracking, provided that significant increases in productivity can be achieved. A key barrier is determining factors that influence the availability of substrates for the EFE reaction in potential microbial hosts. In the presence of O2, EFE catalyzes ethylene formation from the substrates α-ketoglutarate (AKG) and arginine. The concentrations of AKG, a key TCA cycle intermediate, and arginine are tightly controlled by an intricate regulatory system that coordinates carbon and nitrogen metabolism. Therefore, reliably predicting which genetic changes will ultimately lead to increased AKG and arginine availability is challenging. We systematically explored the effects of media composition (rich versus defined), gene copy number, and the addition of exogenous substrates and other metabolites on the formation of ethylene in Escherichia coli expressing EFE. Guided by these results, we tested a number of genetic modifications predicted to improve substrate supply and ethylene production, including knockout of competing pathways and overexpression of key enzymes. Several such modifications led to higher AKG levels and higher ethylene productivity, with the best performing strain more than doubling ethylene productivity (from 81 ± 3 to 188 ± 13 nmol/OD600/mL). Both EFE activity and substrate supply can be limiting factors in ethylene production. Targeted modifications in central carbon metabolism, such as overexpression of isocitrate dehydrogenase, and deletion of glutamate synthase or the

Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome.

PubMed

Bicknell, Louise S; Walker, Sarah; Klingseisen, Anna; Stiff, Tom; Leitch, Andrea; Kerzendorfer, Claudia; Martin, Carol-Anne; Yeyati, Patricia; Al Sanna, Nouriya; Bober, Michael; Johnson, Diana; Wise, Carol; Jackson, Andrew P; O'Driscoll, Mark; Jeggo, Penny A

2011-02-27

Studies into disorders of extreme growth failure (for example, Seckel syndrome and Majewski osteodysplastic primordial dwarfism type II) have implicated fundamental cellular processes of DNA damage response signaling and centrosome function in the regulation of human growth. Here we report that mutations in ORC1, encoding a subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome. We establish that these mutations disrupt known ORC1 functions including pre-replicative complex formation and origin activation. ORC1 deficiency perturbs S-phase entry and S-phase progression. Additionally, we show that Orc1 depletion in zebrafish is sufficient to markedly reduce body size during rapid embryonic growth. Our data suggest a model in which ORC1 mutations impair replication licensing, slowing cell cycle progression and consequently impeding growth during development, particularly at times of rapid proliferation. These findings establish a novel mechanism for the pathogenesis of microcephalic dwarfism and show a surprising but important developmental impact of impaired origin licensing.

Survival curve estimation with dependent left truncated data using Cox's model.

PubMed

Mackenzie, Todd

2012-10-19

The Kaplan-Meier and closely related Lynden-Bell estimators are used to provide nonparametric estimation of the distribution of a left-truncated random variable. These estimators assume that the left-truncation variable is independent of the time-to-event. This paper proposes a semiparametric method for estimating the marginal distribution of the time-to-event that does not require independence. It models the conditional distribution of the time-to-event given the truncation variable using Cox's model for left truncated data, and uses inverse probability weighting. We report the results of simulations and illustrate the method using a survival study.

Biostatistical analysis of mortality data for cohorts of cancer patients.

PubMed Central

Pauling, L

1989-01-01

The Hardin Jones principle states that for a homogeneous cohort of cancer patients the logarithm of the fraction surviving at time t has a constant slope. With use of this principle, the survival times of the members of a heterogeneous cohort can be analyzed to divide the cohort into subcohorts with different mortality rate constants. Probable values of the additional survival time can be estimated for members surviving at the closing date of a clinical trial, permitting them to be included in the biostatistical analysis of the results of the trial in a more significant way than through Kaplan-Meier renormalization. PMID:2726729

[Application of the life table method to the estimation of late complications of normal tissues after radiotherapy].

PubMed

Morita, K; Uchiyama, Y; Tominaga, S

1987-06-01

In order to evaluate the treatment results of radiotherapy it is important to estimate the degree of complications of the surrounding normal tissues as well as the frequency of tumor control. In this report, the cumulative incidence rate of the late radiation injuries of the normal tissues was calculated using the modified actuarial method (Cutler-Ederer's method) or Kaplan-Meier's method, which is usually applied to the calculation of the survival rate. By the use of this method of calculation, an accurate cumulative incidence rate over time can be easily obtained and applied to the statistical evaluation of the late radiation injuries.

Adverse Reactions to Metal on Metal Are Not Exclusive to Large Heads in Total Hip Arthroplasty.

PubMed

Lombardi, Adolph V; Berend, Keith R; Adams, Joanne B; Satterwhite, Keri L

2016-02-01

There is some suggestion that smaller diameter heads in metal-on-metal total hip arthroplasty (MoM THA) may be less prone to the adverse reactions to metal debris (ARMD) seen with large-diameter heads. We reviewed our population of patients with small head (≤ 32 mm) MoM THA to determine (1) the frequency of ARMD; (2) potential risk factors for ARMD in this population; and (3) the etiology of revision and Kaplan-Meier survivorship with revision for all causes. Small-diameter head MoM devices were used in 9% (347 of 3753) of primary THAs during the study period (January 1996 to March 2005). We generally used these implants in younger, more active, higher-demand patients. Three hundred hips (258 patients) had MoM THA using a titanium modular acetabular component with a cobalt-chromium tapered insert and were available for review with minimum 2-year followup (mean, 10 years; range, 2-19 years). Complete followup was available in 86% of hips (300 of 347). Clinical records and radiographs were reviewed to determine the frequency and etiology of revision. Kaplan-Meier survivorship analysis was performed. ARMD frequency was 5% (14 of 300 hips) and represented 70% (14 of 20) of revisions performed. Using multivariate analysis, no variable tested, including height, weight, body mass index, age, cup diameter, cup angle, use of screws, stem diameter, stem type, head diameter, preoperative clinical score, diagnosis, activity level, or sex, was significant as a risk factor for revision. Twenty hips have been revised: two for infection, four for aseptic loosening, and 14 for ARMD. Kaplan-Meier analysis revealed survival free of component revision for all causes was 95% at 10 years (95% confidence interval [CI], 91%-97%), 92% at 15 years (95% CI, 87%-95%), and 72% at 19 years (95% CI, 43%-90%), and survival free of component revision for aseptic causes was 96% at 10 years (95% CI, 92%-98%), 92% at 15 years (95% CI, 88%-95%), and 73% at 19 years (95% CI, 43%-90%). The late onset

Clinical outcomes of gastrointestinal brain metastases treated with radiotherapy.

PubMed

Sanghvi, Samrat M; Lischalk, Jonathan W; Cai, Ling; Collins, Sean; Nair, Mani; Collins, Brain; Unger, Keith

2017-02-28

Brain metastases of gastrointestinal origin are a rare occurrence. Radiation therapy (RT) in the form of stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) is an effective established treatment modality in either the definitive or adjuvant setting. The aim of this study is to assess the long-term clinical outcomes of patients with gastrointestinal (GI) brain metastases treated with SRS or WBRT. In this single institutional retrospective review, we detail the outcomes of patients diagnosed with metastatic brain tumors from an adenocarcinoma gastrointestinal primary. Patients were treated using stereotactic radiosurgery or whole brain radiation therapy. Initial site control (defined as lesions visualized on imaging at time of treatment), new site control (defined as new intracranial lesions visualized on follow-up imaging), and overall survival were calculated using the Kaplan-Meier method. Thirty-three patients were treated from August 2008 to December 2015. Primary malignancy locations were as follows: 18 colon, 6 esophagus, 4 rectum, 5 other. Median total dose delivered was 25 Gy (18-35 Gy) in a median of 4 fractions for SRS and 30 Gy (10.8-40 Gy) in 10 fractions for WBRT. Crude initial site control at last radiographic follow-up was 64.3% after SRS and 41.7% after WBRT. Eleven of the 28 brain lesions (39.3%) treated with SRS had resection of the SRS-treated lesion prior to radiation therapy. Five of the twelve patients (41.7%) undergoing WBRT underwent cranial resection prior to radiation therapy. Crude new site control at last radiographic follow-up was 46.4% after SRS and 83.3% after WBRT. Kaplan-Meier analysis of overall survival did not show any statistically significant difference between WBRT and SRS (p = 0.424). Median overall survival for SRS patients was 5.2 months (0.5-57.5) and for WBRT patients 4.4 months (0-15). Kaplan-Meier analysis of new site control was significantly improved with WBRT versus SRS (p = 0

Photorespiration and carbon limitation determine productivity in temperate seagrasses.

PubMed

Buapet, Pimchanok; Rasmusson, Lina M; Gullström, Martin; Björk, Mats

2013-01-01

The gross primary productivity of two seagrasses, Zostera marina and Ruppia maritima, and one green macroalga, Ulva intestinalis, was assessed in laboratory and field experiments to determine whether the photorespiratory pathway operates at a substantial level in these macrophytes and to what extent it is enhanced by naturally occurring shifts in dissolved inorganic carbon (DIC) and O2 in dense vegetation. To achieve these conditions in laboratory experiments, seawater was incubated with U. intestinalis in light to obtain a range of higher pH and O2 levels and lower DIC levels. Gross photosynthetic O2 evolution was then measured in this pretreated seawater (pH, 7.8-9.8; high to low DIC:O2 ratio) at both natural and low O2 concentrations (adjusted by N2 bubbling). The presence of photorespiration was indicated by a lower gross O2 evolution rate under natural O2 conditions than when O2 was reduced. In all three macrophytes, gross photosynthetic rates were negatively affected by higher pH and lower DIC. However, while both seagrasses exhibited significant photorespiratory activity at increasing pH values, the macroalga U. intestinalis exhibited no such activity. Rates of seagrass photosynthesis were then assessed in seawater collected from the natural habitats (i.e., shallow bays characterized by high macrophyte cover and by low DIC and high pH during daytime) and compared with open baymouth water conditions (where seawater DIC is in equilibrium with air, normal DIC, and pH). The gross photosynthetic rates of both seagrasses were significantly higher when incubated in the baymouth water, indicating that these grasses can be significantly carbon limited in shallow bays. Photorespiration was also detected in both seagrasses under shallow bay water conditions. Our findings indicate that natural carbon limitations caused by high community photosynthesis can enhance photorespiration and cause a significant decline in seagrass primary production in shallow waters.

Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients

PubMed Central

Fu, Tao; Liu, Yanliang; Li, Kai; Wan, Weiwei; Pappou, Emmanouil P.; Iacobuzio-Donahue, Christine A.; Kerner, Zachary; Baylin, Stephen B.; Wolfgang, Christopher L.; Ahuja, Nita

2016-01-01

We previously developed a novel tumor subtype classification model for duodenal adenocarcinomas based on a combination of the CpG island methylator phenotype (CIMP) and MLH1 methylation status. Here, we tested the prognostic value of this model in stage II colorectal cancer (CRC) patients. Tumors were assigned to CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP−/MLH1-U, or CIMP−/MLH1-M groups. Age, tumor location, lymphovascular invasion, and mucin production differed among the four patient subgroups, and CIMP+/MLH1-U tumors were more likely to have lymphovascular invasion and mucin production. Kaplan-Meier analyses revealed differences in both disease-free survival (DFS) and overall survival (OS) among the four groups. In a multivariate analysis, CIMP/MLH1 methylation status was predictive of both DFS and OS, and DFS and OS were shortest in CIMP+/MLH1-U stage II CRC patients. These results suggest that tumor subtype classification based on the combination of CIMP and MLH1 methylation status is informative in stage II CRC patients, and that CIMP+/MLH1-U tumors exhibit aggressive features and are associated with poor clinical outcomes. PMID:27880934

Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients.

PubMed

Fu, Tao; Liu, Yanliang; Li, Kai; Wan, Weiwei; Pappou, Emmanouil P; Iacobuzio-Donahue, Christine A; Kerner, Zachary; Baylin, Stephen B; Wolfgang, Christopher L; Ahuja, Nita

2016-12-27

We previously developed a novel tumor subtype classification model for duodenal adenocarcinomas based on a combination of the CpG island methylator phenotype (CIMP) and MLH1 methylation status. Here, we tested the prognostic value of this model in stage II colorectal cancer (CRC) patients. Tumors were assigned to CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP-/MLH1-U, or CIMP-/MLH1-M groups. Age, tumor location, lymphovascular invasion, and mucin production differed among the four patient subgroups, and CIMP+/MLH1-U tumors were more likely to have lymphovascular invasion and mucin production. Kaplan-Meier analyses revealed differences in both disease-free survival (DFS) and overall survival (OS) among the four groups. In a multivariate analysis, CIMP/MLH1 methylation status was predictive of both DFS and OS, and DFS and OS were shortest in CIMP+/MLH1-U stage II CRC patients. These results suggest that tumor subtype classification based on the combination of CIMP and MLH1 methylation status is informative in stage II CRC patients, and that CIMP+/MLH1-U tumors exhibit aggressive features and are associated with poor clinical outcomes.

Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a randomized historical-control phase III study based in North America.

PubMed

Sperling, Michael R; Harvey, Jay; Grinnell, Todd; Cheng, Hailong; Blum, David

2015-04-01

To assess the efficacy and safety of eslicarbazepine acetate (ESL) as monotherapy in North American patients with partial-onset seizures (POS). This multicenter, randomized, double-blind "withdrawal to monotherapy" study used historical control data as the comparator. Adults with POS medically uncontrolled by one to two antiepileptic drugs gradually converted to ESL monotherapy. Following an 8-week baseline period, patients were randomized 2:1 to receive ESL 1,600 mg (n = 128) or 1,200 mg QD (n = 65) for 18 weeks. The primary end point was the proportion of patients meeting predefined exit criteria (signifying worsening seizure control). Treatment was considered effective if the 95% upper confidence limit (UCL) for the Kaplan-Meier estimated exit rate was lower than the exit rate threshold calculated from the historical control (65.3%). Kaplan-Meier estimated exit rates were: ESL 1,600 mg, 28.7% (95% CI 21.2-38.1%) and 1,200 mg, 44.4% (32.5-58.3%). The difference between doses was not significant (p = 0.07). For both doses, the 95% UCLs for the exit rate were ˂ 65.3%; ESL monotherapy was considered superior to the historical control. There was no statistically significant increase in the risk of study exit related to carbamazepine use. Nine (7.6%) and five patients (8.3%) remained seizure-free during the 10-week monotherapy period, while taking ESL 1,600 and 1,200 mg, respectively. The reductions in median standardized seizure frequency (seizures per 28 days) between baseline and the 18-week treatment period were: ESL 1,600 mg, 42% and 1,200 mg, 31%. Treatment-emergent adverse events (TEAEs) occurring in ≥ 10% of patients were dizziness, headache, fatigue, somnolence, nausea, and nasopharyngitis. The TEAE most frequently leading to discontinuation was hyponatremia (2.1%). ESL was efficacious and well tolerated as monotherapy in North American patients, and led to a reduction in seizure frequency. Exit rates for ESL 1,600 and 1,200 mg QD were superior to the

Opportunities to overcome the current limitations and challenges for efficient microbial production of optically pure lactic acid.

PubMed

Abdel-Rahman, Mohamed Ali; Sonomoto, Kenji

2016-10-20

There has been growing interest in the microbial production of optically pure lactic acid due to the increased demand for lactic acid-derived environmentally friendly products, for example biodegradable plastic (poly-lactic acid), as an alternative to petroleum-derived materials. To maximize the market uptake of these products, their cost should be competitive and this could be achieved by decreasing the production cost of the raw material, that is, lactic acid. It is of great importance to isolate and develop robust and highly efficient microbial lactic acid producers. Alongside the fermentative substrate and concentration, the yield and productivity of lactic acid are key parameters and major factors in determining the final production cost of lactic acid. In this review, we will discuss the current limitations and challenges for cost-efficient microbial production of optically pure lactic acid. The main obstacles to effective fermentation are the use of food resources, indirect utilization of polymeric sugars, sensitivity to inhibitory compounds released during biomass treatments, substrate inhibition, decreased lactic acid yield and productivity, inefficient utilization of mixed sugars, end product inhibition, increased use of neutralizing agents, contamination problems, and decreased optical purity of lactic acid. Furthermore, opportunities to address and overcome these limitations, either by fermentation technology or metabolic engineering approaches, will be introduced and discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Solvent and viscosity effects on the rate-limiting product release step of glucoamylase during maltose hydrolysis.

PubMed

Sierks, M R; Sico, C; Zaw, M

1997-01-01

Release of product from the active site is the rate-limiting step in a number of enzymatic reactions, including maltose hydrolysis by glucoamylase (GA). With GA, an enzymatic conformational change has been associated with the product release step. Solvent characteristics such as viscosity can strongly influence protein conformational changes. Here we show that the rate-limiting step of GA has a rather complex dependence on solvent characteristics. Seven different cosolvents were added to the GA/maltose reaction solution. Five of the cosolvents, all having an ethylene glycol base, resulted in an increase in activity at low concentration of cosolvent and variable decreases in activity at higher concentrations. The increase in enzyme activity was dependent on polymer length of the cosolvent; the longer the polymer, the lower the concentration needed. The maximum increase in catalytic activity at 45 degrees C (40-45%) was obtained with the three longest polymers (degree of polymerization from 200 to 8000). A further increase in activity to 60-65% was obtained at 60 degrees C. The linear relationship between ln(kcat) and (viscosity)2 obtained with all the cosolvents provides further evidence that product release is the rate-limiting step in the GA catalytic mechanism. A substantial increase in the turnover rate of GA by addition of relatively small amounts of a cosolvent has potential applications for the food industry where high-fructose corn syrup (HFCS) is one of the primary products produced with GA. Since maltodextrin hydrolysis by GA is by far the slowest step in the production of HFCS, increasing the catalytic rate of GA can substantially reduce the process time.

Enhanced production of recombinant nattokinase in Bacillus subtilis by the elimination of limiting factors.

PubMed

Chen, Po Ting; Chao, Yun-Peng

2006-10-01

By systematic investigation, glutamate and a mixture of metal ions were identified as factors limiting the production of nattokinase in Bacillus subtilis. Consequently, in medium supplemented with these materials, the recombinant strain secreted 4 times more nattokinase (260 mg l(-1)) than when grown in the unsupplemented medium.

The make or buy debate: Considering the limitations of domestic production in Tanzania

PubMed Central

2012-01-01

Background In order to ensure their population’s regular access to essential medicines, many least developed countries and developing countries are faced with the policy question of whether to import or manufacture drugs locally, in particular for life-saving antiretroviral medicines for HIV/AIDS patients. In order for domestic manufacturing to be viable and cost-effective, the local industry must be able to compete with international suppliers of medicines by producing sufficiently low cost ARVs. Methods This paper considers the ‘make-or-buy’ dilemma by using Tanzania as a case study. Key informant interviews, event-driven observation, and purposive sampling of documents were used to evaluate the case study. The case study focused on Tanzania’s imitation technology transfer agreement to locally manufacture a first-line ARV (3TC + d4T + NVP), reverse engineering the ARV. Results Tanzania is limited by weak political support for the use of TRIPS flexibilities, limited production capacity for ARVs and limited competitiveness in both domestic and regional markets. The Ministry of Health and Social Welfare encourages the use of flexibilities while others push for increased IP protection. Insufficient production capacity and lack of access to donor-financed tenders make it difficult to obtain economies of scale and provide competitive prices. Conclusions Within the “make-or-buy” context, it was determined that there are significant limitations in domestic manufacturing for developing countries. The case study highlights the difficulty of governments to make use of economies of scale and produce low-cost medicines, attract technology transfer, and utilize the flexibilities of the WTO Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). The results demonstrate the importance of evaluating barriers to the use of TRIPS flexibilities and long-term planning across sectors in future technology transfer and manufacturing initiatives

The make or buy debate: considering the limitations of domestic production in Tanzania.

PubMed

Wilson, Kinsley Rose; Kohler, Jillian Clare; Ovtcharenko, Natalia

2012-06-29

In order to ensure their population's regular access to essential medicines, many least developed countries and developing countries are faced with the policy question of whether to import or manufacture drugs locally, in particular for life-saving antiretroviral medicines for HIV/AIDS patients. In order for domestic manufacturing to be viable and cost-effective, the local industry must be able to compete with international suppliers of medicines by producing sufficiently low cost ARVs. This paper considers the 'make-or-buy' dilemma by using Tanzania as a case study. Key informant interviews, event-driven observation, and purposive sampling of documents were used to evaluate the case study. The case study focused on Tanzania's imitation technology transfer agreement to locally manufacture a first-line ARV (3TC + d4T + NVP), reverse engineering the ARV. Tanzania is limited by weak political support for the use of TRIPS flexibilities, limited production capacity for ARVs and limited competitiveness in both domestic and regional markets. The Ministry of Health and Social Welfare encourages the use of flexibilities while others push for increased IP protection. Insufficient production capacity and lack of access to donor-financed tenders make it difficult to obtain economies of scale and provide competitive prices. Within the "make-or-buy" context, it was determined that there are significant limitations in domestic manufacturing for developing countries. The case study highlights the difficulty of governments to make use of economies of scale and produce low-cost medicines, attract technology transfer, and utilize the flexibilities of the WTO Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). The results demonstrate the importance of evaluating barriers to the use of TRIPS flexibilities and long-term planning across sectors in future technology transfer and manufacturing initiatives.

Continuous aryl alcohol oxidase production under growth-limited conditions using a trickle bed reactor.

PubMed

Pardo-Planas, Oscar; Atiyeh, Hasan K; Prade, Rolf A; Müller, Michael; Wilkins, Mark R

2018-05-01

An A. nidulans strain with a pyridoxine marker was used for continuous production of aryl alcohol oxidase (AAO) in a trickle bed reactor (TBR). Modified medium with reduced zinc, no copper, and 5 g/L ascorbic acid that reduced melanin production and increased AAO productivity under growth limited conditions was used. Two air flow rates, 0.11 L/min (0.1 vvm) and 1.1 L/min (1.0 vvm) were tested. More melanin formation and reduced protein productivity were observed with air flow rate of 1.1 L/min. Three random packings were used as support for the fungus inside the TBR column, two of which were hydrophobic and one which was hydrophilic, and three different dilution rates were tested. The use of GEA BCN 030 hydrophobic packing resulted in greater AAO yield and productivity than the other packings. Increasing dilution rates favored melanin formation and citric, lactic and succinic acid accumulation, which decreased AAO yield and productivity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Excess growing-season water limits lowland black spruce productivity

NASA Astrophysics Data System (ADS)

Dymond, S.; Kolka, R. K.; Bolstad, P. V.; Gill, K.; Curzon, M.; D'Amato, A. W.

2015-12-01

The annual growth of many tree species is limited by water availability, with growth increasing as water becomes less scarce. In lowland bogs of northern Minnesota, however, black spruce (Picea mariana) is often exposed to excess water via high water table elevations. These trees grow in thick deposits of organic mucky peat and often have shallow rooting systems to avoid the complete submersion of roots in water. While it is generally believed that black spruce decrease growth rates with rising water table elevations, this hypothesis has not been tested in situ. We used a unique, 50-year record of daily bog water table elevations at the Marcell Experimental Forest (MEF) in northern Minnesota to investigate the relationship between climate and black spruce productivity. Nine 1/20th ha circular plots were established in five different bogs and tree height, diameter-at-breast-height (DBH), and crown class were recorded. Additionally, two perpendicular cores were collected on all trees greater than 10 cm diameter-at-breast-height. Tree cores were sanded, mounted, cross-dated, and de-trended according to standard dendrochronological procedures. Ring width measurements were correlated with precipitation, temperature, and water table elevation using package BootRes in R to determine the climatic variables most associated with stand level productivity. Across the different plots, we found that early growing season water table elevation (May and June) was negatively correlated with both individual and stand-level black spruce growth (p < 0.01), while growth was positively correlated with March temperatures (p < 0.01). No significant relationships existed between black spruce growth and monthly precipitation. If summer water table elevations in these peatland ecosystems rise as is anticipated with more extreme precipitation events due to climate change, we could see an overall decrease in the stand level productivity of black spruce.

Long-Term Pancreas Allograft Survival in Simultaneous Pancreas-Kidney Transplantation by Era

PubMed Central

Waki, Kayo; Terasaki, Paul I.; Kadowaki, Takashi

2010-01-01

OBJECTIVE To determine whether short-term improvement in pancreas graft survival with simultaneous pancreas-kidney (SPK) transplants translated into improved long-term survival, then to examine the implications of that determination. RESEARCH DESIGN AND METHODS We analyzed data for 14,311 diabetic patients who received a first SPK transplant between October 1987 and November 2007, using Kaplan-Meier analysis for graft survival rates and Cox regression analysis for year-of-transplant effect. RESULTS Overall, from 1995 to 2004, 5-year pancreas graft survival stayed about the same (70–71%). Limiting analysis to grafts that survived more than 1 year, 5-year survival from 1987 to 2004 ranged from 80 to 84%. With 1987–1989 as reference, the adjusted hazard ratio for graft failure by year of transplant increased to 1.49 (95% CI 0.97–2.30) in 2000–2004. CONCLUSIONS Long-term pancreas graft survival has remained unchanged despite the dramatic decreases in technical failures and early acute rejection rates that have contributed to prolonged SPK graft survival. PMID:20460444

Treatment of feline intermediate- to high-grade lymphoma with a modified university of Wisconsin-Madison protocol: 119 cases (2004-2012).

PubMed

Collette, S A; Allstadt, S D; Chon, E M; Vernau, W; Smith, A N; Garrett, L D; Choy, K; Rebhun, R B; Rodriguez, C O; Skorupski, K A

2016-08-01

CHOP-based (cyclophosphamide, doxorubicin, vinca alkaloid, prednisolone) chemotherapy protocols are often recommended for treatment of feline lymphoma. While maintenance-free CHOP-based protocols have been published and readily used in dogs, there is limited literature regarding similar maintenance-free protocols in cats. The purpose of this study was to describe the outcome of cats with intermediate- to high-grade lymphoma that were prescribed a modified 25-week University of Wisconsin-Madison (UW-25) chemotherapy protocol. A secondary objective was examination of potential prognostic factors. One hundred and nineteen cats from five institutions treated with a UW-25-based protocol were included. The Kaplan-Meier median progression-free interval (PFI) and survival time (MST) were 56 and 97 (range 2-2019) days, respectively. Cats assessed as having a complete response (CR) to therapy had significantly longer PFI and MST than those with partial or no response (PFI 205 versus 54 versus 21 days, respectively, P < 0.0001 and MST 318 versus 85 versus 27 days, respectively, P < 0.0001). © 2015 John Wiley & Sons Ltd.

Evaluating optimum limited irrigation management strategies for corn production in the ogallala aquifer region

USDA-ARS?s Scientific Manuscript database

Water is the major factor limiting crop production in the Ogallala Aquifer Region of the U.S. Central High Plains. Seasonal precipitation is highly variable, low in amount, and not enough to meet full corn water needs. The Ogallala Aquifer is the major source of irrigation water for commercial agric...

Bioenergy production and sustainable development: science base for policymaking remains limited.

PubMed

Robledo-Abad, Carmenza; Althaus, Hans-Jörg; Berndes, Göran; Bolwig, Simon; Corbera, Esteve; Creutzig, Felix; Garcia-Ulloa, John; Geddes, Anna; Gregg, Jay S; Haberl, Helmut; Hanger, Susanne; Harper, Richard J; Hunsberger, Carol; Larsen, Rasmus K; Lauk, Christian; Leitner, Stefan; Lilliestam, Johan; Lotze-Campen, Hermann; Muys, Bart; Nordborg, Maria; Ölund, Maria; Orlowsky, Boris; Popp, Alexander; Portugal-Pereira, Joana; Reinhard, Jürgen; Scheiffle, Lena; Smith, Pete

2017-03-01

The possibility of using bioenergy as a climate change mitigation measure has sparked a discussion of whether and how bioenergy production contributes to sustainable development. We undertook a systematic review of the scientific literature to illuminate this relationship and found a limited scientific basis for policymaking. Our results indicate that knowledge on the sustainable development impacts of bioenergy production is concentrated in a few well-studied countries, focuses on environmental and economic impacts, and mostly relates to dedicated agricultural biomass plantations. The scope and methodological approaches in studies differ widely and only a small share of the studies sufficiently reports on context and/or baseline conditions, which makes it difficult to get a general understanding of the attribution of impacts. Nevertheless, we identified regional patterns of positive or negative impacts for all categories - environmental, economic, institutional, social and technological. In general, economic and technological impacts were more frequently reported as positive, while social and environmental impacts were more frequently reported as negative (with the exception of impacts on direct substitution of GHG emission from fossil fuel). More focused and transparent research is needed to validate these patterns and develop a strong science underpinning for establishing policies and governance agreements that prevent/mitigate negative and promote positive impacts from bioenergy production.

Advantages and limitations of online communities of patients for research on health products.

PubMed

Ravoire, Sophie; Lang, Marie; Perrin, Elena

2017-02-01

The way patients and their caregivers share information on various online platforms about health topics and their own experiential knowledge presents new potential environments for research, particularly as concerns health products. The information provided individually and voluntarily by patients who are members of these online communities is a new resource for identifying and understanding precisely how health products are used, assessing their effectiveness, quantifying potential adverse effects in real-life situations, detecting subtle signs that are significant for experts in pharmacovigilance and addiction studies, and developing new assessment tools to help form new working hypotheses. How patients freely express their experiences and feelings and the reality of what they share also opens the way for societal research into health products, a field that is still under-explored. Well-established regulations govern research into health products, which uses resources and methodologies that have changed little over the years. However, the development of online communities of patients presents new possibilities in this field. The challenge we face today is defining their place among traditional research techniques. This place cannot be accepted by all stakeholders unless we first establish a firm understanding of the advantages, limitations, and constraints of these communities. The round table on this topic endeavoured to: explore these issues and develop a better understanding of the phenomenon and the different varieties of online communities and networks for patients; identify possible advantages, special features, and methodological, regulatory, and ethical limitations that researchers currently face; and finally, to put forward the first recommendations in this growing field of research. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Analysis and significance of c-MET expression in adenoid cystic carcinoma of the salivary gland.

PubMed

Bell, Diana; Ferrarotto, Renata; Fox, Melanie D; Roberts, Dianna; Hanna, Ehab Y; Weber, Randal S; El-Naggar, Adel K

2015-01-01

Adenoid cystic carcinoma (ACC), a rare salivary gland malignancy, is a histogenetic, morphologic, and clinical heterogeneous disease. Extensive efforts have been made to characterize molecular events associated with these tumors, including the identification of prognostic and predictive biomarkers. Increased copy number gain and amplification of c-Met, the cell surface receptor for hepatocyte growth factor, has been shown to enhance tumor growth and invasiveness and promote metastasis in certain tumor types. In this study, we evaluated the expression of c-Met by immunohistochemistry (IHC) in a large cohort of salivary gland ACCs and examined its clinicopathologic implications. Archival formalin-fixed paraffin-embedded blocks from 200 ACC patients were used in this study. Pathologic patterns and phenotypic expression of c-Met were recorded and compared with clinical factors including gender, age, disease stage at diagnosis, and clinical outcomes. Correlations between c-MET expression and clinical characteristics were assessed by Pearson's chi-square test or by the 2-tailed Fisher exact test. Curves describing overall survival were generated by Kaplan-Meier product limit method. Strong c-MET expression was seen in inner ductal and outer myoepithelial cells in 53.2% of the cases. There was no correlation between c-Met overexpression and clinicopathologic parameters or patient's overall survival ( p = .94074). In conclusion, c-MET expression is high in a significant subgroup of ACC patients. While c-MET expression is not a prognostic factor in ACC, its role as a predictive marker of benefit from MET inhibitors deserves further investigation.

Simpler and equitable allocation of kidneys from postmortem donors primarily based on full HLA-DR compatibility.

PubMed

Doxiadis, Ilias I N; de Fijter, Johan W; Mallat, Marko J K; Haasnoot, Geert W; Ringers, Jan; Persijn, Guido G; Claas, Frans H J

2007-05-15

The introduction of human leukocyte antigen (HLA)-matching in nonliving kidney transplantation has resulted into a better graft outcome, but also in an increase of waiting time, especially for patients with rare HLA phenotypes. We addressed the question of the differential influence of HLA-DR-matching versus HLA-A,B in clinical kidney transplantation. We used Kaplan-Meier product limit method to estimate survival rates, and Cox proportional hazard regression for the estimation of relative risks (Hazard-ratios) for different variables. A single center study (n=456 transplants, performed between 1985 and 1999) showed that full HLA-DR compatibility leads to a lower incidence of biopsy confirmed acute rejections in the first 180 posttransplantation days. These results were substantiated using the Eurotransplant database (n=39,205 transplants performed between 1985 and 2005) where graft survival in the full HLA-DR compatible group was significantly better than in the incompatible. An additional positive effect of HLA-A,B matching was only found in the full HLA-DR compatible group. In both studies, the introduction of a single HLA-DR incompatibility eliminates the HLA-A,B matching effect. We propose to allocate postmortem kidneys only to patients with full HLA-DR compatibility, and use HLA-A,B compatibility as an additional selection criterion. All patients, irrespective of their ethnic origin, will profit since the polymorphism of HLA-DR is by far lower than that of HLA-A,B. Excessive kidney travel and cold ischemia time will be significantly reduced.

40 CFR 63.6006 - How do I demonstrate continuous compliance with the emission limits for tire cord production...

Code of Federal Regulations, 2010 CFR

2010-07-01

... compliance with the emission limits for tire cord production affected sources? 63.6006 Section 63.6006... Hazardous Air Pollutants: Rubber Tire Manufacturing Continuous Compliance Requirements for Tire Cord... tire cord production affected sources? (a) You must demonstrate continuous compliance with each...

Racial Differences in the Overall Survival of Hairy Cell Leukemia in the United States: A Population-Based Analysis of the Surveillance, Epidemiology, and End Results Database.

PubMed

Giri, Smith; Shrestha, Rajesh; Pathak, Ranjan; Bhatt, Vijaya Raj

2015-08-01

Several studies have reported excellent long-term overall survival (OS) of patients with hairy cell leukemia (HCL) without racial disparity. Studies in other cancers have demonstrated worse mortality among African American (AA) individuals. We used the Surveillance, Epidemiology, and End Results 18 database to identify HCL patients diagnosed between 1978 and 2011. Kaplan-Meier curves were plotted to estimate OS. Univariate analysis using the life table method and multivariate Cox regression model were used to determine the independent effect of race on OS. The study population included 78% men and had a median age of 56 years. Race included 93% white, 3.5% Asian/Pacific Islander, and 3.5% AA. The 10-year OS was significantly less for AA as compared with white and Asian/Pacific Islander individuals (54% vs. 72% vs. 75%; P < .001). A Kaplan-Meier survival curve showed a significantly worse OS for AA versus other races (P < .001). In a multivariate analysis, AA race remained an independent predictor for a worse OS (hazard ratio 1.77; 95% confidence interval, 1.30-2.40; P < .001) after adjusting for age, sex, year of diagnosis, and marital status. In this population-based study, only half of AA patients but more than two-thirds of HCL patients from other racial groups were alive at 10 years. Such drastic racial differences in OS of HCL patients at the population level mandates further evaluation of the contributory biological, socioeconomic, health system, and other factors. Understanding and overcoming such racial disparities might close the racial differences in OS of this potentially curable disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Serum Irisin Predicts Mortality Risk in Acute Heart Failure Patients.

PubMed

Shen, Shutong; Gao, Rongrong; Bei, Yihua; Li, Jin; Zhang, Haifeng; Zhou, Yanli; Yao, Wenming; Xu, Dongjie; Zhou, Fang; Jin, Mengchao; Wei, Siqi; Wang, Kai; Xu, Xuejuan; Li, Yongqin; Xiao, Junjie; Li, Xinli

2017-01-01

Irisin is a peptide hormone cleaved from a plasma membrane protein fibronectin type III domain containing protein 5 (FNDC5). Emerging studies have indicated association between serum irisin and many major chronic diseases including cardiovascular diseases. However, the role of serum irisin as a predictor for mortality risk in acute heart failure (AHF) patients is not clear. AHF patients were enrolled and serum was collected at the admission and all patients were followed up for 1 year. Enzyme-linked immunosorbent assay was used to measure serum irisin levels. To explore predictors for AHF mortality, the univariate and multivariate logistic regression analysis, and receiver-operator characteristic (ROC) curve analysis were used. To determine the role of serum irisin levels in predicting survival, Kaplan-Meier survival analysis was used. In this study, 161 AHF patients were enrolled and serum irisin level was found to be significantly higher in patients deceased in 1-year follow-up. The univariate logistic regression analysis identified 18 variables associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 2 variables namely blood urea nitrogen and serum irisin. ROC curve analysis indicated that blood urea nitrogen and the most commonly used biomarker, NT-pro-BNP, displayed poor prognostic value for AHF (AUCs ≤ 0.700) compared to serum irisin (AUC = 0.753). Kaplan-Meier survival analysis demonstrated that AHF patients with higher serum irisin had significantly higher mortality (P<0.001). Collectively, our study identified serum irisin as a predictive biomarker for 1-year all-cause mortality in AHF patients though large multicenter studies are highly needed. © 2017 The Author(s). Published by S. Karger AG, Basel.

A Point System to Forecast Hepatocellular Carcinoma Risk Before and After Treatment Among Persons with Chronic Hepatitis C.

PubMed

Xing, Jian; Spradling, Philip R; Moorman, Anne C; Holmberg, Scott D; Teshale, Eyasu H; Rupp, Loralee B; Gordon, Stuart C; Lu, Mei; Boscarino, Joseph A; Schmidt, Mark A; Trinacty, Connie M; Xu, Fujie

2017-11-01

Risk of hepatocellular carcinoma (HCC) may be difficult to determine in the clinical setting. Develop a scoring system to forecast HCC risk among patients with chronic hepatitis C. Using data from the Chronic Hepatitis Cohort Study collected during 2005-2014, we derived HCC risk scores for males and females using an extended Cox model with aspartate aminotransferase-to-platelet ratio index (APRI) as a time-dependent variables and mean Kaplan-Meier survival functions from patient data at two study sites, and used data collected at two separate sites for external validation. For model calibration, we used the Greenwood-Nam-D'Agostino goodness-of-fit statistic to examine differences between predicted and observed risk. Of 12,469 patients (1628 with a history of sustained viral response [SVR]), 504 developed HCC; median follow-up was 6 years. Final predictors in the model included age, alcohol abuse, interferon-based treatment response, and APRI. Point values, ranging from -3 to 14 (males) and -3 to 12 (females), were established using hazard ratios of the predictors aligned with 1-, 3-, and 5-year Kaplan-Meier survival probabilities of HCC. Discriminatory capacity was high (c-index 0.82 males and 0.84 females) and external calibration demonstrated no differences between predicted and observed HCC risk for 1-, 3-, and 5-year forecasts among males (all p values >0.97) and for 3- and 5-year risk among females (all p values >0.87). This scoring system, based on age, alcohol abuse history, treatment response, and APRI, can be used to forecast up to a 5-year risk of HCC among hepatitis C patients before and after SVR.

Risk of Endophthalmitis and Other Long-Term Complications of Trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS)

PubMed Central

Zahid, Sarwar; Musch, David C.; Niziol, Leslie M.; Lichter, Paul R.

2012-01-01

Purpose To report the risk of endophthalmitis and other long-term complications in patients randomized to trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS). Design A longitudinal cohort study using data collected from a multicenter, randomized clinical trial. Methods Long-term post-operative complications in the 300 patients randomized to trabeculectomy in CIGTS were tabulated. Kaplan-Meier analyses were used to estimate the time-related probability of blebitis, hypotony, and endophthalmitis. Results 285 patients were included in the final trabeculectomy cohort after accounting for assignment refusal and other early events. Patients were followed for an average of 7.2 years. 163 patients (57%) received 5-fluorouracil (5-FU) intraoperatively. Of the 247 patients with at least 5 years of follow-up, 50 required further treatment for glaucoma. Cataract extraction was performed in 57 patients (20%). Forty patients (14%) required bleb revision at least once. Bleb-related complications included bleb leak (N = 15), blebitis (N = 8), and hypotony (N = 4). Three patients were noted to have endophthalmitis, although the diagnosis in two patients was presumptive. The occurrences of blebitis, hypotony, or endophthalmitis were not significantly associated with 5-FU use. The Kaplan-Meier calculated risks of blebitis and hypotony at 5 years were both 1.5%, while the risk of endophthalmitis was 1.1%. Conclusions The potential efficacy of trabeculectomy must be weighed against the long-term risk of complications, especially endophthalmitis, when selecting treatments for patients with open-angle glaucoma. We report a low 5-year risk of endophthalmitis (1.1%) and other bleb-related complications in the trabeculectomy cohort of the CIGTS. PMID:23246272

The association between high on-treatment platelet reactivity and early recurrence of ischemic events after minor stroke or TIA.

PubMed

Rao, Zilong; Zheng, Huaguang; Wang, Fei; Wang, Anxin; Liu, Liping; Dong, Kehui; Zhao, Xingquan; Wang, Yilong; Cao, Yibin

2017-08-01

To evaluate the role of HTPR in predicting early recurrence of ischemic events in patients with minor ischemic stroke or high-risk TIA. From January 2014 to September 2014, a single center continuously enrolled patients with minor ischemic stroke or high-risk TIA and gave them antiplatelet therapy consisting of aspirin with clopidogrel. HTPR was assessed by TEG after 7 days of antiplatelet therapy and detected CYP2C19 genotype. The incidence of recurrent ischemic events was assessed 3 months after onset. The incidence of recurrent ischemic events was compared between the HTPR and NTPR groups with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to determine the risk factors associated with recurrent ischemic events. We enrolled 278 eligible patients with minor ischemic stroke or high-risk TIA. Through TEG testing, patients with HTPR were 22.7%, and carriers were not associated with HTPR to ADP by TEG-ADP(%) (p = 0.193). A total of 265 patients completed 3 months of follow-up, and Kaplan-Meier analysis showed that patients with HTPR had a higher percentage of recurrent ischemic events compared with patients with NTPR (p = 0.002). In multivariate Cox proportional hazards models, history of ischemic stroke or TIA (HR 4.45, 95% CI 1.77-11.16, p = 0.001) and HTPR (HR 3.34, 95% CI 1.41-7.91, p = 0.006) was independently associated with recurrent ischemic events. In patients with minor stroke or TIA, the prevalence of HTPR was 22.7%, and HTPR was independently associated with recurrent ischemic events.

Evaluation of success after second Ahmed glaucoma valve implantation.

PubMed

Nilforushan, Naveed; Yadgari, Maryam; Jazayeri, Anis Alsadat; Karimi, Nasser

2016-03-01

To evaluate the outcome of the second Ahmed glaucoma valve (AGV) surgery in eyes with failed previous AGV surgery. Retrospective case series. Following chart review, 36 eyes of 34 patients with second AGV implantation were enrolled in this study. The primary outcome measure was surgical success defined in terms of intraocular pressure (IOP) control using two criteria: Success was defined as IOP ≤21 mmHg (criterion 1) and IOP ≤16 mmHg (criterion 2), with at least 20% reduction in IOP, either with no medication (complete success) or with no more than two medications (qualified success). Kaplan-Meier survival analysis was used to determine the probability of surgical success. The average age of the patients was 32.7 years (range 4-65), and the mean duration of follow-up was 21.4 months (range 6-96). Preoperatively, the mean IOP was 26.94 mmHg (standard deviation [SD] 7.03), and the patients were using 2.8 glaucoma medications on average (SD 0.9). The mean IOP decreased significantly to 13.28 mmHg (SD 3.59) at the last postoperative visit (P = 0.00) while the patients needed even fewer glaucoma medications on average (1.4 ± 1.1, P = 0.00). Surgical success of second glaucoma drainage devices (Kaplan-Meier analysis), according to criterion 1, at 6, 12, 18, and 42 months was 94%, 85%, 80%, and 53% respectively, and according to criterion 2, was 94%, 85%, 75%, and 45%, respectively. Repeated AGV implantation seems to be a safe modality of treatment with acceptable success rate in cases with failed previous AGV surgery.

Long non-coding RNA PVT1 as a novel potential biomarker for predicting the prognosis of colorectal cancer.

PubMed

Fan, Heng; Zhu, Jian-Hua; Yao, Xue-Qing

2018-05-01

Long non-coding RNA (lncRNA) plays a very important role in the occurrence and development of various tumors, and is a potential biomarker for cancer diagnosis and prognosis. The purpose of this study was to investigate the relationship between the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and the prognostic significance in patients with colorectal cancer. The expression of PVT1 was measured by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in cancerous and adjacent tissues of 210 colorectal cancer patients. The disease-free survival and overall survival of colorectal cancer patients were evaluated by Kaplan-Meier analysis, and univariate and multivariate analysis were performed by Cox proportional-hazards model. Our results revealed that PVT1 expression in cancer tissues of colorectal cancer was significantly higher than that of adjacent tissues ( P<0.001). High PVT1 expression was increased by 51.4% (108/210), which was significantly correlated with the tumor differentiation, the depth of invasion, the stage of tumor, node, metastasis (TNM), and lymphatic metastasis. The Kaplan-Meier analysis showed that high PVT1 expression resulted in a shorter disease-free survival (Log-rank test P<0.001) and overall survival (Log-rank test P<0.001) compared with the low PVT1 expression group in colorectal cancer patients, whether at TNM I/II stage or at TNM III/IV stage. A multivariate Cox regression analysis demonstrated that high PVT1 expression was an independent predictor of poor prognosis in colorectal cancer patients. Our results suggest that high PVT1 expression might be a potential biomarker for assessing tumor recurrence and prognosis in colorectal cancer patients.

Association between ERCC1 and TS mRNA levels and disease free survival in colorectal cancer patients receiving oxaliplatin and fluorouracil (5-FU) adjuvant chemotherapy.

PubMed

Li, Sheng; Zhu, Liangjun; Yao, Li; Xia, Lei; Pan, Liangxi

2014-08-29

Aim was to explore the association of ERCC1 and TS mRNA levels with the disease free survival (DFS) in Chinese colorectal cancer (CRC) patients receiving oxaliplatin and 5-FU based adjuvant chemotherapy. Total 112 Chinese stage II-III CRC patients were respectively treated by four different chemotherapy regimens after curative operation. The TS and ERCC1 mRNA levels in primary tumor were measured by real-time RT-PCR. Kaplan-Meier curves and log-rank tests were used for DFS analysis. The Cox proportional hazards model was used for prognostic analysis. In univariate analysis, the hazard ratio (HR) for the mRNA expression levels of TS and ERCC1 (logTS: HR = 0.820, 95% CI = 0.600 - 1.117, P = 0.210; logERCC1: HR = 1.054, 95% CI = 0.852 - 1.304, P = 0.638) indicated no significant association of DFS with the TS and ERCC1 mRNA levels. In multivariate analyses, tumor stage (IIIc: reference, P = 0.083; IIb: HR = 0.240, 95% CI = 0.080 - 0.724, P = 0.011; IIc: HR < 0.0001, P = 0.977; IIIa: HR = 0.179, 95% CI = 0.012 - 2.593, P = 0.207) was confirmed to be the independent prognostic factor for DFS. Moreover, the Kaplan-Meier DFS curves showed that TS and ERCC1 mRNA levels were not significantly associated with the DFS (TS: P = 0.264; ERCC1: P = 0.484). The mRNA expression of ERCC1 and TS were not applicable to predict the DFS of Chinese stage II-III CRC patients receiving 5-FU and oxaliplatin based adjuvant chemotherapy.

Glioblastoma: Vascular Habitats Detected at Preoperative Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging Predict Survival.

PubMed

Juan-Albarracín, Javier; Fuster-Garcia, Elies; Pérez-Girbés, Alexandre; Aparici-Robles, Fernando; Alberich-Bayarri, Ángel; Revert-Ventura, Antonio; Martí-Bonmatí, Luis; García-Gómez, Juan M

2018-06-01

Purpose To determine if preoperative vascular heterogeneity of glioblastoma is predictive of overall survival of patients undergoing standard-of-care treatment by using an unsupervised multiparametric perfusion-based habitat-discovery algorithm. Materials and Methods Preoperative magnetic resonance (MR) imaging including dynamic susceptibility-weighted contrast material-enhanced perfusion studies in 50 consecutive patients with glioblastoma were retrieved. Perfusion parameters of glioblastoma were analyzed and used to automatically draw four reproducible habitats that describe the tumor vascular heterogeneity: high-angiogenic and low-angiogenic regions of the enhancing tumor, potentially tumor-infiltrated peripheral edema, and vasogenic edema. Kaplan-Meier and Cox proportional hazard analyses were conducted to assess the prognostic potential of the hemodynamic tissue signature to predict patient survival. Results Cox regression analysis yielded a significant correlation between patients' survival and maximum relative cerebral blood volume (rCBV max ) and maximum relative cerebral blood flow (rCBF max ) in high-angiogenic and low-angiogenic habitats (P < .01, false discovery rate-corrected P < .05). Moreover, rCBF max in the potentially tumor-infiltrated peripheral edema habitat was also significantly correlated (P < .05, false discovery rate-corrected P < .05). Kaplan-Meier analysis demonstrated significant differences between the observed survival of populations divided according to the median of the rCBV max or rCBF max at the high-angiogenic and low-angiogenic habitats (log-rank test P < .05, false discovery rate-corrected P < .05), with an average survival increase of 230 days. Conclusion Preoperative perfusion heterogeneity contains relevant information about overall survival in patients who undergo standard-of-care treatment. The hemodynamic tissue signature method automatically describes this heterogeneity, providing a set of vascular habitats with high

The Impact of Engagement in Street-based Income Generation Activities on Stimulant Drug Use Cessation among People who Inject Drugs

PubMed Central

Ti, Lianping; Richardson, Lindsey; DeBeck, Kora; Nguyen, Paul; Montaner, Julio; Wood, Evan; Kerr, Thomas

2014-01-01

Background Despite the growing prevalence of illicit stimulant drug use internationally, and the widespread involvement of people who inject drugs (IDU) within street-based drug markets, little is known about the impact of different types of street-based income generation activities on the cessation of stimulant use among IDU. Methods Data were derived from an open prospective cohort of IDU in Vancouver, Canada. We used Kaplan-Meier methods and Cox proportional hazards regression to examine the effect of different types of street-based income generation activities (e.g., sex work, drug dealing, and scavenging) on time to cessation of stimulant use. Results Between December, 2005 and November, 2012, 887 IDU who use stimulant drugs (cocaine, crack cocaine, or crystal methamphetamine) were prospectively followed-up for a median duration of 47 months. In Kaplan-Meier analyses, compared to those who did not engage in street-based income generation activities, participants who reported sex work, drug dealing, scavenging, or more than one of these activities were significantly less likely to report stimulant drug use cessation (all p<0.001). When considered as time-updated variables and adjusted for potential confounders in a multivariable model, each type of street-based income generation activity remained significantly associated with a slower time to stimulant drug cessation (all p<0.005). Conclusions Our findings highlight the urgent need for strategies to address stimulant dependence, including novel pharmacotherapies. Also important, structural interventions, such as low-threshold employment opportunities, availability of supportive housing, legal reforms regarding drug use, and evidence-based approaches that reduce harm among IDU are urgently required. PMID:24909853

The impact of engagement in street-based income generation activities on stimulant drug use cessation among people who inject drugs.

PubMed

Ti, Lianping; Richardson, Lindsey; DeBeck, Kora; Nguyen, Paul; Montaner, Julio; Wood, Evan; Kerr, Thomas

2014-08-01

Despite the growing prevalence of illicit stimulant drug use internationally, and the widespread involvement of people who inject drugs (IDU) within street-based drug markets, little is known about the impact of different types of street-based income generation activities on the cessation of stimulant use among IDU. Data were derived from an open prospective cohort of IDU in Vancouver, Canada. We used Kaplan-Meier methods and Cox proportional hazards regression to examine the effect of different types of street-based income generation activities (e.g., sex work, drug dealing, and scavenging) on time to cessation of stimulant use. Between December, 2005 and November, 2012, 887 IDU who use stimulant drugs (cocaine, crack cocaine, or crystal methamphetamine) were prospectively followed-up for a median duration of 47 months. In Kaplan-Meier analyses, compared to those who did not engage in street-based income generation activities, participants who reported sex work, drug dealing, scavenging, or more than one of these activities were significantly less likely to report stimulant drug use cessation (all p<0.001). When considered as time-updated variables and adjusted for potential confounders in a multivariable model, each type of street-based income generation activity remained significantly associated with a slower time to stimulant drug cessation (all p<0.005). Our findings highlight the urgent need for strategies to address stimulant dependence, including novel pharmacotherapies. Also important, structural interventions, such as low-threshold employment opportunities, availability of supportive housing, legal reforms regarding drug use, and evidence-based approaches that reduce harm among IDU are urgently required. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A novel systemic immune-inflammation index predicts survival and quality of life of patients after curative resection for esophageal squamous cell carcinoma.

PubMed

Wang, Lu; Wang, Cong; Wang, Jiangfeng; Huang, Xiaochen; Cheng, Yufeng

2017-10-01

A novel systemic immune-inflammation index (SII) based on platelet (P), neutrophil (N), and lymphocyte (L) counts has been reported to be associated with clinical outcomes in several solid tumors. We aimed to investigate its prognostic value in esophageal squamous cell carcinoma (ESCC) and the potential relationship with quality of life (QOL). A total of 280 ESCC patients who underwent esophagectomy were enrolled. SII (SII = P × N/L) was calculated on the basis of data obtained within 1 week before surgery. An optimal cut-off value stratified patients into high (≥560) and low (<560) preoperative SII groups. The widely used EORTC QLQ-C30 and QLQ-OES18 were utilized to assess QOL at cancer diagnosis and 36 months after surgery. Generalized estimating equations (GEEs) were used to evaluate the association of SII with QOL. Kaplan-Meier method and Cox proportional regression were used to analyze the prognostic value of SII. Kaplan-Meier analyses revealed that higher SII correlated significantly with poorer overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p < 0.001) in patients with ESCC. Multivariate analysis identified SII as an independent prognostic factor for OS (p < 0.001; HR 2.578; 95% CI 1.625-4.088) and DFS (p < 0.001; HR 2.699; 95% CI 1.726-4.223). In addition, patients with high SII exhibited notably deteriorating QOL (p < 0.05). The preoperative SII is a promising biomarker for predicting survival and QOL of patients with ESCC. It may help to identify the high-risk patients for treatment strategy decisions.

Pure fetal histology subtype was associated with better prognosis of children with hepatoblastoma: A Chinese population-based study.

PubMed

Qiao, Guo-liang; Chen, Zhen; Wang, Chen; Ge, Juntao; Zhang, Zhen; Li, Long; Ren, Jun

2016-03-01

The aim of this study is to identify the association between histologic types and the prognosis of hepatoblastoma (HB) in a large Asian cohort of a single institution and to explore the interaction of histologic types with other independently risk factors in the process of affecting prognosis of HB. We retrospectively reviewed 176 children with HB (82 female, 94 male) managed in our institution between May 1, 2001 and July 30, 2014. Prognostic factors were evaluated using Kaplan-Meier curves and Cox proportional hazards models. For the entire cohort of 176 patients, the overall median survival was 80.4 months(95% CI: 71.6-89.2 months), and the 5-year event-free survival and overall survival rates were 54.6 and 66.7%. Descriptive survival statistics and Kaplan-Meier curves suggested that alpha fetoprotein levels, tumor metastases, multifocality, histologic types, and Pre-Treatment Extent of Disease staging System stage had prognostic significance in this relatively selected cohort. Moreover, after eliminating the impact of the interaction of different classification methods of histologic types, pure fetal histologic (PFH) was an independent prognostic factor of HB (hazard ratio [HR]: 2.752, P = 0.021). Further stratification analysis showed that the impaction of other identified risk factors on the influence of PFH on the prognosis of HB patients was different. We have confirmed that the HB prognostic factors of HB and PFH was associated with better prognosis of children with HB based on an Asian population. PFH showed different significance in the process of affecting prognosis of HB with the interaction of other independent risk factors. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Muscle strength and physical performance as predictors of mortality, hospitalization, and disability in the oldest old.

PubMed

Legrand, Delphine; Vaes, Bert; Matheï, Catharina; Adriaensen, Wim; Van Pottelbergh, Gijs; Degryse, Jean-Marie

2014-06-01

To evaluate the predictive value of muscle strength and physical performance in the oldest old for all-cause mortality; hospitalization; and the onset of disability, defined as a decline in activities of daily living (ADLs), independent of muscle mass, inflammatory markers, and comorbidities. A prospective, observational, population-based follow-up study. Three well-circumscribed areas of Belgium. Five hundred sixty participants aged 80 and older were followed for 33.5 months (interquartile range 31.1-35.6 months). Grip strength, Short Physical Performance Battery (SPPB) score, and muscle mass were measured at baseline; ADLs at baseline and after 20 months; and all-cause mortality and time to first hospitalization from inclusion onward. Kaplan-Meier curves and Cox proportional hazards models were calculated for all-cause mortality and hospitalization. Logistic regression analysis was used to determine predictors of decline in ADLs. Kaplan-Meier curves showed significantly higher all-cause mortality and hospitalization in subjects in the lowest tertile of grip strength and SPPB score. The adjusted Cox proportional hazards model showed that participants with high grip strength or a high SPPB score had a lower risk of mortality and hospitalization, independent of muscle mass, inflammatory markers, and comorbidity. A relationship was found between SPPB score and decline in ADLs, independent of muscle mass, inflammation, and comorbidity. In people aged 80 and older, physical performance is a strong predictor of mortality, hospitalization, and disability, and muscle strength is a strong predictor of mortality and hospitalization. All of these relationships were independent of muscle mass, inflammatory markers, and comorbidity. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Communicating projected survival with treatments for chronic kidney disease: patient comprehension and perspectives on visual aids.

PubMed

Dowen, Frances; Sidhu, Karishma; Broadbent, Elizabeth; Pilmore, Helen

2017-09-21

Mortality in end stage renal disease (ESRD) is higher than many malignancies. There is no data about the optimal way to present information about projected survival to patients with ESRD. In other areas, graphs have been shown to be more easily understood than narrative. We examined patient comprehension and perspectives on graphs in communicating projected survival in chronic kidney disease (CKD). One hundred seventy-seven patients with CKD were shown 4 different graphs presenting post transplantation survival data. Patients were asked to interpret a Kaplan Meier curve, pie chart, histogram and pictograph and answer a multi-choice question to determine understanding. We measured interpretation, usefulness and preference for the graphs. Most patients correctly interpreted the graphs. There was asignificant difference in the percentage of correct answers when comparing different graph types (p = 0.0439). The pictograph was correctly interpreted by 81% of participants, the histogram by 79%, pie chart by 77% and Kaplan Meier by 69%. Correct interpretation of the histogram was associated with educational level (p = 0.008) and inversely associated with age > 65 (p = 0.008). Of those who interpreted all four graphs correctly, there was an association with employment (p = 0.001) and New Zealand European ethnicity (p = 0.002). 87% of patients found the graphs useful. The pie chart was the most preferred graph (p 0.002). The readability of the graphs may have been improved with an alternative colour choice, especially in the setting of visual impairment. Visual aids, can be beneficial adjuncts to discussing survival in CKD.

Glioblastoma: does the pre-treatment geometry matter? A postcontrast T1 MRI-based study.

PubMed

Pérez-Beteta, Julián; Martínez-González, Alicia; Molina, David; Amo-Salas, Mariano; Luque, Belén; Arregui, Elena; Calvo, Manuel; Borrás, José M; López, Carlos; Claramonte, Marta; Barcia, Juan A; Iglesias, Lidia; Avecillas, Josué; Albillo, David; Navarro, Miguel; Villanueva, José M; Paniagua, Juan C; Martino, Juan; Velásquez, Carlos; Asenjo, Beatriz; Benavides, Manuel; Herruzo, Ismael; Delgado, María Del Carmen; Del Valle, Ana; Falkov, Anthony; Schucht, Philippe; Arana, Estanislao; Pérez-Romasanta, Luis; Pérez-García, Víctor M

2017-03-01

The potential of a tumour's volumetric measures obtained from pretreatment MRI sequences of glioblastoma (GBM) patients as predictors of clinical outcome has been controversial. Mathematical models of GBM growth have suggested a relation between a tumour's geometry and its aggressiveness. A multicenter retrospective clinical study was designed to study volumetric and geometrical measures on pretreatment postcontrast T1 MRIs of 117 GBM patients. Clinical variables were collected, tumours segmented, and measures computed including: contrast enhancing (CE), necrotic, and total volumes; maximal tumour diameter; equivalent spherical CE width and several geometric measures of the CE "rim". The significance of the measures was studied using proportional hazards analysis and Kaplan-Meier curves. Kaplan-Meier and univariate Cox survival analysis showed that total volume [p = 0.034, Hazard ratio (HR) = 1.574], CE volume (p = 0.017, HR = 1.659), spherical rim width (p = 0.007, HR = 1.749), and geometric heterogeneity (p = 0.015, HR = 1.646) were significant parameters in terms of overall survival (OS). Multivariable Cox analysis for OS provided the later two parameters as age-adjusted predictors of OS (p = 0.043, HR = 1.536 and p = 0.032, HR = 1.570, respectively). Patients with tumours having small geometric heterogeneity and/or spherical rim widths had significantly better prognosis. These novel imaging biomarkers have a strong individual and combined prognostic value for GBM patients. • Three-dimensional segmentation on magnetic resonance images allows the study of geometric measures. • Patients with small width of contrast enhancing areas have better prognosis. • The irregularity of contrast enhancing areas predicts survival in glioblastoma patients.

Controlled, prospective, randomized, clinical split-mouth evaluation of partial ceramic crowns luted with a new, universal adhesive system/resin cement: results after 18 months.

PubMed

Vogl, Vanessa; Hiller, Karl-Anton; Buchalla, Wolfgang; Federlin, Marianne; Schmalz, Gottfried

2016-12-01

A new universal adhesive with corresponding luting composite was recently marketed which can be used both, in a self-etch or in an etch-and-rinse mode. In this study, the clinical performance of partial ceramic crowns (PCCs) inserted with this adhesive and the corresponding luting material used in a self-etch or selective etch approach was compared with a self-adhesive universal luting material. Three PCCs were placed in a split-mouth design in 50 patients. Two PCCs were luted with a combination of a universal adhesive/resin cement (Scotchbond Universal/RelyX Ultimate, 3M ESPE) with (SB+E)/without (SB-E) selective enamel etching. Another PCC was luted with a self-adhesive resin cement (RelyX Unicem 2, 3M ESPE). Forty-eight patients were evaluated clinically according to FDI criteria at baseline and 6, 12 and 18 months. For statistical analyses, the chi-square test (α = 0.05) and Kaplan-Meier analysis were applied. Clinically, no statistically significant differences between groups were detected over time. Within groups, clinically significant increase for criterion "marginal staining" was detected for SB-E over 18 months. Kaplan-Meier analysis revealed significantly higher retention rates for SB+E (97.8 %) and SB-E (95.6 %) in comparison to RXU2 (75.6 %). The 18-month clinical performance of a new universal adhesive/composite combination showed no differences with respect to bonding strategy and may be recommended for luting PCCs. Longer-term evaluation is needed to confirm superiority of SB+E over SB-E. At 18 months, the new multi-mode adhesive, Scotchbond Universal, showed clinically reliable results when used for luting PCCs.

Longterm Hydroxychloroquine Therapy and Low-dose Aspirin May Have an Additive Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with Systemic Lupus Erythematosus.

PubMed

Fasano, Serena; Pierro, Luciana; Pantano, Ilenia; Iudici, Michele; Valentini, Gabriele

2017-07-01

Systemic lupus erythematosus (SLE) is associated with an increased risk of cardiovascular disease (CVD). Thromboprophylaxis with low-dose aspirin (ASA) and hydroxychloroquine (HCQ) seems promising in SLE. We investigated the effects of HCQ cumulative dosages (c-HCQ) and the possible synergistic efficacy of ASA and HCQ in preventing a first CV event (CVE) in patients with SLE. Patients consecutively admitted to our center who, at admission, satisfied the 1997 American College of Rheumatology and/or 2012 Systemic Lupus Collaborating Clinics classification criteria for SLE, and had not experienced any CVE, were enrolled. The occurrence of a thrombotic event, use of ASA, and c-HCQ were recorded. Kaplan-Meier analysis was performed to determine the c-HCQ associated with a lower incidence of CVE. Cox regression analysis served to identify factors associated with a first CVE. For the study, 189 patients with SLE were enrolled and monitored for 13 years (median). Ten CVE occurred during followup. At Kaplan-Meier analysis, the CVE-free rate was higher in ASA-treated patients administered a c-HCQ > 600 g (standard HCQ dose for at least 5 yrs) than in patients receiving ASA alone, or with a c-HCQ dose < 600 g (log-rank test chi-square = 4.01, p = 0.04). Multivariate analysis showed that antimalarials plus ASA protected against thrombosis (HR 0.041 and HR 0.047, respectively), while antiphospholipid antibodies (HR 17.965) and hypertension (HR 18.054) increased the risk of a first CVE. Our results suggest that prolonged use of HCQ plus ASA is thromboprotective in SLE and provides additional evidence for its continued use in patients with SLE.

Clinical outcomes of patients treated with a second course of stereotactic radiosurgery for locally or regionally recurrent brain metastases after prior stereotactic radiosurgery.

PubMed

Kim, Daniel H; Schultheiss, Timothy E; Radany, Eric H; Badie, Behnam; Pezner, Richard D

2013-10-01

Patients with metastatic disease are living longer and may be confronted with locally or regionally recurrent brain metastases (BM) after prior stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). This study analyzes outcomes in patients without prior whole brain radiotherapy (WBRT) who were treated with a second course of SRS/FSRT for locally or regionally recurrent BM. We identified 32 patients at our institution who were treated with a second course of SRS/FSRT after initial SRS/FSRT for newly diagnosed BM. We report clinical outcomes including local control, survival, and toxicities. Control rates and survival were calculated using Kaplan-Meier analysis and the multivariate proportional hazards model. The Kaplan-Meier estimate of local control at 6 months was 77 % for targets treated by a second course of SRS/FSRT with 11/71 (15 %) targets experiencing local failure. Multivariate analysis shows that upon re-treatment, local recurrences were more likely to fail than regional recurrences (OR 8.8, p = 0.02). Median survival for all patients from first SRS/FSRT was 14.6 months (5.3-72.2 months) and 7.9 months (0.7-61.1 months) from second SRS/FSRT. Thirty-eight percent of patients ultimately received WBRT as salvage therapy after the second SRS/FSRT. Seventy-one percent of patients died without active neurologic symptoms. The present study demonstrates that the majority of patients who progress after SRS/FSRT for newly diagnosed BM are candidates for salvage SRS/FSRT. By reserving WBRT for later salvage, we believe that a significant proportion of patients can avoid WBRT all together, thus putting fewer patients at risk for neurocognitive toxicity.

Retrospective analysis of dental implants placed and restored by advanced prosthodontic residents.

PubMed

Barias, Pamela A; Lee, Damian J; Yuan, Judy Chia-Chun; Sukotjo, Cortino; Campbell, Stephen D; Knoernschild, Kent L

2013-02-01

The purposes of this retrospective clinical review were to: (1) describe the demographics of implant patients, types of implant treatment and implant-supported prostheses in an Advanced Education in Prosthodontic Program, (2) evaluate the survival rate of dental implants placed by prosthodontic residents from 2006 to 2008, and (3) analyze the relationship between resident year of training and implant survival rate. All patients who received dental implants placed by prosthodontic residents from January 2006 to October of 2008 in the Advanced Prosthodontic Program at the University of Illinois at Chicago College of Dentistry were selected for this study. Age, gender, implant diameter, length, implant locations, surgical and restorative detail, and year of prosthodontic residency training were collected and analyzed. Life-table and Kaplan-Meier survival analyses were performed based on implants overall, locations, year of training, and use of a computer-generated surgical guide. A Logrank statistic was performed between implant survival and year of prosthodontic residency training, location, and use of computer-generated surgical guide (α= 0.05). Three hundred and six implants were placed, and of these, seven failed. Life-table and Kaplan-Meier analyses computed a cumulative survival rate (CSR) of 97% for overall implants and implants placed with a computer-generated surgical guide. No statistical difference was found in implant survival rates as a function of year of training (P= 0.85). Dental implants placed by prosthodontic residents had a CSR comparable to previously published studies by other specialties. The year of prosthodontic residency training and implant failure rate did not have any significant relationship. © 2012 by the American College of Prosthodontists.

Long-Term Survival in Patients With Acute Kidney Injury After Acute Type A Aortic Dissection Repair.

PubMed

Sasabuchi, Yusuke; Kimura, Naoyuki; Shiotsuka, Junji; Komuro, Tetsuya; Mouri, Hideyuki; Ohnuma, Tetsu; Asaka, Kayo; Lefor, Alan K; Yasunaga, Hideo; Yamaguchi, Atsushi; Adachi, Hideo; Sanui, Masamitsu

2016-12-01

Although acute kidney injury (AKI) is known as a serious complication after operation for acute type A aortic dissection (AAAD), the long-term impact of AKI remains unclear. The aim of the present study is to investigate the long-term survival in patients with AKI after operation for AAAD. This study included 403 patients who underwent operation for AAAD from 1990 to 2011 at Jichi Medical University, Saitama Medical Center. Postoperative AKI was identified according to the Kidney Disease Improving Global Outcomes criteria. Kaplan-Meier survival analysis and Cox proportional hazards regression were modeled to analyze the association between the AKI stage and postoperative long-term survival. Of 403 patients, 181 (44.9%) experienced postoperative AKI. Kaplan-Meier estimates for long-term survival were significantly different among patients without AKI and patients with stage 1, 2, and 3 AKI (p < 0.001). Hazard ratios of long-term survival for patients with stages 1, 2, and 3 AKI compared with patients without AKI were 1.38 (95% confidence interval [CI]: 0.84 to 2.26), 1.82 (95% CI: 0.95 to 3.51), and 3.79 (95% CI: 1.95 to 7.37), respectively. More patients with AKI died because of cardiovascular disease after discharge than patients without AKI (1.8% versus 6.0%, p = 0.03). Stage 3 AKI is significantly associated with lower long-term survival after operation for AAAD. Patient follow-up after discharge that focuses on cardiovascular issues may benefit patients who survive AKI after AAAD operation. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

A Review of Arteriovenous Fistulae Creation in Octogenarians.

PubMed

Diandra, Jennifer Clarissa; Lo, Zhiwen Joseph; Ang, Wei-Wen; Feng, Jue Fei; Narayanan, Sriram; Tan, Glenn Wei Leong; Chandrasekar, Sadhana

2018-01-01

To analyze the outcomes of arteriovenous fistulae (AVFs) creation in octogenarians. A retrospective study of 47 AVFs created in patients aged 80 years and above from 2008 to 2014. Patient and AVF characteristics and outcomes were evaluated. Predictors of patency were analyzed with multivariate analysis and Kaplan-Meier patency, and survival analysis was performed. Forty-seven of 1,259 AVFs created were for octogenarians (4%). Mean age was 83 years old (range: 80-91 years), with 27 male (57%) and 35 with tunneled dialysis catheters in situ (75%). There were a total of 15 (32%) radiocephalic AVFs, 30 (64%) brachial-cephalic AVFs, and 2 (4%) brachial-basilic transposition AVFs. At 12 months, assisted primary patency rate was 28% (13 patients) while primary failure rate was 72% (34 patients). Subset analysis showed brachial-cephalic AVFs to have the highest assisted primary patency rate at 33%. Within 24 months, tunneled dialysis catheter-related sepsis rate was 31% (11 patients). Multivariate analysis did not reveal any factor to be statistically significant in predicting AVF patency. Kaplan-Meier survival curve showed a 50% survival rate at 63 months after AVF creation. In view of high AVF primary failure rate and relatively low tunneled dialysis catheter bacteremia rate, long-term tunneled dialysis catheters as the main form of hemodialysis renal access may be a viable option. However, with 50% of end-stage renal failure patients surviving up to 63 months after AVF creation, the risks and benefits of long-term tunneled dialysis catheters must be balanced against those of AVF creation. Copyright © 2017 Elsevier Inc. All rights reserved.

Prospective Randomized Trial Comparing Efficacy of Topical Loteprednol Etabonate 0.5% Versus Cyclosporine-A 0.05% for Treatment of Dry Eye Syndrome Following Hematopoietic Stem Cell Transplantation.

PubMed

Boynton, Grace E; Raoof, Duna; Niziol, Leslie M; Hussain, Munira; Mian, Shahzad I

2015-07-01

To evaluate the safety and efficacy of topical loteprednol etabonate (LE) 0.5% compared with cyclosporine A (CsA) 0.05% for the prophylaxis and treatment of dry eye syndrome (DES) after hematopoietic stem cell transplantation (HSCT). Seventy-five patients were randomized to LE (n = 76 eyes of 38 patients) or CsA (n = 74 eyes of 37 patients) pre-HSCT. Lissamine green and fluorescein staining, tear break-up time, tear osmolarity (Osm), Schirmer score (Sch), intraocular pressure, visual acuity, and Ocular Surface Disease Index were assessed pre-HSCT, 3, 6, 9, and 12 months post-HSCT. There were no differences in DES incidence (P = 0.22; log-rank test) or progression (P = 0.41; log-rank test) between the 2 treatment arms during the course of the study. Among eyes with no DES at enrollment, the Kaplan-Meier analysis yielded a 90% rate of DES development in cyclosporine-treated eyes and a 79% rate of DES development in LE-treated eyes by 12 months post-HSCT. The Kaplan-Meier analysis of eyes with DES at enrollment demonstrated a 38% rate of disease progression among cyclosporine-treated eyes and a 26% rate of disease progression among loteprednol-treated eyes by 12 months. No patient in either group had an elevation of 10 mm Hg or greater from baseline at any study visit, and no patients had their treatment discontinued for elevation in intraocular pressure. Pre-HSCT initiation of LE 0.5% appears to be safe and may be as effective as CsA 0.5% for the treatment and prophylaxis of DES following HSCT.

Endolymphatic sac surgery versus tenotomy of the stapedius and tensor tympani muscles in the management of patients with unilateral definite Meniere's disease.

PubMed

Albu, Silviu; Babighian, Gregorio; Amadori, Maurizio; Trabalzini, Franco

2015-12-01

This study aims to compare the outcomes of patients with Meniere's disease submitted to either endolymphatic mastoid shunt (ES) or tenotomy of the stapedius and tensor tympani muscles (TSTM). This is a retrospective chart review of patients treated with ES or TSTM between 2000 and 2010 and followed up for at least 12 months. The main outcomes were represented by: (1) vertigo class, hearing stage and functional level according to the American Academy of Otolaryngology-Head and Neck Surgery criteria; (2) adjustment of dizziness handicap inventory (DHI) and (3) complete and substantial vertigo control using the Kaplan-Meier survival method. Sixty-three patients met the inclusion criteria: 34 underwent ES and 29 TSTM. The baseline demographic characteristics, the hearing stage, the functional level, the DHI and hearing levels were not different between the two groups. No significant difference in vertigo class was demonstrated: 66 % of TSTM patients attained class A compared to 44 % in the ES group (p = 0.14). Kaplan-Meier survival curves specific to class A showed significant differences, favoring TSTM (log-rank test, p = 0.022). TSTM patients demonstrated significantly improved functional level (p = 0.0004) and improved DHI scores (p = 0.001). Eight ES patients (25 %) demanded a second surgical attempt compared to none in the TSTM. Aural fullness was significantly improved in TSTM group (p = 0.01), while the difference in tinnitus improvement was non-significant. Hearing preservation was significantly better in TSTM group (p = 0.001). TSTM is a safe surgical procedure, with significant vertigo control rates, and important hearing preservation rates. More patients and longer follow-up are needed to support our preliminary findings.

Safety and efficacy of high-dose chemotherapy with autologous stem cell transplantation for patients with malignant astrocytomas.

PubMed

Chen, Benjamin; Ahmed, Tauseef; Mannancheril, Anney; Gruber, Michael; Benzil, Deborah L

2004-05-15

Malignant astrocytomas are among the most resistant tumors to curative treatments. Mean survival without treatment is measured in weeks, and even with maximal surgery and radiation, the mean reported survival is < 1 year. The advent of supportive treatments and newer agents has resulted in benefits for many patients with cancer. The authors investigated the safety and effect on survival of a high-dose thiotepa and carboplatin regimen with autologous stem cell transplantation (ASCT) in patients with malignant astrocytomas who were enrolled in a prospective trial approved by an institutional review board (IRB). Twenty-one patients were enrolled in an IRB-approved, prospective trial. After baseline testing was completed, patients underwent peripheral stem cell mobilization with cyclophosphamide (4 g/m2) and etoposide (450 mg/m2) followed by granulocyte-colony-stimulating factor (10 microg/kg). Peripheral stem cells were harvested when leukocyte counts recovered. Patients received 2 cycles of thiotepa (750 mg/m2) and carboplatin (1600 mg/m2) followed by infusion of the preserved stem cells. The cycles were administered 6-10 weeks apart. Primary outcome measures were patient survival (Kaplan-Meier analysis) and treatment toxicity (using National Cancer Institute common toxicity criteria). Autologous stem cells were harvested effectively and transfused in all patients. Kaplan-Meier survival analysis demonstrated a survival time of 34.3 +/- 5.5 months (range, 9-94 months). Despite significant myelosuppression, only three patients experienced Grade 4 complications and eight experienced Grade 3 complications. High-dose chemotherapy with thiotepa and carboplatin with concomitant ASCT was used safely to treat patients with malignant astrocytomas and may provide a survival advantage. Copyright 2004 American Cancer Society.

Increased pulse wave velocity in patients with acute lacunar infarction doubled the risk of future ischemic stroke.

PubMed

Saji, Naoki; Murotani, Kenta; Shimizu, Hirotaka; Uehara, Toshiyuki; Kita, Yasushi; Toba, Kenji; Sakurai, Takashi

2017-04-01

The aim of this study was to determine whether pulse wave velocity (PWV), a marker of vascular endothelial impairment and arteriosclerosis, predicts future ischemic stroke in patients who developed acute lacunar infarction. Patients with a first-ever ischemic stroke due to acute lacunar infarction were enrolled in this study. An oscillometric device (Form PWV/ABI; Omron Colin, Tokyo, Japan) was used to measure brachial-ankle PWV 1 week after stroke onset. Patients were followed for at least 5 years. The main end point of the study was recurrent ischemic stroke. Event-free survival was analyzed using Kaplan-Meier plots and log-rank tests. The risk of recurrent ischemic stroke was estimated using the Cox proportional-hazards model. Of the 156 patients (61% male, mean age: 69.2±11.3 years) assessed in this study, 29 developed recurrent ischemic stroke. The median brachial-ankle PWV value was 20.4 m s -1 . Patients with high PWV values had a greater risk of recurrent ischemic stroke than patients with low PWV values (28% vs. 15%, P=0.08). Kaplan-Meier curve analysis showed that patients with high PWV values had a less favorable (that is, free of recurrent ischemic stroke) survival time (P=0.015). A multivariate Cox proportional-hazards model identified high PWV as an independent predictor of recurrent ischemic stroke after adjusting for age, sex and blood pressure (hazard ratio 2.35, 95% confidence interval, 1.02-5.70, P=0.044). In patients with acute lacunar infarction, a high PWV predicts a twofold greater risk of future ischemic stroke, independent of patient age, sex and blood pressure levels.

Efficacy of a recombinant endotoxin neutralizing protein in rabbits with Escherichia coli sepsis.

PubMed

Saladino, R; Garcia, C; Thompson, C; Hammer, B; Parsonnet, J; Novitsky, T; Siber, G; Fleisher, G

1994-02-01

Gram-negative bacterial sepsis is associated with endotoxemia and a high mortality rate. In previous studies, we demonstrated the therapeutic benefit of an anti-lipopolysaccharide factor isolated from amebocytes of Limulus polyphemus, and of a recombinant version of this protein, termed endotoxin neutralizing protein (ENP), in rabbits challenged with purified lipopolysaccharides. To assess the benefit of ENP in treating a live bacterial infection, we established a rabbit model of Escherichia coli (E. coli) peritonitis and bacteremia with high mortality despite gentamicin treatment. Twenty-four pairs of New Zealand white rabbits were challenged intraperitoneally (IP) with E. coli O18ac K1 in 5% porcine mucin (mean bacteria per dose = 2.5 x 10(8)). The animals were treated with intravenous (i.v.) gentamicin (2.5 mg/kg), and with either ENP (5 mg/kg) or saline i.v. at 1 hr after E. coli challenge. All rabbits were bacteremic 1 hr after challenge (geometric mean 4.1 +/- 1.2 x 10(4) cfu/mL). Peak geometric mean serum endotoxin (2.62 v 10.54 EU/mL, P = .013) and tumor necrosis factor (TNF) (2540 v 6438 TNF units/mL, P = .046) concentrations were lower in ENP-treated animals as compared to control animals. Seven of 24 animals treated with ENP survived 24 hr compared with 4 of 24 controls (Kaplan-Meier analysis, P = .19). However, in the subgroup of 13 paired animals in whom bacteremia was eliminated by gentamicin treatment, 5 of 13 ENP-treated animals survived 24 hr, compared with 1 of 13 controls (Kaplan-Meier analysis, P = .032).(ABSTRACT TRUNCATED AT 250 WORDS)

Cetuximab Plus Chemoradiotherapy for HIV-Associated Anal Carcinoma: A Phase II AIDS Malignancy Consortium Trial

PubMed Central

Lee, Jeannette Y.; Palefsky, Joel; Henry, David H.; Wachsman, William; Rajdev, Lakshmi; Aboulafia, David; Ratner, Lee; Fitzgerald, Thomas J.; Kachnic, Lisa; Mitsuyasu, Ronald

2017-01-01

Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after definitive chemoradiation (CRT), associated with anogenital human papilloma virus, and often appears in HIV infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus–associated oropharyngeal SCC, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Forty-five patients with stage I to III SCCAC and HIV infection received CRT: 45 to 54 Gy radiation therapy to the primary tumor and regional lymph nodes plus eight once-weekly doses of concurrent cetuximab and two cycles of cisplatin and fluorouracil. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided α, 0.10; power, 90%), assuming a 35% LRF rate from historical data. Results The 3-year LRF rate was 42% (95% CI, 28% to 56%; one-sided P = .9) by binomial proportional estimate using the prespecified end point (LRF or alive without LRF and followed < 3 years), and 20% (95% CI, 10% to 37%) by Kaplan-Meier estimate in post hoc analysis using definitions and methods consistent with historical data. Three-year rates by Kaplan-Meier estimate were 72% (95% CI, 56% to 84%) for progression-free survival and 79% (95% CI, 63% to 89%) for overall survival. Grade 4 toxicity occurred in 26%, and 4% had treatment-associated deaths. Conclusion HIV-associated SCCAC is potentially curable with definitive CRT. Although addition of cetuximab may result in less LRF, the 20% recurrence and 26% grade 4 toxicity rates indicate the continued need for more-effective and less-toxic therapies. PMID:27937092

Report of 111 Consecutive Patients Enrolled in the International Serial Transverse Enteroplasty (STEP) Data Registry: A Retrospective Observational Study

PubMed Central

Jones, Brian A; Hull, Melissa A; Potanos, Kristina M; Zurakowski, David; Fitzgibbons, Shimae C; Ching, Y Avery; Duggan, Christopher; Jaksic, Tom; Kim, Heung Bae

2016-01-01

Background The International Serial Transverse Enteroplasty (STEP) Data Registry is a voluntary online database created in 2004 to collect information on patients undergoing the STEP procedure. The aim of this study was to identify preoperative factors significantly associated with 1) transplantation or death, or 2) attainment of enteral autonomy following STEP. Study Design Data were collected from September 2004 to January 2010. Univariate and multivariate logistic regression analyses were applied to determine predictors of transplantation/death or enteral autonomy post-STEP. Time to reach full enteral nutrition was estimated using a Kaplan-Meier curve. Results Fourteen of the 111 patients in the Registry were excluded due to inadequate follow-up. Of the remaining 97 patients, 11 patients died, and 5 progressed to intestinal transplantation. On multivariate analysis, higher direct bilirubin and shorter pre-STEP bowel length were independently predictive of progression to transplantation or death (p = .05 and p < .001, respectively). Of the 78 patients who were ≥7 days of age and required parenteral nutrition (PN) at the time of STEP, 37 (47%) achieved enteral autonomy after the first STEP. Longer pre-STEP bowel length was also independently associated with enteral autonomy (p = .002). The median time to reach enteral autonomy based on Kaplan-Meier analysis was 21 months (95% CI: 12-30). Conclusions Overall mortality post-STEP was 11%. Pre-STEP risk factors for progressing to transplantation or death were higher direct bilirubin and shorter bowel length. Among patients who underwent STEP for short bowel syndrome, 47% attained full enteral nutrition post-STEP. Patients with longer pre-STEP bowel length were significantly more likely to achieve enteral autonomy. PMID:23357726

Prognostic evaluation of the elastic properties of the ascending aorta in dilated cardiomyopathy.

PubMed

Sciatti, Edoardo; Vizzardi, Enrico; Bonadei, Ivano; Fabbricatore, Davide; Prati, Francesco; Pagnoni, Mattia; Metra, Marco

2018-05-13

Nowadays there is an increased interest in the role of aortic stiffness in the pathophysiology of heart failure (HF), since it is a major determinant of left ventricular (LV) performance. We aimed at assessing the predictive value of the aortic stiffness parameters, measured by echocardiography, in patients affected by non-ischemic dilated cardiomyopathy (DCM) regarding three end-points: death, HF rehospitalization, combined death or HF rehospitalization in a long-term follow-up. 202 patients affected by non-ischemic DCM underwent an outpatient examination by echocardiography and blood pressure check at the brachial artery, in order to calculate aortic elastic properties (i.e., compliance, distensibility, stiffness index, Peterson's elastic modulus, M-mode strain). ROC curves, Kaplan-Meier curves and multivariable Cox regressions (correcting for age, LV ejection fraction (LVEF), atrial fibrillation, cardiac resynchronization therapy (CRT)) were run to assess the predictive ability of aortic elastic properties against the three endpoints. Mean follow-up was 9.83±2.80 years. 24.8% of patients died, while 34.7% were rehospitalized for HF cause and 44.6% experienced the combined endpoint. LVEF did not correlate with aortic elastic properties. ROC curves and Kaplan-Meier curves were elaborated. Aortic stiffness did not predict death in our cohort. Otherwise, all aortic elastic properties predicted HF rehospitalization and combined death or HF rehospitalization, after correcting for age, LVEF, atrial fibrillation, CRT. Elastic properties of the ascending aorta measured by echocardiography in patients with non-ischemic DCM predict long-term HF rehospitalization and combined death or HF rehospitalization, also after correcting for the confounding factors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The Role of Vaginal Brachytherapy in the Treatment of Surgical Stage I Papillary Serous or Clear Cell Endometrial Cancer

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

Barney, Brandon M., E-mail: barney.brandon@mayo.edu; Petersen, Ivy A.; Mariani, Andrea

2013-01-01

Objectives: The optimal adjuvant therapy for International Federation of Gynecology and Obstetrics (FIGO) stage I papillary serous (UPSC) or clear cell (CC) endometrial cancer is unknown. We report on the largest single-institution experience using adjuvant high-dose-rate vaginal brachytherapy (VBT) for surgically staged women with FIGO stage I UPSC or CC endometrial cancer. Methods and Materials: From 1998-2011, 103 women with FIGO 2009 stage I UPSC (n=74), CC (n=21), or mixed UPSC/CC (n=8) endometrial cancer underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by adjuvant high-dose-rate VBT. Nearly all patients (n=98, 95%) also underwent extended lymph node dissection of pelvic andmore » paraortic lymph nodes. All VBT was performed with a vaginal cylinder, treating to a dose of 2100 cGy in 3 fractions. Thirty-five patients (34%) also received adjuvant chemotherapy. Results: At a median follow-up time of 36 months (range, 1-146 months), 2 patients had experienced vaginal recurrence, and the 5-year Kaplan Meier estimate of vaginal recurrence was 3%. The rates of isolated pelvic recurrence, locoregional recurrence (vaginal + pelvic), and extrapelvic recurrence (including intraabdominal) were similarly low, with 5-year Kaplan-Meier estimates of 4%, 7%, and 10%, respectively. The estimated 5-year overall survival was 84%. On univariate analysis, delivery of chemotherapy did not affect recurrence or survival. Conclusions: VBT is effective at preventing vaginal relapse in women with surgical stage I UPSC or CC endometrial cancer. In this cohort of patients who underwent comprehensive surgical staging, the risk of isolated pelvic or extrapelvic relapse was low, implying that more extensive adjuvant radiation therapy is likely unnecessary.« less

OUTCOME OF DOGS WITH INTRANASAL LYMPHOMA TREATED WITH VARIOUS RADIATION AND CHEMOTHERAPY PROTOCOLS: 24 CASES.

PubMed

George, Rebecca; Smith, Annette; Schleis, Stephanie; Brawner, William; Almond, Gregory; Kent, Michael; Wypij, Jackie; Borrego, Juan; Moore, Antony; Keyerleber, Michele; Kraiza, Sarah

2016-05-01

Tumors of the nasal cavity comprise approximately 1% of all neoplasms in dogs. Canine intranasal lymphoma is rare and reports evaluating the outcome of treatment are lacking. The goal of this observational, descriptive, multi-institutional study was to evaluate the overall median survival times (MSTs) in a group of dogs with intranasal lymphoma that were treated with irradiation and/or chemotherapy. Dogs meeting these inclusion criteria were retrospectively recruited from medical archives at multiple institutions. Eighteen cases of intermediate to high grade intranasal lymphoma and six cases of low-grade intranasal lymphoma were identified. The date of diagnosis, method of diagnosis, treatment received (radiation and/or chemotherapy protocols), and date of death were recorded. Kaplan-Meier survival analysis was performed on the intermediate to high grade group to calculate overall MST. Log-rank tests were performed to compare effects of treatment with radiation therapy ± chemotherapy and chemotherapy alone. Kaplan-Meier survival analysis was performed separately on the low-grade group. The overall MST was 375 days for the intermediate to high grade group. Cases treated with radiation ± chemotherapy had an MST of 455 days (n = 12) and those treated with chemotherapy alone (n = 6) had an MST of 157 days in the intermediate to high grade group. The MST was 823 days for the low-grade group. Results support the use of radiation therapy for treatment of canine intranasal lymphoma, however a randomized, controlled, clinical trial would be needed for more definitive recommendations. The role of adjunctive chemotherapy also may require further investigation. © 2016 American College of Veterinary Radiology.

Fracture and distant migration of the Bard Recovery filter: a retrospective review of 363 implantations for potentially life-threatening complications.

PubMed

Tam, Matthew D; Spain, James; Lieber, Michael; Geisinger, Michael; Sands, Mark J; Wang, Weiping

2012-02-01

To report the occurrence of fracture of the Recovery filter and incidence of potentially life-threatening complications associated with fractured fragment migration. A retrospective study of images obtained after placement of Recovery inferior vena cava (IVC) filters from 2003 to 2006 was conducted at a single tertiary-care center. Images were reevaluated for fracture and migration; complications related to filter fracture were investigated. Kaplan-Meier survival analysis was performed to investigate the relationship between time in situ and fracture. A total of 363 Recovery filters were placed; 97 were retrieved, leaving 266 filters in situ (135 patients subsequently died of other causes). The following images were evaluated: 130 chest computed tomography (CT) scans, 153 abdominal CT scans, 254 chest radiographs, 148 radiographs of the abdomen/pelvis, and 106 cavagrams. Mean imaging follow-up interval was 18.4 months (maximum, 81.3 mo). No en bloc migration occurred outside the IVC. Twenty-six limb fractures (all short limbs) were identified in 20 patients; the earliest occurred at 4.1 months. Eight fragment migrations occurred into pulmonary arteries, seven into iliac/femoral veins, one into the right ventricle, and one into the renal vein. Seven fragments were intracaval near the filter, one was extracaval, and one could not be located. Kaplan-Meier survival estimates predicted a fracture rate of 40% at 5.5 years. Of the 20 patients with filter fractures, three died of unrelated causes and 17 remain asymptomatic. Recovery filter fractures occurred at the short limb only, with a suggested 5.5-year fracture risk of 40%. No life-threatening events occurred in patients with filter fracture. Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.

Can Superselective Intra-Arterial Chemoradiotherapy Replace Surgery Followed by Radiation for Advanced Cancer of the Tongue and Floor of the Mouth?

PubMed

Kobayashi, Wataru; Kukobota, Kosei; Ito, Ryohei; Sakaki, Hirotaka; Nakagawa, Hirosi; Teh, Beng Gwan

2016-06-01

The purpose of this study was to compare quality of life (QoL) and the survival rate after surgery with and without radiotherapy versus superselective intra-arterial chemoradiotherapy (SSIACRT) for advanced cancer of the tongue and floor of the mouth. Patients with stage III and IV squamous cell carcinoma of the tongue and floor of the mouth treated between 2000 and 2013 were included in this study. The predictor variables were surgery without radiotherapy, surgery followed by radiotherapy, and SSIACRT. The outcome variables were QoL and the survival rate. The University of Washington QoL questionnaire (UW-QOL) was used for evaluation of QoL. The Kaplan-Meier method was used to estimate the overall survival rate. The UW-QOL was analyzed by analysis of covariance, and the survival rate was analyzed statistically by the log-rank test. Sixty-two patients were eligible for this study. Of these, 13 were treated by surgery without radiotherapy, 29 were treated by surgery plus radiotherapy, and 20 were treated by SSIACRT. The SSIACRT group had the best UW-QOL scores among the 3 groups. The 5-year Kaplan-Meier disease-specific survival rates for these groups were 92.9%, 62.9%, and 83.2%, respectively, with no significant difference (P = .20) shown. The QoL scores of the SSIACRT group were the best among the 3 groups in most domains. The superiority of QoL and the survival rate in the SSIACRT group showed that SSIACRT should be preferred in managing advanced cancer of the tongue and floor of the mouth. Copyright © 2016 The American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Secondary patella resurfacing in painful non-resurfaced total knee arthroplasties : A study of survival and clinical outcome from the Norwegian Arthroplasty Register (1994-2011).

PubMed

Leta, Tesfaye H; Lygre, Stein Håkon L; Skredderstuen, Arne; Hallan, Geir; Gjertsen, Jan-Erik; Rokne, Berit; Furnes, Ove

2016-04-01

In Norway, 19 % of revisions of non-resurfaced total knee arthroplasties done for knee pain between 1994 and 2011 were Secondary Patella Resurfacing (SPR). It is, however, unclear whether SPR actually resolves the pain. The aim was to investigate prostheses survival and clinical outcomes following SPR. A total of 308 knees (301 patients) with SPR were used to assess implant survival, and a sub-cohort (n = 114 out of 301 patients) with Patient Reported Outcome Measures (PROMs) data were used to assess the clinical outcomes. The EuroQol (EQ-5D), the Knee Injury and Osteoarthritis Outcome Score, and Visual Analogue Scales on satisfaction and pain were used to collect PROM data. Outcomes were analysed by Kaplan-Meier, Cox regression, and multiple linear regression. The five- and ten-year Kaplan-Meier survival percentages were 91 % and 87 %, respectively. Overall, 35 knees were re-revised at a median follow-up of eight years and pain alone (10 knees) was the main cause of re-revision. Younger patients (<60 years) had nearly nine times higher risk of re-revision compared to older patients (>70 years) (RR = 8.6; p < 0.001). Mean EQ-5D index score had improved from 0.41 (SD 0.21) preoperative to 0.56 (SD 0.25) postoperative following SPR. A total of 63 % of patients with PROM data were satisfied with the outcomes of SPR. The long-term prostheses survival following SPR was satisfactory, although not as good as for primary knee replacement. Patients' health related quality of life improved significantly following SPR. Still, more than a third of patients with PROMs data were dissatisfied with the outcomes of the SPR procedure.

Induction regimen and survival in simultaneous heart-kidney transplant recipients.

PubMed

Ariyamuthu, Venkatesh K; Amin, Alpesh A; Drazner, Mark H; Araj, Faris; Mammen, Pradeep P A; Ayvaci, Mehmet; Mete, Mutlu; Ozay, Fatih; Ghanta, Mythili; Mohan, Sumit; Mohan, Prince; Tanriover, Bekir

2018-05-01

Induction therapy in simultaneous heart-kidney transplantation (SHKT) is not well studied in the setting of contemporary maintenance immunosuppression consisting of tacrolimus (TAC), mycophenolic acid (MPA), and prednisone (PRED). We analyzed the Organ Procurement and Transplant Network registry from January 1, 2000, to March 3, 2015, for recipients of SHKT (N = 623) maintained on TAC/MPA/PRED at hospital discharge. The study cohort was further stratified into 3 groups by induction choice: induction (n = 232), rabbit anti-thymoglobulin (r-ATG; n = 204), and interleukin-2 receptor-α (n = 187) antagonists. Survival rates were estimated using the Kaplan-Meier estimator. Multivariable inverse probability weighted Cox proportional hazard regression models were used to assess hazard ratios associated with post-transplant mortality as the primary outcome. The study cohort was censored on March 4, 2016, to allow at least 1-year of follow-up. During the study period, the number of SHKTs increased nearly 5-fold. The Kaplan-Meier survival curve showed superior outcomes with r-ATG compared with no induction or interleukin-2 receptor-α induction. Compared with the no-induction group, an inverse probability weighted Cox proportional hazard model showed no independent association of induction therapy with the primary outcome. In sub-group analysis, r-ATG appeared to lower mortality in sensitized patients with panel reactive antibody of 10% or higher (hazard ratio, 0.19; 95% confidence interval, 0.05-0.71). r-ATG may provide a survival benefit in SHKT, especially in sensitized patients maintained on TAC/MPA/PRED at hospital discharge. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Lifetime anxiety disorder and current anxiety symptoms associated with hastened depressive recurrence in bipolar disorder.

PubMed

Shah, Saloni; Kim, Jane P; Park, Dong Yeon; Kim, Hyun; Yuen, Laura D; Do, Dennis; Dell'Osso, Bernardo; Hooshmand, Farnaz; Miller, Shefali; Wang, Po W; Ketter, Terence A

2017-09-01

To assess differential relationships between lifetime anxiety disorder/current anxiety symptoms and longitudinal depressive severity in bipolar disorder (BD). Stanford BD Clinic outpatients enrolled during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation and followed with the STEP-BD Clinical Monitoring Form while receiving naturalistic treatment for up to two years. Baseline unfavorable illness characteristics/current mood symptoms and times to depressive recurrence/recovery were compared in patients with versus without lifetime anxiety disorder/current anxiety symptoms. Among 105 currently recovered patients, lifetime anxiety disorder was significantly associated with 10/27 (37.0%) demographic/other unfavorable illness characteristics/current mood symptoms/current psychotropics, hastened depressive recurrence (driven by earlier onset age), and a significantly (> two-fold) higher Kaplan-Meier estimated depressive recurrence rate, whereas current anxiety symptoms were significantly associated with 10/27 (37.0%) demographic/other unfavorable illness characteristics/current mood symptoms/current psychotropics and hastened depressive recurrence (driven by lifetime anxiety disorder), but only a numerically higher Kaplan-Meier estimated depressive recurrence rate. In contrast, among 153 currently depressed patients, lifetime anxiety disorder/current anxiety symptoms were not significantly associated with time to depressive recovery or depressive recovery rate. American tertiary BD clinic referral sample, open naturalistic treatment. Research is needed regarding differential relationships between lifetime anxiety disorder and current anxiety symptoms and hastened/delayed depressive recurrence/recovery - specifically whether lifetime anxiety disorder versus current anxiety symptoms has marginally more robust association with hastened depressive recurrence, and whether both have marginally more robust

Adjuvant Ab Interno Tumor Treatment After Proton Beam Irradiation.

PubMed

Seibel, Ira; Riechardt, Aline I; Heufelder, Jens; Cordini, Dino; Joussen, Antonia M

2017-06-01

This study was performed to show long-term outcomes concerning globe preservation in uveal melanoma patients after proton beam therapy with the main focus on outcomes according to different adjuvant ab interno surgical procedures. Retrospective cohort study. All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma between June 1998 and June 2015 were included. A total of 2499 patients underwent primary proton beam therapy, with local tumor control and globe preservation rates of 95.9% and 94.8% after 5 years, respectively. A total of 110 (4.4%) patients required secondary enucleation. Unresponsive neovascular glaucoma was the leading cause of secondary enucleation in 78 of the 2499 patients (3.1%). The 5-year enucleation-free survival rate was 94.8% in the endoresection group, 94.3% in the endodrainage group, and 93.5% in the comparator group. The log-rank test showed P = .014 (comparator group vs endoresection group) and P = .06 (comparator group vs endodrainage-vitrectomy group). Patients treated with endoresection or endodrainage-vitrectomy developed less radiation retinopathy (30.5% and 37.4% after 5 years, P = .001 and P = .048 [Kaplan-Meier], respectively) and less neovascular glaucoma (11.6% and 21.3% after 5 years, P = .001 and P = .01 [Kaplan-Meier], respectively) compared with the comparator group (52.3% radiation retinopathy and 57.8% neovascular glaucoma after 5 years). This study suggests that in larger tumors the enucleation and neovascular glaucoma rates might be reduced by adjuvant surgical procedures. Although endoresection is the most promising adjuvant treatment option, the endodrainage-vitrectomy is recommended in patients who are ineligible for endoresection. Copyright © 2017 Elsevier Inc. All rights reserved.

Using mini-rockwool blocks as growing media for limited-cluster tomato production

NASA Technical Reports Server (NTRS)

Logendra, L. S.; Gianfagna, T. J.; Janes, H. W.

2001-01-01

Rockwool is an excellent growing medium for the hydroponic production of tomato; however, the standard size rockwool blocks [4 x 4 x 2.5 inches (10 x 10 x 6.3 cm) or 3 x 3 x 2.5 inches (7.5 x 7.5 x 6.3 cm)] are expensive. The following experiments were conducted with less expensive minirock wool blocks (MRBs), on rayon polyester material (RPM) as a bench top liner, to reduce the production cost of tomatoes (Lycopersicon esculentum) grown in a limited-cluster, ebb and flood hydroponic cultivation system. Fruit yield for single-cluster plants growing in MRBs [2 x 2 x 1.6 inches (5 x 5 x 4 cm) and 1.6 x 1.6 x 1.6 inches (4 x 4 x 4 cm)] was not significantly different from plants grown in larger sized blocks (3 x 3 x 2.5 inches). When the bench top was lined with RPM, roots penetrated the RPM, and an extensive root mat developed between the RPM and the bench top. The fruit yield from plants on RPM was significantly increased compared to plants without RPM due to increases in fruit size and fruit number. RPM also significantly reduced the incidence of blossom-end rot. In a second experiment, single- and double-cluster plants were grown on RPM. Fruit yield for double-cluster plants was 40% greater than for single-cluster plants due to an increase in fruit number, although the fruit were smaller in size. As in the first experiment, fruit yield for all plants grown in MRBs was not significantly different from plants grown in the larger sized blocks. MRBs and a RPM bench liner are an effective combination in the production of limited-cluster hydroponic tomatoes.

Restriction limits and main drivers of fruit production in palm in central Amazonia

NASA Astrophysics Data System (ADS)

Freitas, Cintia; Costa, Flávia R. C.; Barbosa, Carlos Eduardo; Cintra, Renato

2016-11-01

Adult plants incapable of producing viable offspring inflate our perception of the size of population distribution. We propose that species occurrence is limited to a subset of the environmental gradient and that it changes as ontogenetic development progresses. Moreover, fruit production is associated with site-specific environmental conditions. We sampled 2988 adult individuals from nine palm species in 30 plots (40 × 250 m) and used a larger data set including 42 other plots distributed along a continuous topo-edaphic gradient in a terra firme forest near Manaus, Brazil. Five out of nine palm species were more restricted to a sub-section of the topo-edaphic gradient in the adult-size phase. More specifically, reproductive individuals of species Attalea attaleoides and A. microcarpa had even more restricted distributions than adult-sized, non-reproductive plants. Successive environmental filtering and competition probably acting through selective mortality led to increasing habitat restriction, with reproductive adults being restricted to a smaller part of the region than juveniles and adults. Water availability and nutrients limited both the ability to produce fruits and the amount of fruit production. Previous studies have reported stronger habitat associations for older plants than for seedlings or juveniles, but we show here that some species are more restricted at their reproductive stage. Plant specializations to local conditions may be more common than currently acknowledged, and a significant portion of individuals in a population might represent sinks. Such strong environmental limitations of reproductive plants should also be considered in management of species with economic value and in conservation planning.

A population-based study on the association between educational length, prostate-specific antigen testing and use of prostate biopsies.

PubMed

Nordström, Tobias; Bratt, Ola; Örtegren, Joakim; Aly, Markus; Adolfsson, Jan; Grönberg, Henrik

2016-01-01

The aim of this study was to determine whether educational length affects prostate-specific antigen (PSA) testing and the time to prostate biopsy for men with raised PSA values. Using register data on all men in Stockholm County in 2013 (n = 1,052,841), the limited-duration point prevalence of PSA testing and time between test and prostate biopsy or repeat testing were analysed. Patterns of follow-up were assessed using Kaplan-Meier product limit estimators and Cox proportional hazard models. Educational length was categorized as short (≤ 9 years), intermediate (10-12 years) or long (≥ 13 years). PSA testing increased with educational length in all age groups. Among men aged 50-69 years, 61% with long and 54% with short education had had a PSA test within the preceding 10 years (p < 0.001). In men with PSA 4-10 ng/ml, 40% [95% confidence interval (CI) 38-41] with long and 27% (95% CI 26-29) with short education underwent a prostate biopsy within 12 months. After adjusting for PSA level and age, educational length was still associated with the chance of having a prostate biopsy in men with PSA 4-10 ng/ml (hazard ratio 1.22, 95% CI 1.12-1.31), but not in men with higher PSA values. PSA testing increased with educational length. Men with long education were more likely to have a prostate biopsy after an increased PSA value below 10 ng/ml than men with short education. These differences may contribute to the worse prostate cancer outcomes observed among men with lower socioeconomic status.

Risks and costs of end-stage renal disease after heart transplantation.

PubMed

Hornberger, J; Best, J; Geppert, J; McClellan, M

1998-12-27

To estimate the risks and costs of end-stage renal disease (ESRD) after heart transplantation. Previous studies have shown high rates of ESRD among solid-organ transplant patients, but the relevance of these studies for current transplant practices and policies is unclear. Limitations of prior studies include relatively small, single-center samples and estimates made before implementing suggested practice changes to reduce ESRD risk. Medicare beneficiaries who underwent heart transplantation between 1989 and 1994 were eligible for study inclusion (n=2088). Thirty-four patients undergoing dialysis or who had the diagnosis of ESRD before or at transplantation were excluded from the study. ESRD was defined as any patient undergoing renal transplantation or requiring dialysis for more than 3 months. Mortality and ESRD events were recorded up to 1995. ESRD risk was estimated using the Kaplan-Meier product-limit estimator and logistic regression analyses. Linear regression was performed to determine expenditures for treating ESRD, and we developed long-term models of the risk and direct medical costs of ESRD care. The annual risk of ESRD was 0.37% in the first year after transplant and increased to 4.49% by the sixth posttransplant year. There was no significant trend in the risk of ESRD based on the year of transplantation, even after adjusting for patient characteristics. The average cumulative 10-year direct cost of ESRD per patient undergoing heart transplantation exceeded $13,000. In a large, national sample of patients undergoing heart transplantation, ESRD is not rare, even for patients undergoing transplant after the development of new practices intended to reduce its occurrence. ESRD remains an important component of the costs of heart transplantation.

The natural history of HIV infection in intravenous drug users: risk of disease progression in a cohort of seroconverters.

PubMed

Rezza, G; Lazzarin, A; Angarano, G; Sinicco, A; Pristerà, R; Ortona, L; Barbanera, M; Gafà, S; Tirelli, U; Salassa, B

1989-02-01

A multicentre cohort study was carried out to estimate the incidence of AIDS and HIV-related conditions in newly infected intravenous drug users (IVDU). The enrollment criteria included the identification of the seroconversion time. Two hundred and five subjects entered the study, and were followed for a mean of 26 months. Twelve subjects developed clinical AIDS over a 4-year period. The actuarial incidence of AIDS estimated by Kaplan-Meier survival technique was 17.8% by 4 years since seroconversion. The risk of developing AIDS increased significantly after 24 months from seroconversion. Relatively small figures accounted for the lack of statistical association between the risk factors investigated and the disease status.

Markov chains and semi-Markov models in time-to-event analysis.

PubMed

Abner, Erin L; Charnigo, Richard J; Kryscio, Richard J

2013-10-25

A variety of statistical methods are available to investigators for analysis of time-to-event data, often referred to as survival analysis. Kaplan-Meier estimation and Cox proportional hazards regression are commonly employed tools but are not appropriate for all studies, particularly in the presence of competing risks and when multiple or recurrent outcomes are of interest. Markov chain models can accommodate censored data, competing risks (informative censoring), multiple outcomes, recurrent outcomes, frailty, and non-constant survival probabilities. Markov chain models, though often overlooked by investigators in time-to-event analysis, have long been used in clinical studies and have widespread application in other fields.

Markov chains and semi-Markov models in time-to-event analysis

PubMed Central

Abner, Erin L.; Charnigo, Richard J.; Kryscio, Richard J.

2014-01-01

A variety of statistical methods are available to investigators for analysis of time-to-event data, often referred to as survival analysis. Kaplan-Meier estimation and Cox proportional hazards regression are commonly employed tools but are not appropriate for all studies, particularly in the presence of competing risks and when multiple or recurrent outcomes are of interest. Markov chain models can accommodate censored data, competing risks (informative censoring), multiple outcomes, recurrent outcomes, frailty, and non-constant survival probabilities. Markov chain models, though often overlooked by investigators in time-to-event analysis, have long been used in clinical studies and have widespread application in other fields. PMID:24818062

78 FR 56859 - Foreign-Trade Zone 75-Phoenix, Arizona, Authorization of Limited Production Activity, Honeywell...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-16

... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [B-41-2013] Foreign-Trade Zone 75--Phoenix, Arizona, Authorization of Limited Production Activity, Honeywell Aerospace, Inc. (Aircraft Engines, Systems and Components), Phoenix and Tempe, Arizona On May 3, 2013, the City of Phoenix, grantee of FTZ 75...

Protective Role of Comfrey Leave Extracts on UV-induced Zebrafish Fin Damage

PubMed Central

Cheng, Chien-Chung; Chou, Chi-Yuan; Chang, Yao-Chin; Wang, Hsuan-Wen; Wen, Chi-Chung; Chen, Yau-Hung

2014-01-01

In zebrafish, UV exposure leads to fin malformation phenotypes including fin reduction or absence. The present study evaluated UV-protective activities of comfrey leaves extracts in a zebrafish model by recording fin morphological changes. Chemopreventive effects of comfrey leave extracts were evaluated using Kaplan-Meier analysis and Cox proportional hazards regression. The results showed that (1) the mean times of return to normal fin in the UV+comfrey (50 and 100 ppm) groups were 3.43 and 2.86 days and were quicker compared with that in the UV only group (4.21 days); (2) zebrafish fins in the UV+comfrey (50 and 100 ppm) groups were 2.05 and 3.25 times more likely to return to normal than those in the UV only group; and (3) comfrey leave extracts had UV-absorbance abilities and significantly reduced ROS production in UV-exposed zebrafish embryos, which may attenuate UV-mediated apoptosis. In conclusion, comfrey leaves extracts may have the potential to be developed as UV-protective agents to protect zebrafish embryos from UV-induced damage. PMID:25352712

Utilizing high-throughput experimentation to enhance specific productivity of an E.coli T7 expression system by phosphate limitation.

PubMed

Huber, Robert; Roth, Simon; Rahmen, Natalie; Büchs, Jochen

2011-03-17

The specific productivity of cultivation processes can be optimized, amongst others, by using genetic engineering of strains, choice of suitable host/vector systems or process optimization (e.g. choosing the right induction time). A further possibility is to reduce biomass buildup in favor of an enhanced product formation, e.g. by limiting secondary substrates in the medium, such as phosphate. However, with conventional techniques (e.g. small scale cultivations in shake flasks), it is very tedious to establish optimal conditions for cell growth and protein expression, as the start of protein expression (induction time) and the degree of phosphate limitation have to be determined in numerous concerted, manually conducted experiments. We investigated the effect of different induction times and a concurrent phosphate limitation on the specific productivity of the T7 expression system E.coli BL21(DE3) pRhotHi-2-EcFbFP, which produces the model fluorescence protein EcFbFP upon induction. Therefore, specific online-monitoring tools for small scale cultivations (RAMOS, BioLector) as well as a novel cultivation platform (Robo-Lector) were used for rapid process optimization. The RAMOS system monitored the oxygen transfer rate in shake flasks, whereas the BioLector device allowed to monitor microbial growth and the production of EcFbFP in microtiter plates. The Robo-Lector is a combination of a BioLector and a pipetting robot and can conduct high-throughput experiments fully automated. By using these tools, it was possible to determine the optimal induction time and to increase the specific productivity for EcFbFP from 22% (for unlimited conditions) to 31% of total protein content of the E.coli cells via a phosphate limitation. The results revealed that a phosphate limitation at the right induction time was suitable to redirect the available cellular resources during cultivation to protein expression rather than in biomass production. To our knowledge, such an effect was

Mitigation of tip vortex cavitation by means of air injection on a Kaplan turbine scale model

NASA Astrophysics Data System (ADS)

Rivetti, A.; Angulo, M.; Lucino, C.; Liscia, S.

2014-03-01

Kaplan turbines operating at full-load conditions may undergo excessive vibration, noise and cavitation. In such cases, damage by erosion associated to tip vortex cavitation can be observed at the discharge ring. This phenomenon involves design features such as (1) overhang of guide vanes; (2) blade profile; (3) gap increasing size with blade opening; (4) suction head; (5) operation point; and (6) discharge ring stiffness, among others. Tip vortex cavitation may cause erosion at the discharge ring and draft tube inlet following a wavy pattern, in which the number of vanes can be clearly identified. Injection of pressurized air above the runner blade centerline was tested as a mean to mitigate discharge ring cavitation damage on a scale model. Air entrance was observed by means of a high-speed camera in order to track the air trajectory toward its mergence with the tip vortex cavitation core. Post-processing of acceleration signals shows that the level of vibration and the RSI frequency amplitude decrease proportionally with air flow rate injected. These findings reveal the potential mitigating effect of air injection in preventing cavitation damage and will be useful in further tests to be performed on prototype, aiming at determining the optimum air flow rate, size and distribution of the injectors.

Strategies to limit colour changes when fortifying food products with iron.

PubMed

Habeych, Edwin; van Kogelenberg, Violet; Sagalowicz, Laurent; Michel, Martin; Galaffu, Nicola

2016-10-01

Iron, vitamin A, zinc and iodine have been recognized to be the micronutrients with the largest deficiencies worldwide. Among these, iron is highly reactive and may lead to negatively perceived organoleptic changes in products such as dull colour and off-taste. The colour change originated in fortified fruit-containing food products was confirmed to be the result of the complexation of iron and polyphenols. Phenolic compounds with two or more vicinal hydroxy benzyl moieties in their structure, such as catechols and pyrogallols were investigated for their ability to give bathochromic shift phenomena when mixed with iron salts. Furthermore, strategies for limiting colour development were based on: 1) pH adjustment; 2) saturation of polyphenols with unreactive divalent metal ions; 3) suppression of iron reactivity through complexation. Some of these strategies showed a significant improvement in colour stability, with the best results achieved by the latter. The findings in model systems gave a good insight of the mechanisms involved in colour changes, and results were transferable to iron fortified banana puree. Copyright © 2016 Elsevier Ltd. All rights reserved.

Greenhouse tomato limited cluster production systems: crop management practices affect yield

NASA Technical Reports Server (NTRS)

Logendra, L. S.; Gianfagna, T. J.; Specca, D. R.; Janes, H. W.

2001-01-01

Limited-cluster production systems may be a useful strategy to increase crop production and profitability for the greenhouse tomato (Lycopersicon esculentum Mill). In this study, using an ebb-and-flood hydroponics system, we modified plant architecture and spacing and determined the effects on fruit yield and harvest index at two light levels. Single-cluster plants pruned to allow two leaves above the cluster had 25% higher fruit yields than did plants pruned directly above the cluster; this was due to an increase in fruit weight, not fruit number. Both fruit yield and harvest index were greater for all single-cluster plants at the higher light level because of increases in both fruit weight and fruit number. Fruit yield for two-cluster plants was 30% to 40% higher than for single-cluster plants, and there was little difference in the dates or length of the harvest period. Fruit yield for three-cluster plants was not significantly different from that of two-cluster plants; moreover, the harvest period was delayed by 5 days. Plant density (5.5, 7.4, 9.2 plants/m2) affected fruit yield/plant, but not fruit yield/unit area. Given the higher costs for materials and labor associated with higher plant densities, a two-cluster crop at 5.5 plants/m2 with two leaves above the cluster was the best of the production system strategies tested.

A method to combine hydrodynamics and constructive design in the optimization of the runner blades of Kaplan turbines

NASA Astrophysics Data System (ADS)

Miclosina, C. O.; Balint, D. I.; Campian, C. V.; Frunzaverde, D.; Ion, I.

2012-11-01

This paper deals with the optimization of the axial hydraulic turbines of Kaplan type. The optimization of the runner blade is presented systematically from two points of view: hydrodynamic and constructive. Combining these aspects in order to gain a safer operation when unsteady effects occur in the runner of the turbine is attempted. The design and optimization of the runner blade is performed with QTurbo3D software developed at the Center for Research in Hydraulics, Automation and Thermal Processes (CCHAPT) from "Eftimie Murgu" University of Resita, Romania. QTurbo3D software offers possibilities to design the meridian channel of hydraulic turbines design the blades and optimize the runner blade. 3D modeling and motion analysis of the runner blade operating mechanism are accomplished using SolidWorks software. The purpose of motion study is to obtain forces, torques or stresses in the runner blade operating mechanism, necessary to estimate its lifetime. This paper clearly states the importance of combining the hydrodynamics with the structural design in the optimization procedure of the runner of hydraulic turbines.

Torsion limits from t t macr production at the LHC

NASA Astrophysics Data System (ADS)

de Almeida, F. M. L.; de Andrade, F. R.; do Vale, M. A. B.; Nepomuceno, A. A.

2018-04-01

Torsion models constitute a well-known class of extended quantum gravity models. In this work, one investigates the phenomenological consequences of a torsion field interacting with top quarks at the LHC. A torsion field could appear as a new heavy state characterized by its mass and couplings to fermions. This new state would form a resonance decaying into a top antitop pair. The latest ATLAS t t ¯ production results from LHC 13 TeV data are used to set limits on torsion parameters. The integrated luminosity needed to observe torsion resonance at the next LHC upgrades are also evaluated, considering different values for the torsion mass and its couplings to Standard Model fermions. Finally, prospects for torsion exclusion at the future LHC phases II and III are obtained using fast detector simulations.

Improved docosahexaenoic acid production in Aurantiochytrium by glucose limited pH-auxostat fed-batch cultivation.

PubMed

Janthanomsuk, Panyawut; Verduyn, Cornelis; Chauvatcharin, Somchai

2015-11-01

Fed-batch, pH auxostat cultivation of the docosahexaenoic acid (DHA)-producing microorganism Aurantiochytrium B072 was performed to obtain high cell density and record high productivity of both total fatty acid (TFA) and DHA. Using glucose feeding by carbon excess (C-excess) and by C-limitation at various feeding rates (70%, 50% or 20% of C-excess), high biomass density was obtained and DHA/TFA content (w/w) was improved from 30% to 37% with a 50% glucose feed rate when compared with C-excess. To understand the biochemistry behind these improvements, lipogenic enzyme assays and in silico metabolic flux calculations were used and revealed that enzyme activity and C-fluxes to TFA were reduced with C-limited feeding but that the carbon flux to the polyketide synthase pathway increased relative to the fatty acid synthase pathway. As a result, a new strategy to improve the DHA to TFA content while maintaining relatively high DHA productivity is proposed. Copyright © 2015 Elsevier Ltd. All rights reserved.

How Do Executive Functions Fit with the Cattell-Horn-Carroll Model? Some Evidence from a Joint Factor Analysis of the Delis-Kaplan Executive Function System and the Woodcock-Johnson III Tests of Cognitive Abilities

ERIC Educational Resources Information Center

Floyd, Randy G.; Bergeron, Renee; Hamilton, Gloria; Parra, Gilbert R.

2010-01-01

This study investigated the relations among executive functions and cognitive abilities through a joint exploratory factor analysis and joint confirmatory factor analysis of 25 test scores from the Delis-Kaplan Executive Function System and the Woodcock-Johnson III Tests of Cognitive Abilities. Participants were 100 children and adolescents…

Evaluating Protocol Lifecycle Time Intervals in HIV/AIDS Clinical Trials

PubMed Central

Schouten, Jeffrey T.; Dixon, Dennis; Varghese, Suresh; Cope, Marie T.; Marci, Joe; Kagan, Jonathan M.

2014-01-01

Background Identifying efficacious interventions for the prevention and treatment of human diseases depends on the efficient development and implementation of controlled clinical trials. Essential to reducing the time and burden of completing the clinical trial lifecycle is determining which aspects take the longest, delay other stages, and may lead to better resource utilization without diminishing scientific quality, safety, or the protection of human subjects. Purpose In this study we modeled time-to-event data to explore relationships between clinical trial protocol development and implementation times, as well as identify potential correlates of prolonged development and implementation. Methods We obtained time interval and participant accrual data from 111 interventional clinical trials initiated between 2006 and 2011 by NIH’s HIV/AIDS Clinical Trials Networks. We determined the time (in days) required to complete defined phases of clinical trial protocol development and implementation. Kaplan-Meier estimates were used to assess the rates at which protocols reached specified terminal events, stratified by study purpose (therapeutic, prevention) and phase group (pilot/phase I, phase II, and phase III/ IV). We also examined several potential correlates to prolonged development and implementation intervals. Results Even though phase grouping did not determine development or implementation times of either therapeutic or prevention studies, overall we observed wide variation in protocol development times. Moreover, we detected a trend toward phase III/IV therapeutic protocols exhibiting longer developmental (median 2 ½ years) and implementation times (>3years). We also found that protocols exceeding the median number of days for completing the development interval had significantly longer implementation. Limitations The use of a relatively small set of protocols may have limited our ability to detect differences across phase groupings. Some timing effects

MFGE8 inhibits inflammasome-induced IL-1β production and limits postischemic cerebral injury.

PubMed

Deroide, Nicolas; Li, Xuan; Lerouet, Dominique; Van Vré, Emily; Baker, Lauren; Harrison, James; Poittevin, Marine; Masters, Leanne; Nih, Lina; Margaill, Isabelle; Iwakura, Yoichiro; Ryffel, Bernhard; Pocard, Marc; Tedgui, Alain; Kubis, Nathalie; Mallat, Ziad

2013-03-01

Milk fat globule-EGF 8 (MFGE8) plays important, nonredundant roles in several biological processes, including apoptotic cell clearance, angiogenesis, and adaptive immunity. Several recent studies have reported a potential role for MFGE8 in regulation of the innate immune response; however, the precise mechanisms underlying this role are poorly understood. Here, we show that MFGE8 is an endogenous inhibitor of inflammasome-induced IL-1β production. MFGE8 inhibited necrotic cell-induced and ATP-dependent IL-1β production by macrophages through mediation of integrin β(3) and P2X7 receptor interactions in primed cells. Itgb3 deficiency in macrophages abrogated the inhibitory effect of MFGE8 on ATP-induced IL-1β production. In a setting of postischemic cerebral injury in mice, MFGE8 deficiency was associated with enhanced IL-1β production and larger infarct size; the latter was abolished after treatment with IL-1 receptor antagonist. MFGE8 supplementation significantly dampened caspase-1 activation and IL-1β production and reduced infarct size in wild-type mice, but did not limit cerebral necrosis in Il1b-, Itgb3-, or P2rx7-deficient animals. In conclusion, we demonstrated that MFGE8 regulates innate immunity through inhibition of inflammasome-induced IL-1β production.

Reduced production of creatinine limits its use as marker of kidney injury in sepsis.

PubMed

Doi, Kent; Yuen, Peter S T; Eisner, Christoph; Hu, Xuzhen; Leelahavanichkul, Asada; Schnermann, Jürgen; Star, Robert A

2009-06-01

Although diagnosis and staging of acute kidney injury uses serum creatinine, acute changes in creatinine lag behind both renal injury and recovery. The risk for mortality increases when acute kidney injury accompanies sepsis; therefore, we sought to explore the limitations of serum creatinine in this setting. In mice, induction of sepsis by cecal ligation and puncture in bilaterally nephrectomized mice increased markers of nonrenal organ injury and serum TNF-alpha. Serum creatinine, however, was significantly lower in septic animals than in animals subjected to bilateral nephrectomy and sham cecal ligation and puncture. Under these conditions treatment with chloroquine decreased nonrenal organ injury markers but paradoxically increased serum creatinine. Sepsis dramatically decreased production of creatinine in nephrectomized mice, without changes in body weight, hematocrit, or extracellular fluid volume. In conclusion, sepsis reduces production of creatinine, which blunts the increase in serum creatinine after sepsis, potentially limiting the early detection of acute kidney injury. This may partially explain why small absolute increases in serum creatinine levels are associated with poor clinical outcomes. These data support the need for new biomarkers that provide better measures of renal injury, especially in patients with sepsis.

Increasing productivity by matching farming system management and genotype in water-limited environments.

PubMed

Kirkegaard, J A; Hunt, J R

2010-10-01

Improvements in water productivity and yield arise from interactions between varieties (G) and their management (M). Most G×M interactions considered by breeders and physiologists focus on in-crop management (e.g. sowing time, plant density, N management). However, opportunities exist to capture more water and use it more effectively that involve judicious management of prior crops and fallows (e.g. crop sequence, weed control, residue management). The dry-land wheat production system of southern Australia, augmented by simulation studies, is used to demonstrate the relative impacts and interactions of a range of pre-crop and in-crop management decisions on water productivity. A specific case study reveals how a novel genetic trait, long coleoptiles that enable deeper sowing, can interact with different management options to increase the water-limited yield of wheat from 1.6 t ha(-1) to 4.5 t ha(-1), reflecting the experience of leading growers. Understanding such interactions will be necessary to capture benefits from new varieties within the farming systems of the future.

Resource-limited heterotrophic prokaryote production and its potential environmental impact associated with Mn nodule exploitation in the northeast equatorial pacific.

PubMed

Hyun, Jung-Ho

2006-08-01

Shipboard enrichment incubation experiments were performed to elucidate the limiting resources for heterotrophic prokaryotic production and to discuss the potential impact of bottom water and sediment discharges in relation to manganese (Mn) nodule exploitation on the heterotrophic prokaryotes in the oligotrophic northeast equatorial Pacific. Compared to an unamended control, the production of heterotrophic prokaryotes increased 25-fold in water samples supplemented with amino acids (i.e., organic carbon plus nitrogen), whereas the production increased five and two times, respectively, in samples supplemented with either glucose or ammonium alone. These results indicate that heterotrophic prokaryote production in the northeast equatorial Pacific was co-limited by the availability of dissolved organic carbon and inorganic nitrogen. In samples from the nutrient-depleted surface mixed layer (10-m depth), the addition of a slurry of bottom water and sediment doubled heterotrophic prokaryote production compared to an unamended control, whereas sonicating the slurry prior to addition quadrupled the production rate. However, little difference was observed between an unamended control and slurry-amended samples in the subsurface chlorophyll a (Chl a) maximum (SCM) layer. Thus, the impact of slurry discharge is more significant at the nutrient-depleted surface mixed layer than at the high-nutrient SCM layer. The greatly enhanced prokaryote production resulting from the addition of sonicated slurry further suggests that dissociated organic carbon may directly stimulate heterotrophic prokaryote production in the surface mixed layer. Overall, the results suggest that the surface discharge of bottom water and sediments during manganese nodule exploitation could have a significant environmental impact on the production of heterotrophic prokaryotes that are currently resource limited.

Identification of physical habitats limiting the production of coho salmon in western Oregon and Washington.

Treesearch

G.H. Reeves; F.H. Everest; T.E. Nickelson

1989-01-01

Fishery managers are currently spending millions of dollars per year on habitat enhancement for anadromous salmonids but often do not have the tools needed to ensure success. An analysis of factors limiting production of salmonids in streams must be completed before any habitat-enhancement program is begun. This paper outlines the first formal procedure for identifying...

Techniques used for limiting degradation products of polymeric materials for use in the space environment

NASA Technical Reports Server (NTRS)

Vest, C. E.; Park, J. J.

1978-01-01

Techniques are discussed for limiting or controlling the degradation products (outgassing) of polymeric materials in the space environment. One technique, now ASTM E-595-77, is used to screen out those materials which lose greater than 1% Total Mass Loss when in vacuum for 24 hours at 125 C and which have more than 0.10% Collected Volatile Condensable Materials condensing on a collector surface at 25 C. Examples of silicone materials which are high and low in outgassing are given. The numerous mechanical motions in spacecraft experiments require liquid lubricants which also might degrade in space. Labyrinth seals and barrier films are utilized to limit the degradation of or from these lubricants. A recoverable in-flight experiment has been proposed for making definitive measurements of how effective these techniques are in limiting the amounts and escape paths of outgassed molecules.

Genetic Polymorphisms in RNA Binding Proteins Contribute to Breast Cancer Survival

PubMed Central

Upadhyay, Rohit; Sanduja, Sandhya; Kaza, Vimala; Dixon, Dan A.

2012-01-01

The RNA-binding proteins TTP and HuR control expression of numerous genes associated with breast cancer pathogenesis by regulating mRNA stability. However, the role of genetic variation in TTP (ZFP36) and HuR (ELAVL1) genes is unknown in breast cancer prognosis. A total of 251 breast cancer patients (170 Caucasians and 81 African-Americans) were enrolled and followed-up from 2001 to 2011 (or until death). Genotyping was performed for 10 SNPs in ZFP36 and 7 in ELAVL1 genes. On comparing both races with one another, significant differences were found for clinical and genetic variables. The influence of genetic polymorphisms on survival was analyzed by using Cox-regression, Kaplan-Meier analysis, and the log-rank test. Univariate (Kaplan-Meier/Cox-regression) and multivariate (Cox-regression) analysis showed that the TTP gene polymorphism ZFP36*2 A>G was significantly associated with poor prognosis of Caucasian patients (HR = 2.03; 95% CI = 1.09–3.76; P = 0.025; log-rank P = 0.022). None of the haplotypes, but presence of more than six risk genotypes in Caucasian patients, was significantly associated with poor prognosis (HR=2.42; 95% CI=1.17–4.99; P = 0.017; log-rank P = 0.007). The effect of ZFP36*2 A>G on gene expression was evaluated from patients' tissue samples. Both TTP mRNA and protein expression was significantly decreased in ZFP36*2 G allele carriers compared to A allele homozygotes. Conversely, upregulation of the TTP-target gene COX-2 was observed ZFP36*2 G allele carriers. Through its ability to attenuate TTP gene expression, the ZFP36*2 A>G gene polymorphism has appeared as a novel prognostic breast cancer marker in Caucasian patients. PMID:22907529

[Value of the albumin to globulin ratio in predicting severity and prognosis in myasthenia gravis patients].

PubMed

Yang, D H; Su, Z Q; Chen, Y; Chen, Z B; Ding, Z N; Weng, Y Y; Li, J; Li, X; Tong, Q L; Han, Y X; Zhang, X

2016-03-08

To assess the predictive value of the albumin to globulin ratio (AGR) in evaluation of disease severity and prognosis in myasthenia gravis patients. A total of 135 myasthenia gravis (MG) patients were enrolled between February 2009 and March 2015. The AGR was detected on the first day of hospitalization and ranked from lowest to highest, and the patients were divided into three equal tertiles according to the AGR values, which were T1 (AGR <1.34), T2 (1.34≤AGR≤1.53) and T3 (AGR>1.53). The Kaplan-Meier curve was used to evaluate the prognostic value of AGR. Cox model analysis was used to evaluate the relevant factors. Multivariate Logistic regression analysis was used to find the predictors of myasthenia crisis during hospitalization. The median length of hospital stay for each tertile was: for the T1 21 days (15-35.5), T2 18 days (14-27.5), and T3 16 days (12-22.5) (P<0.01), and Kaplan-Meier curves showed significant difference among the three groups. In the univariate model, serum albumin, creatinine, AGR and MGFA clinical classification were related to prognosis of myasthenia gravis. At the multivariate Cox regression analysis, the AGR (P<0.001) and MGFA clinical classification (P<0.001) were independent predictive factors of disease severity and prognosis in myasthenia gravis patients. Respectively, the hazard ratio (HR) were 4.655 (95% CI: 2.355-9.202) and 0.596 (95% CI: 0.492-0.723). Multivariate Logistic regression analysis showed the AGR (P<0.001) and MGFA clinical classification were related to myasthenia crisis. The AGR may represent a simple, potentially useful predictive biomarker for evaluating the disease severity and prognosis of patients with myasthenia gravis.

Evaluation of the platelet-to-lymphocyte ratio as a prognostic indicator in a European cohort of patients with prostate cancer treated with radiotherapy.

PubMed

Langsenlehner, Tanja; Pichler, Martin; Thurner, Eva-Maria; Krenn-Pilko, Sabine; Stojakovic, Tatjana; Gerger, Armin; Langsenlehner, Uwe

2015-05-01

Recent evidence suggests that the presence of a systemic inflammatory response plays an important role in the progression of several solid tumors. The platelet-to-lymphocyte ratio (PLR) has been proposed as an easily assessable marker of systemic inflammation and has been shown to represent a prognostic marker in different cancer entities. To evaluate the prognostic value of the PLR in prostate cancer, we performed the present study. Data from 374 consecutive patients with prostate cancer, treated with 3D conformal radiotherapy from 1999 to 2007, were analyzed. Distant metastases-free survival (MFS), cancer-specific survival (CSS), overall survival (OS), biochemical disease-free survival, and time to salvage systemic therapy were assessed using the Kaplan-Meier method. Cox proportional hazards analysis was performed to calculate hazard ratio (HR) and 95% CI. Multivariate Cox regression analysis was performed to adjust for other covariates. Using receiver operating characteristics analysis, the optimal cutoff level for the PLR was 190. Kaplan-Meier analyses revealed that PLR≥190 was a prognostic factor for decreased MFS (P = 0.004), CSS (P = 0.004), and OS (P = 0.024) whereas a significant association of an elevated PLR with biochemical disease-free survival (P = 0.740) and time to salvage systemic therapy (P = 0.063) was not detected. In multivariate analysis, an increased PLR remained a significant prognostic factor for poor MFS (HR = 2.24, 95% CI: 1.06-4.76, P = 0.036), CSS (HR = 3.99, 95% CI: 1.19-13.4, P = 0.025), and OS (HR = 1.87, 95% CI: 1.02-3.42, P = 0.044). Our findings indicate that the PLR may predict prognosis in patients with prostate cancer and may contribute to future individual risk assessment in them. Copyright © 2015 Elsevier Inc. All rights reserved.

Retrospective clinical evaluation of ceramic onlays placed by dental students.

PubMed

Archibald, Jennifer J; Santos, Gildo Coelho; Moraes Coelho Santos, Maria Jacinta

2017-09-16

Indirect restorations with partial or complete occlusal surface coverage have been recommended to restore teeth with weakened walls in order to prevent cusp fracture. The success of these restorations when performed by dental students is unknown. The purpose of this retrospective study was to evaluate the clinical performance of adhesively bonded ceramic onlay restorations placed by third- and fourth-year dental students. Sixty-five ceramic onlays were placed in patients between 2009 and 2015. The onlays were laboratory or chairside fabricated with a computer-aided design and computer-aided manufacturing (CAD-CAM) system, using either IPS e.max Press or IPS e.max CAD. An adhesive technique and luting composite resin agent were used to cement the restorations. Thirty-seven onlays were evaluated clinically using the modified United States Public Health Service (USPHS) criteria. Data were statistically analyzed using the Cox proportional hazards model to compare tooth type and failures and the Fisher exact and McNemar tests to compare the USPHS criteria for significant differences (α=.05). Survival probability was calculated using the Kaplan-Meier algorithm. Five onlays were considered to be failures and needed replacement. According to the Kaplan-Meier analysis, the estimated survival rate was 96.3% after 2 years and 91.5% at 4 years. All 5 of the failures occurred on molars (13.5%) and none on premolars (P=.025). A statistically significant difference was found for marginal discoloration between onlays placed within 0 to 3 years and 3 to 6 years (P<.05) but no differences between any other criteria. Ceramic onlays placed by dental students demonstrated acceptable long-term clinical performance. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Is mitral valve repair superior to replacement for chronic ischemic mitral regurgitation with left ventricular dysfunction?

PubMed Central

2010-01-01

Background This study was undertaken to compare mitral valve repair and replacement as treatments for ischemic mitral regurgitation (IMR) with left ventricular dysfunction (LVD). Specifically, we sought to determine whether the choice of mitral valve procedure affected survival, and discover which patients were predicted to benefit from mitral valve repair and which from replacement. Methods A total of 218 consecutive patients underwent either mitral valve repair (MVP, n = 112) or mitral valve replacement (MVR, n = 106). We retrospectively reviewed the clinical material, operation methods, echocardiography check during operation and follow-up. Patients details and follow-up outcomes were compared using multivariate and Kaplan-Meier analyses. Results No statistical difference was found between the two groups in term of intraoperative data. Early mortality was 3.2% (MVP 2.7% and MVR 3.8%). At discharge, Left ventricular end-systolic and end-diastolic diameter and left ventricular ejection fraction (LVEF) were improved more in the MVP group than MVR group (P < 0.05), however, in follow-up no statistically significant difference was observed between the MVR and MVP group (P > 0.05). Follow-up mitral regurgitation grade was significantly improved in the MVR group compared with the MVP group (P < 0.05). The Kaplan-Meier survival estimates at 1, 3, and 5 years were simlar between MVP and MVR group. Logistic regression revealed poor survival was associated with old age(#75), preoperative renal insufficiency and low left ventricular ejection fraction (< 30%). Conclusion Mitral valve repair is the procedure of choice in the majority of patients having surgery for severe ischemic mitral regurgitation with left ventricular dysfunction. Early results of MVP treatment seem to be satisfactory, but several lines of data indicate that mitral valve repair provided less long-term benefit than mitral valve replacement in the LVD patients. PMID:21059216

A modified TNM staging system for non-metastatic colorectal cancer based on nomogram analysis of SEER database.

PubMed

Kong, Xiangxing; Li, Jun; Cai, Yibo; Tian, Yu; Chi, Shengqiang; Tong, Danyang; Hu, Yeting; Yang, Qi; Li, Jingsong; Poston, Graeme; Yuan, Ying; Ding, Kefeng

2018-01-08

To revise the American Joint Committee on Cancer TNM staging system for colorectal cancer (CRC) based on a nomogram analysis of Surveillance, Epidemiology, and End Results (SEER) database, and to prove the rationality of enhancing T stage's weighting in our previously proposed T-plus staging system. Total 115,377 non-metastatic CRC patients from SEER were randomly grouped as training and testing set by ratio 1:1. The Nomo-staging system was established via three nomograms based on 1-year, 2-year and 3-year disease specific survival (DSS) Logistic regression analysis of the training set. The predictive value of Nomo-staging system for the testing set was evaluated by concordance index (c-index), likelihood ratio (L.R.) and Akaike information criteria (AIC) for 1-year, 2-year, 3-year overall survival (OS) and DSS. Kaplan-Meier survival curve was used to valuate discrimination and gradient monotonicity. And an external validation was performed on database from the Second Affiliated Hospital of Zhejiang University (SAHZU). Patients with T1-2 N1 and T1N2a were classified into stage II while T4 N0 patients were classified into stage III in Nomo-staging system. Kaplan-Meier survival curves of OS and DSS in testing set showed Nomo-staging system performed better in discrimination and gradient monotonicity, and the external validation in SAHZU database also showed distinctly better discrimination. The Nomo-staging system showed higher value in L.R. and c-index, and lower value in AIC when predicting OS and DSS in testing set. The Nomo-staging system showed better performance in prognosis prediction and the weight of lymph nodes status in prognosis prediction should be cautiously reconsidered.

Maintenance steroid use at 30 days post-transplant and outcomes of pediatric heart transplantation: A propensity matched analysis of the Pediatric Heart Transplant Study database.

PubMed

Auerbach, Scott R; Kukreja, Manisha; Gilbert, Deborah; Bastardi, Heather; Feingold, Brian; Knecht, Kenneth; Kaufman, Beth D; Brown, Robert N; Miyamoto, Shelley D

2015-08-01

Maintenance steroid (MS) use in pediatric heart transplantation is variable. The purpose of this study was to evaluate the impact of MS use on graft outcomes. All patients <18 years old in the Pediatric Heart Transplant Study database at the time of first heart transplant between 1993 and 2011 who survived ≥30 days post-transplant and were from centers with a protocolized approach to MS use were included (N = 2,178). Patients were grouped by MS use at 30 days post-transplant as MS+ or MS- (no MS use). Propensity score analysis was used to generate matched groups of MS+ and MS- patients based on pre-transplant and peri-transplant factors. Kaplan-Meier survival analysis was used to compare freedom from graft loss, graft loss secondary to rejection, rejection, rejection with severe hemodynamic compromise (RSHC), malignancy, and infection between groups. Of patients, 1,393 (64%) were MS+ and 785 (36%) were MS-. There were 315 MS- patients who had propensity matched MS+ controls. Kaplan-Meier estimates showed no difference in graft loss (p = 0.9) or graft loss secondary to rejection (p = 0.09). At 1 year post-transplant, there was no difference in freedom from rejection (p = 0.15) or malignancy (p = 0.07), but there was lower freedom from RSHC and infection in the MS- group (p = 0.05 and p = 0.02, respectively). MS use at 30 days post-transplant was not associated with enhanced graft survival after pediatric heart transplant. MS- patients had a higher incidence of RSHC and infection. These risks should be taken into consideration when determining MS use for pediatric recipients of heart transplants. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Long-Term Outcomes With Intraoperative Radiotherapy as a Component of Treatment for Locally Advanced or Recurrent Uterine Sarcoma

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

Barney, Brandon M., E-mail: barney.brandon@mayo.edu; Petersen, Ivy A.; Dowdy, Sean C.

2012-05-01

Purpose: To report our institutional experience with intraoperative radiotherapy (IORT) as a component of treatment for women with locally advanced or recurrent uterine sarcoma. Methods and Materials: From 1990 to 2010, 16 women with primary (n = 3) or locoregionally recurrent (n = 13) uterine sarcoma received IORT as a component of combined modality treatment. Tumor histology studies found leiomyosarcoma (n = 9), endometrial stromal sarcoma (n = 4), and carcinosarcoma (n = 3). Surgery consisted of gross total resection in 2 patients, subtotal resection in 6 patients, and resection with close surgical margins in 8 patients. The median IORTmore » dose was 12.5 Gy (range, 10-20 Gy). All patients received perioperative external beam radiotherapy (EBRT; median dose, 50.4 Gy; range, 20-62.5 Gy), and 6 patients also received perioperative systemic therapy. Results: Seven of the 16 patients are alive at a median follow-up of 44 months (range, 11-203 months). The 3-year Kaplan-Meier estimate of local relapse (within the EBRT field) was 7%, and central control (within the IORT field) was 100%. No local failures occurred in any of the 6 patients who underwent subtotal resection. The 3-year freedom from distant relapse was 48%, with failures occurring most frequently in the lungs or mediastinum. Median survival was 18 months, and 3-year Kaplan-Meier estimates of cause-specific and overall survival were 58% and 53%, respectively. Three patients (19%) experienced late Grade 3 toxicity. Conclusions: A combined modality approach with perioperative EBRT, surgery, and IORT for locally advanced or recurrent uterine sarcoma resulted in excellent local disease control with acceptable toxicity, even in patients with positive resection margins. With this approach, some patients were able to experience long-term freedom from recurrence.« less

Long-Term Outcomes and Complications in Patients With Craniopharyngioma: The British Columbia Cancer Agency Experience

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

Lo, Andrea C., E-mail: andrealo@gmail.com; Department of Surgery, University of British Columbia, Vancouver, British Columbia; Howard, A. Fuchsia

2014-04-01

Purpose: We report long-term outcomes and complications of craniopharyngioma patients referred to our institution. Methods and Materials: Between 1971 and 2010, 123 consecutive patients received primary treatment for craniopharyngioma in British Columbia and were referred to our institution. The median age was 30 years (range, 2-80 years). Thirty-nine percent of patients were treated primarily with subtotal resection (STR) and radiation therapy (RT), 28% with STR alone, 15% with gross total resection, 11% with cyst drainage (CD) alone, 5% with CD+RT, and 2% with RT alone. Eight percent of patients received intracystic bleomycin (ICB) therapy. Results: Median follow-up was 8.9 years,more » and study endpoints were reported at 10 years. Ten-year Kaplan-Meier progression-free survival (PFS) was 46%. Patients treated with STR+RT or CD+RT had the highest PFS (82% and 83%, respectively). There were no significant differences between PFS after adjuvant versus salvage RT (84% vs 74%, respectively; P=.6). Disease-specific survival (DSS) was 88%, and overall survival (OS) was 80%. Primary treatment modality did not affect DSS or OS, while older age was a negative prognostic factor for OS but not DSS. Kaplan-Meier rates for visual deterioration, anterior pituitary hormone deficiency, diabetes insipidus, seizure disorder, and cerebrovascular events (CVE) due to treatment, not tumor progression, were 27%, 76%, 45%, 16%, and 11%, respectively. The CVE rate was 29% in patients who received ICB compared to 10% in those who did not (P=.07). Conclusions: We report favorable PFS in patients with craniopharyngioma, especially in those who received RT after surgery. DSS and OS rates were excellent regardless of primary treatment modality. We observed a high incidence of hypopituitarism, visual deterioration, and seizure disorder. Eleven percent of patients experienced CVEs after treatment. There was a suggestion of increased CVE risk in patients treated with ICB.« less

Immunohistochemical detection of HIF-1alpha and CAIX in advanced head-and-neck cancer. Prognostic role and correlation with tumor markers and tumor oxygenation parameters.

PubMed

Kappler, Matthias; Taubert, Helge; Holzhausen, Hans-Jürgen; Reddemann, Rolf; Rot, Swetlann; Becker, Axel; Kuhnt, Thomas; Dellas, Kathrin; Dunst, Jürgen; Vordermark, Dirk; Hänsgen, Gabriele; Bache, Matthias

2008-08-01

Tumor hypoxia has an impact on the outcome of cancer patients treated with radiotherapy. The validity of endogenous markers such as hypoxia-inducible factor-1alpha (HIF-1alpha) and carbonic anhydrase isozyme IX (CAIX) to detect therapeutically relevant Levels of hypoxia within tumors is controversially discussed. Furthermore, the association of these hypoxia markers with tumor markers or tumor oxygenation parameters is of importance for understanding the relationship between the different factors. Tumortissue sections of 34 patients with advanced head-and-neck cancertreated with radio(chemo)therapy were assessed by immunohistochemistry for the expression of HIF-1alpha and CAIX. The relationships of both markers with tumor oxygenation parameters, molecular factors like P53, OPN, VEGF, VHL, survivin, and Ki67 levels, and clinical parameters were studied. Bivariate analysis showed a significant correlation of HIF-1alpha expression with high P53 and high OPN expression, high serum VEGF Levels, and low VHL and low Ki67 expression. The CAIX expression was inversely correlated with pH value and directly correlated with T-stage. However, no correlation was found between HIF-1alpha and CAIX expression. Neither in a univariate Cox proportional hazard regression nor in a Kaplan-Meier analysis did expression of HIF-1alpha or CAIX have a significant impact on clinical outcome. However, in a Kaplan-Meier analysis, the combination of both factors showed that patients with intratumoral overexpression of either HIF-1alpha or CAIX or both markers died on average 2 years earlier than patients whose tumors had low expression of both factors (p < 0.05). Expression of HIF-1alpha and CAIX was correlated with different tumor parameters. Only combined HIF-1alpha and CAIX expression was significantly predictive of patients' overall survival.

Prevalence and mortality of cancer among HIV-infected inpatients in Beijing, China.

PubMed

Yang, Jun; Su, Shu; Zhao, Hongxin; Wang, Dennis; Wang, Jiali; Zhang, Fujie; Zhao, Yan

2016-02-16

Cancer is responsible for elevated HIV-related morbidity and mortality. Research on HIV-infected patients with concurrent cancer is rare in China. The purpose of our study was to investigate the prevalence and risk factors associated with cancer among HIV-infected inpatients in Beijing, and to investigate the mortality and risk factors among HIV-infected inpatients with cancer. Hospital records from a total of 1946 HIV-infected patients were collected from the Beijing Ditan Hospital. The data, from 2008 to 2013, were collected retrospectively. The cancer diagnoses included AIDS-defining cancers (ADC) and non-AIDS defining cancers (NADC). Logistic regression was used to identify risk factors predicting the concurrence of cancer with HIV. Mortality was examined using Kaplan-Meier estimates and Cox proportional hazards models. 7.7 % (149 cases) of all HIV-infected inpatients had concurrent cancer at their first hospital admission; of those, 33.6 % (50 cases) had ADCs, and 66.4 % (99 cases) had NADCs. The most prevalent NADCs were Hodgkin's lymphoma, gastrointestinal cancer, liver cancer, and lung cancer. Patients who did not accept antiretroviral therapy (ART) were more likely to suffer from cancer [AOR = 2.07 (1.42-3.01), p = 0.001]. Kaplan-Meier curves indicated that the survival probability of HIV-positive cancer patients was significantly lower than that of HIV-positive cancer-free patients (log-rank test, p < 0.001). For patients diagnosed with cancer, the mortality was also higher among those who did not receive ART [AHR = 2.19 (1.84-2.61), p < 0.001]. The prevalence of cancer concurrence among hospitalized HIV-infected patients was 7.7 %. Concurrent cancer also increased mortality among HIV-infected patients. ART was protective against concurrent cancer as well as mortality among HIV-infected cancer patients. These results highlight the importance of promoting cancer screening and early ART initiation among HIV-infected patients.

Chemokine-like factor-like MARVEL transmembrane domain-containing 3 expression is associated with a favorable prognosis in esophageal squamous cell carcinoma.

PubMed

Han, Tianci; Shu, Tianci; Dong, Siyuan; Li, Peiwen; Li, Weinan; Liu, Dali; Qi, Ruiqun; Zhang, Shuguang; Zhang, Lin

2017-05-01

Decreased expression of human chemokine-like factor-like MARVEL transmembrane domain-containing 3 (CMTM3) has been identified in a number of human tumors and tumor cell lines, including gastric and testicular cancer, and PC3, CAL27 and Tca-83 cell lines. However, the association between CMTM3 expression and the clinicopathological features and prognosis of esophageal squamous cell carcinoma (ESCC) patients remains unclear. The aim of the present study was to investigate the correlation between CMTM3 expression and clinicopathological parameters and prognosis in ESCC. CMTM3 mRNA and protein expression was analyzed in ESCC and paired non-tumor tissues by quantitative real-time polymerase chain reaction, western blotting and immunohistochemical analysis. The Kaplan-Meier method was used to plot survival curves and the Cox proportional hazards regression model was also used for univariate and multivariate survival analysis. The results revealed that CMTM3 mRNA and protein expression levels were lower in 82.5% (30/40) and 75% (30/40) of ESCC tissues, respectively, when compared with matched non-tumor tissues. Statistical analysis demonstrated that CMTM3 expression was significantly correlated with lymph node metastasis (P=0.002) and clinical stage (P<0.001) in ESCC tissues. Furthermore, the survival time of ESCC patients exhibiting low CMTM3 expression was significantly shorter than that of ESCC patients exhibiting high CMTM3 expression (P=0.01). In addition, Kaplan-Meier survival analysis revealed that the overall survival time of patients exhibiting low CMTM3 expression was significantly decreased compared with patients exhibiting high CMTM3 expression (P=0.010). Cox multivariate analysis indicated that CMTM3 protein expression was an independent prognostic predictor for ESCC after resection. This study indicated that CMTM3 expression is significantly decreased in ESCC tissues and CMTM3 protein expression in resected tumors may present an effective prognostic

Three- to nine-year survival estimates and fracture mechanisms of zirconia- and alumina-based restorations using standardized criteria to distinguish the severity of ceramic fractures.

PubMed

Moráguez, Osvaldo D; Wiskott, H W Anselm; Scherrer, Susanne S

2015-12-01

The aims of this study were set as follows: 1. To provide verifiable criteria to categorize the ceramic fractures into non-critical (i.e., amenable to polishing) or critical (i.e., in need of replacement) 2. To establish the corresponding survival rates for alumina and zirconia restorations 3. To establish the mechanism of fracture using fractography Fifty-eight patients restored with 115 alumina-/zirconia-based crowns and 26 zirconia-based fixed dental prostheses (FDPs) were included. Ceramic fractures were classified into four types and further subclassified into "critical" or "non-critical." Kaplan-Meier survival estimates were calculated for "critical fractures only" and "all fractures." Intra-oral replicas were taken for fractographic analyses. Kaplan-Meier survival estimates for "critical fractures only" and "all fractures" were respectively: Alumina single crowns: 90.9 and 68.3 % after 9.5 years (mean 5.71 ± 2.6 years). Zirconia single crowns: 89.4 and 80.9 % after 6.3 years (mean 3.88 ± 1.2 years). Zirconia FDPs: 68.6 % (critical fractures) and 24.6 % (all fractures) after 7.2 and 4.6 years respectively (FDP mean observation time 3.02 ± 1.4 years). No core/framework fractures were detected. Survival estimates varied significantly depending on whether "all" fractures were considered as failures or only those deemed as "critical". For all restorations, fractographic analyses of failed veneering ceramics systematically demonstrated heavy occlusal wear at the failure origin. Therefore, the relief of local contact pressures on unsupported ceramic is recommended. Occlusal contacts on mesial or distal ridges should systematically be eliminated. A classification standard for ceramic fractures into four categories with subtypes "critical" and "non-critical" provides a differentiated view of the survival of ceramic restorations.

Dynamic contrast–enhanced magnetic resonance imaging in patients with pulmonary arterial hypertension

PubMed Central

Condliffe, Robin; Marshall, Helen; Elliot, Charlie; Kiely, David G.; Wild, Jim M.

2014-01-01

Abstract Dynamic contrast–enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique whereby the passage of an intravenous contrast bolus can be tracked through the pulmonary vascular system. The aim of this study was to investigate the prognostic significance of DCE-MR pulmonary blood transit times in patients with pulmonary arterial hypertension (PAH). Seventy-nine patients diagnosed with PAH underwent pulmonary DCE imaging at 1.5 T using a time-resolved three-dimensional spoiled gradient echo sequence. The prognostic significance of two DCE parameters, full width at half maximum (FWHM) of the first-pass clearance curve and pulmonary transit time (PTT), along with demographic and invasive catheter measurements, was evaluated by univariate and bivariate Cox proportional hazards regression and Kaplan-Meier analysis. DCE-MR transit times were most closely correlated with cardiac index (CI) and pulmonary vascular resistance index (PVRI) and were both found to be accurate for detecting reduced CI (FWHM area under the curve [AUC] at receiver operating characteristic analysis = 0.91 and PTT AUC = 0.92, respectively) and for detecting elevated PVRI (FWHM AUC = 0.88 and PTT AUC = 0.84, respectively). During the follow-up period, 25 patients died. Patients with longer measurements of FWHM (P = 0.0014) and PTT (P = 0.004) were associated with poor outcome at Kaplan-Meier analysis, and both parameters were strong predictors of adverse outcome from Cox proportional hazards analysis (P = 0.013 and 0.010, respectively). At bivariate analysis, DCE measurements predicted mortality independent of age, gender, and World Health Organization functional class; however, invasive hemodynamic indexes CI, PVRI, and DCE measurements were not independent of one another. In conclusion, DCE-MR transit times predict mortality in patients with PAH and are closely associated with clinical gold standards CI and PVRI. PMID:25006422

Dynamic contrast-enhanced magnetic resonance imaging in patients with pulmonary arterial hypertension.

PubMed

Swift, Andrew J; Telfer, Adam; Rajaram, Smitha; Condliffe, Robin; Marshall, Helen; Capener, Dave; Hurdman, Judith; Elliot, Charlie; Kiely, David G; Wild, Jim M

2014-03-01

Dynamic contrast-enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique whereby the passage of an intravenous contrast bolus can be tracked through the pulmonary vascular system. The aim of this study was to investigate the prognostic significance of DCE-MR pulmonary blood transit times in patients with pulmonary arterial hypertension (PAH). Seventy-nine patients diagnosed with PAH underwent pulmonary DCE imaging at 1.5 T using a time-resolved three-dimensional spoiled gradient echo sequence. The prognostic significance of two DCE parameters, full width at half maximum (FWHM) of the first-pass clearance curve and pulmonary transit time (PTT), along with demographic and invasive catheter measurements, was evaluated by univariate and bivariate Cox proportional hazards regression and Kaplan-Meier analysis. DCE-MR transit times were most closely correlated with cardiac index (CI) and pulmonary vascular resistance index (PVRI) and were both found to be accurate for detecting reduced CI (FWHM area under the curve [AUC] at receiver operating characteristic analysis = 0.91 and PTT AUC = 0.92, respectively) and for detecting elevated PVRI (FWHM AUC = 0.88 and PTT AUC = 0.84, respectively). During the follow-up period, 25 patients died. Patients with longer measurements of FWHM (P = 0.0014) and PTT (P = 0.004) were associated with poor outcome at Kaplan-Meier analysis, and both parameters were strong predictors of adverse outcome from Cox proportional hazards analysis (P = 0.013 and 0.010, respectively). At bivariate analysis, DCE measurements predicted mortality independent of age, gender, and World Health Organization functional class; however, invasive hemodynamic indexes CI, PVRI, and DCE measurements were not independent of one another. In conclusion, DCE-MR transit times predict mortality in patients with PAH and are closely associated with clinical gold standards CI and PVRI.

Trends and territorial inequalities of incidence and survival of childhood leukaemia and their relations to socioeconomic status in Hungary, 1971-2015.

PubMed

Jakab, Zsuzsanna; Juhasz, Attila; Nagy, Csilla; Schuler, Dezso; Garami, Miklos

2017-09-01

The Hungarian Childhood Cancer Registry, a population-based national registry of the Hungarian Paediatric Haemato-Oncology Network founded in 1971, monitors the incidence and mortality of childhood cancer. Our aims were to carry out a longitudinal study to investigate the trends and spatial inequalities of incidence and survival of leukaemia, and the association between survival and deprivation in Hungary. All cases of childhood leukaemia and myelodysplasia were analysed (3157 cases, 1971-2015, age: 0-14 years). Time trends and the annual percentage change in direct standardized incidence and mortality were assessed. Survival and association with deprivation were assessed using the Kaplan-Meier method and Cox regression. Incidence rates of leukaemia (23.5-56.0/million) increased with an average annual percent change (AAPC) of 1%, determined by an increase in the incidence of acute lymphoblastic leukaemia (14.6-39.2/million, AAPC: 1.25%). Kaplan-Meier analysis showed a significant improvement in overall survival over the study period. Starting from 25% of cases surviving 5 years in the 70s; the overall 5-year survival reached 80% by 2010. Survival differences were observed with sex, leukaemia type and age at diagnosis. A reverse association was found in the survival probability of leukaemia by degree of deprivation. The Cox proportional hazards model verified a significant reverse association with deprivation [hazard ratio=1.08 (1.04-1.12)]. This is the first nationwide study to confirm the prognostic role of deprivation on the basis of a large cohort of patients with childhood leukaemia during a 45-year period. To maintain further improvement in treatment results, it is important to detect inequalities. Our results showed that deprivation may also be important in the survival of leukaemia.

A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer.

PubMed

Soh, Sheila X; Siddiqui, Fahad J; Allen, John C; Kim, Go Woon; Lee, Jae Cheol; Yatabe, Yasushi; Soda, Manabu; Mano, Hiroyuki; Soo, Ross A; Chin, Tan-Min; Ebi, Hiromichi; Yano, Seiji; Matsuo, Keitaro; Niu, Xiaomin; Lu, Shun; Isobe, Kazutoshi; Lee, Jih-Hsiang; Yang, James C; Zhao, Mingchuan; Zhou, Caicun; Lee, June-Koo; Lee, Se-Hoon; Lee, Ji Yun; Ahn, Myung-Ju; Tan, Tira J; Tan, Daniel S; Tan, Eng-Huat; Ong, S Tiong; Lim, Wan-Teck

2017-06-20

A germline deletion in the BIM (BCL2L11) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor outcomes in TKI-treated non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a systematic review and meta-analysis on both aggregate and individual patient data to address this issue. In an aggregate data meta-analysis (n = 1429), the BIM deletion was associated with inferior PFS (HR = 1.51, 95%CI = 1.06-2.13, P = 0.02). Using individual patient data (n = 1200), we found a significant interaction between the deletion and ethnicity. Amongst non-Koreans, the deletion was an independent predictor of shorter PFS (Chinese: HR = 1.607, 95%CI = 1.251-2.065, P = 0.0002; Japanese: HR = 2.636, 95%CI = 1.603-4.335, P = 0.0001), and OS (HR = 1.457, 95% CI = 1.063-1.997, P = 0.019). In Kaplan-Meier analyses, the BIM deletion was associated with shorter survival in non-Koreans (PFS: 8.0 months v 11.1 months, P < 0.0005; OS: 25.7 v 30.0 months, P = 0.042). In Koreans, the BIM deletion was not predictive of PFS or OS. 10 published and 3 unpublished studies that reported survival outcomes in NSCLC patients stratified according to BIM deletion were identified from PubMed and Embase. Summary risk estimates were calculated from aggregate patient data using a random-effects model. For individual patient data, Kaplan-Meier analyses were supported by multivariate Cox regression to estimate hazard ratios (HRs) for PFS and OS. In selected populations, the BIM deletion is a significant predictor of shorter PFS and OS on EGFR-TKIs. Further studies to determine its effect on response to other BIM-dependent therapeutic agents are needed, so that alternative treatment strategies may be devised.

Miners' return to work following injuries in coal mines.

PubMed

Bhattacherjee, Ashis; Kunar, Bijay Mihir

2016-12-22

The occupational injuries in mines are common and result in severe socio-economical consequences. Earlier studies have revealed the role of multiple factors such as demographic factors, behavioral factors, health-related factors, working environment, and working conditions for mine injuries. However, there is a dearth of information about the role of some of these factors in delayed return to work (RTW) following a miner's injury. These factors may likely include personal characteristics of injured persons and his or her family, the injured person's social and economic status, and job characteristics. This study was conducted to assess the role of some of these factors for the return to work following coal miners' injuries. A study was conducted for 109 injured workers from an underground coal mine in the years 2000-2009. A questionnaire, which was completed by the personnel interviews, included among others age, height, weight, seniority, alcohol consumption, sleeping duration, presence of diseases, job stress, job satisfaction, and injury type. The data was analyzed using the Kaplan-Meier estimates and the Cox proportional hazard model. According to Kaplan-Meier estimate it was revealed that a lower number of dependents, longer sleep duration, no job stress, no disease, no alcohol addiction, and higher monthly income have a great impact on early return to work after injury. The Cox regression analysis revealed that the significant risk factors which influenced miners' return to work included presence of disease, job satisfaction and injury type. The mine management should pay attention to significant risk factors for injuries in order to develop effective preventive measures. Med Pr 2016;67(6):729-742. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Progression to Legal Blindness in Patients With Normal Tension Glaucoma: Hospital-Based Study.

PubMed

Sawada, Akira; Rivera, Jonathan A; Takagi, Daisuke; Nishida, Takashi; Yamamoto, Tetsuya

2015-06-01

To determine the probability of an eye with normal tension glaucoma (NTG) progressing to legal blindness under standard ophthalmic care. Patients diagnosed with NTG (n = 382) between 1985 and 2007 at Gifu University Hospital were followed for at least 5 years under standard ophthalmic care. The collected data included the best-corrected visual acuity (BCVA), intraocular pressure (IOP), and visual field status. Blindness was defined as a BCVA of <20/400 or a constriction of the central visual field to <10° according to the World Health Organization criteria. Kaplan-Meier life table analysis was used to estimate the probability of progressing to blindness in one or both eyes. The mean follow-up period after diagnosis was 13.3 ± 5.4 years with a range of 5.0 to 29.1 years. At diagnosis, 18 patients (4.7%) had unilateral blindness due to glaucoma. At final examination, 34 patients had progressed to unilateral blindness and 5 to bilateral blindness. The Kaplan-Meier life table analysis estimate for unilateral blindness was 5.8 ± 1.3% at 10 years and 9.9 ± 1.9% at 20 years. Similarly, that for bilateral blindness was 0.3 ± 0.3% at 10 years and 1.4 ± 0.8% at 20 years. A Cox proportional hazard model analysis showed that a lower initial BCVA (P < 0.001), a worse initial AGIS (Advanced Glaucoma Intervention Study) score (P = 0.002), and the frequency of changing glaucoma medications during the follow-up periods (P < 0.001) were significantly correlated with the development of blindness in at least one eye. The probability of blindness in eyes with NTG is much lower than previously reported in patients with high-tension glaucoma. Nevertheless, special care should be taken to follow NTG patients, and especially those with worse BCVA and more advanced visual field loss at diagnosis.

Red cell distribution width and its association with mortality in neonatal sepsis.

PubMed

Martin, Snehal L; Desai, Saumil; Nanavati, Ruchi; Colah, Roshan B; Ghosh, Kanjaksha; Mukherjee, Malay B

2018-01-08

Neonatal sepsis is a major cause of mortality in the developing countries. However, with current severity scores and laboratory parameters, predicting outcomes of neonatal sepsis is a serious challenge. Red cell distribution width (RDW) is a readily available pragmatic means to predict outcomes of various comorbidities in adults and children, without causing any additional blood loss. However, its utility in neonates remains unexplored. Hence, the objective of the present study was to evaluate the association of RDW with neonatal sepsis and its role as a predictive marker for mortality. This Prospective observational study was carried out in a Level IIIB NICU for a period of 3 years. It involved comparison of RDW values of septic neonates with those of controls (matched for gestational age and birth weight) with an equal allocation ratio. A total of 251 septic neonates along with 251 controls >28 weeks of gestational age were enrolled. The RDW was derived from complete blood count done within first 6 hours of life. After arranging the RDW (median; interquartile range (IQR)), the values were categorized as those above the 50th percentile i.e. ≥20% and those below the 50th percentile i.e. <20%. The cumulative survival rates of the above two groups were assessed using the Kaplan-Meier curve and the log rank test. RDW levels were significantly higher among the neonatal sepsis cases (19.90%) as compared to the controls (18.90%) with a p value of < .001. RDW was significantly higher amongst the nonsurvivors than survivors (p < .003). Kaplan-Meier curve showed that septic neonates having RDW values ≥20% had significantly increased mortality (p < .02) with a hazard ratio of 0.5. High RDW is associated with neonatal sepsis and is an independent outcome predictor for mortality associated with neonatal sepsis.

The prognosis of root canal therapy: a 10-year retrospective cohort study on 411 patients with 1175 endodontically treated teeth.

PubMed

Fonzar, Federica; Fonzar, Alberto; Buttolo, Piercarlo; Worthington, Helen V; Esposito, Marco

2009-01-01

To evaluate the 10-year prognosis of consecutively endodontically treated or retreated teeth and to investigate some of the prognostic factors which could predict the long-term outcome of endodontic therapy. This retrospective cohort study included any patient who had endodontically treated or retreated teeth from 1986 to 1998 by a single operator in a private practice. Outcome measures were clinical and radiographic success assessed by the operator, radiographic success assessed by an independent outcome assessor and complications evaluated 10 years after treatment. Descriptive statistics, life table, Kaplan-Meier and Cox regression analyses for success were fitted. A total of 411 patients with 1175 endodontically treated teeth were identified. Ten years after treatment 102 patients (24.8%) with 223 (19.0%) teeth were lost at the follow-up. The number of teeth that were originally treated and retreated were 704 and 471, respectively. Thirty-two teeth (2.7%) had one complication, which was successfully treated. A total of 988 (84.1%) teeth were considered a complete success, 46 (3.9%) a partial success, 52 (4.4%) a partial failure and 68 (5.8%) had to be extracted according to the treating clinician. For 21 teeth (1.8%) there was no follow-up information. The radiographic healing of 1086 teeth was evaluated by an independent assessor: 980 (90.2%) showed complete healing, 52 (4.8%) improvement, and 54 (5.0%) no change or worsening. The life-table analysis showed 93% of teeth surviving at 10 years after endodontic treatment. There were no differences for survival rates between teeth treated for the first time and those that were retreated (Kaplan-Meier). Teeth retreated because of symptoms or for a periapical/lateral radiolucency were more likely to fail. Approximately 7% of endodontically treated teeth were extracted 10 years after treatment. Symptoms and radiolucency of teeth needing retreatment may be important predictors for failure.

The prognostic value of family history among patients with urinary bladder cancer.

PubMed

Egbers, Lieke; Grotenhuis, Anne J; Aben, Katja K; Alfred Witjes, J; Kiemeney, Lambertus A; Vermeulen, Sita H

2015-03-01

A history of urinary bladder cancer (UBC) in first-degree relatives increases UBC risk by twofold. The influence of positive family history on UBC prognosis is unknown. Here, we investigated association of first-degree UBC family history with clinicopathological characteristics and prognosis of UBC patients. Detailed clinical data of 1,465 non-muscle-invasive bladder cancer (NMIBC) and 250 muscle-invasive or metastatic bladder cancer (MIBC) patients, diagnosed from 1995 to 2010, were collected through medical file review. Competing risk analyses were used to compare recurrence-free survival (RFS) and progression-free survival (PFS) of NMIBC patients according to self-reported UBC family history. Overall survival in MIBC patients was estimated using Kaplan-Meier analysis. The added value of family history in prediction of NMIBC prognosis was quantified with Harrell's concordance-index. Hundred (6.8%) NMIBC and 14 (5.6%) MIBC patients reported UBC in first-degree relatives. Positive family history was statistically significantly associated with smaller tumor size and non-significantly with more favorable distribution of other tumor characteristics. In univariable analyses, positive family history correlated with longer RFS (p = 0.11) and PFS (p = 0.04). Hazard ratios for positive vs. negative family history after adjustment for clinicopathological characteristics were 0.75 (95% CI = 0.53-1.07) and 0.45 (95% CI = 0.18-1.12) for RFS and PFS, respectively. Five familial and 48 sporadic MIBC patients (Kaplan-Meier 10-year risk: 41% and 25%) died within 10 years. Family history did not improve the c-index of prediction models. This study shows that a first-degree family history of UBC is not clearly associated with NMIBC prognosis. Family history does not aid in prediction of NMIBC recurrence or progression. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

Vasodilator-Stimulated Phosphoprotein (VASP) depletion from breast cancer MDA-MB-231 cells inhibits tumor spheroid invasion through downregulation of Migfilin, β-catenin and urokinase-plasminogen activator (uPA)

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

Gkretsi, Vasiliki; Stylianou, Andreas; Stylianopoulos, Triantafyllos, E-mail: tstylian@ucy.ac.cy

A hallmark of cancer cells is their ability to invade surrounding tissues and form metastases. Cell-extracellular matrix (ECM)-adhesion proteins are crucial in metastasis, connecting tumor ECM with actin cytoskeleton thus enabling cells to respond to mechanical cues. Vasodilator-stimulated phosphoprotein (VASP) is an actin-polymerization regulator which interacts with cell-ECM adhesion protein Migfilin, and regulates cell migration. We compared VASP expression in MCF-7 and MDA-MB-231 breast cancer (BC) cells and found that more invasive MDA-MB-231 cells overexpress VASP. We then utilized a 3-dimensional (3D) approach to study metastasis in MDA-MB-231 cells using a system that considers mechanical forces exerted by the ECM.more » We prepared 3D collagen I gels of increasing concentration, imaged them by atomic force microscopy, and used them to either embed cells or tumor spheroids, in the presence or absence of VASP. We show, for the first time, that VASP silencing downregulated Migfilin, β-catenin and urokinase plasminogen activator both in 2D and 3D, suggesting a matrix-independent mechanism. Tumor spheroids lacking VASP demonstrated impaired invasion, indicating VASP’s involvement in metastasis, which was corroborated by Kaplan-Meier plotter showing high VASP expression to be associated with poor remission-free survival in lymph node-positive BC patients. Hence, VASP may be a novel BC metastasis biomarker. - Highlights: • More invasive MDA-MB-231 overexpress VASP compared to MCF-7 breast cancer cells. • We prepared 3D collagen I gels of increasing concentration and characterized them. • VASP silencing downregulated Migfilin, β-catenin and uPA both in 2D and 3D culture. • Tumor spheroids lacking VASP demonstrated impaired invasion. • Kaplan-Meier plotter shows association of high VASP expression with poor survival.« less

Bias Correction Methods Explain Much of the Variation Seen in Breast Cancer Risks of BRCA1/2 Mutation Carriers.

PubMed

Vos, Janet R; Hsu, Li; Brohet, Richard M; Mourits, Marian J E; de Vries, Jakob; Malone, Kathleen E; Oosterwijk, Jan C; de Bock, Geertruida H

2015-08-10

Recommendations for treating patients who carry a BRCA1/2 gene are mainly based on cumulative lifetime risks (CLTRs) of breast cancer determined from retrospective cohorts. These risks vary widely (27% to 88%), and it is important to understand why. We analyzed the effects of methods of risk estimation and bias correction and of population factors on CLTRs in this retrospective clinical cohort of BRCA1/2 carriers. The following methods to estimate the breast cancer risk of BRCA1/2 carriers were identified from the literature: Kaplan-Meier, frailty, and modified segregation analyses with bias correction consisting of including or excluding index patients combined with including or excluding first-degree relatives (FDRs) or different conditional likelihoods. These were applied to clinical data of BRCA1/2 families derived from our family cancer clinic for whom a simulation was also performed to evaluate the methods. CLTRs and 95% CIs were estimated and compared with the reference CLTRs. CLTRs ranged from 35% to 83% for BRCA1 and 41% to 86% for BRCA2 carriers at age 70 years width of 95% CIs: 10% to 35% and 13% to 46%, respectively). Relative bias varied from -38% to +16%. Bias correction with inclusion of index patients and untested FDRs gave the smallest bias: +2% (SD, 2%) in BRCA1 and +0.9% (SD, 3.6%) in BRCA2. Much of the variation in breast cancer CLTRs in retrospective clinical BRCA1/2 cohorts is due to the bias-correction method, whereas a smaller part is due to population differences. Kaplan-Meier analyses with bias correction that includes index patients and a proportion of untested FDRs provide suitable CLTRs for carriers counseled in the clinic. © 2015 by American Society of Clinical Oncology.

Long-term results of Gamma-knife stereotactic radiosurgery for vestibular schwannomas in patients with type 2 neurofibromatosis.

PubMed

Spatola, G; Carron, R; Delsanti, C; Thomassin, J-M; Roche, P-H; Régis, J

2016-08-12

The aim of this study was to analyze the long-term results of Gamma-knife radiosurgery treatment of vestibular schwannomas in type 2 neurofibromatosis patients. A cohort of 129 treatments for vestibular schwannomas in 103 patients was selected from a prospectively-maintained clinical database. Tumor control was assessed by volumetric analysis of the tumor at the last follow-up. Any need of a further procedure such as microsurgical removal or second treatment was regarded as a failure of tumor control. Hearing function was assessed based on Gardner-Robertson classification. Progression-free survival and functional hearing preservation rates were estimated using the Kaplan-Meier method. The median age at treatment was 34 years with no gender predominance. The median tumor volume was 1.5cm 3 . At a median clinical follow-up of 5.9 years, five patients had died, four underwent a second radiosurgical procedure and eight underwent microsurgical resection. Progression-free survival was 88 and 75% respectively at 5 and 10 years. Hearing was considered serviceable in 70 ears and remained functional in 28 ears. Kaplan-Meier estimates for 5 and 10 years functional hearing was 47 and 34%, respectively. Three patients developed new facial nerve palsy after radiosurgery at 15 days, 6 and 19 months respectively and only one partially recovered. Five patients complained of a subjective instability worsening. Four cases developed trigeminal neuropathy. No predictive factors were found to be statistically correlated with a better hearing outcome or an improved tumor growth control. Results prove less satisfying than in sporadic unilateral schwannomas. However, the lower rate of mortality and morbidity compared with microsurgical resection may support a proactive role of Gamma-knife in this pathology. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Primary Cryotherapy for High-Grade Clinically Localized Prostate Cancer: Oncologic and Functional Outcomes from the COLD Registry.

PubMed

Tay, Kae Jack; Polascik, Thomas J; Elshafei, Ahmed; Cher, Michael L; Given, Robert W; Mouraviev, Vladimir; Ross, Ashley E; Jones, J Stephen

2016-01-01

To evaluate the oncological and functional outcomes of primary cryotherapy in men with clinically localized, high-grade prostate cancer. We included all men with biopsy Gleason score ≥8, localized (cT1-2) disease with a serum prostate-specific antigen (PSA) ≤50 ng/mL from the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression free survival (BPFS) as defined by the Phoenix criteria (nadir PSA +2 ng/mL). Secondary outcomes of continence (defined as strictly no leak) and potency (able to have intercourse) were patient reported. Factors influencing BPFS were evaluated individually using Kaplan Meier and in a multivariate model using Cox regression. Altogether, 300 men were included for analysis. The median follow-up was 18.2 months (mean 28.4) and median BPFS was 69.8 months. Based on Kaplan-Meier analysis, the estimated 2- and 5-year BPFS rate was 77.2% and 59.1%, respectively. Neoadjuvant hormonal therapy was administered to 41% of men and this tended to occur in men with larger prostates, likely as a technical consideration for downsizing before cryosurgery. At multivariate analysis, the presence of Gleason score 9 or 10 (Hazard Ratio [HR] 1.9) and a posttreatment PSA nadir of ≥0.4 ng/mL (HR 5.7) were the only significant variables associated with biochemical progression using Cox regression. Complete continence was noted in 90.5% of men and potency in 17% of men at the 12-month follow-up. The incidence of rectourethral fistulae and urinary retention requiring intervention beyond temporary catheterization was 1.3% and 3.3%, respectively. Primary cryotherapy appears to be effective and safe in the community setting for high-grade, clinically localized prostate cancer in the short term.

Increased expression of hepatocyte nuclear factor 4 alpha transcribed by promoter 2 indicates a poor prognosis in hepatocellular carcinoma.

PubMed

Cai, Shao-Hang; Lu, Shi-Xun; Liu, Li-Li; Zhang, Chris Zhiyi; Yun, Jing-Ping

2017-10-01

Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4α transcribed by promoter 1 (P1-HNF4α) is expressed at relatively low levels in HCC and its presence predicts a favourable outcome for hepatocellular carcinoma (HCC) patients. However, the role of HNF4α transcribed by promoter 2 (P2-HNF4α) in HCC remains unclear. A total of 615 HCC specimens were obtained to construct tissue microarrays and perform immunohistochemistry. The relationship between P2-HNF4α and clinical features of HCC patients were analysed. Kaplan-Meier analysis was conducted to assess the prognostic value of P2-HNF4α. The results showed that the expression of P2-HNF4α in HCC was noticeably increased in HCC tissues compared with the nontumourous tissues. In addition, P1-HNF4α expression was negatively correlated with P2-HNF4α expression ( p  = 0.023). High P2-HNF4α expression was significantly associated with poor differentiation of HCC ( p = 0.002) and vascular invasion ( p = 0.017). Kaplan-Meier analysis showed that P2-HNF4α expression was closely correlated with overall survival in the training group ( p = 0.01), validation group ( p = 0.034), and overall group of patients with HCC ( p < 0.001). Our data show that the role of HNF4α in cancer development needs to be further refined. P2-HNF4α, different from P1-HNF4α, is markedly upregulated and serves as an oncogene-associated protein in HCC. Our study therefore provides a promising biomarker for prognostic prediction and a potential therapeutic target for HCC.

Safety, Efficacy, and Persistence of Long-Term Mirabegron Treatment for Overactive Bladder in the Daily Clinical Setting: Interim (1-Year) Report from a Japanese Post-Marketing Surveillance Study.

PubMed

Kato, Daisuke; Tabuchi, Hiromi; Uno, Satoshi

2017-08-01

To report interim 1-year results from a 3-year surveillance study evaluating safety, efficacy, and persistence of long-term mirabegron for overactive bladder (OAB). Patients starting treatment with mirabegron for urinary urgency, daytime frequency, and urgency incontinence associated with OAB were registered and followed up for 3 years. Data were collected on adverse drug reactions (ADR), changes in OAB symptoms, changes in Overactive Bladder Symptom Score (OABSS), and treatment discontinuations. Treatment persistence rates were calculated by Kaplan-Meier analysis. Eighty-one ADR were observed in 72/1139 patients (6.3%) through 1 year of mirabegron treatment, with the incidence highest during the first month. No significant change in residual urine volume was observed at any observation point up to 1 year of mirabegron treatment. Mirabegron was deemed "effective" in 883/1091 patients (80.9%) at 1 year/discontinuation. Total OABSS was decreased with statistical significance at 3 months, 6 months, and 1 year, or at discontinuation (P < 0.001 at each time point). Kaplan-Meier treatment persistence rates were 84.8% at 3 months, 77.6% at 6 months, and 66.0% at 1 year. Treatment persistence rates were similar for male and female patients but significantly higher for patients aged ≥65 years (67.3%; n = 908) compared with those aged <65 years (59.8%; n = 231; log-rank test: P = 0.032). Long-term OAB treatment with mirabegron was well-tolerated, with effectiveness maintained through 1 year. Mirabegron treatment persistence was higher than has been previously reported, and was greater in patients aged ≥65 years compared with those aged <65 years. © 2017 John Wiley & Sons Australia, Ltd.

Statins Reduces the Risk of Dementia in Patients with Late-Onset Depression: A Retrospective Cohort Study.

PubMed

Yang, Ya-Hsu; Teng, Hao-Wei; Lai, Yen-Ting; Li, Szu-Yuan; Lin, Chih-Ching; Yang, Albert C; Chan, Hsiang-Lin; Hsieh, Yi-Hsuan; Lin, Chiao-Fan; Hsu, Fu-Ying; Liu, Chih-Kuang; Liu, Wen-Sheng

2015-01-01

Patients with late-onset depression (LOD) have been reported to run a higher risk of subsequent dementia. The present study was conducted to assess whether statins can reduce the risk of dementia in these patients. We used the data from National Health Insurance of Taiwan during 1996-2009. Standardized Incidence Ratios (SIRs) were calculated for LOD and subsequent dementia. The criteria for LOD diagnoses included age ≥65 years, diagnosis of depression after 65 years of age, at least three service claims, and treatment with antidepressants. The time-dependent Cox proportional hazards model was applied for multivariate analyses. Propensity scores with the one-to-one nearest-neighbor matching model were used to select matching patients for validation studies. Kaplan-Meier curve estimate was used to measure the group of patients with dementia living after diagnosis of LOD. Totally 45,973 patients aged ≥65 years were enrolled. The prevalence of LOD was 12.9% (5,952/45,973). Patients with LOD showed to have a higher incidence of subsequent dementia compared with those without LOD (Odds Ratio: 2.785; 95% CI 2.619-2.958). Among patients with LOD, lipid lowering agent (LLA) users (for at least 3 months) had lower incidence of subsequent dementia than non-users (Hazard Ratio = 0.781, 95% CI 0.685-0.891). Nevertheless, only statins users showed to have reduced risk of dementia (Hazard Ratio = 0.674, 95% CI 0.547-0.832) while other LLAs did not, which was further validated by Kaplan-Meier estimates after we used the propensity scores with the one-to-one nearest-neighbor matching model to control the confounding factors. Statins may reduce the risk of subsequent dementia in patients with LOD.

Impact of smoking history on the outcomes of women with early-stage breast cancer: a secondary analysis of a randomized study.

PubMed

Abdel-Rahman, Omar; Cheung, Winson Y

2018-04-11

To assess the impact of smoking history on the outcomes of early-stage breast cancer patients treated with sequential anthracyclines-taxanes in a randomized study. This is a secondary analysis of patient-level data of 1242 breast cancer patients referred for adjuvant chemotherapy in the BCIRG005 clinical trial. Overall survival was assessed according to smoking history through Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses of factors affecting overall and relapse-free survival were subsequently conducted. Factors that were evaluated included: age, performance status, number of chemotherapy cycles, T stage, lymph node ratio, estrogen receptor status, adjuvant radiotherapy and smoking history. Kaplan-Meier analysis of overall survival according to smoking status (ever smoker vs. never smoker) was conducted. There was a trend toward a better overall survival among never smokers compared to ever smokers; however, it was not statistically significant (P = 0.098). The following factors were associated with better overall survival in multivariate analysis: older age (P = 0.011), complete chemotherapy course (P = 0.002), lower T stage (P < 0.0001), lower lymph node ratio (P < 0.0001) and positive estrogen receptor status (P = 0.006). Otherwise, the following factors were associated with better relapse-free survival in multivariate analysis: older age (P = 0.001), never smoking status (P = 0.021), lower T stage (P = 0.028), lower lymph node ratio (P < 0.0001) and positive estrogen receptor status (P < 0.0001). Early-stage breast cancer patients with a positive smoking history experienced worse relapse-free survival compared to never smokers. Physicians managing breast cancer patients should prioritize discussion about the benefits of smoking cessation when counseling their patients.

Pre-Treatment Anemia Is a Poor Prognostic Factor in Soft Tissue Sarcoma Patients

PubMed Central

Szkandera, Joanna; Gerger, Armin; Liegl-Atzwanger, Bernadette; Stotz, Michael; Samonigg, Hellmut; Ploner, Ferdinand; Stojakovic, Tatjana; Leithner, Andreas; Pichler, Martin

2014-01-01

Background Anemia refers to low hemoglobin (Hb) levels, represents a common symptom and complication in cancer patients and was reported to negatively influence survival in patients with various malignancies. In the present study, we aimed to explore the prognostic impact of pre-operative Hb levels on clinical outcome in a large cohort of soft tissue sarcoma (STS) patients after curative surgery. Methods Retrospective data from 367 STS patients, which were operated between 1998 and 2013, were included in the study. Cut-off levels for anemia were defined as Hb<13 g/dl in males and Hb<12 g/dl in females according to the current WHO guidelines. The impact of pre-operative Hb levels on cancer-specific survival (CSS) and overall survival (OS) was assessed using Kaplan-Meier curves. Additionally, Hb levels were compared for the prognostic influence on CSS and OS applying univariate and multivariate Cox proportional models. Results Hb level was associated with established prognostic factors, including age, tumor grade, size and depth (p<0.05). Kaplan-Meier curves showed that low Hb levels were significantly associated with decreased CSS and OS in STS patients (p<0.001 for both endpoints, log-rank test). In multivariate analysis, we found an independent association between low Hb levels and poor CSS and OS (HR = 0.46, Cl 95% = 0.25–0.85, p = 0.012; HR = 0.34, Cl 95% = 0.23–0.51, p<0.001). Conclusion The present data underline a negative prognostic impact of low pre-operative Hb levels on clinical outcome in STS patients. Thus, Hb levels may provide an additional and cost-effective tool to discriminate between STS patients that are at high risk of mortality. PMID:25207808

The role of the AMOP domain in MUC4/Y-promoted tumour angiogenesis and metastasis in pancreatic cancer.

PubMed

Tang, Jie; Zhu, Yi; Xie, Kunling; Zhang, Xiaoyu; Zhi, Xiaofei; Wang, Weizhi; Li, Zheng; Zhang, Qun; Wang, Linjun; Wang, Jiwei; Xu, Zekuan

2016-06-10

MUC4 is a high molecular weight membrane protein that is overexpressed in pancreatic cancer (PC) and is associated with the development and progression of this disease. However, the exact mechanisms through which MUC4 domains promote these biological processes have rarely been studied, partly because of its high molecular weight, difficulty to overexpress it. Here, we use MUC4/Y, one of the MUC4 transcript variants, as a model molecule to investigate the AMOP-domain of MUC4(MUC/Y). We used cell proliferation, migration, invasion and tube formation assays in vitro to explore the abilities of AMOP domain in PC. In vivo, the matrigel plug assay, orthotopic implantation and Kaplan-Meier survival curves were used to check the results we observed in vitro. Finally, we discovered the underlying mechanism through western blot and immunofluorescence. We found that MUC4/Y overexpression could enhance the angiogenic and metastatic properties of PC cells, both in vitro and in vivo. However, the deletion of AMOP domain could cutback these phenomena. Additionally, Kaplan-Meier survival curves showed that mice injected with MUC4/Y overexpressed cells had shorter survival time, compared with empty-vector-transfected cells (MUC4/Y-EV), or cells expressing MUC4/Y without the AMOP domain (MUC4/Y-AMOP(△)). Our data also showed that overexpression of MUC4/Y could activate NOTCH3 signaling, increasing the expression of downstream genes: VEGF-A, MMP-9 and ANG-2. The AMOP domain had an important role in MUC4/Y (MUC4)-mediated tumour angiogenesis and metastasis of PC cells; and the NOTCH3 signaling was involved. These findings provided new insights into PC therapies. Our study also supplies a new method to study other high molecular membrane proteins.

Survivorship Analysis and Clinical Outcomes of Transtibial Pullout Repair for Medial Meniscus Posterior Root Tears: A 5- to 10-Year Follow-up Study.

PubMed

Chung, Kyu Sung; Noh, June Mo; Ha, Jeong Ku; Ra, Ho Jong; Park, Sung Bae; Kim, Hyung Kook; Kim, Jin Goo

2018-02-01

This study investigated the clinical outcomes and mid- to long-term survival rates in patients undergoing transtibial pullout repair of medial meniscus posterior root tears (MMPRTs) after a minimum follow-up of 5 years. Between 2005 and 2011, patients with MMPRTs who had been followed for at least 5 years after undergoing transtibial pullout repair were recruited. Participants were identified using medical records and information in a prospectively collected database. Clinical outcomes were assessed based on a comparison of patient preoperative Lysholm scores and their scores at the final follow-up. A Kaplan-Meier survival analysis was used to investigate the survival rates of repair procedures. Clinical failures were defined as cases requiring conversion to total knee arthroplasty (TKA) or having final Lysholm score <65 or less than their preoperative scores. Overall, 91 patients (mean age, 58.7 ± 9.7 years) were included: the mean follow-up duration was 84.8 ± 13.8 months. Among these patients, the mean Lysholm score improved significantly from 51.8 ± 7.9 preoperatively to 83.0 ± 11.1 at the final follow-up (P < .001). Overall, 4 patients failed due to conversion to TKA (n = 1) or having final Lysholm scores <65 or less than the preoperative scores (n = 3). The overall Kaplan-Meier probabilities of survival after repair were 99% at 5 years, 98% at 6 years, 95% at 7 years, and 92% at 8 years. Among patients with MMPRTs, transtibial pullout repair demonstrated a high clinical survival rate and the patients demonstrated clinical improvement, based on mid- and long-term follow-up examinations. Level IV, retrospective uncontrolled case series. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Baseline and annual repeat rounds of screening: implications for optimal regimens of screening.

PubMed

Henschke, Claudia I; Salvatore, Mary; Cham, Matthew; Powell, Charles A; DiFabrizio, Larry; Flores, Raja; Kaufman, Andrew; Eber, Corey; Yip, Rowena; Yankelevitz, David F

2018-03-01

Differences in results of baseline and subsequent annual repeat rounds provide important information for optimising the regimen of screening. A prospective cohort study of 65,374 was reviewed to examine the frequency/percentages of the largest noncalcified nodule (NCN), lung cancer cell types and Kaplan-Meier (K-M) survival rates, separately for baseline and annual rounds. Of 65,374 baseline screenings, NCNs were identified in 28,279 (43.3%); lung cancer in 737 (1.1%). Of 74,482 annual repeat screenings, new NCNs were identified in 4959 (7%); lung cancer in 179 (0.24%). Only adenocarcinoma was diagnosed in subsolid NCNs. Percentages of lung cancers by cell type were significantly different (p < 0.0001) in the baseline round compared with annual rounds, reflecting length bias, as were the ratios, reflecting lead times. Long-term K-M survival rate was 100% for typical carcinoids and for adenocarcinomas manifesting as subsolid NCNs; 85% (95% CI 81-89%) for adenocarcinoma, 74% (95% CI 63-85%) for squamous cell, 48% (95% CI 34-62%) for small cell. The rank ordering by lead time was the same as the rank ordering by survival rates. The significant differences in the frequency of NCNs and frequency and aggressiveness of diagnosed cancers in baseline and annual repeat need to be recognised for an optimal regimen of screening. • Lung cancer aggressiveness varies considerably by cell type and nodule consistency. • Kaplan-Meier survival rates varied by cell type between 100% and 48%. • The percentages of lung cancers by cell type in screening rounds reflect screening biases. • Rank ordering by cell type survival is consistent with that by lead times. • Empirical evidence provides critical information for the regimen of screening.

Perioperative and mid-term oncologic outcomes of robotic assisted radical cystectomy with totally intracorporeal neobladder: Results of a propensity score matched comparison with open cohort from a single-centre series.

PubMed

Simone, Giuseppe; Tuderti, Gabriele; Misuraca, Leonardo; Anceschi, Umberto; Ferriero, Mariaconsiglia; Minisola, Francesco; Guaglianone, Salvatore; Gallucci, Michele

2018-04-17

In this study, we compared perioperative and oncologic outcomes of patients treated with either open or robot-assisted radical cystectomy and intracorporeal neobladder at a tertiary care center. The institutional prospective bladder cancer database was queried for "cystectomy with curative intent" and "neobladder". All patients underwent robot-assisted radical cystectomy and intracorporeal neobladder or open radical cystectomy and orthotopic neobladder for high-grade non-muscle invasive bladder cancer or muscle invasive bladder cancer with a follow-up length ≥2 years were included. A 1:1 propensity score matching analysis was used. Kaplan-Meier method was performed to compare oncologic outcomes of selected cohorts. Survival rates were computed at 1,2,3 and 4 years after surgery and the log rank test was applied to assess statistical significance between the matched groups. Overall, 363 patients (299 open and 64 robotic) were included. Open radical cystectomy patients were more frequently male (p = 0.08), with higher pT stages (p = 0.003), lower incidence of urothelial histologies (p = 0.05) and lesser adoption of neoadjuvant chemotherapy (<0.001). After applying the propensity score matching, 64 robot-assisted radical cystectomy patients were matched with 46 open radical cystectomy cases (all p ≥ 0.22). Open cohort showed a higher rate of perioperative overall complications (91.3% vs 42.2%, p 0.001). At Kaplan-Meier analysis robotic and open cohorts displayed comparable disease-free survival (log-rank p = 0.746), cancer-specific survival (p = 0.753) and overall-survival rates (p = 0.909). Robot-assisted radical cystectomy and intracorporeal neobladder provides comparable oncologic outcomes of open radical cystectomy and orthotopic neobladder at intermediate term survival analysis. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

CHIP involves in non-small cell lung cancer prognosis through VEGF pathway.

PubMed

Tingting, Qian; Jiao, Wang; Qingfeng, Wang; Yancheng, Liu; Shijun, Y U; Zhaoqi, Wang; Dongmei, Sun; ShiLong, Wang

2016-10-01

CHIP (c-terminal Hsp70-interacting protein) is an E3 ligase playing vital roles in various cancers. The VEGF pathway has become an important therapeutic target in non-small cell lung cancer (NSCLC). However, little is known about the role of CHIP and the relationship between CHIP and VEGF-VEGFR2 (VEGF receptor 2) pathway in NSCLC. In this study we aimed to investigate the clinical function of CHIP in NSCLC and explore the relevant regulatory mechanism. QRT-PCR was performed to detect CHIP expression in NSCLC tissues. The association of CHIP expression and clinical parameters was analyzed using the Chi-square test. Kaplan- Meier and Cox analyses were performed to identify the role of CHIP in the prognosis of NSCLC patients. ELISA test was used to detect the VEGF secretion of NSCLC cells and western blot were used to detected the protein expression of VEGFR2 in NSCLC cells. and the results revealed that CHIP expression was decreased in NSCLC tissues and significantly correlated with clinical stages, lymph node metastasis and distant metastasis (P<0.05). Moreover, Kaplan-Meier and Cox regression analyses showed that patients with negative expression of CHIP had a shorter survival time and CHIP could be an independent prognostic biomarker. In addition, ELISA tests showed that CHIP negatively regulated the secretion level of VEGF. Furthermore, western blot assay indicated that the VEGFR2 protein level was reduced after CHIP over-expression. Taken together, our findings demonstrate for the first time that CHIP may serve as a promising prognostic biomarker for NSCLC patients and it may be involved in NSCLC angiogenesis through regulating VEGF secretion and expression of VEGFR2. Copyright © 2016. Published by Elsevier Masson SAS.

Lymph node density as a prognostic predictor in patients with betel nut-related oral squamous cell carcinoma.

PubMed

Chang, Wei-Chin; Lin, Chun-Shu; Yang, Cheng-Yu; Lin, Chih-Kung; Chen, Yuan-Wu

2018-04-01

Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a poor prognostic factor. The histopathologic stage (e.g., pN) is used to evaluate the severity of lymph node metastasis; however, the current staging system insufficiently predicts survival and recurrence. We investigated clinical outcomes and lymph node density (LND) in betel nut-chewing individuals. We retrospectively analyzed 389 betel nut-exposed patients with primary OSCC who underwent surgical resection in 2002-2015. The prognostic significance of LND was evaluated by overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. Kaplan-Meier analyses showed that the 5-year OS and DFS rates in all patients were 60.9 and 48.9%, respectively. Multivariate analysis showed that variables independently prognostic for OS were aged population (hazard ratio [HR] = 1.6, 95% confidence interval [95% CI] = 1.1-2.5; P = .025), and cell differentiation classification (HR = 2.4, 95% CI = 1.4-4.2; P = .002). In pathologic N-positive patients, a receiver operating characteristic (ROC) curve for OS was used and indicated the best cutoff of 0.05, and the multivariate analysis showed that LND was an independent predictor of OS (HR = 2.2, 95% CI = 1.3-3.7; P = .004). Lymph node density, at a cutoff of 0.05, was an independent predictor of OS and DFS. OS and DFS underwent multiple analyses, and LND remained significant. The pathologic N stage had no influence in the OS analysis. LND is a more reliable predictor of survival in betel nut-chewing patients for further post operation adjuvant treatment, such as reoperation or adjuvant radiotherapy.

Coronary artery bypass surgery: are outcomes influenced by demographics or ability to pay?

PubMed

Mancini, M C; Cush, E M; Sweatman, K; Dansby, J

2001-05-01

To examine the relation of financial status and demographics to the outcomes of coronary artery bypass surgery (CABG) in the public hospital setting. Coronary artery bypass surgery is one of the most expensive and frequently performed surgical procedures in the United States. Considerable controversy surrounds the accessibility to quality cardiac care of indigent and minority populations. This study examines the hypothesis that demographics rather than access to care and economics influences outcomes in CABG. A retrospective review of 1,556 charts of patients who underwent CABG at Louisiana State University Health Sciences Center-Shreveport, a public hospital, during a 10-year period was performed. The parameters analyzed included sex, age, race, education, ejection fraction, comorbidities, surgical parameters, economics, complications, and cost of care. Comparisons were made between the insured and uninsured groups. Univariate statistical analysis was used to assess differences between groups. Kaplan-Meier survival curves were also generated. Two thirds of the patients were uninsured. The mean age of the uninsured patients was significantly lower than that of the insured patients. Ejection fractions were comparable. Comorbidities were similar, with a greater percentage of tobacco use in the uninsured population. Kaplan-Meier survival curves showed that the uninsured group had better overall survival and that the insured group manifested an increased rate of late death. The financially challenged population appears to present for treatment earlier in life with coronary artery disease. Risk factors between the two groups were similar, except that tobacco use appears to be a significant problem in the disadvantaged population. The disease severity in both populations appeared to be similar; however, the uninsured patients had equivalent early survival with better late survival. Access to care in both groups was equal. In the public hospital setting for the disease

Adherence to Drug-Refill Is a Useful Early Warning Indicator of Virologic and Immunologic Failure among HIV Patients on First-Line ART in South Africa

PubMed Central

El-Khatib, Ziad; Katzenstein, David; Marrone, Gaetano; Laher, Fatima; Mohapi, Lerato; Petzold, Max; Morris, Lynn; Ekström, Anna Mia

2011-01-01

Background Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa. Methods In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12–99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO). Results After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2–6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2–3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02). Conclusion One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure. PMID:21408071

Satisfactory Results of the Exeter Revision Femoral Stem Used for Primary Total Hip Arthroplasty.

PubMed

Desy, Nicholas M; Johnson, Joshua D; Sierra, Rafael J

2017-02-01

The Exeter cemented femoral stem has demonstrated excellent clinical and radiographic outcomes as well as long-term survivorship free from aseptic loosening. A shorter revision stem (125 mm) with a 44 offset became available for the purpose of cement-in-cement revision situations. In certain cases, this shorter revision stem may be used for various primary total hip arthroplasties (THAs) where the standard length stem would require distally reaming the femoral canal. We sought to report on the early to midterm results of this specific stem when used for primary THA regarding (1) clinical and radiographic outcomes, (2) complications, and (3) survivorship. Twenty-nine patients (33 hips) underwent a hybrid THA using the smaller revision Exeter cemented femoral stem. Twenty-five patients (28 hips) had at least 2 years of follow-up and were assessed for clinical and radiographic outcomes. All 33 hips were included in the analysis of complications and survivorship. The Kaplan-Meier survivorship was performed using revision for all causes and for aseptic loosening as the end points. The average clinical follow-up was 4 years (range, 2-7). Harris Hip Scores improved from a mean preoperative value of 56 (range, 23-96) to 90 (range, 51-100) at the latest follow-up. All patients demonstrated superior cement mantles with no signs of loosening. One patient suffered a B2 periprosthetic fracture and 1 patient experienced 2 episodes of instability. The 5-year Kaplan-Meier survivorship was 96.7% for all causes of revision and was 100% using aseptic loosening as the end point. The shorter Exeter revision cemented femoral stem has favorable early to midterm clinical and radiographic outcomes when used for primary THA with a low complication rate and is a viable option in patients with narrow femoral canals where uncemented stem fixation is not desired. Copyright © 2016 Elsevier Inc. All rights reserved.

Validating a Local Failure Risk Stratification for Use in Prospective Studies of Adjuvant Radiation Therapy for Bladder Cancer

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

Baumann, Brian C.; He, Jiwei; Hwang, Wei-Ting

Purpose: To inform prospective trials of adjuvant radiation therapy (adj-RT) for bladder cancer after radical cystectomy, a locoregional failure (LF) risk stratification was proposed. This stratification was developed and validated using surgical databases that may not reflect the outcomes expected in prospective trials. Our purpose was to assess sources of bias that may affect the stratification model's validity or alter the LF risk estimates for each subgroup: time bias due to evolving surgical techniques; trial accrual bias due to inclusion of patients who would be ineligible for adj-RT trials because of early disease progression, death, or loss to follow-up shortlymore » after cystectomy; bias due to different statistical methods to estimate LF; and subgrouping bias due to different definitions of the LF subgroups. Methods and Materials: The LF risk stratification was developed using a single-institution cohort (n=442, 1990-2008) and the multi-institutional SWOG 8710 cohort (n=264, 1987-1998) treated with radical cystectomy with or without chemotherapy. We evaluated the sensitivity of the stratification to sources of bias using Fine-Gray regression and Kaplan-Meier analyses. Results: Year of radical cystectomy was not associated with LF risk on univariate or multivariate analysis after controlling for risk group. By use of more stringent inclusion criteria, 26 SWOG patients (10%) and 60 patients from the single-institution cohort (14%) were excluded. Analysis of the remaining patients confirmed 3 subgroups with significantly different LF risks with 3-year rates of 7%, 17%, and 36%, respectively (P<.01), nearly identical to the rates without correcting for trial accrual bias. Kaplan-Meier techniques estimated higher subgroup LF rates than competing risk analysis. The subgroup definitions used in the NRG-GU001 adj-RT trial were validated. Conclusions: These sources of bias did not invalidate the LF risk stratification or substantially change the model's LF

Hyperfibrinogenemia is a poor prognostic factor in diffuse large B cell lymphoma.

PubMed

Niu, Jun-Ying; Tian, Tian; Zhu, Hua-Yuan; Liang, Jin-Hua; Wu, Wei; Cao, Lei; Lu, Rui-Nan; Wang, Li; Li, Jian-Yong; Xu, Wei

2018-06-02

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas worldwide. Previous studies indicated that hyperfibrinogenemia was a poor predictor in various tumors. The purpose of our study was to evaluate the prognostic effect of hyperfibrinogenemia in DLBCL. Data of 228 patients, who were diagnosed with DLBCL in our hospital between May 2009 and February 2016, were analyzed retrospectively. The Kaplan-Meier method and Cox regression were performed to find prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curve and the areas under the curve were used to evaluate the predictive accuracy of predictors. Comparison of characters between groups indicated that patients with high National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score (4-8) and advanced stage (III-IV) were more likely to suffer from hyperfibrinogenemia. The Kaplan-Meier method revealed that patients with hyperfibrinogenemia showed inferior PFS (P < 0.001) and OS (P < 0.001) than those without hyperfibrinogenemia. Multivariate analysis showed that hyperfibrinogenemia was an independent prognostic factor associated with poor outcomes (HR = 1.90, 95% CI: 1.15-3.16 for PFS, P = 0.013; HR = 2.65, 95% CI: 1.46-4.79 for OS, P = 0.001). We combined hyperfibrinogenemia and NCCN-IPI to build a new prognostic index (NPI). The NPI was demonstrated to have a superior predictive effect on prognosis (P = 0.0194 for PFS, P = 0.0034 for OS). Hyperfibrinogenemia was demonstrated to be able to predict poor outcome in DLBCL, especially for patients with advanced stage and high NCCN-IPI score. Adding hyperfibrinogenemia to NCCN-IPI could significantly improve the predictive effect of NCCN-IPI.

Setting the stage for medieval plague: Pre-black death trends in survival and mortality.

PubMed

DeWitte, Sharon N

2015-11-01

The 14(th) -century Black Death was one of the most devastating epidemics in human history, killing tens of millions of people in a short period of time. It is not clear why mortality rates during the epidemic were so high. One possibility is that the affected human populations were particularly stressed in the 14(th) century, perhaps as a result of repeated famines in areas such as England. This project examines survival and mortality in two pre-Black Death time periods, 11-12(th) centuries vs 13(th) century CE, to determine if demographic conditions were deteriorating before the epidemic occurred. This study is done using a sample of individuals from several London cemeteries that have been dated, in whole or in part, either to the 11-12(th) centuries (n = 339) or 13(th) century (n = 258). Temporal trends in survivorship and mortality are assessed via Kaplan-Meier survival analysis and by modeling time period as a covariate affecting the Gompertz hazard of adult mortality. The age-at-death distributions from the two pre-Black Death time periods are significantly different, with fewer older adults in 13(th) century. The results of Kaplan-Meier survival analysis indicate reductions in survival before the Black Death, with significantly lower survival in the 13(th) century (Mantel Cox p < 0.001). Last, hazard analysis reveals increases in mortality rates before the Black Death. Together, these results suggest that health in general was declining in the 13(th) century, and this might have led to high mortality during the Black Death. This highlights the importance of considering human context to understand disease in past and living human populations. © 2015 Wiley Periodicals, Inc.

Hypermethylation of testis derived transcript gene promoter significantly correlates with worse outcomes in glioblastoma patients.

PubMed

Wang, Li-jia; Bai, Yu; Bao, Zhao-shi; Chen, Yan; Yan, Zhuo-hong; Zhang, Wei; Zhang, Quan-geng

2013-01-01

Glioblastoma is the most common and lethal cancer of the central nervous system. Global genomic hypomethylation and some CpG island hypermethylation are common hallmarks of these malignancies, but the effects of these methylation abnormalities on glioblastomas are still largely unclear. Methylation of the O6-methylguanine-DNA methyltransferase promoter is currently an only confirmed molecular predictor of better outcome in temozolomide treatment. To better understand the relationship between CpG island methylation status and patient outcome, this study launched DNA methylation profiles for thirty-three primary glioblastomas (pGBMs) and nine secondary glioblastomas (sGBMs) with the expectation to identify valuable prognostic and therapeutic targets. We evaluated the methylation status of testis derived transcript (TES) gene promoter by microarray analysis of glioblastomas and the prognostic value for TES methylation in the clinical outcome of pGBM patients. Significance analysis of microarrays was used for genes significantly differently methylated between 33 pGBM and nine sGBM. Survival curves were calculated according to the Kaplan-Meier method, and differences between curves were assessed using the log-rank test. Then, we treated glioblastoma cell lines (U87 and U251) with 5-aza-2-deoxycytidines (5-aza-dC) and detected cell biological behaviors. Microarray data analysis identified TES promoter was hypermethylated in pGBMs compared with sGBMs (P < 0.05). Survival curves from the Kaplan-Meier method analysis revealed that the patients with TES hypermethylation had a short overall survival (P < 0.05). This abnormality is also confirmed in glioblastoma cell lines (U87 and U251). Treating these cells with 5-aza-dC released TES protein expression resulted in significant inhibition of cell growth (P = 0.013). Hypermethylation of TES gene promoter highly correlated with worse outcome in pGBM patients. TES might represent a valuable prognostic marker for glioblastoma.

PPFIA1 is upregulated in liver metastasis of breast cancer and is a potential poor prognostic indicator of metastatic relapse.

PubMed

Yang, Jing; Wu, Ning-Ni; Huang, De-Jia; Luo, Yao-Chang; Huang, Jun-Zhen; He, Hai-Yuan; Lu, Hai-Lin; Song, Wen-Ling

2017-07-01

Although the oncogenic role of PPFIA1 (liprin-α1) in breast cancer has been reported, whether its dysregulation is associated with metastasis risk or survival outcomes in breast cancer patients is not clear. Our primary data showed that PPFIA1 expression was significantly higher in liver metastatic breast tumors than in the primary tumors. Then, we tried to pool previous annotated genomic data to assess the prognostic value of PPFIA1 in distant metastasis-free survival, the risk of metastatic relapse, and metastatic relapse-free survival in breast cancer patients by data mining in two large databases, Kaplan-Meier plotter and bc-GenExMiner 4.0. Results from Kaplan-Meier plotter showed that although high PPFIA1 expression was generally associated with decreased distant metastasis-free survival in estrogen receptor+ patients, subgroup analysis only confirmed significant association in estrogen receptor+/N- (nodal negative) group (median survival, high PPFIA1 group vs low PPFIA1 cohort: 191.21 vs 236.22 months; hazard ratio: 2.23, 95% confidence interval: 1.42-3.5, p < 0.001), but not in estrogen receptor+/N+ (nodal positive) group (hazard ratio: 1.63, 95% confidence interval: 0.88-3.03, p = 0.12). In estrogen receptor- patients, there was no association between PPFIA1 expression and distant metastasis-free survival, no matter in Nm (nodal status mixed), N-, or N+ subgroups. In bc-GenExMiner 4.0, Nottingham Prognostic Index- and Adjuvant! Online-adjusted analysis validated the independent prognostic value of PPFIA1 in metastatic risks in estrogen receptor+/N- patients. Based on these findings, we infer that high PPFIA1 expression might be an independent prognostic indicator of increased metastatic relapse risk in patients with estrogen receptor+/N- breast cancer, but not in estrogen receptor+/N+ or estrogen receptor- patients.

Proton Beam Radiotherapy for Uveal Melanomas at Nice Teaching Hospital: 16 Years' Experience

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

Caujolle, Jean-Pierre, E-mail: ncaujolle@aol.co; Mammar, Hamid; Chamorey, Emmanuel Phar

2010-09-01

Purpose: To present the results of uveal melanomas treated at Nice Teaching Hospital. Methods and Materials: This retrospective study included 886 consecutive patients referred to our clinic for the treatment of uveal melanomas by proton beam radiotherapy from June 1991 to December 2007. Survival rates were determined by using Kaplan-Meier estimates, and prognostic factors were evaluated using the log-rank test or Cox model. Results: The number (percent total) of subjects staged according to the TNM classification system (6th edition) of malignant tumors included 39 stage T1 (4.4%), 420 stage T2 (47.40%), 409 stage T3 (46.16%), and 18 stage T4 (2.03%)more » patients. The median follow-up was 63.7 months. The Kaplan-Meier overall survival rate at 5 years according to the sixth edition TNM classification was 92% for T1, 89% for T2, 67% for T3, and 62% for T4; and at 10 years, 86% for T1, 78% for T2, 43% for T3, and 41% for T4. Five factors were found to be associated with an increased death rate: advanced age, tumor thickness, largest tumor basal diameter, tumor volume, and tumor volume-to-eyeball volume ratio. The metastasis-free survival rates were 88.3 % at 5 years and 76.4 % at 10 years. The local control rates were 93.9% at 5 years and 92.1% at 10 years. The ocular conservation rates were 91.1% at 5 years and 87.3% at 10 years. Conclusions: We report the results of a large series of patients treated for uveal melanomas with a very long follow-up. Despite the large tumor volume treated, our results were similar to previously published findings relating to proton beam therapy.« less

Impact of Age on the Prognosis of Operable Gastric Cancer Patients: An Analysis Based on SEER Database.

PubMed

Chen, Jie; Chen, Jinggui; Xu, Yu; Long, Ziwen; Zhou, Ye; Zhu, Huiyan; Wang, Yanong; Shi, Yingqiang

2016-06-01

To investigate the impact of age on the clinicopathological features and survival of patients with gastric cancer (GC), and hope to better define age-specific patterns of GC and possible associated risk factors.Using the surveillance, epidemiology, and end results (SEER) database to search the patients who diagnosed GC between 2007 and 2011 with a known age. The overall and 5-year gastric cancer specific survival (CSS) data were obtained using Kaplan-Meier plots. Multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors.A total of 7762 GC patients treated with surgery during the 4-year study period were included in the final study cohort. We divided into five subgroups according to the different age ranges. The overall 5-year cause-specific survival (CSS) was 60.3% in Group 1 (below 45 years), 60.3% in the Group 2 (45-55 years), 61.2% in Group 3 (56-65 years), 59.2% in Group 4 (66-75 years), and 59.2% in Group 5 (older than 76 years). Kaplan-Meier plots showed that patients older than 76 years had the worst 5-year CSS of 56.0% rate in all the subgroups. Age, tumor size, primary site, histological type, and Tumor Node Metastasis stage were identified as significant risk factors for poor survival on univariate analysis (all P < 0.001, log-rank test). Additionally, as the age increased, the risk of death for GC demonstrated a significant increase.In conclusion, our analysis of the SEER database revealed that the prognosis of GC varies with age. Patients at age 56 to 65 group have more favorable clinicopathologic characteristics and better CSS than other groups.

The influence of sarcopenia on survival and surgical complications in ovarian cancer patients undergoing primary debulking surgery.

PubMed

Rutten, I J G; Ubachs, J; Kruitwagen, R F P M; van Dijk, D P J; Beets-Tan, R G H; Massuger, L F A G; Olde Damink, S W M; Van Gorp, T

2017-04-01

Sarcopenia, severe skeletal muscle loss, has been identified as a prognostic factor in various malignancies. This study aims to investigate whether sarcopenia is associated with overall survival (OS) and surgical complications in patients with advanced ovarian cancer undergoing primary debulking surgery (PDS). Ovarian cancer patients (n = 216) treated with PDS were enrolled retrospectively. Total skeletal muscle surface area was measured on axial computed tomography at the level of the third lumbar vertebra. Optimum stratification was used to find the optimal skeletal muscle index cut-off to define sarcopenia (≤38.73 cm 2 /m 2 ). Cox-regression and Kaplan-Meier analysis were used to analyse the relationship between sarcopenia and OS. The effect of sarcopenia on the development of major surgical complications was studied with logistic regression. Kaplan-Meier analysis showed a significant survival disadvantage for patients with sarcopenia compared to patients without sarcopenia (p = 0.010). Sarcopenia univariably predicted OS (HR 1.536 (95% CI 1.105-2.134), p = 0.011) but was not significant in multivariable Cox-regression analysis (HR 1.362 (95% CI 0.968-1.916), p = 0.076). Significant predictors for OS in multivariable Cox-regression analysis were complete PDS, treatment in a specialised centre and the development of major complications. Sarcopenia was not predictive of major complications. Sarcopenia was not predictive of OS or major complications in ovarian cancer patients undergoing primary debulking surgery. However a strong trend towards a survival disadvantage for patients with sarcopenia was seen. Future prospective studies should focus on interventions to prevent or reverse sarcopenia and possibly increase ovarian cancer survival. Complete cytoreduction remains the strongest predictor of ovarian cancer survival. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights

A prospective observational study comparing a physiological scoring system with time-based discharge criteria in pediatric ambulatory surgical patients.

PubMed

Armstrong, James; Forrest, Helen; Crawford, Mark W

2015-10-01

Discharge criteria based on physiological scoring systems can be used in the postanesthesia care unit (PACU) to fast-track patients after ambulatory surgery; however, studies comparing physiological scoring systems with traditional time-based discharge criteria are lacking. The purpose of this study was to compare PACU discharge readiness times using physiological vs time-based discharge criteria in pediatric ambulatory surgical patients. We recorded physiological observations from consecutive American Society of Anesthesiologists physical status I-III patients aged 1-18 yr who were admitted to the PACU after undergoing ambulatory surgery in a tertiary academic pediatric hospital. The physiological score was a combination of the Aldrete and Chung systems. Scores were recorded every 15 min starting upon arrival in the PACU. Patients were considered fit for discharge once they attained a score ≥12 (maximum score, 14), provided no score was zero, with the time to achieve a score ≥12 defining the criteria-based discharge (CBD) time. Patients were discharged from the PACU when both the CBD and the existing time-based discharge (TBD) criteria were met. The CBD and TBD data were compared using Kaplan-Meier and log-rank analysis. Observations from 506 children are presented. Median (interquartile range [IQR]) age was 5.5 [2.8-9.9] yr. Median [IQR] CBD and TBD PACU discharge readiness times were 30 [15-45] min and 60 [45-60] min, respectively. Analysis of Kaplan-Meier curves indicated a significant difference in discharge times using the different criteria (hazard ratio, 5.43; 95% confidence interval, 4.51 to 6.53; P < 0.001). All patients were discharged home without incident. This prospective study suggests that discharge decisions based on physiological criteria have the potential for significantly speeding the transit of children through the PACU, thereby enhancing PACU efficiency and resource utilization.

Validation of a two-tier grading system in an unselected, consecutive cohort of serous ovarian cancer patients.

PubMed

Battista, Marco Johannes; Cotarelo, Cristina; Almstedt, Katrin; Heimes, Anne-Sophie; Makris, Georgios-Marios; Weyer, Veronika; Schmidt, Marcus

2016-09-01

New insights into the carcinogenesis of ovarian cancer (OC) lead to the definition of low-grade and high-grade serous OC. In this study, we validated the MD Anderson Cancer Center (MDACC) two-tier grading system and compared it with the traditional three-tier grading system as suggested by the International Federation of Gynecology and Obstetrics (FIGO). Consecutive patients with serous OC were enrolled. These two grading systems were assessed independently from each other. Kaplan-Meier estimates and Cox-regression analyses were performed to validate and compare their prognostic impact. 143 consecutive patients entered the study. According to the Kaplan-Meier estimates, the MDACC grading system (p = 0.001) predicted the progression free survival (PFS) more precisely than the FIGO system (p = 0.025). The MDACC grading system (p = 0.008) but not the FIGO system (p = 0.329) showed a statistically significant difference in terms of disease specific survival (DSS). Multivariable Cox-regression analyses revealed an independent prognostic impact of the MDACC grading system but not of the FIGO system for PFS (HR 1.570; 95 % CI 1.007-2.449; p = 0.047, and HR 0.712; 95 % CI 0.476-1.066; p = 0.099, respectively). Concerning DSS, the two-tier grading system but not the FIGO system showed a prognostic impact in a univariable Cox-regression analysis (HR 2.152; 95 % CI 1.207-3.835; p = 0.009, and HR 1.258; 95 % CI 0.801-1.975; p = 0.319, respectively). We were able to validate the MDACC grading system in serous OC. Moreover, this grading system was stronger associated with survival than the FIGO system.

Eigentumors for prediction of treatment failure in patients with early-stage breast cancer using dynamic contrast-enhanced MRI: a feasibility study

NASA Astrophysics Data System (ADS)

Chan, H. M.; van der Velden, B. H. M.; E Loo, C.; Gilhuijs, K. G. A.

2017-08-01

We present a radiomics model to discriminate between patients at low risk and those at high risk of treatment failure at long-term follow-up based on eigentumors: principal components computed from volumes encompassing tumors in washin and washout images of pre-treatment dynamic contrast-enhanced (DCE-) MR images. Eigentumors were computed from the images of 563 patients from the MARGINS study. Subsequently, a least absolute shrinkage selection operator (LASSO) selected candidates from the components that contained 90% of the variance of the data. The model for prediction of survival after treatment (median follow-up time 86 months) was based on logistic regression. Receiver operating characteristic (ROC) analysis was applied and area-under-the-curve (AUC) values were computed as measures of training and cross-validated performances. The discriminating potential of the model was confirmed using Kaplan-Meier survival curves and log-rank tests. From the 322 principal components that explained 90% of the variance of the data, the LASSO selected 28 components. The ROC curves of the model yielded AUC values of 0.88, 0.77 and 0.73, for the training, leave-one-out cross-validated and bootstrapped performances, respectively. The bootstrapped Kaplan-Meier survival curves confirmed significant separation for all tumors (P  <  0.0001). Survival analysis on immunohistochemical subgroups shows significant separation for the estrogen-receptor subtype tumors (P  <  0.0001) and the triple-negative subtype tumors (P  =  0.0039), but not for tumors of the HER2 subtype (P  =  0.41). The results of this retrospective study show the potential of early-stage pre-treatment eigentumors for use in prediction of treatment failure of breast cancer.

21 CFR 211.111 - Time limitations on production.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Production and... completion of each phase of production shall be established to assure the quality of the drug product...

21 CFR 211.111 - Time limitations on production.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Production and... completion of each phase of production shall be established to assure the quality of the drug product...

Bladder Function Preservation With Brachytherapy, External Beam Radiation Therapy, and Limited Surger in Bladder Cancer Patients: Long-Term Results

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

Aluwini, Shafak, E-mail: s.aluwini@erasmusmc.nl; Rooij, Peter H.E. van; Kirkels, Wim J.

2014-03-01

Purpose: To report long-term results of a bladder preservation strategy for muscle-invasive bladder cancer (MIBC) using external beam radiation therapy and brachytherapy/interstitial radiation therapy (IRT). Methods and Materials: Between May 1989 and October 2011, 192 selected patients with MIBC were treated with a combined regimen of preoperative external beam radiation therapy and subsequent surgical exploration with or without partial cystectomy and insertion of source carrier tubes for afterloading IRT using low dose rate and pulsed dose rate. Data for oncologic and functional outcomes were prospectively collected. The primary endpoints were local recurrence-free survival (LRFS), bladder function preservation survival, and salvage cystectomy-freemore » survival. The endpoints were constructed according to the Kaplan-Meier method. Results: The mean follow-up period was 105.5 months. The LRFS rate was 80% and 73% at 5 and 10 years, respectively. Salvage cystectomy-free survival at 5 and 10 years was 93% and 85%. The 5- and 10-year overall survival rates were 65% and 46%, whereas cancer-specific survival at 5 and 10 years was 75% and 67%. The distant metastases-free survival rate was 76% and 69% at 5 and 10 years. Multivariate analysis revealed no independent predictors of LRFS. Radiation Therapy Oncology Group grade ≥3 late bladder and rectum toxicity were recorded in 11 patients (5.7%) and 2 patients (1%), respectively. Conclusions: A multimodality bladder-sparing regimen using IRT offers excellent long-term oncologic outcome in selected patients with MIBC. The late toxicity rate is low, and the majority of patients preserve their functional bladder.« less

Potential impurities in drug substances: Compound-specific toxicology limits for 20 synthetic reagents and by-products, and a class-specific toxicology limit for alkyl bromides.

PubMed

Bercu, J P; Galloway, S M; Parris, P; Teasdale, A; Masuda-Herrera, M; Dobo, K; Heard, P; Kenyon, M; Nicolette, J; Vock, E; Ku, W; Harvey, J; White, A; Glowienke, S; Martin, E A; Custer, L; Jolly, R A; Thybaud, V

2018-04-01

This paper provides compound-specific toxicology limits for 20 widely used synthetic reagents and common by-products that are potential impurities in drug substances. In addition, a 15 μg/day class-specific limit was developed for monofunctional alkyl bromides, aligning this with the class-specific limit previously defined for monofunctional alkyl chlorides. Both the compound- and class-specific toxicology limits assume a lifetime chronic exposure for the general population (including sensitive subpopulations) by all routes of exposure for pharmaceuticals. Inhalation-specific toxicology limits were also derived for acrolein, formaldehyde, and methyl bromide because of their localized toxicity via that route. Mode of action was an important consideration for a compound-specific toxicology limit. Acceptable intake (AI) calculations for certain mutagenic carcinogens assumed a linear dose-response for tumor induction, and permissible daily exposure (PDE) determination assumed a non-linear dose-response. Several compounds evaluated have been previously incorrectly assumed to be mutagenic, or to be mutagenic carcinogens, but the evidence reported here for such compounds indicates a lack of mutagenicity, and a non-mutagenic mode of action for tumor induction. For non-mutagens with insufficient data to develop a toxicology limit, the ICH Q3A qualification thresholds are recommended. The compound- and class-specific toxicology limits described here may be adjusted for an individual drug substance based on treatment duration, dosing schedule, severity of the disease and therapeutic indication. Copyright © 2018. Published by Elsevier Inc.

New signatures and limits on R-parity violation from resonant squark production

DOE PAGES

Monteux, Angelo

2016-03-31

Here, we discuss resonant squark production at the LHC via baryonic R-parity violating interactions. The cross section easily exceeds pair-production and a new set of signatures can be used to probe squarks, particularly stops. These include dijet resonances, same-sign top quarks and four-jet resonances with large b-jet multiplicities, as well as the possibility of displaced neutralino decays. We use publicly available searches at √s = 8 TeV and first results from collisions at √s = 13 TeV to set upper limits on R-parity violating couplings, with particular focus on simplified models with light stops and neutralinos. The exclusion reach ofmore » these signatures is comparable to R-parity-conserving searches, m t ~ ≃ 500–700 GeV. In addition, we find that O(1) couplings involving the stop can be excluded well into the multi-TeV range, and stress that new searches for single- and pair-produced four-jet resonances will be necessary to exclude sub-TeV stops for a natural SUSY spectrum with light higgsinos.« less